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Barnard S, Gattu R, Baragi VM, Alzohaili O, Benson R. Identifying Growth Hormone Deficiency in Brain-Injured Patients: The Quality of Life Scale-99. J Neurotrauma 2025; 42:379-390. [PMID: 39681340 DOI: 10.1089/neu.2024.0114] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2024] Open
Abstract
Traumatic brain injury (TBI) is frequently associated with hypopituitarism. The hypothalamic-pituitary axis appears to be susceptible to the same forces that cause injury to the parenchyma of the brain. Following even a mild TBI (mTBI), patients may suffer transient or permanent decreases in anterior pituitary hormones, including somatotropin (growth hormone [GH]), gonadotropins (luteinizing hormone and follicle-stimulating hormone), thyrotropin, and adrenocorticotropic hormone, with the most frequent long-term deficiency being GH deficiency (GHD). GHD is common after mTBI and is often the cause of persistent post-concussive symptoms a year or more post-injury. GHD is known to cause physical and cognitive fatigue, cognitive inefficiency, metabolic changes, and a range of psychological symptoms. Confusing the picture is that some symptoms of GHD are also common to brain injury itself. To facilitate the detection of GHD when comorbid with TBI, we utilized a new symptom inventory, the Quality-of-Life Scale-99 (QoLS-99), and administered it to a cohort of chronic TBI subjects with and without GHD, distinguished using the insulin tolerance test (ITT). Between 2018 and 2023, 371 patients completed the QoLS-99, of which 263 underwent GH testing with the ITT. Of these 263 patients, 136 (52%) were diagnosed with GHD. A retrospective comparison of QoLS-99 scores found that loss of libido (p < 0.006), a reliance on sleep aids (p < 0.011), and feeling overweight (p < 0.015) were the strongest univariate predictors of GHD. Most survey items did not elicit a significant difference in response between the GHD groups, and for those that did, effect sizes were mild to moderate. Still, initial findings demonstrate strong predictive value in a subset of survey items (i.e., GHD symptoms) that are most discriminating in the sample of patients with TBI. A multivariate prediction model using this subset of questions was able to differentiate GHD status in patients with TBI, correctly identifying 88% of GHD cases with a 37% false positive rate. Based on these findings, we recommend that clinicians inquire about libido, insomnia, and body image as potential markers for GHD. Furthermore, given the amenability of patients with GHD to growth hormone replacement therapy, we strongly encourage clinicians and basic scientists to develop interventions for the large and underserved population of patients with TBI with comorbid GHD.
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Wang HJ, Fan W, Liu S, Kim K, Matsushima A, Ogawa S, Kang HG, Zhu J, Estepa G, He M, Crossley L, Liddle C, Kim MS, Truitt ML, Yu RT, Atkins AR, Downes M, Evans RM. BCL6 coordinates muscle mass homeostasis with nutritional states. Proc Natl Acad Sci U S A 2025; 122:e2408896122. [PMID: 39841144 PMCID: PMC11789089 DOI: 10.1073/pnas.2408896122] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2024] [Accepted: 12/16/2024] [Indexed: 01/23/2025] Open
Abstract
Nutritional status is a determining factor for growth during development and homeostatic maintenance in adulthood. In the context of muscle, growth hormone (GH) coordinates growth with nutritional status; however, the detailed mechanisms remain to be fully elucidated. Here, we show that the transcriptional repressor B cell lymphoma 6 (BCL6) maintains muscle mass by sustaining GH action. Muscle-specific genetic deletion of BCL6 at either perinatal or adult stages profoundly reduces muscle mass and compromises muscle strength. Conversely, muscle-directed viral overexpression of BCL6 significantly reverses the loss of muscle mass and strength. Mechanistically, we show that BCL6 transcriptionally represses the suppressor of cytokine signaling 2 to sustain the anabolic actions of GH in muscle. Additionally, we find that GH itself transcriptionally inhibits BCL6 through the Janus kinase and signal transducer and activator of transcription 5 (JAK/STAT5) pathway. Supporting the physiologic relevance of this feedback regulation, we show the coordinated suppression of muscle Bcl6 expression with the induction of GH in the fasted state. These findings reveal the complexity of the feedback controls modulating GH signaling and identify BCL6 as a key homeostatic regulator coordinating muscle mass with nutrient availability. Moreover, these studies open avenues for targeted therapeutic strategies to combat muscle-wasting conditions.
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Affiliation(s)
- Hui J. Wang
- Gene Expression Laboratory, Salk Institute, La Jolla, CA92037-1002
| | - Weiwei Fan
- Gene Expression Laboratory, Salk Institute, La Jolla, CA92037-1002
| | - Sihao Liu
- Gene Expression Laboratory, Salk Institute, La Jolla, CA92037-1002
| | - Kyeongkyu Kim
- Gene Expression Laboratory, Salk Institute, La Jolla, CA92037-1002
| | - Ayami Matsushima
- Department of Chemistry, Faculty of Science, Kyushu University, Fukuoka819-0395, Japan
| | - Satoshi Ogawa
- Gene Expression Laboratory, Salk Institute, La Jolla, CA92037-1002
| | - Hyun Gyu Kang
- Gene Expression Laboratory, Salk Institute, La Jolla, CA92037-1002
| | - Jonathan Zhu
- Gene Expression Laboratory, Salk Institute, La Jolla, CA92037-1002
| | - Gabriela Estepa
- Gene Expression Laboratory, Salk Institute, La Jolla, CA92037-1002
| | - Mingxiao He
- Gene Expression Laboratory, Salk Institute, La Jolla, CA92037-1002
| | - Lillian Crossley
- Gene Expression Laboratory, Salk Institute, La Jolla, CA92037-1002
| | - Christopher Liddle
- Storr Liver Centre, Westmead Institute for Medical Research and Sydney Medical School, University of Sydney, Westmead, NSW2124, Australia
| | - Minseok S. Kim
- Department of New Biology, Daegu Gyeongbuk Institute of Science and Technology, Daegu42988, Republic of Korea
| | - Morgan L. Truitt
- Gene Expression Laboratory, Salk Institute, La Jolla, CA92037-1002
| | - Ruth T. Yu
- Gene Expression Laboratory, Salk Institute, La Jolla, CA92037-1002
| | | | - Michael Downes
- Gene Expression Laboratory, Salk Institute, La Jolla, CA92037-1002
| | - Ronald M. Evans
- Gene Expression Laboratory, Salk Institute, La Jolla, CA92037-1002
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Kumari A, Pal A, Dada R. Effects of Yogic Practices Synchronized With Bandha and Kumbhaka on Biological and Psychological Factors of Aging in COVID-19-Recovered Patients: A Randomized Controlled Trial. Cureus 2024; 16:e71884. [PMID: 39559592 PMCID: PMC11573461 DOI: 10.7759/cureus.71884] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/19/2024] [Indexed: 11/20/2024] Open
Abstract
Background and objectives Accelerated biological aging and age-associated diseases are strong risk factors for mortality and morbidity. Oxidative stress (OS) and anemia are possible pathophysiological causes of the various organ dysfunctions observed during COVID-19, decreasing health and life span. Ancient Yogic science seems to optimize all dimensions of human existence. As mentioned in ancient Yogic scriptures and documented in various studies, Yoga has been found to control accelerated biological aging and associated diseases. The study's objective was to authenticate and look into the effect of Yogic practices specifically synchronized with Kumbhaka and Bandha on markers of accelerated aging. Methods This randomized controlled trial was carried out in Mahendergarh city of Haryana on COVID-19-recovered adults aged between 30 and 60 years; 126 adults were randomized into two groups from Mahendergarh city: a control group (CG), 61 adults, and the experimental group (EG), 65 adults. During the final analysis, 56 adults in the experimental group received Yogic intervention for 120 days, and 61 adults remained the same in the control group during the intervention period. Consenting participants were randomized using computer-generated block randomization. The Yogic intervention was done 60 minutes/day five days a week for six months. Both groups' laboratory tests were carried out, which included malondialdehyde (MDA) level, total antioxidant capacity (TAC), glutathione (GSH) levels, hemoglobin (Hgb) level, body mass index (BMI), mental stress (perceived stress), and quality of life (QOL), which were estimated before and after the Yogic intervention. Results Yoga practice for 120 days (three mandals) in the experimental group has significantly reduced MDA level (p = 0.03) and perceived stress level (Perceived Stress Scale {PSS}) (p = 0.047), and BMI decreased in the Yoga group from 24.2 ± 4.8 to 23.6 ± 4.8, but no significant difference was observed in the values of BMI (p = 0.54). Improved antioxidant levels such as GSH level (p = 0.02), serum ferric-reducing antioxidant power (FRAP)/TAC activity (p = 0.04), and Hgb level (p = 0.02) were reported; with this, improved quality of life, World Health Organization Quality of Life (WHOQOL) Physical (p = 0.03), WHOQOL Psychological (p = 0.02), WHOQOL Social (p = 0.04), and WHOQOL Environment (p = 0.006), has been observed in the experimental group, whereas in the control group, we observed no significant difference in MDA level (p = 0.38), GSH level (p = 0.97), TAC level (p = 0.96), Hgb level (p = 1), BMI (p = 0.85), PSS (p = 0.83), and quality of life, WHOQOL Physical (p = 0.37), WHOQOL Psychological (p = 0.88), WHOQOL Social (p = 0.96), and WHOQOL Environment (p = 0.32). Conclusion These findings suggest that Yoga synchronized with Kumbhaka and Bandha may be a useful strategy for lowering oxidative stress and mental stress and improving antioxidant defense, hemoglobin level, and overall quality of life in COVID-19-recovered people, which might help reverse the biological decline of the human body and mind. The results of this study show that Yoga may break the link between old age and ill health. Hence, Yoga (with Bandha and Kumbhaka) may be the most reproducible way to extend the life span of humans, as mentioned in ancient Yogic scriptures.
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Affiliation(s)
- Anuj Kumari
- Yoga Sciences, Central University of Haryana, Mahendergarh, IND
| | - Ajay Pal
- Yoga Sciences, Central University of Haryana, Mahendergarh, IND
| | - Rima Dada
- Anatomy, Laboratory for Molecular Reproduction and Genetics, All India Institute of Medical Sciences, New Delhi, New Delhi, IND
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Wójcik M, Zieba DA, Bochenek J, Krawczyńska A, Barszcz M, Gajewska A, Antushevich H, Herman AP. The Effect of Endotoxin-Induced Inflammation on the Activity of the Somatotropic Axis in Sheep. Int J Inflam 2024; 2024:1057299. [PMID: 39149693 PMCID: PMC11325012 DOI: 10.1155/2024/1057299] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2024] [Revised: 05/31/2024] [Accepted: 07/27/2024] [Indexed: 08/17/2024] Open
Abstract
The hypothalamic-pituitary-somatotropic (HPS) axis controls many physiological and pathophysiological processes. The phenomenon of insensitivity to growth hormone resistance (GHres) was previously reported to be due to the development of inflammation. Therefore, the primary aim of the study was to determine the impact of inflammation caused by lipopolysaccharides (LPS) on the secretory activity of the HPS axis in sheep. The further goal was to determine the effect of inflammatory factors on individual components involved in intracellular signal transduction to GH via the GH receptor (GHR). The research was carried out on 24 seasonal sheep kept under a short-day photoperiod, randomly divided into two groups. Before the experiment, the sheep estrous cycles were synchronized. The results of the current study in a sheep model showed that inflammation impairs the activity of the somatotropic axis. On the one hand, LPS injection stimulated (p < 0.01) GH secretion, and on the other hand, it reduced the liver's sensitivity to this hormone by directly reducing (p < 0.01) GHR expression and activating the GHR inhibitory signal transduction mechanism. A symptom of such an inhibitory postreceptor signaling pathway may be due to an increase in SOCS3 expression (p < 0.01). The effect of various inhibition pathways is a significant reduction in the expression of the main transcription activator IGF1-STAT5B (p < 0.05). The action of GHres in the liver resulted in the inhibition of IGF1 secretion, which in the long term may have negative consequences for growth and development. Our study suggests that disruption of the GH cell signaling pathway may be one of the important elements of the pathophysiology of inflammation. It can suppress growth and hepatic metabolism to spare energy expenditure.
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Affiliation(s)
- Maciej Wójcik
- The Kielanowski Institute of Animal Physiology and Nutrition Polish Academy of Sciences, Instytucka 3 Street, Jabłonna 05-110, Poland
| | - Dorota Anna Zieba
- Department of Nutrition and Animal Biotechnology, and Fisheries Faculty of Animal Sciences University of Agriculture in Krakow, Krakow 31-120, Poland
| | - Joanna Bochenek
- The Kielanowski Institute of Animal Physiology and Nutrition Polish Academy of Sciences, Instytucka 3 Street, Jabłonna 05-110, Poland
| | - Agata Krawczyńska
- The Kielanowski Institute of Animal Physiology and Nutrition Polish Academy of Sciences, Instytucka 3 Street, Jabłonna 05-110, Poland
| | - Marcin Barszcz
- The Kielanowski Institute of Animal Physiology and Nutrition Polish Academy of Sciences, Instytucka 3 Street, Jabłonna 05-110, Poland
| | - Alina Gajewska
- The Kielanowski Institute of Animal Physiology and Nutrition Polish Academy of Sciences, Instytucka 3 Street, Jabłonna 05-110, Poland
| | - Hanna Antushevich
- The Kielanowski Institute of Animal Physiology and Nutrition Polish Academy of Sciences, Instytucka 3 Street, Jabłonna 05-110, Poland
| | - Andrzej Przemysław Herman
- The Kielanowski Institute of Animal Physiology and Nutrition Polish Academy of Sciences, Instytucka 3 Street, Jabłonna 05-110, Poland
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Nadarajah N, Ssemmondo E, Brooks S, Akinyombo R, Adeleke K, Deshmukh H, Sathyapalan T. Baseline Clinical Factors Associated with Cessation of Growth Hormone Therapy in Patients with Severe Growth Hormone Deficiency - Real World Evidence. Int J Endocrinol Metab 2024; 22:e147825. [PMID: 39839805 PMCID: PMC11742744 DOI: 10.5812/ijem-147825] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/06/2024] [Revised: 07/23/2024] [Accepted: 09/17/2024] [Indexed: 01/23/2025] Open
Abstract
Background Growth hormone replacement is indicated in adults with severe growth hormone (GH) deficiency, adult growth hormone deficiency assessment (AGHDA) score of at least 11 and are receiving treatment for other pituitary hormone deficiencies. There are no data looking at the cessation of GH replacement in adult patients with severe GH deficiency and the factors that predict the likelihood of patients continuing or stopping growth hormone replacement. Methods We audited patients on the GH register between January 2006 and January 2023 in Hull University Teaching Hospitals NHS foundation Trust, a UK tertiary hospital. Baseline characteristics, the cause of GH deficiency, AGHDA score at diagnosis and the reason for stopping GH were collected. Proportions were compared between patients adhering to GH replacement and those who had ceased it. Logistic regression analysis was used to identify factors independently associated with cessation of GH. Results The study comprised 141 adult patients with a mean age of 52 years, of which 75 (53%) were female. 54 (38%) individuals had discontinued GH replacement therapy. Predominant reasons for discontinuation were lack of therapeutic benefit (46%) and a change in clinical indication (26%). Among patients who discontinued GH therapy, the most frequent cause of GH deficiency was idiopathic (57%), while for those on GH replacement, pituitary surgery was the leading cause of GH deficiency (53%). Logistic regression analysis showed no baseline factor was statistically significantly associated with GH cessation, except female gender which had a borderline significance (P = 0.05). Conclusions In this real-world investigation of patients with severe GH deficiency, over two in five individuals who discontinued GH therapy cited the absence of perceived benefits. We show a borderline association of female gender with GH cessation and large population-based studies will be needed to investigate this and other causes of GH cessation.
