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Alvarez M, Donato A, Rincon J, Rincon O, Lancheros N, Mancera P, Guzman I. Evaluation of pituitary tumor volume as a prognostic factor in acromegaly: A cross-sectional study in two centers. World J Radiol 2025; 17:100168. [DOI: 10.4329/wjr.v17.i3.100168] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/08/2024] [Revised: 01/14/2025] [Accepted: 02/14/2025] [Indexed: 03/27/2025] Open
Abstract
BACKGROUND Acromegaly is caused by a pituitary neuroendocrine tumor (PitNET) with excessive production of growth hormone (GH), leading to multisystem complications. Previous studies have identified predictors of disease persistence following surgery and poor response to medical treatment, including tumor size, vertical and horizontal extensions of the adenoma, hyperintensity in T2-weighted magnetic resonance imaging, granulation density, and pre- and postoperative GH and insulin-like growth factor 1 (IGF-1) levels.
AIM To evaluate PitNET volume as a complementary prognostic factor in patients with acromegaly.
METHODS This is a retrospective descriptive study with an analytical component evaluating the correlation between the volumetric analysis of GH-producing PitNETs, IGF-1 levels before and after surgery, disease control during follow-up, and the line of therapy required for disease control in a cohort of patients treated at two centers: Endocrinology Department of the Central Military Hospital and Centros Médicos Colsanitas, Bogotá, Colombia.
RESULTS A total of 77 patients with acromegaly (42 men, 35 women) were included in this study. The mean age at diagnosis was 42 years (SD: 12), with a mean disease duration of 9.9 years (SD: 7.2). The mean pituitary tumor volume was 4358 mm³ (SD: 6291, interquartile range [IQR]: 13602). Patients with controlled acromegaly had a mean PitNET volume of 3202 mm³ (SD: 4845, 95%CI: 621-5784) compared to 5513 mm³ (SD: 7447, 95%CI: 1545-9482) in the uncontrolled group (P = 0.15). A PitNET volume exceeding 3697 mm³ was associated with a higher likelihood of requiring third or fourth-line therapy (50% vs 36%; P = 0.03).
CONCLUSION PitNET volume was associated with the need for higher-line therapy to manage acromegaly but did not correlate with long-term disease control or with pre- or postsurgical IGF-1 levels. Nevertheless, a trend towards an inverse relationship between tumor volume and future disease control was observed. While macroadenoma classification remains crucial, among patients with macroadenomas, those with a volume exceeding 3697 mm³ could have worse prognosis.
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Affiliation(s)
- Mauricio Alvarez
- Department of Endocrinology, Hospital Militar Central, Bogota 110221, Distrito Capital de Bogotá, Colombia
| | - Angel Donato
- Department of Neuroradiology, Hospital Militar Central, Bogota 110221, Distrito Capital de Bogotá, Colombia
| | - Juliana Rincon
- Department of Epidemiology, Fundación Universitaria Sanitas, Bogota 110221, Distrito Capital de Bogotá, Colombia
| | - Oswaldo Rincon
- Department of Endocrinology, Hospital Militar Central, Bogota 110221, Distrito Capital de Bogotá, Colombia
| | - Natalia Lancheros
- Department of Clinical Medicine, Centros Médicos Colsanitas, Bogota 110221, Distrito Capital de Bogotá, Colombia
| | - Pedro Mancera
- Department of Endocrinology, Universidad Militar Nueva Granada, Bogota 110221, Distrito Capital de Bogotá, Colombia
| | - Isaac Guzman
- Department of Endocrinology, Hospital Militar Central, Bogota 110221, Distrito Capital de Bogotá, Colombia
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Alnaaim SA, Al-Kuraishy HM, Zailaie MM, Alexiou A, Papadakis M, Saad HM, Batiha GES. The potential link between acromegaly and risk of acute ischemic stroke in patients with pituitary adenoma: a new perspective. Acta Neurol Belg 2024; 124:755-766. [PMID: 37584889 PMCID: PMC11139727 DOI: 10.1007/s13760-023-02354-3] [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: 03/23/2023] [Accepted: 07/25/2023] [Indexed: 08/17/2023]
Abstract
Acromegaly is an endocrine disorder due to the excess production of growth hormone (GH) from the anterior pituitary gland after closed epiphyseal growth plates. Acromegaly is mainly caused by benign GH-secreting pituitary adenoma. Acute ischemic stroke (AIS) is one of the most common cardiovascular complications. It ranks second after ischemic heart disease (IHD) as a cause of disability and death in high-income countries globally. Thus, this review aimed to elucidate the possible link between acromegaly and the development of AIS. The local effects of acromegaly in the development of AIS are related to the development of pituitary adenoma and associated surgical and radiotherapies. Pituitary adenoma triggers the development of AIS through different mechanisms, particularly aneurysmal formation, associated thrombosis, and alteration of cerebral microcirculation. Cardiovascular complications and mortality were higher in patients with pituitary adenoma. The systemic effect of acromegaly-induced cardio-metabolic disorders may increase the risk for the development of AIS. Additionally, acromegaly contributes to the development of endothelial dysfunction (ED), inflammatory and oxidative stress, and induction of thrombosis that increases the risk for the development of AIS. Moreover, activated signaling pathways, including activator of transcription 3 (STAT3), nuclear factor kappa B (NF-κB), nod-like receptor pyrin 3 (NLRP3) inflammasome, and mitogen-activated protein kinase (MAPK) in acromegaly may induce systemic inflammation with the development of cardiovascular complications mainly AIS. Taken together, acromegaly triggers the development of AIS through local and systemic effects by inducing the formation of a cerebral vessel aneurysm, the release of pro-inflammatory cytokines, the development of oxidative stress, ED, and thrombosis correspondingly.