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Affiliation(s)
- Nageswary Nadarajah
- Allam Diabetes Centre, Hull University Teaching Hospitals NHS Foundation Trust, Hull, UK
| | - Emmanuel Ssemmondo
- Allam Diabetes Centre, Hull University Teaching Hospitals NHS Foundation Trust, Hull, UK
- Academic Diabetes, Endocrinology and Metabolism, Allam Diabetes Centre, University of Hull, Hull, UK
| | - Shani Brooks
- Allam Diabetes Centre, Hull University Teaching Hospitals NHS Foundation Trust, Hull, UK
| | - Remi Akinyombo
- Allam Diabetes Centre, Hull University Teaching Hospitals NHS Foundation Trust, Hull, UK
| | | | - Harshal Deshmukh
- Allam Diabetes Centre, Hull University Teaching Hospitals NHS Foundation Trust, Hull, UK
- Academic Diabetes, Endocrinology and Metabolism, Allam Diabetes Centre, University of Hull, Hull, UK
| | - Thozhukat Sathyapalan
- Allam Diabetes Centre, Hull University Teaching Hospitals NHS Foundation Trust, Hull, UK
- Academic Diabetes, Endocrinology and Metabolism, Allam Diabetes Centre, University of Hull, Hull, UK
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Yang H, Chen M, Xu H, Zhen Y, Zhang Y, Wang L, Duan L, Gong F, Zhu H, Pan H. Bone mineral density in adults growth hormone deficiency with different ages of onset: a real-world retrospective study. Endocrine 2024; 85:347-355. [PMID: 38536548 DOI: 10.1007/s12020-024-03786-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/25/2023] [Accepted: 03/12/2024] [Indexed: 07/14/2024]
Abstract
PURPOSE Bone mineral density (BMD) impairment is one of the critical factors for long-term quality of life in adults growth hormone deficiency (AGHD). This study aims to investigate the annual changes in BMD in AGHD patients with different ages of onset and to identify predicting factors that influence BMD. METHODS AGHD patients (n = 160) with available data for 4 years follow-up from a major tertiary medical center in China were retrospectively included (110 [68.8%] childhood-onset, 119 [74.4%] male). BMD of the axial bone (including total hip, neck of femur, and L1-4) derived from dual X-ray absorptiometry and final height were investigated at the first visit, 12 months, 24 months, 36 months, and 48 months thereafter. Low BMD was defined as Z-score ≤ -2. RESULTS The prevalence of low BMD was 30.0% at baseline and 12.5% at 4 years of follow-up. The CO AGHD group presented a significantly lower BMD than the AO AGHD group at the baseline (P = 0.009). In contrast, the CO AGHD group had significantly greater median annual BMD change than the AO AGHD group (0.044 vs. -0.0003 g/cm2/year in L1-4, P < 0.001), indicating a significant difference in the overall BMD trend between CO and AO groups. Childhood-onset (odds ratio [OR] 0.326, P = 0.012), low serum testosterone (OR 0.847; P = 0.004) and FT4 (OR 0.595; P = 0.039) level were independent risk factors for BMD loss. CONCLUSION The annual changes of BMD show a different pattern in AGHD patients with varying ages of onset. Patients with CO AGHD have a lower bone mass, and in general, appropriate replacement therapy is necessary for long-term bone health in AGHD patients.
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Affiliation(s)
- Hongbo Yang
- Key Laboratory of Endocrinology of National Health Commission, Department of Endocrinology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, No. 1 Shuaifuyuan, Dongcheng District, Beijing, China
| | - Meiping Chen
- Key Laboratory of Endocrinology of National Health Commission, Department of Endocrinology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, No. 1 Shuaifuyuan, Dongcheng District, Beijing, China
| | - Hanyuan Xu
- Key Laboratory of Endocrinology of National Health Commission, Department of Endocrinology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, No. 1 Shuaifuyuan, Dongcheng District, Beijing, China
- Department of Clinical Nutrition, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, No. 1 Shuaifuyuan, Dongcheng District, Beijing, China
| | - Yunfeng Zhen
- Department of Endocrinology, Hebei General Hospital, Shijiazhuang, Hebei, China
| | - Yuelun Zhang
- Medical Research Center, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 1 Shuaifuyuan, Dongcheng District, Beijing, China
| | - Linjie Wang
- Key Laboratory of Endocrinology of National Health Commission, Department of Endocrinology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, No. 1 Shuaifuyuan, Dongcheng District, Beijing, China
| | - Lian Duan
- Key Laboratory of Endocrinology of National Health Commission, Department of Endocrinology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, No. 1 Shuaifuyuan, Dongcheng District, Beijing, China
| | - Fengying Gong
- Key Laboratory of Endocrinology of National Health Commission, Department of Endocrinology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, No. 1 Shuaifuyuan, Dongcheng District, Beijing, China
| | - Huijuan Zhu
- Key Laboratory of Endocrinology of National Health Commission, Department of Endocrinology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, No. 1 Shuaifuyuan, Dongcheng District, Beijing, China.
| | - Hui Pan
- Key Laboratory of Endocrinology of National Health Commission, Department of Endocrinology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, No. 1 Shuaifuyuan, Dongcheng District, Beijing, China.
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Ebrahimi F, Andereggen L, Christ ER. Morbidities and mortality among hospitalized patients with hypopituitarism: Prevalence, causes and management. Rev Endocr Metab Disord 2024; 25:599-608. [PMID: 38802643 PMCID: PMC11162375 DOI: 10.1007/s11154-024-09888-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 03/15/2024] [Indexed: 05/29/2024]
Abstract
Hypopituitarism is a highly heterogeneous multisystem disorder that can have a major impact on long-term morbidity and mortality, but even more so during acute medical conditions requiring hospitalization. Recent studies suggest a significant in-hospital burden with prolonged length of stay, increased rate of intensive care unit (ICU) admission, and initiation of mechanical ventilation - all of which may lead to an increased risk of in-hospital mortality. On the one hand, patients with hypopituitarism are often burdened by metabolic complications, including obesity, hypertension, dyslipidemia, and hyperglycemia, which alone, or in combination, are known to significantly alter relevant physiological mechanisms, including metabolism, innate and adaptive immune responses, coagulation, and wound healing, thereby contributing to adverse in-hospital outcomes. On the other hand, depending on the extent and the number of pituitary hormone deficiencies, early recognition of hormone deficiencies and appropriate management and replacement strategy within a well-organized multidisciplinary team are even stronger determinants of short-term outcomes during acute hospitalization in this vulnerable patient population. This review aims to provide an up-to-date summary of recent advances in pathophysiologic understanding, clinical implications, and recommendations for optimized multidisciplinary management of hospitalized patients with hypopituitarism.
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Affiliation(s)
- Fahim Ebrahimi
- Department of Endocrinology, Diabetes and Metabolism, University Hospital Basel, Basel, Switzerland.
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, 17177, Stockholm, Sweden.
- Department of Gastroenterology and Hepatology, Clarunis University Center for Gastrointestinal and Liver Diseases, Basel, Switzerland.
| | - Lukas Andereggen
- Department of Neurosurgery, Cantonal Hospital Aarau, Aarau, Switzerland
- Faculty of Medicine, University of Bern, Bern, Switzerland
| | - Emanuel R Christ
- Department of Endocrinology, Diabetes and Metabolism, University Hospital Basel, Basel, Switzerland
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Shah DN, Chorya HP, Ramesh NN, Gnanasekaram S, Patel N, Sethi Y, Kaka N. Myopathies of endocrine origin: A review for physicians. Dis Mon 2024; 70:101628. [PMID: 37718136 DOI: 10.1016/j.disamonth.2023.101628] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/19/2023]
Abstract
Myopathies are a common manifestation of endocrine disorders. Endocrine myopathies are often overlooked while considering differential diagnoses in patients with musculoskeletal symptoms. The hindrance to mobility and the musculoskeletal discomfort owing to these myopathies are important causes of disability and depreciated quality of life in these patients. Endocrine myopathies occur due to the effects of endogenous or iatrogenic hormonal imbalance on skeletal muscle protein and glucose metabolism, disrupting the excitation-contraction coupling. Abnormalities of the pituitary, thyroid, parathyroid, adrenal, and gonadal hormones have all been associated with myopathies and musculoskeletal symptoms. Endocrine myopathies can either be the complication of a secondary endocrine disorder or a presenting symptom of a missed underlying disorder. Therefore, an underlying endocrine abnormality must always be excluded in all patients with musculoskeletal symptoms. This review presents a compilation of various endocrine myopathies, their etiopathogenesis, clinical presentation, diagnostic modalities, and treatment protocols.
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Affiliation(s)
- Devarsh N Shah
- Government Medical College Baroda, India; PearResearch, India
| | | | - N Nishitha Ramesh
- PearResearch, India; Father Muller Medical College, Mangalore, India
| | | | - Neil Patel
- PearResearch, India; GMERS Medical College, Himmatnagar, Gujarat, India
| | - Yashendra Sethi
- PearResearch, India; Government Doon Medical College, HNB Uttarakhand Medical Education University, Dehradun, Uttarakhand, India
| | - Nirja Kaka
- PearResearch, India; GMERS Medical College, Himmatnagar, Gujarat, India.
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Hepprich M, Ebrahimi F, Christ E. Dyslipidaemia and growth hormone deficiency - A comprehensive review. Best Pract Res Clin Endocrinol Metab 2023; 37:101821. [PMID: 37821339 DOI: 10.1016/j.beem.2023.101821] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/13/2023]
Abstract
Growth hormone deficiency (GHD) is a common complication of several pituitary and hypothalamic disorders and dependent on the onset of disease. It may have severe clinical implications ranging from growth retardation in childhood-onset, to impaired lipid metabolism and increased cardiovascular risk and mortality in adults. GH effectively modulates lipid metabolism at multiple levels and GHD has been associated with an atherogenic lipid profile, that can be reversed by GH replacement therapy. Despite increasing knowledge on the effects of GH on several key enzymes regulating lipid metabolism and recent breakthroughs in the development and wider availability of recombinant GH preparations, several questions remain regarding the replacement therapy in adults with GHD. This review aims to comprehensively summarize the current knowledge on (i) lipid profile abnormalities in individuals with GHD, (ii) proposed mechanisms of action of GH on lipid and lipoprotein metabolism, and (iii) clinical implications of GH replacement therapy in individuals diagnosed with GHD.
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Affiliation(s)
- Matthias Hepprich
- Department of Endocrinology, Diabetes and Metabolism, University Hospital Basel, Basel, Switzerland; Metabolic Centre, Cantonal Hospital Olten, Olten, Switzerland
| | - Fahim Ebrahimi
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Department of Gastroenterology and Hepatology, Clarunis University Center for Gastrointestinal and Liver Diseases, Basel, Switzerland
| | - Emanuel Christ
- Department of Endocrinology, Diabetes and Metabolism, University Hospital Basel, Basel, Switzerland.
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10
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Herodes M, Legaspi A, Garcia JM. Mild traumatic brain injury as a cause of adult growth hormone deficiency: Diagnosis and treatment. Best Pract Res Clin Endocrinol Metab 2023; 37:101818. [PMID: 37666680 DOI: 10.1016/j.beem.2023.101818] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 09/06/2023]
Abstract
In recent years, mild traumatic brain injury (mTBI) has been recognized as a cause of acquired growth hormone deficiency (AGHD) and is likely much more prevalent than previous estimates. There is great overlap between persistent symptoms following mTBI and those of AGHD and it is possible that these persistent symptoms of mTBI are, at least in part, due to or aggravated by AGHD. This article reviews the current literature of AGHD following mTBI, and proposes practice recommendations for the screening, diagnosis, and management of patients with AGHD following mTBI.
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Affiliation(s)
- Megan Herodes
- Geriatric Research, Education and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle, WA, USA; Division of Gerontology and Geriatric Medicine, Department of Medicine, University of Washington School of Medicine, Seattle, WA, USA.
| | - Aviel Legaspi
- Geriatric Research, Education and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle, WA, USA.
| | - Jose M Garcia
- Geriatric Research, Education and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle, WA, USA; Division of Gerontology and Geriatric Medicine, Department of Medicine, University of Washington School of Medicine, Seattle, WA, USA.
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11
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Herodes M, Le N, Anderson LJ, Migula D, Miranda G, Paulsen L, Garcia JM. Metabolic and quality of life effects of growth hormone replacement in patients with TBI and AGHD: A pilot study. Growth Horm IGF Res 2023; 71:101544. [PMID: 37295336 PMCID: PMC10527000 DOI: 10.1016/j.ghir.2023.101544] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/11/2023] [Revised: 05/25/2023] [Accepted: 05/27/2023] [Indexed: 06/12/2023]
Abstract
OBJECTIVE Traumatic brain injury (TBI), a common cause of adult growth hormone deficiency (AGHD), affects 20% of Veterans returning from Iraq and Afghanistan (OEF/OIF/OND). Growth hormone replacement therapy (GHRT) improves quality of life (QoL) in AGHD but remains unexplored in this population. This pilot, observational study investigates the feasibility and efficacy of GHRT in AGHD following TBI. DESIGN In this 6-month study of combat Veterans with AGHD and TBI starting GHRT (N = 7), feasibility (completion rate and rhGH adherence) and efficacy (improvements in self-reported QoL) of GHRT were measured (primary outcomes). Secondary outcomes included body composition, physical and cognitive function, psychological and somatic symptoms, physical activity, IGF-1 levels and safety parameters. It was hypothesized that participants would adhere to GHRT and that QoL would significantly improve after six months. RESULTS Five subjects (71%) completed all study visits. All patients administered daily rhGH injections, 6 (86%) of whom consistently administered the clinically-prescribed dose. While QoL demonstrated numeric improvement, this change did not reach statistical significance (p = 0.17). Significant improvements were observed in total lean mass (p = 0.02), latissimus dorsi strength (p = 0.05), verbal learning (Trial 1, p = 0.02; Trial 5, p = 0.03), attention (p = 0.02), short-term memory (p = 0.04), and post-traumatic stress disorder (PTSD) symptoms (p = 0.03). Body weight (p = 0.02) and total fat mass (p = 0.03) increased significantly. CONCLUSION GHRT is a feasible and well-tolerated intervention for U.S. Veterans with TBI-related AGHD. It improved key areas impacted by AGHD and symptoms of PTSD. Larger, placebo-controlled studies testing the efficacy and safety of this intervention in this population are warranted.
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Affiliation(s)
- Megan Herodes
- Geriatric Research, Education and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle, WA, USA; Division of Gerontology and Geriatric Medicine, University of Washington School of Medicine, Seattle, WA, USA
| | - Nancy Le
- Geriatric Research, Education and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle, WA, USA
| | - Lindsey J Anderson
- Geriatric Research, Education and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle, WA, USA
| | - Dorota Migula
- Geriatric Research, Education and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle, WA, USA
| | - Gary Miranda
- Geriatric Research, Education and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle, WA, USA; Division of Gerontology and Geriatric Medicine, University of Washington School of Medicine, Seattle, WA, USA
| | - Lauren Paulsen
- Geriatric Research, Education and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle, WA, USA
| | - Jose M Garcia
- Geriatric Research, Education and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle, WA, USA; Division of Gerontology and Geriatric Medicine, University of Washington School of Medicine, Seattle, WA, USA.
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12
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Abstract
Growth hormone (GH) regulates metabolic and physical health in the adult human. Because the GH system is regulated by estrogens, therapeutic estrogen compounds are likely to affect metabolic health. Estrogens are available for oral and parenteral use in natural, prodrug, and synthetic formulations including selective estrogen receptor modulators (SERMs). This review covers the pharmacology of estrogen and the effects on GH action to inform judicious use in the pituitary patient. The effects on the GH system are route dependent due to first-pass hepatic metabolism. Oral but not parenteral estrogen compounds inhibit GH action, reducing hepatic insulin-like growth factor-1 (IGF-1) production, protein anabolism, and fat utilization. In patients with GH deficiency, oral estrogen therapy exacerbates the degree of hyposomatotrophism and attenuates the beneficial effects of GH replacement therapy, effects that are greater with contraceptive than replacement doses. Surveys report that less than one-fifth of hypopituitary women are appropriately replaced by a transdermal route and up to half on oral therapy are inappropriately treated with contraceptive steroids. In acromegaly, however, estrogens, especially synthetic formulations of greater potency, reduce IGF-1, improving disease control, an effect also observed in men treated with SERMs. The route-dependent effects and potency of estrogen formulations are important considerations for optimizing the management of hypogonadal patients with pituitary disease, in particular GH deficiency and acromegaly. For hypopituitary women, estrogens should be replaced by a nonoral route. For acromegaly, oral estrogen formulations can be considered as simple adjuvant therapy for disease control.
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Affiliation(s)
- Nicholas Shoung
- Department of Diabetes and Endocrinology, Saint Vincent's Hospital, Sydney, NSW 2010, Australia
- Department of Medicine, Saint Vincent's Clinical School UNSW, Sydney, NSW 2010, Australia
| | - Ken K Y Ho
- Correspondence: Ken K. Y. Ho, MD, The Garvan Institute of Medical Research, 384 Victoria St, Darlinghurst, Sydney, NSW 2010, Australia.
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13
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García-Arnés JA, García-Casares N. Doping and sports endocrinology: growth hormone, IGF-1, insulin, and erythropoietin. Rev Clin Esp 2023; 223:181-187. [PMID: 36736729 DOI: 10.1016/j.rceng.2023.01.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
Among the substances prohibited by the World Anti-Doping Agency, "peptide hormones, growth factors, related substances, and mimetics" are classified as prohibited both in- and out-of-competition in section S2. This work reviews growth hormone and its releasing peptides, insulin-like growth factor 1 as the main growth factor, insulin, and erythropoietin and other agents that affect erythropoiesis. This review analyzes the prevalence of use among professional athletes and gym clients, the forms of use, dosing, ergogenic effects and effects on physical performance, as well as side effects and anti-doping detection methods.
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Affiliation(s)
- J A García-Arnés
- Departamento de Farmacología, Facultad de Medicina, Universidad de Málaga, Málaga, Spain.
| | - N García-Casares
- Departamento de Medicina, Facultad de Medicina, Universidad de Málaga, Málaga, Spain; Centro de Investigaciones Médico-Sanitarias (CIMES), Universidad de Málaga, Málaga, Spain; Instituto de Investigación Biomédica de Málaga (IBIMA), Málaga, Spain
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14
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Ebrahimi F, Christ E. Why do patients with hypopituitarism still present an increased mortality? ANNALES D'ENDOCRINOLOGIE 2023; 84:285-290. [PMID: 36809815 DOI: 10.1016/j.ando.2023.02.002] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/13/2023] [Revised: 02/10/2023] [Accepted: 02/13/2023] [Indexed: 02/21/2023]
Abstract
Hypopituitarism is defined as a lack or decreased secretion of one or several pituitary hormones. It can result from diseases of the pituitary gland or from pathologies of the superior regulatory center, i.e. the hypothalamus, thereby decreasing hypothalamic releasing hormones and consequently the pituitary hormones. It is still a rare disease with an estimated prevalence of 30-45 patients/100,000 and an incidence of 4-5/100,000/year. This review summarizes the currently available data with a focus on etiologies of hypopituitarism, evidence on mortality rates in patients with hypopituitarism, temporal trends in mortality , and associated diseases, pathophysiological mechanisms and risk factors that affect mortality risk in these patients.
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Affiliation(s)
- Fahim Ebrahimi
- Division of Endocrinology, Diabetology and Metabolism, University Hospital Basel, Basel, Switzerland; University Center for Gastrointestinal and Liver Diseases, St. Clara Hospital and University Hospital, Basel, Switzerland; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
| | - Emanuel Christ
- Division of Endocrinology, Diabetology and Metabolism, University Hospital Basel, Basel, Switzerland.
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15
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García-Arnés J, García-Casares N. Endocrinología del dopaje y los deportes: hormona de crecimiento, IGF-1, insulina y eritropoyetina. Rev Clin Esp 2023. [DOI: 10.1016/j.rce.2022.12.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/22/2023]
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16
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Ferruzzi A, Vrech M, Pietrobelli A, Cavarzere P, Zerman N, Guzzo A, Flodmark CE, Piacentini G, Antoniazzi F. The influence of growth hormone on pediatric body composition: A systematic review. Front Endocrinol (Lausanne) 2023; 14:1093691. [PMID: 36843617 PMCID: PMC9947344 DOI: 10.3389/fendo.2023.1093691] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/09/2022] [Accepted: 01/30/2023] [Indexed: 02/11/2023] Open
Abstract
BACKGROUND Growth hormone (GH) affects metabolism and regulates growth in childhood. The most prominent feature of GH deficiency (GHD) in children is diminished height velocity that eventually leads to short stature. In adult-onset GHD, lean body mass (LBM) is reduced, and visceral fat mass (FM) increased. Beneficial effects of GH treatment on body composition in adults with GHD, including an increase in muscle mass and a decrease in FM, are well established. Relatively few studies have investigated the effects of GH treatment on the body composition of pediatric patients with idiopathic or hypothalamic-pituitary disease-associated GH deficiency. This systematic review aimed to summarize available evidence relating to the effects of GH treatment on body composition in children with GHD. METHODS The PubMed, Science Direct, Cochrane Trials, and Embase databases, were searched with keywords including "GH", "body composition", "children", and "growth hormone" for English-language articles, published between January 1999 and March 2021. Two reviewers independently evaluated the search results and identified studies for inclusion based on the following criteria: participants had a confirmed diagnosis of GHD (as defined in each study); participants were pediatric patients who were receiving GH or had stopped GH treatment, regardless of whether they were pre- or post-pubertal; the intervention was recombinant human GH (rhGH; somatropin); and outcomes included changes in body composition during or after stopping GH therapy. Data extracted from each study included study quality, study sample characteristics, study interventions, and body composition. Data on fat-free mass and LBM were combined into a single category of LBM. RESULTS Sixteen studies reporting changes in body composition (i.e., FM and LBM) associated with GH treatment in children with GHD were identified and included in the review. Collectively, these studies demonstrated that FM decreased, and LBM increased in response to GH replacement therapy. CONCLUSION Despite study limitations (i.e., potential effects of diet and physical activity were not considered), we concluded that a periodic body composition assessment is required to ensure that a satisfactory body composition is achieved during GH replacement therapy in children with GHD.
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Affiliation(s)
- Alessandro Ferruzzi
- Department of Surgical Science, Dentistry, Gynecology and Pediatrics, Pediatric Unit, Verona University Medical School, Verona, Italy
| | - Massimiliano Vrech
- Department of Surgical Science, Dentistry, Gynecology and Pediatrics, Pediatric Unit, Verona University Medical School, Verona, Italy
| | - Angelo Pietrobelli
- Department of Surgical Science, Dentistry, Gynecology and Pediatrics, Pediatric Unit, Verona University Medical School, Verona, Italy
- Pennington Biomedical Research Center, Louisiana State University (LSU) System, Baton Rouge, LA, United States
- *Correspondence: Angelo Pietrobelli,
| | - Paolo Cavarzere
- Department of Surgical Science, Dentistry, Gynecology and Pediatrics, Pediatric Unit, Verona University Medical School, Verona, Italy
| | - Nicoletta Zerman
- Department of Surgical Science, Dentistry, Gynecology and Pediatrics, University of Verona, Verona, Italy
| | - Alessandra Guzzo
- Section of Clinical Biochemistry, Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, Verona, Italy
| | - Carl-Erik Flodmark
- Department of Clinical Sciences in Malmö, Lunds University, Lund, Sweden
| | - Giorgio Piacentini
- Department of Surgical Science, Dentistry, Gynecology and Pediatrics, Pediatric Unit, Verona University Medical School, Verona, Italy
| | - Franco Antoniazzi
- Department of Surgical Science, Dentistry, Gynecology and Pediatrics, Pediatric Unit, Verona University Medical School, Verona, Italy
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17
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van Abswoude DH, Pellikaan K, Rosenberg AGW, Davidse K, Coupaye M, Høybye C, Markovic TP, Grugni G, Crinò A, Caixàs A, Poitou C, Mosbah H, Weir T, van Vlimmeren LA, Rutges JPHJ, De Klerk LWL, Zillikens MC, van der Lely AJ, de Graaff LCG. Bone Health in Adults With Prader-Willi Syndrome: Clinical Recommendations Based on a Multicenter Cohort Study. J Clin Endocrinol Metab 2022; 108:59-84. [PMID: 36149817 PMCID: PMC9759176 DOI: 10.1210/clinem/dgac556] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/12/2022] [Revised: 09/13/2022] [Indexed: 02/03/2023]
Abstract
CONTEXT Prader-Willi syndrome (PWS) is a rare complex genetic syndrome, characterized by delayed psychomotor development, hypotonia, and hyperphagia. Hormone deficiencies such as hypogonadism, hypothyroidism, and growth hormone deficiency are common. The combination of hypotonia, low physical activity, and hypogonadism might lead to a decrease in bone mass and increase in fracture risk. Moreover, one would expect an increased risk of scoliosis due to hypotonia and low physical activity. OBJECTIVE To study the prevalence and risk factors for skeletal problems (reduced bone mineral density, fractures, and scoliosis) in adults with PWS. METHODS We retrospectively collected patient characteristics, medical history, medication, biochemical measurements, dual-energy X-ray absorptiometry scans, and spinal X-rays and reviewed the current literature. RESULTS We included 354 adults with PWS (median age 31 years; 43% males), of whom 51 (14%) had osteoporosis (T-score below -2.5) and 143 (54%) had osteopenia (T-score -1 to -2.5). The most prevalent modifiable risk factors for osteoporosis were hypogonadism, insufficient dairy intake, sedentary lifestyle, and corticosteroid use. Male sex was associated with osteoporosis (P = .005). Growth hormone treatment was not associated with osteoporosis. A history of vertebral fractures was present in 10 (3%) and nonvertebral fractures in 59 (17%). Scoliosis was present in 263 (80%), but no modifiable risk factors were identified. CONCLUSION Besides scoliosis, osteoporosis is common in adults with PWS. Based on the literature and the risk factors for osteoporosis found in our cohort, we provide practical clinical recommendations to avoid skeletal complications in these vulnerable patients.
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Affiliation(s)
| | | | - Anna G W Rosenberg
- Department of Internal Medicine, Division of Endocrinology, Erasmus Medical
Center, University Medical Center Rotterdam, 3015 GD
Rotterdam, The Netherlands
- Center for Adults with Rare Genetic Syndromes, Department of Internal
Medicine, Division of Endocrinology, Erasmus Medical Center, University Medical Center
Rotterdam, 3015 GD Rotterdam, The Netherlands
- Dutch Center of Reference for Prader-Willi Syndrome,
3015 GD Rotterdam, The
Netherlands
- Academic Center for Growth Disorders, Erasmus Medical Center, University
Medical Center Rotterdam, 3015 GD Rotterdam,
The Netherlands
| | - Kirsten Davidse
- Department of Internal Medicine, Division of Endocrinology, Erasmus Medical
Center, University Medical Center Rotterdam, 3015 GD
Rotterdam, The Netherlands
- Center for Adults with Rare Genetic Syndromes, Department of Internal
Medicine, Division of Endocrinology, Erasmus Medical Center, University Medical Center
Rotterdam, 3015 GD Rotterdam, The Netherlands
- Dutch Center of Reference for Prader-Willi Syndrome,
3015 GD Rotterdam, The
Netherlands
- Academic Center for Growth Disorders, Erasmus Medical Center, University
Medical Center Rotterdam, 3015 GD Rotterdam,
The Netherlands
| | - Muriel Coupaye
- Assistance Publique-Hôpitaux de Paris, Rare Diseases Center of reference
‘Prader-Willi Syndrome and obesity with eating disorders’ (PRADORT), Nutrition
Department, Institute of Cardiometabolism and Nutrition, ICAN, Pitié-Salpêtrière
Hospital, Sorbonne Université, INSERM, Nutriomics, F75013
Paris, France
- International Network for Research, Management & Education on adults
with Prader-Willi Syndrome (INfoRMEd-PWS)
| | - Charlotte Høybye
- International Network for Research, Management & Education on adults
with Prader-Willi Syndrome (INfoRMEd-PWS)
- ENDO-ERN (European Reference Network)
- Department of Molecular Medicine and Surgery, Karolinska Institute and
Karolinska University Hospital, Stockholm,
Sweden
- Department of Endocrinology, Karolinska Institute and Karolinska University
Hospital, Stockholm, Sweden
| | - Tania P Markovic
- International Network for Research, Management & Education on adults
with Prader-Willi Syndrome (INfoRMEd-PWS)
- Metabolism & Obesity Services, Royal Prince Alfred
Hospital, Camperdown, Australia
- Boden Initiative, Charles Perkins Centre, University of
Sydney, SydneyAustralia
| | - Graziano Grugni
- International Network for Research, Management & Education on adults
with Prader-Willi Syndrome (INfoRMEd-PWS)
- ENDO-ERN (European Reference Network)
- Divison of Auxology, Istituto Auxologico Italiano, IRCCS,
Piancavallo (VB), Italy
| | - Antonino Crinò
- International Network for Research, Management & Education on adults
with Prader-Willi Syndrome (INfoRMEd-PWS)
- Reference Center for Prader-Willi syndrome, Bambino Gesù Hospital, Research
Institute, Palidoro (Rome), Italy
| | - Assumpta Caixàs
- International Network for Research, Management & Education on adults
with Prader-Willi Syndrome (INfoRMEd-PWS)
- Department of Endocrinology and Nutrition, Hospital Universitari Parc
Taulí, Institut d’Investigació i Innovació Parc Taulí (I3PT), Universitat Autònoma de
Barcelona, Sabadell, Spain
- Department of Medicine, Universitat Autònoma de Barcelona,
Sabadell, Spain
| | - Christine Poitou
- Assistance Publique-Hôpitaux de Paris, Rare Diseases Center of reference
‘Prader-Willi Syndrome and obesity with eating disorders’ (PRADORT), Nutrition
Department, Institute of Cardiometabolism and Nutrition, ICAN, Pitié-Salpêtrière
Hospital, Sorbonne Université, INSERM, Nutriomics, F75013
Paris, France
- International Network for Research, Management & Education on adults
with Prader-Willi Syndrome (INfoRMEd-PWS)
- ENDO-ERN (European Reference Network)
| | - Helena Mosbah
- Assistance Publique-Hôpitaux de Paris, Rare Diseases Center of reference
‘Prader-Willi Syndrome and obesity with eating disorders’ (PRADORT), Nutrition
Department, Institute of Cardiometabolism and Nutrition, ICAN, Pitié-Salpêtrière
Hospital, Sorbonne Université, INSERM, Nutriomics, F75013
Paris, France
| | - Tessa Weir
- Department of Endocrinology, Nepean-Blue Mountains Hospital,
Sydney, NSW, Australia
- Northern Clinical School, Faculty of Medicine and Health, University of
Sydney, Sydney, NSW, Australia
| | - Leo A van Vlimmeren
- Department of Rehabilitation and Pediatric Physical Therapy, Radboud
University Medical Centrum, 6525 GA Nijmegen,
The Netherlands
| | - Joost P H J Rutges
- Department of Orthopedic surgery, Erasmus Medical Center, University
Medical Center Rotterdam, 3015 GD Rotterdam,
The Netherlands
| | - Luuk W L De Klerk
- Department of Orthopedic surgery, Sint Maartensclinic,
6500 GM Nijmegen, The
Netherlands
| | - M Carola Zillikens
- Department of Internal Medicine, Division of Endocrinology, Erasmus Medical
Center, University Medical Center Rotterdam, 3015 GD
Rotterdam, The Netherlands
- ENDO-ERN (European Reference Network)
- Academic Center for Rare Bone Disorders, Erasmus Medical Center, University
Medical Center Rotterdam, 3015 GD Rotterdam,
The Netherlands
- European Reference Network for rare bone diseases (ERN BOND)
| | - Aart J van der Lely
- Department of Internal Medicine, Division of Endocrinology, Erasmus Medical
Center, University Medical Center Rotterdam, 3015 GD
Rotterdam, The Netherlands
| | - Laura C G de Graaff
- Correspondence: Laura de Graaff, MD, PhD, Dept. of Internal Medicine, Erasmus
MC, University Medical Center, Dr. Molewaterplein 40, 3015 GD Rotterdam, The Netherlands.
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Irisin and Bone in Sickness and in Health: A Narrative Review of the Literature. J Clin Med 2022; 11:jcm11226863. [PMID: 36431340 PMCID: PMC9699623 DOI: 10.3390/jcm11226863] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2022] [Revised: 11/09/2022] [Accepted: 11/15/2022] [Indexed: 11/24/2022] Open
Abstract
Irisin is a hormone-like myokine produced by the skeletal muscle in response to exercise. Upon its release into the circulation, it is involved in the browning process and thermogenesis, but recent evidence indicates that this myokine could also regulate the functions of osteoblasts, osteoclasts, and osteocytes. Most human studies have reported that serum irisin levels decrease with age and in conditions involving bone diseases, including both primary and secondary osteoporosis. However, it should be emphasized that recent findings have called into question the importance of circulating irisin, as well as the validity and reproducibility of current methods of irisin measurement. In this review, we summarize data pertaining to the role of irisin in the bone homeostasis of healthy children and adults, as well as in the context of primary and secondary osteoporosis. Additional research is required to address methodological issues, and functional studies are required to clarify whether muscle and bone damage per se affect circulating levels of irisin or whether the modulation of this myokine is caused by the inherent mechanisms of underlying diseases, such as genetic or inflammatory causes. These investigations would shed further light on the effects of irisin on bone homeostasis and bone disease.
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Liu S, Yang H, Xu H, Zhou Z, Bai X, Wang L, Duan L, Gong F, Zhu H, Pan H. Reduced Bone Mineral Density in Middle-Aged Male Patients with Adult Growth Hormone Deficiency. Horm Metab Res 2022; 54:450-457. [PMID: 35556240 DOI: 10.1055/a-1850-7461] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 05/12/2022] [Indexed: 11/04/2022]
Abstract
The aim of the work was to investigate the bone mineral density (BMD) in middle-aged male patients with both childhood-onset (CO) and adulthood-onset (AO) adult growth hormone deficiency (AGHD). In this retrospective cross-sectional study in a major medical center in China, dual X-ray absorptiometry was performed in 50 male AGHD patients (average age was 35.2±9.8 years) and 50 age- and BMI-matched non-athletic healthy men. BMD was compared between AGHD patients and controls. Compared with healthy controls, AGHD group had significantly decreased IGF-1 (p1<0.001) and IGF-1 SDS (p1<0.001). Serum testosterone levels were significantly lower in AGHD patients (p1<0.001), mainly in AO AGHD patients (p3<0.001). The BMD of the femoral neck, trochanter, femoral shaft, total hip, and lumbar spine were significantly lower in all AGHD patients compared with healthy controls (all p1<0.05), especially in CO AGHD patients (all p2<0.05). Multiple stepwise linear regression indicated AGHD was negatively correlated with BMD at each site (β<0, p<0.05). Additionally, serum testosterone level was an independent influencing factor of BMD of the femoral neck (β=0.256, p=0.018) and lumbar spine (β=0.219, p=0.040). BMD was significantly reduced in AGHD patients, especially in CO AGHD patients. Our data suggested that the status of growth hormone deficiency and testosterone level were important for maintaining of bone mineral density in middle-aged male patients with AGHD.