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Affiliation(s)
- Saud A Alnaaim
- Clinical Neurosciences Department, College of Medicine, King Faisal University, Hofuf, Saudi Arabia
| | - Hayder M Al-Kuraishy
- Department of Pharmacology, Toxicology and Medicine, Medical Faculty, College of Medicine, Al-Mustansiriyah University, PO Box 14132, Baghdad, Iraq
| | | | - Athanasios Alexiou
- Department of Science and Engineering, Novel Global Community Educational Foundation, Hebersham, NSW, 2770, Australia
- AFNP Med, 1030, Vienna, Austria
| | - Marios Papadakis
- Department of Surgery II, University Hospital Witten-Herdecke, University of Witten-Herdecke, Heusnerstrasse 40, 42283, Wuppertal, Germany.
| | - Hebatallah M Saad
- Department of Pathology, Faculty of Veterinary Medicine, Matrouh University, Marsa Matruh, 51744, Egypt
| | - Gaber El-Saber Batiha
- Department of Pharmacology and Therapeutics, Faculty of Veterinary Medicine, Damanhour University, Damanhour, 22511, Egypt
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Kim K, Ku CR, Lee EJ. Multiomics Approach to Acromegaly: Unveiling Translational Insights for Precision Medicine. Endocrinol Metab (Seoul) 2023; 38:463-471. [PMID: 37828709 PMCID: PMC10613768 DOI: 10.3803/enm.2023.1820] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/06/2023] [Revised: 09/24/2023] [Accepted: 10/04/2023] [Indexed: 10/14/2023] Open
Abstract
The clinical characteristics and prognoses of acromegaly vary among patients. Assessment of current and novel predictors can lead to multilevel categorization of patients, allowing integration into new clinical guidelines and a reduction in the increased morbidity and mortality associated with acromegaly. Despite advances in the diagnosis and treatment of acromegaly, its pathophysiology remains unclear. Recent advancements in multiomics technologies, including genomics, transcriptomics, proteomics, metabolomics, and radiomics, have offered new opportunities to unravel the complex pathophysiology of acromegaly. This review comprehensively explores the emerging role of multiomics approaches in elucidating the molecular landscape of acromegaly. We discuss the potential implications of multiomics data integration in the development of novel diagnostic tools, identification of therapeutic targets, and the prospects of precision medicine in acromegaly management. By integrating diverse omics datasets, these approaches can provide valuable insights into disease mechanisms, facilitate the identification of diagnostic biomarkers, and identify potential therapeutic targets for precision medicine in the management of acromegaly.