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Affiliation(s)
- Shanshan Liu
- Endocrinology, Peking Union Medical College Hospital, Dongcheng-qu, China
- Graduate School, Hebei North University, Zhangjiakou, China
| | - Hongbo Yang
- Department of Endocrinology, Peking Union Medical College Hospital, Dongcheng-qu, China
| | - Hanyuan Xu
- Endocrinology, Peking Union Medical College Hospital, Beijing, China
| | - Zhibo Zhou
- Department of Endocrinology, Peking Union Medical College Hospital, Dongcheng-qu, China
| | - Xi Bai
- Endocrinology, Peking Union Medical College Hospital Department of Endocrinology, Beijing, China
| | - Linjie Wang
- Department of Endocrinology, Peking Union Medical College Hospital, Dongcheng-qu, China
| | - Lian Duan
- Endocrinology, Peking Union Medical College Hospital, Beijing, China
| | - Fengying Gong
- Endocrinology, Peking Union Medical College Hospital, Dongcheng-qu, China
| | - Huijuan Zhu
- Endocrinology Dept., Peking Union Medical College Hospital, Dongcheng-qu, China
| | - Hui Pan
- Department of Endocrinology, Peking Union Medical College Hospital, Dongcheng-qu, China
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20
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Cerbone M, Katugampola H, Simpson HL, Dattani MT. Approach to the Patient: Management of Pituitary Hormone Replacement Through Transition. J Clin Endocrinol Metab 2022; 107:2077-2091. [PMID: 35262704 PMCID: PMC9202712 DOI: 10.1210/clinem/dgac129] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/17/2021] [Indexed: 11/19/2022]
Abstract
Hypopituitarism in childhood is a rare, complex disorder that can present with highly variable phenotypes, which may continue into adult life. Pituitary deficits can evolve over time, with unpredictable patterns resulting in significant morbidity and mortality. Hypopituitarism and hypothalamic dysfunction may be associated with challenging comorbidities such as obesity, learning difficulties, behavioral issues, sleep disturbance, and visual impairment. Transition is the purposeful planned movement of adolescents and young adults with chronic conditions from child-centered to adult-oriented health care systems with a shift from parent- to patient-focused care. To achieve effective transition within a health care setting, the inherent challenges involved in the evolution from a dependent child to an independent adult must be recognized. Transition is a critical time medically for patients with hypopituitarism. Complex issues with respect to puberty, attainment of optimal stature, adherence to treatment, and acceptance of the need for life-sustaining medications need to be addressed. For health care professionals, transition is an opportunity for reassessment of the pituitary deficits and the need for lifelong replacement therapies, often against a background of complex psychological issues. We present 4 illustrative cases of hypopituitarism of differing etiologies with diverse clinical presentations. Diagnostic and management processes from clinical presentation to young adulthood are discussed, with a particular focus on needs and outcomes through transition.
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Affiliation(s)
- Manuela Cerbone
- London Centre for Paediatric Endocrinology and Diabetes at Great Ormond Street Children’s Hospital and University College London Hospitals, London WC1N 1EH, UK
- Section of Molecular Basis of Rare Disease, Genetics and Genomic Medicine Programme, University College London Great Ormond Street Institute of Child Health, London WC1N 1EH, UK
| | - Harshini Katugampola
- London Centre for Paediatric Endocrinology and Diabetes at Great Ormond Street Children’s Hospital and University College London Hospitals, London WC1N 1EH, UK
- Section of Molecular Basis of Rare Disease, Genetics and Genomic Medicine Programme, University College London Great Ormond Street Institute of Child Health, London WC1N 1EH, UK
| | - Helen L Simpson
- Section of Molecular Basis of Rare Disease, Genetics and Genomic Medicine Programme, University College London Great Ormond Street Institute of Child Health, London WC1N 1EH, UK
- Department of Diabetes and Endocrinology, University College London Hospitals NHS Trust, London NW1 2BU, UK
| | - Mehul T Dattani
- London Centre for Paediatric Endocrinology and Diabetes at Great Ormond Street Children’s Hospital and University College London Hospitals, London WC1N 1EH, UK
- Section of Molecular Basis of Rare Disease, Genetics and Genomic Medicine Programme, University College London Great Ormond Street Institute of Child Health, London WC1N 1EH, UK
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21
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Zargaran D, Zoller F, Zargaran A, Weyrich T, Mosahebi A. Facial Skin Aging: key concepts and overview of processes. Int J Cosmet Sci 2022; 44:414-420. [PMID: 35426152 PMCID: PMC9543134 DOI: 10.1111/ics.12779] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2022] [Revised: 03/16/2022] [Accepted: 03/19/2022] [Indexed: 11/28/2022]
Abstract
Introduction The face is a cosmetically sensitive region where the process of ageing is most clearly manifested. With increased focus on anti‐ageing and longevity, more anti‐senescent treatments are being proposed despite limited evidence. This study outlines the pathways and mechanisms underpinning the biological process of ageing in the face. Methods Comprehensive searches of MEDLINE, EMBASE, Cochrane Library and CINAHL from inception to 2020. Inclusion criteria included all empirical human research studies specific to facial ageing features, written in the English language. Results A total of 65 papers met inclusion criteria for analysis. Pathways were subdivided into intrinsic and extrinsic senescence mechanisms. Intrinsic pathways included genetics, generation of reactive oxygen species and hormonal changes. Extrinsic pathways included photoageing and damage to skin layers. The combined intrinsic and extrinsic pathway alterations result in wrinkles, higher laxity, slackness and thinning of the skin. Skin functions such as barrier immune function, wound healing, thermoregulation and sensory function are also impaired. Conclusion The ageing process is unique to the individual and depends on the interplay between an individual's genetics and external environmental factors. Through understanding the molecular and cellular mechanisms, an appreciation of the consequent structural and functional changes can be achieved. Based on this knowledge, further research can focus on how to slow or impede the ageing process and identify specific targets to develop and evolve new treatment strategies.
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Affiliation(s)
- David Zargaran
- Department of Plastic Surgery, Royal Free Hospital University College London London UK
| | - Florence Zoller
- Department of Plastic Surgery, Royal Free Hospital University College London London UK
| | - Alexander Zargaran
- Department of Plastic Surgery, Royal Free Hospital University College London London UK
| | - Tim Weyrich
- Department of Computer Science University College London London UK
- Friedrich‐Alexander University (FAU) Erlangen‐ Nürnberg Germany
| | - Afshin Mosahebi
- Department of Plastic Surgery, Royal Free Hospital University College London London UK
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22
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Ratku B, Sebestyén V, Erdei A, Nagy EV, Szabó Z, Somodi S. Effects of adult growth hormone deficiency and replacement therapy on the cardiometabolic risk profile. Pituitary 2022; 25:211-228. [PMID: 35106704 PMCID: PMC8894188 DOI: 10.1007/s11102-022-01207-1] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 01/10/2022] [Indexed: 12/12/2022]
Abstract
Adult growth hormone deficiency (AGHD) is considered a rare endocrine disorder involving patients with childhood-onset and adult-onset growth hormone deficiency (AoGHD) and characterized by adverse cardiometabolic risk profile. Besides traditional cardiovascular risk factors, endothelial dysfunction, low-grade inflammation, impaired adipokine profile, oxidative stress and hypovitaminosis D may also contribute to the development of premature atherosclerosis and higher cardiovascular risk in patients with AGHD. Growth hormone replacement has been proved to exert beneficial effects on several cardiovascular risk factors, but it is also apparent that hormone substitution in itself does not eliminate all cardiometabolic abnormalities associated with the disease. Novel biomarkers and diagnostic techniques discussed in this review may help to evaluate individual cardiovascular risk and identify patients with adverse cardiometabolic risk profile. In the absence of disease-specific guidelines detailing how to assess the cardiovascular status of these patients, we generally recommend close follow-up of the cardiovascular status as well as low threshold for a more detailed evaluation.
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Affiliation(s)
- Balázs Ratku
- Department of Emergency Medicine, Faculty of Medicine, University of Debrecen, Egyetem tér 1, Debrecen, 4032, Hungary
- Doctoral School of Health Sciences, University of Debrecen, Debrecen, Hungary
- Department of Emergency and Oxyology, Faculty of Health, University of Debrecen, Debrecen, Hungary
| | - Veronika Sebestyén
- Department of Emergency Medicine, Faculty of Medicine, University of Debrecen, Egyetem tér 1, Debrecen, 4032, Hungary
- Doctoral School of Health Sciences, University of Debrecen, Debrecen, Hungary
| | - Annamária Erdei
- Division of Endocrinology, Department of Internal Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
| | - Endre V Nagy
- Division of Endocrinology, Department of Internal Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
| | - Zoltán Szabó
- Department of Emergency Medicine, Faculty of Medicine, University of Debrecen, Egyetem tér 1, Debrecen, 4032, Hungary
| | - Sándor Somodi
- Department of Emergency Medicine, Faculty of Medicine, University of Debrecen, Egyetem tér 1, Debrecen, 4032, Hungary.
- Division of Endocrinology, Department of Internal Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.
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23
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Pricci F, Rotondi D, Villa M, Valerio A, Agazio E, Roazzi P. Somatropin therapy in italian adults with growth hormone deficiency. BMC Endocr Disord 2022; 22:52. [PMID: 35241041 PMCID: PMC8895664 DOI: 10.1186/s12902-022-00960-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/20/2021] [Accepted: 02/11/2022] [Indexed: 11/18/2022] Open
Abstract
BACKGROUND In adult population, Growth Hormone Deficiency (GHD) is a complex clinical condition with heterogeneity of causes and duration. Growth Hormone (GH) replacement therapy has beneficial effects entailing a chronic and expensive use. Therefore, entity, appropriateness and standardization of GHD treatment need to be accurately analysed. In Italy, the epidemiological surveillance on somatropin therapy is entrusted to the National Register of Growth Hormone Therapy (Registro Nazionale degli Assuntori dell'Ormone della Crescita-RNAOC) by the Italian Regulation, in accordance of which the RNAOC-database is collecting the notifications of somatropin prescriptions. METHODS Aim of this study is to analyse data on somatropin-treated adult population communicated to the RNAOC by the specialist centres of 15 Italian regions and 2 autonomous provinces. RESULTS From 2011 to 2019, the somatropin-treated adults were 970 with 4061 examinations (1.21 ± 0.33 visits/year). The diagnoses were: hypopituitarism (n = 579); hypophysectomy (n = 383); and congenital GHD (n = 3). Five subjects were addressed with diagnoses not included in the regulation. The starting posology of somatropin was 0.320 (± 0.212) mg/day, 0.292 (± 0.167) mg/day in male and 0.360 (± 0.258) in female patients, with 7 administrations/week in 70.31% of the prescriptions. The differences in posology by gender persisted at 10th year of the follow-up. Starting dosage was higher in patients diagnosed with adult GHD before the age of 30 (0.420 ± 0.225 mg/day), with a progressive decrease of the dosage during the follow-up. CONCLUSIONS This is the first report on adult GH treatment, describing numbers, diagnoses, and pharmaceutical prescriptions associated to somatropin therapy in a large cohort of Italian GHD-adults.
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Affiliation(s)
- Flavia Pricci
- Department of Cardiovascular, Endocrine-Metabolic Diseases, and Aging, Istituto Superiore di Sanità, Rome, Italy
| | - Daniela Rotondi
- Department of Cardiovascular, Endocrine-Metabolic Diseases, and Aging, Istituto Superiore di Sanità, Rome, Italy
| | - Marika Villa
- Department of Cardiovascular, Endocrine-Metabolic Diseases, and Aging, Istituto Superiore di Sanità, Rome, Italy
| | - Arianna Valerio
- Department of Cardiovascular, Endocrine-Metabolic Diseases, and Aging, Istituto Superiore di Sanità, Rome, Italy
| | - Elvira Agazio
- Department of Cardiovascular, Endocrine-Metabolic Diseases, and Aging, Istituto Superiore di Sanità, Rome, Italy
| | - Paolo Roazzi
- National Centre for Health Technology Assessment, Istituto Superiore di Sanità, Rome, Italy
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24
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Goetz TG, Nair N, Shiau S, Recker RR, Lappe JM, Dempster DW, Zhou H, Zhao B, Guo X, Shen W, Nickolas TL, Kamanda-Kosseh M, Bucovsky M, Stubby J, Shane E, Cohen A. In premenopausal women with idiopathic osteoporosis, lower bone formation rate is associated with higher body fat and higher IGF-1. Osteoporos Int 2022; 33:659-672. [PMID: 34665288 PMCID: PMC9927557 DOI: 10.1007/s00198-021-06196-8] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/28/2021] [Accepted: 10/05/2021] [Indexed: 10/20/2022]
Abstract
UNLABELLED We examined serum IGF-1 in premenopausal IOP, finding relationships that were opposite to those expected: higher IGF-1 was associated with lower bone formation and higher body fat, and lower BMD response to teriparatide. These paradoxical relationships between serum IGF-1, bone, and fat may contribute to the mechanism of idiopathic osteoporosis in premenopausal women. INTRODUCTION Premenopausal women with idiopathic osteoporosis (IOP) have marked deficits in bone microarchitecture but variable bone remodeling. We previously reported that those with low tissue-level bone formation rate (BFR) are less responsive to teriparatide and have higher serum IGF-1, a hormone anabolic for osteoblasts and other tissues. The IGF-1 data were unexpected because IGF-1 is low in other forms of low turnover osteoporosis-leading us to hypothesize that IGF-1 relationships are paradoxical in IOP. This study aimed to determine whether IOP women with low BFR have higher IGF-1 and paradoxical IGF-1 relationships in skeletal and non-skeletal tissues, and whether IGF-1 and the related measures predict teriparatide response. METHODS This research is an ancillary study to a 24 month clinical trial of teriparatide for IOP. Baseline assessments were related to trial outcomes: BMD, bone remodeling. SUBJECTS Premenopausal women with IOP(n = 34); bone remodeling status was defined by baseline cancellous BFR/BS on bone biopsy. MEASURES Serum IGF-1 parameters, compartmental adiposity (DXA, CT, MRI), serum hormones, and cardiovascular-risk-markers related to fat distribution. RESULTS As seen in other populations, lower BFR was associated with higher body fat and poorer teriparatide response. However, in contrast to observations in other populations, low BFR, higher body fat, and poorer teriparatide response were all related to higher IGF-1: IGF-1 Z-score was inversely related to BFR at all bone surfaces (r = - 0.39 to - 0.46; p < 0.05), directly related to central fat (p = 0.05) and leptin (p = 0.03). IGF-1 inversely related to 24 month hip BMD %change (r = - 0.46; p = 0.01). CONCLUSIONS Paradoxical IGF-1 relationships suggest that abnormal or atypical regulation of bone and fat may contribute to osteoporosis mechanisms in premenopausal IOP.
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Affiliation(s)
- T G Goetz
- Columbia University Vagelos College of Physicians & Surgeons, New York, NY, USA
| | - N Nair
- Department of Medicine, Columbia University Vagelos College of Physicians & Surgeons, NY, New York, USA
| | - S Shiau
- Department of Biostatistics and Epidemiology, Rutgers School of Public Health, Piscataway, NJ, USA
| | - R R Recker
- Department of Medicine, Creighton University Medical Center, Omaha, NE, USA
| | - J M Lappe
- Department of Medicine, Creighton University Medical Center, Omaha, NE, USA
| | - D W Dempster
- Department of Pathology and Cell Biology, Columbia University Vagelos College of Physicians & Surgeons, New York, NY, USA
| | - H Zhou
- Regional Bone Center, Helen Hayes Hospital, West Haverstraw, NY, USA
| | - B Zhao
- Department of Radiology, Columbia University Vagelos College of Physicians & Surgeons, New York, NY, USA
| | - X Guo
- Department of Radiology, Columbia University Vagelos College of Physicians & Surgeons, New York, NY, USA
| | - W Shen
- Department of Pediatrics, Columbia University Vagelos College of Physicians & Surgeons, New York, NY, USA
- Institute of Human Nutrition, Columbia University Irving Medical Center, New York, NY, USA
- Columbia Magnetic Resonance Research Center (CMRRC), Columbia University, New York, NY, USA
| | - T L Nickolas
- Department of Medicine, Columbia University Vagelos College of Physicians & Surgeons, NY, New York, USA
| | - M Kamanda-Kosseh
- Department of Medicine, Columbia University Vagelos College of Physicians & Surgeons, NY, New York, USA
| | - M Bucovsky
- Department of Medicine, Columbia University Vagelos College of Physicians & Surgeons, NY, New York, USA
| | - J Stubby
- Department of Medicine, Creighton University Medical Center, Omaha, NE, USA
| | - E Shane
- Department of Medicine, Columbia University Vagelos College of Physicians & Surgeons, NY, New York, USA
| | - A Cohen
- Department of Medicine, Columbia University Vagelos College of Physicians & Surgeons, NY, New York, USA.
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25
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Sodero G, Agresti P, Triarico S, Romano A, Mastrangelo S, Attinà G, Maurizi P, Cipolla C, Ruggiero A. Growth Hormone replacement therapy in pediatric brain tumor survivors. Minerva Pediatr (Torino) 2022; 74:340-348. [PMID: 35142454 DOI: 10.23736/s2724-5276.22.06799-4] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
Brain tumors are the most frequent type of solid neoplasms in children with a recognized 5-year survival rate between 57 and 65%. The survival rate progressively increased in the last few years, due to the improvements in their treatment based on chemotherapy, radiotherapy, and surgery. At the same time, at long term follow-up, clinicians should carefully evaluate comorbidities and long term sequelae secondary to the disease and its treatment. Growth Hormone Deficiency (GHD) is an endocrinopathy commonly found among pediatric cancer survivors, with a negative effect on the child's final height and entire metabolism. GH replacement therapy (GHRT), with a synthetic hormone analog, may improve the growth rate and finally adult height, ameliorating the quality of life after cancer treatment. However, in clinical practice, GHRT is adopted with caution for fear of cancer recurrence or the onset of second malignancies. In our review, we perform a focus on the GH structure and function, comparing benefits and risks of GHRT, derived from the analysis of the data currently available in the literature.
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Affiliation(s)
- Giorgio Sodero
- Istituto di Pediatria, Università Cattolica del Sacro Cuore, Rome, Italy -
| | - Pierpaolo Agresti
- Istituto di Pediatria, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Silvia Triarico
- Pediatric Oncology Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica Sacro Cuore, Rome, Italy
| | - Alberto Romano
- Istituto di Pediatria, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Stefano Mastrangelo
- Pediatric Oncology Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica Sacro Cuore, Rome, Italy.,Università Cattolica del Sacro Cuore Sede di Roma, Italy
| | - Giorgio Attinà
- Pediatric Oncology Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica Sacro Cuore, Rome, Italy
| | - Palma Maurizi
- Pediatric Oncology Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica Sacro Cuore, Rome, Italy
| | - Clelia Cipolla
- Department of Woman and Child Health and Public Health, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
| | - Antonio Ruggiero
- Pediatric Oncology Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica Sacro Cuore, Rome, Italy.,Università Cattolica del Sacro Cuore Sede di Roma, Italy
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26
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Irisin and Secondary Osteoporosis in Humans. Int J Mol Sci 2022; 23:ijms23020690. [PMID: 35054874 PMCID: PMC8775753 DOI: 10.3390/ijms23020690] [Citation(s) in RCA: 23] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2021] [Revised: 12/31/2021] [Accepted: 01/05/2022] [Indexed: 02/06/2023] Open
Abstract
Irisin is a peptide secreted by skeletal muscle following exercise that plays an important role in bone metabolism. Numerous experiments in vitro and in mouse models have shown that the administration of recombinant irisin promotes osteogenesis, protects osteocytes from dexamethasone-induced apoptosis, prevents disuse-induced loss of bone and muscle mass, and accelerates fracture healing. Although some aspects still need to be elucidated, such as the dose- and frequency-dependent effects of irisin in cell cultures and mouse models, ample clinical evidence is emerging to support its physiological relevance on bone in humans. A reduction in serum irisin levels, associated with an increased risk of osteoporosis and bone fractures, was observed in postmenopausal women and in both men and women during aging, Recently, cohort studies of subjects with secondary osteoporosis showed that these patients have lower circulating levels of irisin, suggesting that this myokine could be a novel marker to monitor bone quality in this disease. Although there are still few studies, this review discusses the emerging data that are highlighting the involvement of irisin in some diseases that cause secondary osteoporosis.
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27
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Bioletto F, Prencipe N, Berton AM, Bona C, Parasiliti-Caprino M, Faletti R, Ghigo E, Grottoli S, Gasco V. MRI Assessment of Cardiac Function and Morphology in Adult Patients With Growth Hormone Deficiency: A Systematic Review and Meta-Analysis. Front Endocrinol (Lausanne) 2022; 13:910575. [PMID: 35757407 PMCID: PMC9226436 DOI: 10.3389/fendo.2022.910575] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/01/2022] [Accepted: 05/09/2022] [Indexed: 11/13/2022] Open
Abstract
BACKGROUND Adult GH deficiency (GHD) has been described as a heterogeneous condition characterized by many clinical modifications, such as metabolic alterations, impaired quality of life, and increased mortality. The clinical relevance of cardiac involvement remains, however, only partially elucidated. METHODS PubMed/Medline, EMBASE, Cochrane library, OVID and CINAHL databases were systematically searched until February 2022 for studies evaluating cardiac function and morphology by magnetic resonance imaging in adult patients with GHD. Effect sizes were pooled through a random-effect model. RESULTS Four studies were considered in the meta-analysis. With respect to the left ventricle, GHD patients were characterized by a lower stroke-volume-index (-3.6 ml/m2, standardized mean difference (SMD) -0.60, 95%CI [-1.15,-0.05], p=0.03), lower end-diastolic-volume-index (-6.2 ml/m2, SMD -0.54, 95%CI [-0.97,-0.10], p=0.02) and, after accounting for possible biases, lower mass-index (-15.0 g/m2, SMD -1.03, 95%CI [-1.89,-0.16], p=0.02). With respect to the right ventricle, a lower end-diastolic-volume-index (-16.6 ml/m2, SMD -1.04, 95%CI [-2.04,-0.03], p=0.04) and a borderline-significant lower stroke-volume-index (-5.0 ml/m2, SMD -0.84, 95%CI [-1.77,0.08], p=0.07) could be observed. Data about the effect of GH replacement therapy highlighted a significant increase in left ventricular mass-index after treatment initiation (+3.7 g/m2, 95%CI [1.6,5.7], p<0.01). CONCLUSION With respect to the left ventricle, our results confirmed those retrieved by echocardiographic studies. In addition, significant alterations were demonstrated also for the right ventricle, for which echocardiographic data are nearly absent. This supports the thesis of a biventricular cardiac involvement in patients with GHD, with a similar pattern of morphological and functional alterations in both ventricles.
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Affiliation(s)
- Fabio Bioletto
- Endocrinology, Diabetology and Metabolism, Department of Medical Sciences, University of Turin, Turin, Italy
- *Correspondence: Fabio Bioletto, , orcid.org/0000-0001-7550-7023
| | - Nunzia Prencipe
- Endocrinology, Diabetology and Metabolism, Department of Medical Sciences, University of Turin, Turin, Italy
| | - Alessandro Maria Berton
- Endocrinology, Diabetology and Metabolism, Department of Medical Sciences, University of Turin, Turin, Italy
| | - Chiara Bona
- Endocrinology, Diabetology and Metabolism, Department of Medical Sciences, University of Turin, Turin, Italy
| | - Mirko Parasiliti-Caprino
- Endocrinology, Diabetology and Metabolism, Department of Medical Sciences, University of Turin, Turin, Italy
| | - Riccardo Faletti
- Radiology Unit, Department of Surgical Sciences, University of Turin, Turin, Italy
| | - Ezio Ghigo
- Endocrinology, Diabetology and Metabolism, Department of Medical Sciences, University of Turin, Turin, Italy
| | - Silvia Grottoli
- Endocrinology, Diabetology and Metabolism, Department of Medical Sciences, University of Turin, Turin, Italy
| | - Valentina Gasco
- Endocrinology, Diabetology and Metabolism, Department of Medical Sciences, University of Turin, Turin, Italy
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28
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Osorio RC, Oh JY, Choudhary N, Lad M, Savastano L, Aghi MK. Pituitary adenomas and cerebrovascular disease: A review on pathophysiology, prevalence, and treatment. Front Endocrinol (Lausanne) 2022; 13:1064216. [PMID: 36578965 PMCID: PMC9791098 DOI: 10.3389/fendo.2022.1064216] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/08/2022] [Accepted: 11/28/2022] [Indexed: 12/14/2022] Open
Abstract
Pituitary adenomas (PAs) have been shown to cause excess cardiovascular disease comorbidity and mortality. Cerebrovascular disease (CeVD) is a small subset of cardiovascular disease with high morbidity, and its risk in patients with pituitary adenomas has been sparingly explored. In this review, we examine what is known about the prevalence of cerebrovascular disease in patients with PAs, from its initial discovery in 1970 to present. An abundance of literature describes increased cerebrovascular mortality in patients with acromegaly, while research on other PA subtypes is less frequent but shows a similarly elevated CeVD mortality relative to healthy populations. We also review how cerebrovascular risk changes after PAs are treated, with PA treatment appearing to prevent further accumulation of cerebrovascular risk without reversing prior elevations. While acromegaly-associated CeVD appears to be caused by elevated growth hormone (GH) levels and Cushing disease's elevated glucocorticoids similarly cause durable alterations in cerebrovascular structure and function, less is known about the mechanisms behind CeVD in other PA subpopulations. Proposed pathophysiologies include growth hormone deficiency inducing vessel wall damage or other hormone deficits causing increased atherosclerotic disease. Early diagnosis and treatment of PAs may be the key to minimizing lifetime CeVD risk elevations. More research is needed to better understand the mechanisms behind the increased CeVD seen in patients with PAs. Physicians caring for PA patients must remain vigilant for signs and symptoms of cerebrovascular disease in this patient population.
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29
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Saad N, Mahajan A, Chin A, Stewart D, Kline GA. Prevalence of growth hormone deficiency in patients with unexplained chronic fatigue after undergoing bone marrow transplantation in adulthood. J Endocrinol Invest 2021; 44:2809-2817. [PMID: 34003462 DOI: 10.1007/s40618-021-01589-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/25/2020] [Accepted: 05/06/2021] [Indexed: 10/21/2022]
Abstract
PURPOSE Many patients who undergo bone marrow transplantation (BMT) in adulthood experience unexplained chronic fatigue which can have a major impact on their health-related quality of life (QoL). Pre-BMT treatment regimens increase the risk of developing acquired growth hormone deficiency (GHD), which results in a clinical syndrome with decreased energy and has additionally been linked to metabolic syndrome. METHODS Using the gold-standard insulin hypoglycemic test (IHT), we evaluated the prevalence of GHD in 18 post-BMT adult patients with unexplained chronic fatigue, as well as the correlation between peak serum GH response and QoL scores, the metabolic syndrome, and insulin resistance. Peak serum GH cut-point less than 3.0 ug/L was used for the diagnosis of severe GHD. The Fatigue Severity Scale and Quality of Life in Adult GHD Assessment questionnaires were used to quantify fatigue symptoms. RESULTS The prevalence of severe GHD within this sample of 18 patients was 50%. A trend between lower peak serum GH response and higher fatigue and QoL-AGHDA scores was observed. CONCLUSIONS GHD may represent a remediable contributor to post-BMT chronic fatigue in adults, further studies are needed to evaluate the potential role of screening and GH replacement therapy in this vulnerable patient population. IMPLICATIONS FOR CANCER SURVIVORS GHD may be a treatable explanation for disabling post-BMT fatigue pending results of intervention studies.
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Affiliation(s)
- N Saad
- Division of Endocrinology, Department of Medicine, Cumming School of Medicine, University of Calgary, 1820 Richmond Rd SW, Calgary, AB, T2T 5C7, Canada
| | - A Mahajan
- Division of Endocrinology, Department of Medicine, Cumming School of Medicine, University of Calgary, 1820 Richmond Rd SW, Calgary, AB, T2T 5C7, Canada
| | - A Chin
- Department of Pathology and Laboratory Medicine, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
| | - D Stewart
- Departments of Oncology and Medicine, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
| | - G A Kline
- Division of Endocrinology, Department of Medicine, Cumming School of Medicine, University of Calgary, 1820 Richmond Rd SW, Calgary, AB, T2T 5C7, Canada.
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30
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Raj R, Elshimy G, Mishra R, Jha N, Joseph V, Bratman R, Tella SH, Correa R. Dermatologic Manifestations of Endocrine Disorders. Cureus 2021; 13:e18327. [PMID: 34692360 PMCID: PMC8526081 DOI: 10.7759/cureus.18327] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/27/2021] [Indexed: 11/05/2022] Open
Abstract
Endocrine disorders are known to involve all organ systems of the body, including the skin. The cutaneous manifestations of endocrine disorders can range from common findings such as acanthosis nigricans, pretibial myxedema, acne, hirsutism, hyper or hypopigmentation to rare cutaneous findings such as miliaria rubra, calciphylaxis, lentigines, and calcinosis cutis. These cutaneous symptoms can sometimes be the presenting symptoms or can even be pathognomonic of the underlying endocrine condition. In some cases, the cutaneous symptoms from an underlying endocrine abnormality may be the most prominent. These symptoms can significantly affect the quality of life of individuals. Often, individuals may seek health care from a dermatologist or primary care physician for isolated skin symptoms. Therefore, it is imperative for physicians to recognize the skin symptoms as the manifestation of the endocrine disorder for prompt diagnosis and treatment of the underlying endocrine disorder.
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Affiliation(s)
- Rishi Raj
- Endocrinology, Diabetes and Metabolism, Pikeville Medical Center, Pikeville, USA
| | - Ghada Elshimy
- Endocrinology, Diabetes and Metabolism, Augusta University Medical College of Georgia, Augusta, USA
| | - Rahul Mishra
- Internal Medicine, Maulana Azad Medical College, Delhi, IND
| | - Nivedita Jha
- Internal Medicine, Adichunchanagiri Institute of Medical Sciences, Karnataka, IND
| | - Vismaya Joseph
- Data Science, University of Texas at Dallas, Richardson, USA
| | - Russell Bratman
- Endocrinology, Diabetes and Metabolism, Brown University, Rhode Island, USA
| | | | - Ricardo Correa
- Endocrinology, Diabetes and Metabolism, University of Arizona College of Medicine - Phoenix, Phoenix, USA
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31
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Slagboom TNA, Deijen JB, Van Bunderen CC, Knoop HA, Drent ML. Psychological well-being and illness perceptions in patients with hypopituitarism. Pituitary 2021; 24:542-554. [PMID: 33606176 PMCID: PMC8270855 DOI: 10.1007/s11102-021-01131-w] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 02/04/2021] [Indexed: 11/25/2022]
Abstract
OBJECTIVE The primary aim of the current study was to objectify a spectrum of persisting subjective psychological complaints in patients with hypopituitarism, at least six months after normalizing of the hormonal disturbances. Also, gender differences on these outcomes were investigated. The secondary aim was to identify illness perceptions and causal attributions within this patient group. METHODS A total of 42 adult participants (60% females) with treated hypopituitarism once filled out a number of psychological questionnaires. The Profile of Mood States (POMS) and the Hospital Anxiety and Depression Scale (HADS) assessed mood and the Symptom Checklist-90 (SCL-90) and the Work and Social Adjustment Scale (WSAS) assessed well-being. Illness perceptions were identified using the Illness Perceptions Questionnaire-Brief Dutch Language Version (IPQ-B DLV) and causal attributions by using the Causal Attribution List (CAL). Patient outcomes were compared to reference values of healthy norm groups. RESULTS Participants scored significantly worse on the POMS depression, anger, fatigue and tension subscales, the SCL-90 psychoneuroticism, depression, inadequacy of thinking and acting and sleeping problems subscales and all subscales of the WSAS when compared to reference data. Women also scored worse on depression (HADS) and somatic symptoms (SCL-90). Compared to other illnesses, patients with hypopituitarism have more negative and realistic illness perceptions on consequences, timeline, identity and emotions. Participants attributed their complaints more to physical causes than psychological causes. CONCLUSION Despite normalization of hormonal disturbances, patients with hypopituitarism in general can still experience problems during daily living, such as negative mood states and a decreased psychological well-being.