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Affiliation(s)
- Kyungwon Kim
- Endocrinology, Institute of Endocrine Research, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - Cheol Ryong Ku
- Endocrinology, Institute of Endocrine Research, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - Eun Jig Lee
- Endocrinology, Institute of Endocrine Research, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
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Coskun M, Altinova AE, Babayeva A, Sel AT, Yapar D, Karaca M, Yalcin MM, Akturk M, Toruner FB, Karakoc MA, Yetkin I. Leukocyte Telomere Length and Neuregulin-4 Levels in Female Patients with Acromegaly: The Relationship between Disease Activity and Body Fat Distribution. J Clin Med 2023; 12:4108. [PMID: 37373801 DOI: 10.3390/jcm12124108] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2023] [Revised: 06/06/2023] [Accepted: 06/15/2023] [Indexed: 06/29/2023] Open
Abstract
The study aimed to examine leukocyte telomere length (LTL) and serum neuregulin-4 levels and their relationship with disease activity, co-morbidities and body fat distribution in female acromegaly patients. Forty female patients with acromegaly and thirty-nine age and body mass index (BMI) similar healthy female volunteers were included in the study. Patients were classified into two groups: active acromegaly (AA) and controlled acromegaly (CA). The quantitative polymerase chain reaction (PCR) method was used to study LTL, and T/S ratio < 1 was accepted as shortened telomere length. Neuregulin-4 was studied by ELISA. There was no difference in median LTL between acromegaly and the control group (p = 0.530). The percentage of T/S < 1 in patients with acromegaly (60.0%) was similar to that of the control group (43.6%) (p = 0.144). However, serum neuregulin-4 was significantly higher in patients with acromegaly than those in the control group (p = 0.037). There were no significant differences concerning LTL, percentage of T/S < 1 and neuregulin-4 levels between active and controlled acromegaly groups (p > 0.05). Neuregulin-4 correlated positively with fasting glucose, triglyceride (TG), triglyceride/glucose (TyG) index, and lean body mass in the acromegaly group. A negative correlation was observed between LTL and neuregulin-4 in the control group (p = 0.039). When the factors affecting neuregulin-4 were evaluated by multivariate linear regression analysis with an enter method, TG (β: 0.316, p = 0.025) was independently and positively associated with neuregulin-4. Our findings indicate that acromegaly is associated with unchanged LTL and high neuregulin-4 levels in female patients. However, the relationship between acromegaly, the aging process, and neuregulin-4 involves complex mechanisms, and further studies are needed.
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Affiliation(s)
- Meric Coskun
- Department of Endocrinology and Metabolism, Faculty of Medicine, Gazi University, Ankara 06100, Turkey
| | - Alev Eroglu Altinova
- Department of Endocrinology and Metabolism, Faculty of Medicine, Gazi University, Ankara 06100, Turkey
| | - Afruz Babayeva
- Department of Endocrinology and Metabolism, Faculty of Medicine, Gazi University, Ankara 06100, Turkey
| | - Aydin Tuncer Sel
- Department of Endocrinology and Metabolism, Faculty of Medicine, Gazi University, Ankara 06100, Turkey
| | - Dilek Yapar
- Department of Public Health, Faculty of Medicine, Gazi University, Ankara 06100, Turkey
| | - Mine Karaca
- Department of Internal Medicine, Faculty of Medicine, Gazi University, Ankara 06100, Turkey
| | - Mehmet Muhittin Yalcin
- Department of Endocrinology and Metabolism, Faculty of Medicine, Gazi University, Ankara 06100, Turkey
| | - Mujde Akturk
- Department of Endocrinology and Metabolism, Faculty of Medicine, Gazi University, Ankara 06100, Turkey
| | - Fusun Balos Toruner
- Department of Endocrinology and Metabolism, Faculty of Medicine, Gazi University, Ankara 06100, Turkey
| | - Mehmet Ayhan Karakoc
- Department of Endocrinology and Metabolism, Faculty of Medicine, Gazi University, Ankara 06100, Turkey
| | - Ilhan Yetkin
- Department of Endocrinology and Metabolism, Faculty of Medicine, Gazi University, Ankara 06100, Turkey
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Kizilgul M, Karakis R, Dogan N, Bostan H, Yapici MM, Gul U, Ucan B, Duman E, Duger H, Cakal E, Akin O. Real-time detection of acromegaly from facial images with artificial intelligence. Eur J Endocrinol 2023; 188:6986588. [PMID: 36747333 DOI: 10.1093/ejendo/lvad005] [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: 10/12/2022] [Revised: 11/21/2022] [Accepted: 01/05/2023] [Indexed: 01/15/2023]
Abstract
OBJECTIVE Despite improvements in diagnostic methods, acromegaly is still a late-diagnosed disease. In this study, it was aimed to automatically recognize acromegaly disease from facial images by using deep learning methods and to facilitate the detection of the disease. DESIGN Cross-sectional, single-centre study. METHODS The study included 77 acromegaly (52.56 ± 11.74, 34 males/43 females) patients and 71 healthy controls (48.47 ± 8.91, 39 males/32 females), considering gender and age compatibility. At the time of the photography, 56/77 (73%) of the acromegaly patients were in remission. Normalized images were obtained by scaling, aligning, and cropping video frames. Three architectures named ResNet50, DenseNet121, and InceptionV3 were used for the transfer learning-based convolutional neural network (CNN) model developed to classify face images as "Healthy" or "Acromegaly". Additionally, we trained and integrated these CNN machine learning methods to create an Ensemble Method (EM) for facial detection of acromegaly. RESULTS The positive predictive values obtained for acromegaly with the ResNet50, DenseNet121, InceptionV3, and EM were calculated as 0.958, 0.965, 0.962, and 0.997, respectively. The average sensitivity, specificity, precision, and correlation coefficient values calculated for each of the ResNet50, DenseNet121, and InceptionV3 models are quite close. On the other hand, EM outperformed these three CNN architectures and provided the best overall performance in terms of sensitivity, specificity, accuracy, and precision as 0.997, 0.997, 0.997, and 0.998, respectively. CONCLUSIONS The present study provided evidence that the proposed AcroEnsemble Model might detect acromegaly from facial images with high performance. This highlights that artificial intelligence programs are promising methods for detecting acromegaly in the future.