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Affiliation(s)
- Tessa N. A. Slagboom
- Section of Endocrinology, Department of Internal Medicine, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam Neuroscience, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands
| | - Jan Berend Deijen
- Section of Clinical Neuropsychology, Department of Clinical, Neuro- & Developmental Psychology, Faculty of Behavioural and Movement Sciences, Vrije Universiteit, Van der Boechorstraat 7, 1081 BT Amsterdam, The Netherlands
- Hersencentrum Mental Health Institute Amsterdam, Amsterdam, The Netherlands
| | - Christa C. Van Bunderen
- Section of Endocrinology, Department of Internal Medicine, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam Neuroscience, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands
- Division of Endocrinology, Department of Internal Medicine, Radboud University Medical Center, Nijmegen, the Netherlands
| | - Hans A. Knoop
- Department of Medical Psychology, Amsterdam UMC, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands
| | - Madeleine L. Drent
- Section of Endocrinology, Department of Internal Medicine, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam Neuroscience, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands
- Section of Clinical Neuropsychology, Department of Clinical, Neuro- & Developmental Psychology, Faculty of Behavioural and Movement Sciences, Vrije Universiteit, Van der Boechorstraat 7, 1081 BT Amsterdam, The Netherlands
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Gruen A, Exner S, Kühl JS, von Stackelberg A, Budach V, Stromberger C, Boehmer D. Total body irradiation as part of conditioning regimens in childhood leukemia-long-term outcome, toxicity, and secondary malignancies. Strahlenther Onkol 2021; 198:33-38. [PMID: 34282476 PMCID: PMC8760188 DOI: 10.1007/s00066-021-01810-4] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2021] [Accepted: 06/13/2021] [Indexed: 11/28/2022]
Abstract
Background Total body irradiation (TBI) is an established part of conditioning regimens prior to stem cell transplantation in childhood leukemia but is associated with long-term toxicity. We retrospectively analyzed survival, long-term toxicity, and secondary malignancies in a pooled cohort of pediatric patients (pts.) treated with the same TBI regimen. Methods Analyzed were 109 pts. treated between September 1996 and November 2015. Conditioning treatment according to EBMT guidelines and the ALL SCTped 2012 FORUM trial consisted of chemotherapy (CT) and TBI with 2 Gy b.i.d. on 3 consecutive days to a total dose of 12 Gy. Median follow-up was 97.9 months (2–228 months). Results Overall survival (OS) in our cohort at 2, 5, and 10 years was 86.1, 75.5, and 63.0%, respectively. Median survival was not reached. Long-term toxicity developed in 47 pts. After chronically abnormal liver and kidney parameters in 31 and 7 pts., respectively, growth retardation was the most frequent finding as seen in 13 pts. Secondary malignancies were rare (n = 3). Conclusion TBI-containing conditioning regimens in pediatric stem cell transplantation (SCT) are highly effective. Efforts to replace TBI- with CT-containing regimens have only been successful in subgroups of pts. Although we could show long-term toxicity in 43% of pts., overall survival was 63% at 10 years. Still, long-term effects such as growth retardation can permanently impact the pts.’ quality of life and functioning. Along with new substances, efforts should be undertaken to optimize TBI techniques and accompany the treatment by systematic follow-up programs beyond 5 years to improve detection of rare events.
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Affiliation(s)
- Arne Gruen
- Department for Radiation Oncology and Radiotherapy, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Campus Virchow-Clinic, Augustenburger Platz 1, 13353, Berlin, Germany.
| | - Sebastian Exner
- Strahlenzentrum Hamburg MVZ, Langenhorner Chaussee 369, 22419, Hamburg, Germany
| | - Jörn-Sven Kühl
- Department for Pediatric Oncology, Hematology and Hemostaseology, University Clinic Leipzig, Liebigstraße 22, Haus 7, 04103, Leipzig, Germany
| | - Arend von Stackelberg
- Department for Pediatric Hematology, Oncology and Stem Cell Transplantation, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
| | - Volker Budach
- Department for Radiation Oncology and Radiotherapy, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Campus Virchow-Clinic, Augustenburger Platz 1, 13353, Berlin, Germany
| | - Carmen Stromberger
- Department for Radiation Oncology and Radiotherapy, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Campus Virchow-Clinic, Augustenburger Platz 1, 13353, Berlin, Germany
| | - Dirk Boehmer
- Department for Radiation Oncology and Radiotherapy, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Campus Virchow-Clinic, Augustenburger Platz 1, 13353, Berlin, Germany
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Gogna R, Jung C, McLachlan K, Krishnamurthy B, Hong A, Derbyshire M, Kiburg KV, Zacharin M, MacIsaac RJ, Sachithanandan N, Caputo C. Reducing adverse events associated with the glucagon stimulation test for the assessment of growth hormone deficiency in adults with a high prevalence of pituitary hormone deficiencies. Clin Endocrinol (Oxf) 2021; 95:125-133. [PMID: 33728673 DOI: 10.1111/cen.14464] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/19/2020] [Revised: 03/04/2021] [Accepted: 03/14/2021] [Indexed: 11/30/2022]
Abstract
DESIGN A retrospective review of the adverse events (AEs) in 78 patients during the glucagon stimulation test (GST) for the assessment of growth hormone deficiency (GHD) before and after protocol amendments which aimed to reduce AEs in a group of patients with a high prevalence of pituitary hormone deficiencies. PATIENTS Based on our observations of frequent AEs during the standard GST protocol in an initial 25 patients (cohort 1), a modified protocol was introduced to include the routine administration of 20 mg of hydrocortisone pre-GST in a subsequent 53 patients (cohort 2). Post hoc analysis of the effect of glucocorticoid dosing pre-GST on AEs was examined in those receiving <20 mg hydrocortisone (group A, n = 19) vs ≥20 mg hydrocortisone (group B, n = 59). MEASUREMENTS AEs including hypotension, hypoglycaemia and nausea/vomiting. RESULTS Of the 78 patients undergoing the GST, 79% had ≥2 hormone deficiencies. Rates of AEs were 41% vs 30% for hypotension, 60% vs 28% for hypoglycaemia (p < .05) and 20% vs 13% for nausea/vomiting in cohort 1 compared with cohort 2, respectively. Post hoc analysis revealed lower rates of AEs in those receiving ≥20 mg hydrocortisone (group B) compared to those receiving <20 mg due to a reduction in hypoglycaemic events (82% vs 26%, p < .001) and hypotension (50% vs 27%, p = .05). Similar numbers of patients in group A and group B met criteria for GHD. CONCLUSIONS In patients with a high prevalence of pituitary deficiencies, a modified GST protocol of additional stress dose glucocorticoid attenuated the frequency of AEs without appearing to compromise the performance of the GST.
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Affiliation(s)
- Reetu Gogna
- Department of Endocrinology & Diabetes, St. Vincent's Hospital Melbourne, Fitzroy, Vic., Australia
| | - Caroline Jung
- Department of Endocrinology & Diabetes, St. Vincent's Hospital Melbourne, Fitzroy, Vic., Australia
- Department of Medicine, St Vincent's Hospital Melbourne, The University of Melbourne, Fitzroy, Vic., Australia
| | - Kylie McLachlan
- Department of Endocrinology & Diabetes, St. Vincent's Hospital Melbourne, Fitzroy, Vic., Australia
| | - Balasubramanian Krishnamurthy
- Department of Endocrinology & Diabetes, St. Vincent's Hospital Melbourne, Fitzroy, Vic., Australia
- Department of Medicine, St Vincent's Hospital Melbourne, The University of Melbourne, Fitzroy, Vic., Australia
- St. Vincent's Institute, Fitzroy, Vic., Australia
| | - Alice Hong
- Department of Endocrinology & Diabetes, St. Vincent's Hospital Melbourne, Fitzroy, Vic., Australia
| | - Maresa Derbyshire
- Department of Endocrinology & Diabetes, St. Vincent's Hospital Melbourne, Fitzroy, Vic., Australia
| | - Katerina V Kiburg
- Department of Endocrinology & Diabetes, St. Vincent's Hospital Melbourne, Fitzroy, Vic., Australia
- Department of Medicine, St Vincent's Hospital Melbourne, The University of Melbourne, Fitzroy, Vic., Australia
- St. Vincent's Institute, Fitzroy, Vic., Australia
| | - Margaret Zacharin
- Hormone Research, Murdoch Children's Research Institute, Parkville, Vic., Australia
- Department of Endocrinology, Royal Children's Hospital, Parkville, Vic., Australia
- Department of Paediatrics, University of Melbourne, Parkville, Vic., Australia
| | - Richard J MacIsaac
- Department of Endocrinology & Diabetes, St. Vincent's Hospital Melbourne, Fitzroy, Vic., Australia
- Department of Medicine, St Vincent's Hospital Melbourne, The University of Melbourne, Fitzroy, Vic., Australia
- St. Vincent's Institute, Fitzroy, Vic., Australia
| | - Nirupa Sachithanandan
- Department of Endocrinology & Diabetes, St. Vincent's Hospital Melbourne, Fitzroy, Vic., Australia
- Department of Medicine, St Vincent's Hospital Melbourne, The University of Melbourne, Fitzroy, Vic., Australia
| | - Carmela Caputo
- Department of Endocrinology & Diabetes, St. Vincent's Hospital Melbourne, Fitzroy, Vic., Australia
- Department of Medicine, St Vincent's Hospital Melbourne, The University of Melbourne, Fitzroy, Vic., Australia
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Jansson JO, Dalmau Gasull A, Schéle E, Dickson SL, Palsdottir V, Palmquist A, Gironès FF, Bellman J, Anesten F, Hägg D, Ohlsson C. A Body Weight Sensor Regulates Prepubertal Growth via the Somatotropic Axis in Male Rats. Endocrinology 2021; 162:6167823. [PMID: 33693673 PMCID: PMC8143665 DOI: 10.1210/endocr/bqab053] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/07/2020] [Indexed: 12/20/2022]
Abstract
In healthy conditions, prepubertal growth follows an individual specific growth channel. Growth hormone (GH) is undoubtedly the major regulator of growth. However, the homeostatic regulation to maintain the individual specific growth channel during growth is unclear. We recently hypothesized a body weight sensing homeostatic regulation of body weight during adulthood, the gravitostat. We now investigated if sensing of body weight also contributes to the strict homeostatic regulation to maintain the individual specific growth channel during prepubertal growth. To evaluate the effect of increased artificial loading on prepubertal growth, we implanted heavy (20% of body weight) or light (2% of the body weight) capsules into the abdomen of 26-day-old male rats. The body growth, as determined by change in biological body weight and growth of the long bones and the axial skeleton, was reduced in rats bearing a heavy load compared with light load. Removal of the increased load resulted in a catch-up growth and a normalization of body weight. Loading decreased hypothalamic growth hormone releasing hormone mRNA, liver insulin-like growth factor (IGF)-1 mRNA, and serum IGF-1, suggesting that the reduced body growth was caused by a negative feedback regulation on the somatotropic axis and this notion was supported by the fact that increased loading did not reduce body growth in GH-treated rats. Based on these data, we propose the gravitostat hypothesis for the regulation of prepubertal growth. This states that there is a homeostatic regulation to maintain the individual specific growth channel via body weight sensing, regulating the somatotropic axis and explaining catch-up growth.
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Affiliation(s)
- John-Olov Jansson
- Department of Physiology, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden
- Correspondence: John-Olov Jansson, University of Gothenburg, Institute of Neuroscience and Physiology, Vita Stråket 11, 41390 Gothenburg, Sweden.
| | - Adria Dalmau Gasull
- Department of Physiology, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden
| | - Erik Schéle
- Department of Physiology, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden
| | - Suzanne L Dickson
- Department of Physiology, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden
| | - Vilborg Palsdottir
- Department of Physiology, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden
| | - Anders Palmquist
- Department of Biomaterials, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Ferran Font Gironès
- Department of Physiology, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden
| | - Jakob Bellman
- Department of Physiology, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden
| | - Fredrik Anesten
- Department of Physiology, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden
| | - Daniel Hägg
- Department of Physiology, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden
- Centre for Bone and Arthritis Research, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, the Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden
- Region Västra Götaland, Sahlgrenska University Hospital, Department of Drug Treatment, Gothenburg, Sweden
| | - Claes Ohlsson
- Centre for Bone and Arthritis Research, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, the Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden
- Region Västra Götaland, Sahlgrenska University Hospital, Department of Drug Treatment, Gothenburg, Sweden
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Lee J, Anderson LJ, Migula D, Yuen KCJ, McPeak L, Garcia JM. Experience of a Pituitary Clinic for US Military Veterans With Traumatic Brain Injury. J Endocr Soc 2021; 5:bvab005. [PMID: 33655093 DOI: 10.1210/jendso/bvab005] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/22/2020] [Indexed: 01/02/2023] Open
Abstract
Context Traumatic brain injury (TBI) is considered the "signature" injury of veterans returning from wartime conflicts in Iraq and Afghanistan. While moderate/severe TBI is associated with pituitary dysfunction, this association has not been well established in the military setting and in mild TBI (mTBI). Screening for pituitary dysfunction resulting from TBI in veteran populations is inconsistent across Veterans Affairs (VA) institutions, and such dysfunction often goes unrecognized and untreated. Objective This work aims to report the experience of a pituitary clinic in screening for and diagnosis of pituitary dysfunction. Methods A retrospective analysis was conducted in a US tertiary care center of veterans referred to the VA Puget Sound Healthcare System pituitary clinic with a history of TBI at least 12 months prior. Main outcome measures included demographics, medical history, symptom burden, baseline hormonal evaluation, brain imaging, and provocative testing for adrenal insufficiency (AI) and adult-onset growth hormone deficiency (AGHD). Results Fatigue, cognitive/memory problems, insomnia, and posttraumatic stress disorder were reported in at least two-thirds of the 58 patients evaluated. Twenty-two (37.9%) were diagnosed with at least one pituitary hormone deficiency, including 13 (22.4%) AI, 12 (20.7%) AGHD, 2 (3.4%) secondary hypogonadism, and 5 (8.6%) hyperprolactinemia diagnoses; there were no cases of thyrotropin deficiency. Conclusion A high prevalence of chronic AI and AGHD was observed among veterans with TBI. Prospective, larger studies are needed to confirm these results and determine the effects of hormone replacement on long-term outcomes in this setting.
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Affiliation(s)
- Jonathan Lee
- Geriatric Research, Education and Clinical Center (GRECC), VA Puget Sound Health Care System, and Department of Medicine, Division of Gerontology & Geriatric Medicine, University of Washington School of Medicine, Seattle, Washington, USA
| | - Lindsey J Anderson
- Geriatric Research, Education and Clinical Center (GRECC), VA Puget Sound Health Care System, and Department of Medicine, Division of Gerontology & Geriatric Medicine, University of Washington School of Medicine, Seattle, Washington, USA
| | - Dorota Migula
- Geriatric Research, Education and Clinical Center (GRECC), VA Puget Sound Health Care System, and Department of Medicine, Division of Gerontology & Geriatric Medicine, University of Washington School of Medicine, Seattle, Washington, USA
| | - Kevin C J Yuen
- Barrow Pituitary Center, Barrow Neurological Institute and St. Joseph's Hospital and Medical Center, University of Arizona College of Medicine and Creighton School of Medicine, Phoenix, Arizona, USA
| | - Lisa McPeak
- Center for Polytrauma Care, Rehabilitation Care Services, VA Puget Sound Health Care System, Seattle, Washington, USA
| | - Jose M Garcia
- Geriatric Research, Education and Clinical Center (GRECC), VA Puget Sound Health Care System, and Department of Medicine, Division of Gerontology & Geriatric Medicine, University of Washington School of Medicine, Seattle, Washington, USA
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Guha N, Nevitt SP, Francis M, Böhning W, Böhning D, Sönksen PH, Holt RIG. The effects of recombinant human insulin-like growth factor-1/insulin-like growth factor binding protein-3 administration on lipid and carbohydrate metabolism in recreational athletes. Clin Endocrinol (Oxf) 2021; 94:551-562. [PMID: 33249593 DOI: 10.1111/cen.14370] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/30/2020] [Revised: 10/06/2020] [Accepted: 10/11/2020] [Indexed: 11/28/2022]
Abstract
OBJECTIVE Previous studies suggested that recombinant human IGF-1 (rhIGF-1) administration affects carbohydrate and lipid metabolism in healthy people and in people with diabetes. This study aimed to determine the effects of rhIGF-1/rhIGF binding protein-3 (rhIGFBP-3) administration on glucose homeostasis and lipid metabolism in healthy recreational athletes. DESIGN AND SETTING Randomized, double-blind, placebo-controlled rhIGF-1/rhIGFBP-3 administration study at Southampton General Hospital, UK. PARTICIPANTS 56 recreational athletes (30 men, 26 women). METHODS Participants were randomly assigned to receive placebo, low-dose rhIGF-1/rhIGFBP-3 (30 mg/day) or high-dose rhIGF-1/rhIGFBP-3 (60 mg/day) for 28 days. The following variables were measured before and immediately after the treatment period: fasting lipids, glucose, insulin, C-peptide and glycated haemoglobin. The homeostatic model assessment (HOMA-IR) was used to estimate insulin sensitivity and indirect calorimetry to assess substrate oxidation rates. The general linear model approach was used to compare treatment group changes with the placebo group. RESULTS Compared with the placebo group, there was a significant reduction in fasting triglycerides in participants treated with high-dose rhIGF-1/rhIGFBP-3 (p = .030), but not in the low-dose group (p = .390). In women, but not in men, there were significant increases in total cholesterol (p = .003), HDL cholesterol (p = .001) and LDL cholesterol (p = .008). These lipid changes were associated with reduced fasting insulin (p = .010), C-peptide (p = .001) and HOMA-IR (p = .018) in women and reduced C-peptide (p = .046) in men. CONCLUSIONS rhIGF-1/rhIGFBP-3 administration for 28 days reduced insulin concentration, improved insulin sensitivity and had significant effects on lipid profile including decreased fasting triglycerides.
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Affiliation(s)
- Nishan Guha
- Human Development and Health, Faculty of Medicine, University of Southampton and University Hospital Southampton NHS Foundation Trust, Southampton, UK
- Department of Clinical Biochemistry, Oxford University Hospitals NHS Foundation Trust, Oxford, UK
| | - Simon P Nevitt
- Human Development and Health, Faculty of Medicine, University of Southampton and University Hospital Southampton NHS Foundation Trust, Southampton, UK
| | - Michael Francis
- Human Development and Health, Faculty of Medicine, University of Southampton and University Hospital Southampton NHS Foundation Trust, Southampton, UK
| | - Walailuck Böhning
- Human Development and Health, Faculty of Medicine, University of Southampton and University Hospital Southampton NHS Foundation Trust, Southampton, UK
| | - Dankmar Böhning
- Southampton Statistical Sciences Research Institute, University of Southampton, Southampton, UK
| | - Peter H Sönksen
- Human Development and Health, Faculty of Medicine, University of Southampton and University Hospital Southampton NHS Foundation Trust, Southampton, UK
| | - Richard I G Holt
- Human Development and Health, Faculty of Medicine, University of Southampton and University Hospital Southampton NHS Foundation Trust, Southampton, UK
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Manandhar M, Chun E, Romesberg FE. Genetic Code Expansion: Inception, Development, Commercialization. J Am Chem Soc 2021; 143:4859-4878. [DOI: 10.1021/jacs.0c11938] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Affiliation(s)
- Miglena Manandhar
- Synthorx, a Sanofi Company, La Jolla, California 92037, United States
| | - Eugene Chun
- Synthorx, a Sanofi Company, La Jolla, California 92037, United States
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Pataky MW, Young WF, Nair KS. Hormonal and Metabolic Changes of Aging and the Influence of Lifestyle Modifications. Mayo Clin Proc 2021; 96:788-814. [PMID: 33673927 PMCID: PMC8020896 DOI: 10.1016/j.mayocp.2020.07.033] [Citation(s) in RCA: 78] [Impact Index Per Article: 19.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/30/2020] [Revised: 06/01/2020] [Accepted: 07/02/2020] [Indexed: 02/07/2023]
Abstract
Increased life expectancy combined with the aging baby boomer generation has resulted in an unprecedented global expansion of the elderly population. The growing population of older adults and increased rate of age-related chronic illness has caused a substantial socioeconomic burden. The gradual and progressive age-related decline in hormone production and action has a detrimental impact on human health by increasing risk for chronic disease and reducing life span. This article reviews the age-related decline in hormone production, as well as age-related biochemical and body composition changes that reduce the bioavailability and actions of some hormones. The impact of hormonal changes on various chronic conditions including frailty, diabetes, cardiovascular disease, and dementia are also discussed. Hormone replacement therapy has been attempted in many clinical trials to reverse and/or prevent the hormonal decline in aging to combat the progression of age-related diseases. Unfortunately, hormone replacement therapy is not a panacea, as it often results in various adverse events that outweigh its potential health benefits. Therefore, except in some specific individual cases, hormone replacement is not recommended. Rather, positive lifestyle modifications such as regular aerobic and resistance exercise programs and/or healthy calorically restricted diet can favorably affect endocrine and metabolic functions and act as countermeasures to various age-related diseases. We provide a critical review of the available data and offer recommendations that hopefully will form the groundwork for physicians/scientists to develop and optimize new endocrine-targeted therapies and lifestyle modifications that can better address age-related decline in heath.
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Affiliation(s)
- Mark W Pataky
- Division of Endocrinology, Diabetes, Metabolism, and Nutrition, Mayo Clinic, Rochester, MN
| | - William F Young
- Division of Endocrinology, Diabetes, Metabolism, and Nutrition, Mayo Clinic, Rochester, MN
| | - K Sreekumaran Nair
- Division of Endocrinology, Diabetes, Metabolism, and Nutrition, Mayo Clinic, Rochester, MN.
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Scarano E, Riccio E, Somma T, Arianna R, Romano F, Di Benedetto E, de Alteriis G, Colao A, Di Somma C. Impact of Long-Term Growth Hormone Replacement Therapy on Metabolic and Cardiovascular Parameters in Adult Growth Hormone Deficiency: Comparison Between Adult and Elderly Patients. Front Endocrinol (Lausanne) 2021; 12:635983. [PMID: 33716985 PMCID: PMC7947790 DOI: 10.3389/fendo.2021.635983] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/30/2020] [Accepted: 01/14/2021] [Indexed: 11/13/2022] Open
Abstract
Growth hormone deficiency (GHD) in adults is due to a reduced growth hormone (GH) secretion by the anterior pituitary gland which leads to a well-known syndrome characterized by decreased cognitive function and quality of life (QoL), decreased bone mineral density (BMD), increased central adiposity with a reduction in lean body mass, decreased exercise tolerance, hyperlipidemia and increased predisposition to atherogenesis. Considering some similar features between aging and GHD, it was thought that the relative GH insufficiency of the elderly person could make an important contribution to the fragility of elderly. GH stimulation tests are able to differentiate GHD in elderly patients (EGHD) from the physiological reduction of GH secretion that occurs with aging. Although there is no evidence that rhGH replacement therapy increases the risk of developing Diabetes Mellitus (DM), reducing insulin sensitivity and inducing cardiac hypertrophy, long-term monitoring is, however, also mandatory in terms of glucose metabolism and cardiovascular measurements. In our experience comparing the impact of seven years of rhGH treatment on metabolic and cardiovascular parameters in GHD patients divided in two groups [adult (AGHD) and elderly (EGHD) GHD patients], effects on body composition are evident especially in AGHD, but not in EGHD patients. The improvements in lipid profile were sustained in all groups of patients, and they had a lower prevalence of dyslipidemia than the general population. The effects on glucose metabolism were conflicting, but approximately unchanged. The risk of DM type 2 is, however, probably increased in obese GHD adults with impaired glucose homeostasis at baseline, but the prevalence of DM in GHD is like that of the general population. The increases in glucose levels, BMI, and SBP in GHD negatively affected the prevalence of Metabolic Syndrome (MS) in the long term, especially in AGHD patients. Our results are in accordance to other long-term studies in which the effects on body composition and lipid profile are prominent.
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Affiliation(s)
- Elisabetta Scarano
- Dipartimento di Medicina Clinica e Chirurgia, Sezione di Endocrinologia, Università degli Studi di Napoli Federico II, Naples, Italy
| | - Enrico Riccio
- Dipartimento di Medicina Clinica e Chirurgia, Sezione di Endocrinologia, Università degli Studi di Napoli Federico II, Naples, Italy
| | - Teresa Somma
- Dipartimento di Neuroscienze e Scienze Riproduttive e Odontostomatologiche, Divisione di Neurochirurgia, Università degli Studi di Napoli Federico II, Naples, Italy
| | - Rossana Arianna
- Dipartimento di Medicina Clinica e Chirurgia, Sezione di Endocrinologia, Università degli Studi di Napoli Federico II, Naples, Italy
| | - Fiammetta Romano
- Dipartimento di Medicina Clinica e Chirurgia, Sezione di Endocrinologia, Università degli Studi di Napoli Federico II, Naples, Italy
| | - Elea Di Benedetto
- Dipartimento di Medicina Clinica e Chirurgia, Sezione di Endocrinologia, Università degli Studi di Napoli Federico II, Naples, Italy
| | - Giulia de Alteriis
- Dipartimento di Medicina Clinica e Chirurgia, Sezione di Endocrinologia, Università degli Studi di Napoli Federico II, Naples, Italy
| | - Annamaria Colao
- Dipartimento di Medicina Clinica e Chirurgia, Sezione di Endocrinologia, Università degli Studi di Napoli Federico II, Naples, Italy
| | - Carolina Di Somma
- Dipartimento di Medicina Clinica e Chirurgia, Sezione di Endocrinologia, Università degli Studi di Napoli Federico II, Naples, Italy
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Neuroendocrine manifestations of Erdheim-Chester disease. HANDBOOK OF CLINICAL NEUROLOGY 2021; 181:137-147. [PMID: 34238453 DOI: 10.1016/b978-0-12-820683-6.00010-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
Neuroendocrine manifestations are common in Erdheim-Chester disease (ECD) patients. ECD is a rare non-Langerhans form of histiocytosis with multisystemic infiltration. The involvement of the hypothalamo-pituitary axis is common and central diabetes insipidus (CDI) is one of the most common endocrine manifestations in ECD patients. CDI is the first manifestation of ECD in 25%-48% of the cases. Suprasellar region extension, due to the infiltration of ECD lesions, can cause neurologic manifestations by mass effects, such as headache, visual disturbance, and cranial nerve palsies. Recent studies have revealed that disorders affecting anterior pituitary hormones are common in ECD patients. Secondary adrenal insufficiency, secondary hypothyroidism, (adult) growth hormone deficiency, hypogonadotropic hypogonadism, hyperprolactinemia, and hypoprolactinemia can develop as the neuroendocrine manifestations of ECD. Since the symptoms of anterior pituitary hormone deficiencies tend to be nonspecific, the diagnosis of anterior pituitary hormone dysfunctions can be delayed. Some anterior pituitary dysfunctions such as adrenocorticotropic hormone and/or thyroid-stimulating hormone deficiencies can be life-threatening without adequate hormone supplementation therapies. An endocrinological evaluation of the function of the pituitary gland should be performed at the initial diagnosis of ECD. It is important to recognize that endocrine dysfunctions can develop later during the follow-up of ECD.
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Liu JT, Su PH. Amelioration of cognitive impairment following growth hormone replacement therapy: A case report and review of literature. World J Clin Cases 2020; 8:5773-5780. [PMID: 33344573 PMCID: PMC7716333 DOI: 10.12998/wjcc.v8.i22.5773] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/07/2020] [Revised: 09/30/2020] [Accepted: 10/20/2020] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Stroke is one of the leading causes of death and disability worldwide. In patients suffering from strokes and other acute brain injuries, the prevalence of pituitary dysfunction is high, and growth hormone deficiency is commonly found. Previous studies have demonstrated that administration of recombinant human growth hormone provides adult growth hormone deficiency (AGHD) patients with beneficial effects such as improving body compositions and quality of life. Nevertheless, other physiological benefits of growth hormone substitution are still controversial and inconclusive.
CASE SUMMARY A female with a history of hypertension suffered intracranial hemorrhage, intraventricular hemorrhage, and hydrocephalus at 56 years of age. Her mobility, fluency of speech, and mentality were impaired ever since the event occurred. After five years, the 61-year-old patient was further diagnosed with AGHD and received six-month growth hormone replacement therapy (GHRT). After six months of GHRT, the patient’s body composition was improved. A substantial improvement in Mini-Mental State Examination score was also observed, accompanying with ameliorations in mobility, fluency of speech, and mentality.
CONCLUSION In addition to improvements in body composition, GHRT for AGHD may provide further beneficial effects in patients with cognitive or motor impairments due to intracerebral hemorrhage.
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Affiliation(s)
- Jung-Tung Liu
- Department of Neurosurgery, Chung Shan Medical University Hospital, Taichung 40201, Taiwan
- Department of School of Medicine, Chung-Shan Medical University, Taichung 40201, Taiwan
| | - Pen-Hua Su
- Department of School of Medicine, Chung-Shan Medical University, Taichung 40201, Taiwan
- Department of Pediatrics and Genetics, Chung Shan Medical University Hospital, Taichung 40201, Taiwan
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Höybye C, Beck-Peccoz P, Simsek S, Zabransky M, Zouater H, Stalla G, Murray RD. Safety of current recombinant human growth hormone treatments for adults with growth hormone deficiency and unmet needs. Expert Opin Drug Saf 2020; 19:1539-1548. [PMID: 33089723 DOI: 10.1080/14740338.2020.1839410] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
INTRODUCTION Growth hormone (GH) deficiency (GHD) in adults is characterized by abnormal body composition, unfavorable cardiovascular risk factors, and poor quality of life. The diagnosis is made within appropriate clinical settings and according to established guidelines. Numerous studies have shown that GH treatment improves body composition, cardiovascular risk factors, physical capacity, and quality of life while issues on safety, in particular long-term safety, remain. AREAS COVERED Short- and long-term safety of GH replacement in adults with GHD. EXPERT OPINION Adults with GHD are an inhomogeneous group of patients and GH replacement requires individual considerations. Most adverse effects are mild and transient and related to fluid retention and GH dose. In patients without comorbidities long-term GH treatment is safe and development of diabetes, cardiovascular disease, or tumors are not increased. Furthermore, mortality is not increased. Patients with risk factors should be identified before GH treatment is initiated and an optimal balance between benefit and risk established. Studies with sufficient duration and power to identify the development of cardiovascular diseases and cancers are still awaited. Effective management of comorbidities can be expected to decrease morbidity and mortality and improve quality of life. Studies with long-acting GH formulations are ongoing and available data indicate similar effects and short-time safety.
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Affiliation(s)
- Charlotte Höybye
- Department Molecular Medicine and Surgery, Karolinska institute and Department of Endocrinology, Karolinska University Hospital , Stockholm, Sweden
| | - Paolo Beck-Peccoz
- Clinical Sciences and Community Health, Fondazione Istituto Di Ricovero E Cura a Carattere Scientifico Cà Granda Ospedale Maggiore Policlinico , Milano, Italy
| | - Suat Simsek
- Internal medicine, Northwest Clinics , Netherlands
| | | | | | - Günter Stalla
- Medicover Neuroendokrinologie , Munich, Germany.,Planck Institute of psychiatry, Medizinische Klinik Und Poliklinik IV Der Ludwig-Maximilians-Universität , Munich, Germany
| | - Robert D Murray
- Leeds Centre for Diabetes & Endocrinology, St James's University Hospital , Leeds, UK
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Ekhzaimy A, Beshyah SA, Al Dahmani KM, AlMalki MH. Physician' attitudes to growth hormone replacement therapy in adults following pituitary surgery: Results of an online survey. Avicenna J Med 2020; 10:215-222. [PMID: 33437693 PMCID: PMC7791281 DOI: 10.4103/ajm.ajm_46_20] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/02/2022] Open
Abstract
OBJECTIVE The aim of this study was to evaluate physician attitudes and practices in the management of adult growth hormone deficiency (GHD) following pituitary surgery. MATERIALS AND METHODS An online questionnaire survey was sent to a sample group of physicians. RESULTS A total of 131 respondents provided usable responses. More than three quarters were senior physicians, with most practicing in tertiary care centers (73%). Four-fifths of the respondents see at least 1 to 5 patients with GHD following pituitary surgery per year. Seventy-four percent acknowledge the benefit in principle of growth hormone replacement therapy (GHRT) for patients with GHD after pituitary surgery. Most respondents (84%) would only consider GHRT for symptomatic patients. However, 16% stated that patients with GHD after pituitary surgery generally suffer from the side effects of GHRT. Forty-four percent said that the serum insulin-like growth factor-1 (IGF-1) level is the best screening test for assessing GHD after pituitary surgery but 57% of the respondents would use IGF-I levels, and 29% the insulin tolerance test (ITT), in patients with a documented deficiency in three pituitary axes. The main barriers to long-term GHRT use were that it requires injections (67%), and is costly with limited supply (61%). Other reasons not to use GHRT include an absence of GHD symptoms and apparent GHT ineffectiveness (44%), physician lack of familiarity with the medication (40%), and lack of adherence to available guidelines (38%). CONCLUSION This survey addressed physician attitudes and practices in recognizing and treating GHD in adult's post-pituitary surgery. Regional guidelines must be developed to help address/tackle these issues and assist physicians in understanding and treating this condition.