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Affiliation(s)
- Muhammed Kizilgul
- University of Health Sciences, Diskapi Yildirim Beyazit Training and Research Hospital, Department of Endocrinology, Ankara, Turkey
| | - Rukiye Karakis
- Sivas Cumhuriyet University, Faculty of Technology, Software Engineering Department, Sivas, Turkey
| | - Nurettin Dogan
- Selçuk University, Faculty of Technology, Computer Engineering Department, Konya, Turkey
| | - Hayri Bostan
- University of Health Sciences, Diskapi Yildirim Beyazit Training and Research Hospital, Department of Endocrinology, Ankara, Turkey
| | - Muhammed Mutlu Yapici
- Ankara University, Elmadağ Vocational School, Computer Technologies Department, Ankara, Turkey
| | - Umran Gul
- University of Health Sciences, Diskapi Yildirim Beyazit Training and Research Hospital, Department of Endocrinology, Ankara, Turkey
| | - Bekir Ucan
- University of Health Sciences, Diskapi Yildirim Beyazit Training and Research Hospital, Department of Endocrinology, Ankara, Turkey
| | - Elvan Duman
- Burdur Mehmet Akif Ersoy University, Faculty of Technology, Software Engineering Department, Burdur, Turkey
| | - Hakan Duger
- University of Health Sciences, Diskapi Yildirim Beyazit Training and Research Hospital, Department of Endocrinology, Ankara, Turkey
| | - Erman Cakal
- University of Health Sciences, Diskapi Yildirim Beyazit Training and Research Hospital, Department of Endocrinology, Ankara, Turkey
| | - Omer Akin
- TOBB ETU, Faculty of Science and Literature, Mathematics Department, Ankara, Turkey
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Chhabra R, Kumar A, Virk RS, Dutta P, Ahuja C, Mohanty M, Dhandapani S. Outcomes in pituitary adenoma causing acromegaly following endoscopic endonasal transsphenoidal surgery. J Neurosci Rural Pract 2022; 13:696-704. [PMID: 36743751 PMCID: PMC9894003 DOI: 10.25259/jnrp-2022-3-28-r1-(2453)] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2022] [Accepted: 09/20/2022] [Indexed: 12/10/2022] Open
Abstract
Objectives The objectives of the study were to study the analysis of outcomes after endoscopic endonasal transsphenoidal surgery (EETSS) in acromegaly in terms of surgical complications, clinical improvement, endocrinological remission, achievement of prognostically critical growth hormone (GH) level, and requirement of additional treatment. Materials and Methods The study included 28 acromegaly patients, who underwent EETSS. A 2010 consensus criterion was used for defining remission. Assessment of prognostically critical GH level (random value <2.5 ng/ml), the extent of resection and additional treatment, was done at post-operative week (POW) 12. Results All adenomas were macroadenomas; with a mean volume of 16.34 cm3 (range, 0.4-99 cm3). Most adenomas had high-grade extensions. Most common suprasellar, infrasellar, anterior, and posterior extension grades were 3 (n = 13), 1 (n = 16), 1 (n = 14), and 0 (n = 20), respectively. Knosp Grade 3 was common on both sides (right, n = 9 and left, n = 8). One patient had already been operated on with EETSS, 1.5 years back from current surgery. Sixteen patients were on hormonal support, preoperatively. Four patients died during follow-up. Post-operative common complications were diabetes insipidus (DI, n = 18), cerebrospinal fluid rhinorrhea (n = 10), surgical site hematoma (n = 3), meningitis (n = 3), hydrocephalus (n = 2), and syndrome of inappropriate antidiuretic hormone (n = 1). The mean hospital stay was 11.62 days and 12.17 months were the mean follow-up period. At 12 POW, no improvement was seen in body enlargement and visual complaints, but all other complaints improved significantly except perspiration. Adenomas were decreased in all extensions except posterior and mean adenoma volume was reduced from 16.34 cm3 to 2.92 cm3 after surgery. Sub-total resection (STR, n = 10), near-total resection (NTR, n = 7), gross-total resection (GTR, n = 5), and partial resection (PR, n = 2) were achieved. Endocrinological remission and prognostically critical GH levels were attained in 29.17% (n = 7) and 66.67% (n = 16), respectively. NTR, GTR, STR, and PR were associated with 57.14%, 40%, 10%, and 0% endocrinological remission, respectively. Additional treatment was required in a total of 17 patients, three in GTR, nine in STR, three in NTR, and two in PR. Ten were treated with Gamma Knife radiosurgery along with medical treatment and seven with medical treatment alone. Conclusion A successful EETSS can reduce adenoma volume to achieve clinical improvement, endocrinologic remission, and prognostically critical GH level with some complications related to surgery. Pre-operative larger volume and higher extension grades affect these outcomes adversely.
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Affiliation(s)
- Rajesh Chhabra
- Department of Neurosurgery, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Ashwani Kumar
- Department of Neurosurgery, Government Medical College and Hospital, Chandigarh, India
| | - R. S. Virk
- Department of Otorhinolaryngology, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Pinaki Dutta
- Department of Endocrinology, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Chirag Ahuja
- Department of Neuroradiology, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Manju Mohanty
- Department of Neurosurgery, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Sivashanmugam Dhandapani
- Department of Neurosurgery, Post Graduate Institute of Medical Education and Research, Chandigarh, India
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Ogedegbe OJ, Cheema AY, Khan MA, Junaid SZS, Erebo JK, Ayirebi-Acquah E, Okpara J, Bofah D, Okon JG, Munir M, Alugba G, Ezekiel A, Okun O, Ojo TK, Mejulu EO, Jimoh A. A Comprehensive Review of Four Clinical Practice Guidelines of Acromegaly. Cureus 2022; 14:e28722. [PMID: 36105896 PMCID: PMC9453869 DOI: 10.7759/cureus.28722] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/03/2022] [Indexed: 11/29/2022] Open
Abstract
Acromegaly is an endocrine disorder characterized by dysregulated hypersecretion of growth hormone (GH), leading to an overproduction of insulin-like growth factor 1 (IGF-1). The etiology is usually a GH-secreting pituitary adenoma with the resultant presentation of coarse facial features, frontal bossing, arthritis, prognathism (protrusion of the mandible), and impaired glucose tolerance, among others. Most pituitary adenomas arise due to sporadic mutations that lead to unregulated cellular division, subsequent tumor formation, and resultant GH hypersecretion. Major scientific organizations and authorities in endocrinology release regularly updated guidelines for diagnosing and managing acromegaly. We have holistically evaluated four data-driven and evidentiary approaches in the management of acromegaly to compare and contrast these guidelines and show their salient differences. These guidelines have been reviewed because they are major authorities in acromegaly management. In this comprehensive article, differences in the diagnosis and treatment recommendations of the discussed guidelines have been highlighted. Our findings showed that diagnosing modalities were similar among the four approaches; however, some guidelines were more specific about additional supporting investigations to confirm a diagnosis of acromegaly. For management options, each guideline had suggestions about ideal therapeutic outcomes. Treatment options were identical but salient differences were noticed, such as the addition of combination therapy and alternative therapy in the setting of failure to respond to first and second-line treatments. Reviewing clinical guidelines for various pathologies encourages sharing ideas among medical practitioners and ensures that global best practices are adopted. Therefore, a constant review of these clinical practice guidelines is necessary to keep clinicians up to date with the latest trends in patient management.
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Chhabra R, Kumar A, Virk RS, Dutta P, Ahuja C, Mohanty M, Dhandapani S. Outcomes in Pituitary Adenoma Causing Acromegaly Following Endoscopic Endonasal Transsphenoidal Surgery. J Neurosci Rural Pract 2022. [DOI: 10.1055/s-0042-1751226] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/17/2022] Open
Abstract
Abstract
Objectives The objective of this study was the analysis of outcomes after endoscopic endonasal transsphenoidal surgery (EETSS) in acromegaly in terms of surgical complications, clinical improvement, endocrinological remission, achievement of prognostically critical growth hormone (GH) level, and requirement of additional treatment.
Materials and Methods The study included 28 acromegaly patients, who underwent EETSS. 2010 consensus criterion was used for defining remission. Assessment of prognostically critical GH level (random value less than 2.5 ng/mL), the extent of resection, and additional treatment was done at postoperative week (POW) 12.