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Affiliation(s)
- Aishah Ekhzaimy
- Department of Medicine, Endocrinology Division, King Saud University, King Saud University Medical City, Riyadh, Saudi Arabia
| | - Salem A. Beshyah
- Department of Endocrinology, Mediclinic Airport Road Hospital, Abu Dhabi, United Arab Emirates, Riyadh, Saudi Arabia
- Department of Medicine, Dubai Medical College, Dubai, United Arab Emirates, Riyadh, Saudi Arabia
| | - Khaled M. Al Dahmani
- Department of Medicine, United Arab Emirates University, United Arab Emirates, Riyadh, Saudi Arabia
- Division of Endocrinology, Tawam Hospital, Al Ain, United Arab Emirates, Riyadh, Saudi Arabia
| | - Mussa H. AlMalki
- Obesity, Endocrine and Metabolism Centre, King Fahad Medical City, Riyadh, Saudi Arabia
- College of Medicine, King Fahad Medical City, King Saud bin Abdul Aziz University for Health Sciences, Riyadh, Saudi Arabia
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Associations of types of dairy consumption with adiposity: cross-sectional findings from over 12 000 adults in the Fenland Study, UK. Br J Nutr 2020; 122:928-935. [PMID: 31342887 DOI: 10.1017/s0007114519001776] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Evidence from randomised controlled trials supports beneficial effects of total dairy products on body weight, fat and lean mass, but evidence on associations of dairy types with distributions of body fat and lean mass is limited. We aimed to investigate associations of total and different types of dairy products with markers of adiposity, and body fat and lean mass distribution. We evaluated cross-sectional data from 12 065 adults aged 30-65 years recruited to the Fenland Study between 2005 and 2015 in Cambridgeshire, UK. Diet was assessed with an FFQ. We estimated regression coefficients (or percentage differences) and their 95 % CI using multiple linear regression models. The medians of milk, yogurt and cheese consumption were 293 (interquartile range (IQR) 146-439), 35·3 (IQR 8·8-71·8) and 14·6 (IQR 4·8-26·9) g/d, respectively. Low-fat dairy consumption was inversely associated with visceral:subcutaneous fat ratio estimated with dual-energy X-ray absorptiometry (-2·58 % (95 % CI -3·91, -1·23 %) per serving/d). Habitual consumption per serving/d (200 g) of milk was associated with 0·33 (95 % CI 0·19, 0·46) kg higher lean mass. Other associations were not significant after false discovery correction. Our findings suggest that the influence of milk consumption on lean mass and of low-fat dairy consumption on fat mass distribution may be potential pathways for the link between dairy consumption and metabolic risk. Our cross-sectional findings warrant further research in prospective and experimental studies in diverse populations.
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Wright T, Urban R, Durham W, Dillon EL, Randolph KM, Danesi C, Gilkison C, Karmonik C, Zgaljardic DJ, Masel B, Bishop J, Pyles R, Seidler R, Hierholzer AH, Sheffield-Moore M. Growth Hormone Alters Brain Morphometry, Connectivity, and Behavior in Subjects with Fatigue after Mild Traumatic Brain Injury. J Neurotrauma 2020; 37:1052-1066. [PMID: 31797721 PMCID: PMC7185353 DOI: 10.1089/neu.2019.6690] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/13/2023] Open
Abstract
Pituitary dysfunction with reduced growth hormone (GH) secretion is common in patients following traumatic brain injury (TBI), and these patients often develop chronic symptoms including fatigue and altered cognition. We examined 18 subjects with a history of mild TBI, fatigue, and insufficient GH secretion. Subjects received GH replacement in a year-long, double-blind, placebo-controlled, crossover study, and were assessed for changes in physical performance, body composition, resting energy expenditure, fatigue, sleep, mood, and neuropsychological status. Additionally, magnetic resonance imaging (MRI) was used to assess changes in brain structure and resting state functional connectivity. GH replacement resulted in decreased fatigue, sleep disturbance, and anxiety, as well as increased resting energy expenditure, improved body composition, and altered perception of submaximal effort when performing exercise testing. Associated brain changes included increased frontal cortical thickness and gray matter volume and resting state connectivity changes in regions associated with somatosensory networks. GH replacement altered brain morphology and connectivity and reduced fatigue and related symptoms in mild TBI patients. Additional studies are needed to understand the mechanisms causing TBI-related fatigue and symptom relief with GH replacement.
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Affiliation(s)
- Traver Wright
- Department of Internal Medicine, University of Texas Medical Branch, Galveston, Texas
- Department of Health and Kinesiology, Texas A&M University, College Station, Texas
| | - Randall Urban
- Department of Internal Medicine, University of Texas Medical Branch, Galveston, Texas
| | - William Durham
- Department of Internal Medicine, University of Texas Medical Branch, Galveston, Texas
| | - E. Lichar Dillon
- Department of Internal Medicine, University of Texas Medical Branch, Galveston, Texas
| | - Kathleen M. Randolph
- Department of Internal Medicine, University of Texas Medical Branch, Galveston, Texas
- Department of Health and Kinesiology, Texas A&M University, College Station, Texas
| | - Christopher Danesi
- Department of Internal Medicine, University of Texas Medical Branch, Galveston, Texas
| | - Charles Gilkison
- Department of Internal Medicine, University of Texas Medical Branch, Galveston, Texas
| | - Christof Karmonik
- Radiology Department, Houston Methodist Research Institute, Houston, Texas
| | | | - Brent Masel
- Center for Neuro Skills, Bakersfield, California
| | - James Bishop
- Department of Radiology, Stanford University, Stanford, California
| | - Richard Pyles
- Department of Pediatrics, University of Texas Medical Branch, Galveston, Texas
| | - Rachael Seidler
- Department of Applied Physiology and Kinesiology, University of Florida, Gainesville, Florida
| | - Ashton H. Hierholzer
- Department of School of Medicine, University of Texas Medical Branch, Galveston, Texas
| | - Melinda Sheffield-Moore
- Department of Internal Medicine, University of Texas Medical Branch, Galveston, Texas
- Department of Health and Kinesiology, Texas A&M University, College Station, Texas
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Yu AP, Ugwu FN, Tam BT, Lee PH, Ma V, Pang S, Chow AS, Cheng KK, Lai CW, Wong CS, Siu PM. Obestatin and growth hormone reveal the interaction of central obesity and other cardiometabolic risk factors of metabolic syndrome. Sci Rep 2020; 10:5495. [PMID: 32218464 PMCID: PMC7099091 DOI: 10.1038/s41598-020-62271-w] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2017] [Accepted: 03/11/2020] [Indexed: 02/07/2023] Open
Abstract
Metabolic syndrome (MetS) is a multi-factorial disorder including central obesity (CO), insulin resistance, hyperglycemia, dyslipidemia and hypertension which increases the risk of diabetes mellitus and cardiovascular diseases. CO is considered as an essential component of MetS according to International Diabetes Federation (IDF), which may further modulate distinct signalling pathways compared with the other four MetS risk factors. Given that ghrelin signalling and the growth hormone/insulin-like growth factor-1 (GH/IGF-1) axis regulates energy balance and metabolic homeostasis, this study examined the changes in various ghrelin products and circulating hormones in response to the interaction between CO and other MetS components including blood pressure, fasting blood glucose, triglycerides, and high-density lipoprotein cholesterol in 133 Hong Kong Chinese adults. Circulating obestatin and GH were increased and reduced, respectively, by either CO or the other 4-risk factor cluster. These changes were further augmented by the presence of all MetS risk factors. However, changes of ghrelin levels were not mediated by CO but the other MetS risk factors. Our findings suggest that CO does not predict all the dysregulation of signalling pathways in individuals with MetS. Although CO and other MetS may share common signalling targets (i.e., obestatin and GH), CO does not contribute to the perturbation of ghrelin signalling.
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Affiliation(s)
- Angus P Yu
- Division of Kinesiology, School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong, China
| | - Felix N Ugwu
- Department of Health Technology and Informatics, Faculty of Health and Social Sciences, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong, China
| | - Bjorn T Tam
- Department of Health, Kinesiology and Applied Physiology, Concordia University, Montreal, QC, Canada
| | - Paul H Lee
- School of Nursing, Faculty of Health and Social Sciences, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong, China
| | - Vicki Ma
- Department of Health Technology and Informatics, Faculty of Health and Social Sciences, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong, China
| | - Simon Pang
- Department of Health Technology and Informatics, Faculty of Health and Social Sciences, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong, China
| | - Angel S Chow
- Department of Health Technology and Informatics, Faculty of Health and Social Sciences, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong, China
| | - Kenneth K Cheng
- Department of Health Technology and Informatics, Faculty of Health and Social Sciences, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong, China
| | | | - Cesar S Wong
- Department of Health Technology and Informatics, Faculty of Health and Social Sciences, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong, China
| | - Parco M Siu
- Division of Kinesiology, School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong, China.
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Chanson P. The heart in growth hormone (GH) deficiency and the cardiovascular effects of GH. ANNALES D'ENDOCRINOLOGIE 2020; 82:210-213. [PMID: 32473787 DOI: 10.1016/j.ando.2020.03.005] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
Abstract
Besides its effects on longitudinal growth in childhood and its metabolic effects with consequences on body composition and lipid levels, growth hormone (GH) has important roles on maintaining the structure and function of the normal adult heart. GH/insulin like growth factor-I (IGF-I) also interacts with the vascular system and plays a role in the regulation of vascular tone. GH deficiency (GHD) in adulthood is associated with increased fat mass (particularly visceral) and abnormal lipid profile, which may contribute to the excess cardiovascular mortality observed in patients with panhypopituitarism. Treatment with GH improved body composition (by increasing lean mass and decreasing fat mass) and improved lipid profile. It also has beneficial effects on vascular walls. The improvement in cardiovascular morbidity and mortality induced by GH is less clear as data are scarce and obtained on small populations. The importance of alteration in cardiac morphology and function observed in GHD is debated, particularly when cardiac magnetic resonance is used rather than echocardiography. The effects of treatment with GH on heart function and morphology are modest when studied by echocardiography.
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Affiliation(s)
- Philippe Chanson
- Service d'endocrinologie et des maladies de la reproduction, centre de référence des maladies rares de l'hypophyse, Assistance publique-hôpitaux de Paris, hôpital Bicêtre, 78, rue du Général-Leclerc, 94275, Le Kremlin-Bicêtre, France; Université Paris-Saclay, université Paris-Sud, Inserm, signalisation hormonale, physiopathologie endocrinienne et métabolique, 94276, Le Kremlin-Bicêtre, France.
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Soga A, Fukuda I, Kobayashi S, Tahara S, Morita A, Sugihara H. Preoperative growth hormone (GH) peak values during a GH releasing peptide-2 test reflect the severity of hypopituitarism and the postoperative recovery of GH secretion in patients with non-functioning pituitary adenomas. Endocr J 2020; 67:167-175. [PMID: 31776295 DOI: 10.1507/endocrj.ej19-0288] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
Abstract
Non-functioning pituitary adenoma (NFPA) is one common cause of adult growth hormone deficiency (AGHD). In Japan, a GH-releasing peptide (GHRP)-2 test is used to evaluate GH secretion. Although the cut-off for peak GH during a GHRP-2 test for severe AGHD is ≤9 ng/mL, severe AGHD may further diminish responses (range, nearly no-response to ≤9 ng/mL). We studied whether the peak GH responses during a GHRP-2 test could be predicted based on clinical characteristics of patients with NFPA. We compared patients with almost no-response during a GHRP-2 test with other patients considered as severe AGHD. Among the 76 patients with NFPA who were admitted to our institution, 36 patients (mean age, 61 years; male/female, n = 23/n = 13) were diagnosed with severe AGHD based on a preoperative GHRP-2 test. Based on the preoperative median peak GH concentration (2.83 ng/mL), patients were divided into two groups (<median = low or group L, n = 18; ≥median = moderate or group M, n = 18). Clinical manifestations, body mass index, severity of hypopituitarism and tumor size, volume, and extension were analyzed retrospectively. Compared with group M, group L patients were significantly older and more gonadotropin and ACTH deficient. A lower peak GH release during a GHRP-2 test was associated with a higher number of anterior pituitary hormone deficiencies across all 76 patients. Postoperatively, seven in group M and no patient in group L were assessed as having no longer severe AGHD, respectively. Preoperative peak GH concentrations assessed during a GHRP-2 test reflected the severity of hypopituitarism and the recovery of postoperative GH secretion.
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Affiliation(s)
- Akimi Soga
- Department of Endocrinology, Diabetes and Metabolism, Graduate School of Medicine, Nippon Medical School, Tokyo 113-8603, Japan
| | - Izumi Fukuda
- Department of Endocrinology, Diabetes and Metabolism, Graduate School of Medicine, Nippon Medical School, Tokyo 113-8603, Japan
| | - Shunsuke Kobayashi
- Department of Endocrinology, Diabetes and Metabolism, Graduate School of Medicine, Nippon Medical School, Tokyo 113-8603, Japan
| | - Shigeyuki Tahara
- Department of Neurosurgery, Graduate School of Medicine, Nippon Medical School, Tokyo 113-8603, Japan
| | - Akio Morita
- Department of Neurosurgery, Graduate School of Medicine, Nippon Medical School, Tokyo 113-8603, Japan
| | - Hitoshi Sugihara
- Department of Endocrinology, Diabetes and Metabolism, Graduate School of Medicine, Nippon Medical School, Tokyo 113-8603, Japan
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Abstract
Growth hormone deficiency (GHD) is a severe pathology that greatly affects the quality of life, and increases morbidity and mortality of patients owing to the augmentation of cardiovascular events. Treatment of GHD is challenging, mainly because there is no specific characteristic sign or symptom that can be used to make a clear diagnosis. There is need for an unequivocal diagnosis of GHD to avoid unnecessary treatment with GH, because the available provocative tests (GH stimulation tests) are not specific and sensitive enough, and are contraindicated in some patients. Ghrelin is an endogenous peptide that stimulates GH secretion by interacting with a G-protein-coupled receptor named ghrelin receptor (GH secretagogue receptor 1a, GHS-R1a). Given this, a GH stimulation test using ghrelin or its analogues appears to be attractive. In this paper, a modified tripeptide first named JMV-1843 in the laboratory is briefly presented. It is potent and selective in stimulating the release of GH and is orally active. It has been recently commercialised for the diagnosis of adult GH deficiency under the tradename Macrilen. The test using this compound appears to be reliable, well tolerated, and simple.
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Kobylińska M, Malak R, Majewska K, Kędzia A, Samborski W. Assessment of anterior-posterior spinal curvatures in children suffering from hypopituitarism. BMC Endocr Disord 2019; 19:137. [PMID: 31829163 PMCID: PMC6907119 DOI: 10.1186/s12902-019-0462-4] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/19/2019] [Accepted: 11/27/2019] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND Body posture may be disordered by vestibular dysfunction, neurological disorders, problems with the distribution of muscle tone, brain injuries, and other dysfunctions. Growth hormone deficiency (GHD) can lead to many disorders, particularly of the musculoskeletal system. During treatment with recombinant human growth hormone (rhGH), an increase in muscle mass and an improvement in bone structure can be observed in children suffering from hypopituitarism from GHD. METHODS The study involved 33 children suffering from hypopituitarism with GHD (9 girls and 24 boys), aged 10-14 years old. Measurements of the magnitude of their anterior-posterior spinal curvatures were made using an inclinometer. The children were examined at the medianus of the sacrum bone, the Th12-L1 intervertebral area, and the C7-Th1 intervertebral area. In order to characterize the anterior-posterior curvature of the spine, the results were compared with the general norms reported by Saunders. Statistical calculations were carried out using the statistical package Statistica 10 PL. RESULTS Lumbar lordosis angles were higher in the patients currently receiving growth hormone (GH) treatment than in those who had yet to receive it. There is a statistically significant positive correlation between the length of growth hormone treatment and the alpha angle. There are also statistically significant correlations between age at the beginning of growth hormone therapy and the angle of lordosis. Statistically significant correlations were also seen between age at the beginning of growth hormone therapy and the alpha angle. CONCLUSIONS Although there may be changes in posture at the beginning of rhGH treatment, the sooner growth hormone therapy begins, the better the body posture. The longer the growth hormone treatment, the better the posture, as expressed by the alpha angle in the sagittal plane.
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Affiliation(s)
- Magdalena Kobylińska
- Department of Clinical Auxology and Pediatrics Nursing Faculty of Health Sciences, Poznań University of Medical Sciences, Szpitalna 27/33, 60-572 Poznań, Poland
| | - Roksana Malak
- Department and Clinic of Rheumatology and Rehabilitation, Poznan University of Medical Sciences, 28 Czerwca 1956 nr 135/147, 61-545 Poznań, Poland
| | - Katarzyna Majewska
- Department of Clinical Auxology and Pediatrics Nursing Faculty of Health Sciences, Poznań University of Medical Sciences, Szpitalna 27/33, 60-572 Poznań, Poland
| | - Andrzej Kędzia
- Department of Clinical Auxology and Pediatrics Nursing Faculty of Health Sciences, Poznań University of Medical Sciences, Szpitalna 27/33, 60-572 Poznań, Poland
| | - Włodzimierz Samborski
- Department and Clinic of Rheumatology and Rehabilitation, Poznan University of Medical Sciences, 28 Czerwca 1956 nr 135/147, 61-545 Poznań, Poland
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