Results All adenomas were macroadenomas, with the mean volume of 16.34 cm3 (range, 0.4–99 cm3). Most adenomas had high-grade extensions. Most common suprasellar, infrasellar, anterior, and posterior extension grades were 3 (n = 13), 1(n = 16), 1(n = 14), and 0 (n = 20), respectively. Knosp grade 3 was common on both sides (right, n = 9 and left, n = 8). One patient had already been operated on with EETSS, 1.5 years back from current surgery. Sixteen patients were on hormonal support, preoperatively. Four patients died during follow-up. Postoperative common complications were diabetes insipidus (n = 18), cerebrospinal fluid rhinorrhea (n = 10), surgical site hematoma (n = 3), meningitis (n = 3), hydrocephalus (n = 2), and syndrome of inappropriate antidiuretic hormone (n = 1). The mean hospital stay was 11.62 days, and 12.17 months was the mean follow-up period. At 12 POW, no improvement was seen in body enlargement and visual complaints, but all other complaints improved significantly except perspiration. Adenomas were decreased in all extensions except posterior, and mean adenoma volume was reduced from 16.34 to 2.92 cm3 after surgery. Subtotal resection (STR, n = 10), near-total resection (NTR, n = 7), gross-total resection (GTR, n = 5), and partial resection (PR, n = 2) were achieved. Endocrinological remission and prognostically critical GH levels were attained in 29.17% (n = 7) and 66.67% (n = 16), respectively. NTR, GTR, STR, and PR were associated with 57.14, 40, 10, and 0% endocrinological remission, respectively. Additional treatment was required in a total of 17 patients: 3 GTR, 9 STR, 3 NTR, and 2 PR patients. Ten patients were treated with gamma knife radiosurgery along with medical treatment and seven with medical treatment alone.
Conclusion A successful EETSS can reduce adenoma volume to achieve clinical improvement, endocrinological remission, and prognostically critical GH level with some complications related to surgery. Preoperative larger volume and higher extension grades affect these outcomes adversely.
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Affiliation(s)
- Rajesh Chhabra
- Department of Neurosurgery, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Ashwani Kumar
- Department of Neurosurgery, Government Medical College and Hospital, Chandigarh, India
| | - R S Virk
- Department of Otorhinolaryngology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Pinaki Dutta
- Department of Endocrinology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Chirag Ahuja
- Department of Neuroradiology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Manju Mohanty
- Department of Neurosurgery, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Sivashanmugam Dhandapani
- Department of Neurosurgery, Postgraduate Institute of Medical Education and Research, Chandigarh, India
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Peixe C, Sánchez-García M, Grossman AB, Korbonits M, Marques P. Biochemical discrepancies in the evaluation of the somatotroph axis: Elevated GH or IGF-1 levels do not always diagnose acromegaly. Growth Horm IGF Res 2022; 64:101467. [PMID: 35609487 DOI: 10.1016/j.ghir.2022.101467] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/27/2022] [Revised: 03/30/2022] [Accepted: 05/12/2022] [Indexed: 12/29/2022]
Abstract
The most frequent diagnosis underlying the finding of an elevated growth hormone (GH) and insulin-like growth factor-1 (IGF-1) is acromegaly due to a GH-secreting pituitary tumour. However, GH and IGF-1 levels can be discordant in patients with acromegaly due to early or partially treated disease, or there might be another cause of high GH or high IGF-1 unrelated to acromegaly, such as pre-analytical and technical pitfalls, physiological circumstances and pathological conditions. High GH and normal or low serum IGF-1, or alternatively, normal GH with elevated serum IGF-1, should be carefully assessed to avoid misinterpreting the activity of acromegaly or misdiagnosing a patient with acromegaly. We summarise here these biochemical discrepancies in the evaluation of the somatotroph axis.
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Affiliation(s)
- Carolina Peixe
- Endocrinology Department, Hospital de Santa Maria, Centro Hospitalar Universitário de Lisboa Norte, Lisbon, Portugal
| | - Miriam Sánchez-García
- Centre for Endocrinology, William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK; Servicio de Endocrinología, Hospital General de Zona Número 8, Instituto Mexicano del Seguro Social, Ciudad de México, México
| | - Ashley B Grossman
- Centre for Endocrinology, William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK
| | - Márta Korbonits
- Centre for Endocrinology, William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK
| | - Pedro Marques
- Endocrinology Department, Hospital de Santa Maria, Centro Hospitalar Universitário de Lisboa Norte, Lisbon, Portugal; Centre for Endocrinology, William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
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Giantini-Larsen AM, Uribe-Cardenas R, Juthani RG. Acromegaly. Otolaryngol Clin North Am 2022; 55:331-341. [DOI: 10.1016/j.otc.2021.12.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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11
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Can M, Kocabas M, Karakose M, Yerlikaya FH, Alsancak Y, Turkmen K, Kulaksizoglu M, Karakurt F. Arterial stiffness, carotid intima-media thickness, endocan and A disintegrin-like and metalloprotease with thrombospondin type I motif 9 levels and their relationship with disease activity in acromegaly patients with and without cardiovascular risk factors. Endocr Pract 2021; 28:298-303. [PMID: 34843972 DOI: 10.1016/j.eprac.2021.11.084] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/10/2021] [Revised: 10/20/2021] [Accepted: 11/20/2021] [Indexed: 11/03/2022]
Abstract
OBJECTIVE Cardiovascular complications such as cardiomyopathy and endothelial dysfunction, which are frequently seen in patients with acromegaly, are among the most important causes of morbidity and mortality. In this study, we aimed to investigate arterial stiffness, carotid intima-media thickness, endocan and A disintegrin-like and metalloprotease with thrombospondin type I motif 9 (ADAMTS9) levels and their relationship with disease activity in acromegaly patients with and without cardiovascular risk factors. DESIGN A total of 60 patients with acromegaly, 25 with active disease, 26 with well-controlled disease, and 9 newly diagnosed, and 60 age-, sex- and body mass index (BMI)-matched healthy control subjects were enrolled in this study. All subjects' height, weight, BMI, systolic blood pressure (SBP), distolic blood pressure (DBP), fasting plasma glucose (FPG), insulin, hemoglobin A1c (HbA1c), C-reactive protein (CRP), lipid, endocan, ADAMTS9, pulse wave velocity (PWV) and carotid intima-media thickness (CIMT) measurements were performed. RESULTS SBP, DBP, FPG, HbA1c and PWV levels of the acromegaly group were higher than the control group. In acromegaly patients with cardiovascular disease (CVD) risk factors, PWV was higher than the control group, and in acromegaly patients without CVD risk factor, PWV was similar to the control group. In the correlation analysis, a positive correlation was found between PWV and age, BMI, SBP, DBP, FPG and HbA1c levels in the acromegaly group. CONCLUSIONS In our study, we found that arterial stiffness increased in acromegaly patients with CVD risk factors, and that increased arterial stiffness was associated with hemodynamic (SBP, DBP) and metabolic (BMI, FPG, HBA1C) parameters.
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Affiliation(s)
- Mustafa Can
- Department of Endocrinology and Metabolism, Meram Faculty of Medicine, Necmettin Erbakan University, Konya, Turkey.
| | - Muhammet Kocabas
- Department of Endocrinology and Metabolism, Meram Faculty of Medicine, Necmettin Erbakan University, Konya, Turkey
| | - Melia Karakose
- Department of Endocrinology and Metabolism, Meram Faculty of Medicine, Necmettin Erbakan University, Konya, Turkey
| | | | - Yakup Alsancak
- Department of Cardiology, Meram Faculty of Medicine, Necmettin Erbakan University, Konya, Turkey
| | - Kultigin Turkmen
- Department of Nephrology, Meram Faculty of Medicine, Necmettin Erbakan University, Konya, Turkey
| | - Mustafa Kulaksizoglu
- Department of Endocrinology and Metabolism, Meram Faculty of Medicine, Necmettin Erbakan University, Konya, Turkey
| | - Feridun Karakurt
- Department of Endocrinology and Metabolism, Meram Faculty of Medicine, Necmettin Erbakan University, Konya, Turkey
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Villabona C, Oriola J, Serrano T, Guerrero-Pérez F, Valdés N, Chiara M, Robledo M. The recurrent p.(Pro540Ser) MEN1 genetic variant should be considered nonpathogenic: A case report. Am J Med Genet A 2021; 185:3872-3876. [PMID: 34313384 DOI: 10.1002/ajmg.a.62444] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2021] [Revised: 07/01/2021] [Accepted: 07/09/2021] [Indexed: 11/09/2022]
Abstract
Pheochromocytoma/paraganglioma (Pheo/PGL) associated with pituitary adenoma (PA) is rare in clinical practice, and a common pathogenic mechanism has been suggested owing to the germline pathogenic variants found in some cases. Our aim is to propose a reassignment for a recurrent MEN1 genetic variant found in a 54-year-old male patient with bilateral pheochromocytoma and GH-secreting PA. Pheo/PGL genes study was carried out in DNA samples from Pheo as well as PA and no pathological variants or large deletions were detected. Additionally, a MEN1 gene analysis was performed, and a heterozygous germline variant in exon 10: c.1618C>T; p.(Pro540Ser) was found. No MEN1 gene deletions/duplications were detected. In evaluating a causal relationship between the c.1618C>T MEN1 variant and both tumors, we took into account that missense variants are common pathogenic variants in MEN1, and the population frequency of this variant is too high to be considered pathogenic. His son (aged 38 and carrier) is asymptomatic, and computational analysis showed discrepancies. We propose that this recurrent variant, previously considered as likely pathogenic, subsequently as variant of uncertain significance, and likely benign should now be reclassified as benign.
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Affiliation(s)
- Carles Villabona
- Department of Endocrinology, Hospital Universitari de Bellvitge, Barcelona, Spain
| | - Josep Oriola
- Department of Biochemistry and Molecular Genetics, CDB, Hospital Clinic, Barcelona, Spain
| | - Teresa Serrano
- Department of Pathology, Hospital Universitari de Bellvitge, Barcelona, Spain
| | | | - Nuria Valdés
- Institute of Sanitary Research of Asturias, Institute of Oncology of Asturias (IUOPA), CIBERONC, Hospital Central de Asturias, Universidad de Oviedo, Oviedo, Spain
| | - Mariló Chiara
- Institute of Sanitary Research of Asturias, Institute of Oncology of Asturias (IUOPA), CIBERONC, Hospital Central de Asturias, Universidad de Oviedo, Oviedo, Spain
| | - Mercedes Robledo
- Hereditary Endocrine Cancer Group, Spanish National Cancer Centre, Madrid, Spain.,Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Madrid, Spain
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13
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Cardinal T, Rutkowski MJ, Micko A, Shiroishi M, Jason Liu CS, Wrobel B, Carmichael J, Zada G. Impact of tumor characteristics and pre- and postoperative hormone levels on hormonal remission following endoscopic transsphenoidal surgery in patients with acromegaly. Neurosurg Focus 2021; 48:E10. [PMID: 32480366 DOI: 10.3171/2020.3.focus2080] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2020] [Accepted: 03/31/2020] [Indexed: 11/06/2022]
Abstract
OBJECTIVE Acromegaly is a disease of acral enlargement and elevated serum levels of insulin-like growth factor-1 (IGF-1) and growth hormone (GH), usually caused by a pituitary adenoma. A lack of consensus on factors that reliably predict outcomes in acromegalic patients following endoscopic endonasal transsphenoidal surgery (EETS) warrants additional investigation. METHODS The authors identified 52 patients with acromegaly who underwent an endoscopic endonasal approach (EEA) for resection of a GH-secreting pituitary adenoma. Preoperative and postoperative tumor and endocrinological characteristics such as tumor size, invasiveness, and GH/IGF-1 levels were evaluated as potential indicators of postoperative hormonal remission. Endocrinological remission was defined as postoperative IGF-1 levels at or below the age- and sex-normalized values. RESULTS The 52 patients had a mean age of 50.7 ± 13.4 years and a mean follow-up duration of 24.4 ± 19.1 months. Ten patients (19%) had microadenomas and 42 (81%) had macroadenomas. Five patients (9.6%) had giant adenomas. Forty-four tumors (85%) had extrasellar extension, with 40 (77%) exhibiting infrasellar invasion, 18 (35%) extending above the sella, and 7 (13%) invading the cavernous sinuses. Thirty-six patients (69%) underwent gross-total resection (GTR; mean maximal tumor diameter 1.47 cm), and 16 (31%) underwent subtotal resection (STR; mean maximal tumor diameter 2.74 cm). Invasive tumors were significantly larger, and Knosp scores were negatively correlated with GTR. Thirty-eight patients (73%) achieved hormonal remission after EEA resection alone, which increased to 87% with adjunctive medical therapy. Ninety percent of patients with microadenomas and 86% of patients with macroadenomas achieved hormonal remission. Preoperative IGF-1 and postoperative day 1 (POD1) GH levels were inversely correlated with hormonal remission. Postoperative CSF leakage occurred in 2 patients (4%), and none experienced vision loss, death, or injury to internal carotid arteries or cranial nerves. CONCLUSIONS Endoscopic transsphenoidal resection of GH-secreting pituitary adenomas is a safe and highly effective treatment for achieving hormonal remission and tumor control in up to 87% of patients with acromegaly when combined with postoperative medical therapy. Patients with lower preoperative IGF-1 and POD1 GH levels, with less invasive pituitary adenomas, and who undergo GTR are more likely to achieve postoperative biochemical remission.
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Affiliation(s)
- Tyler Cardinal
- 1Department of Neurosurgery, USC Pituitary Center, Keck School of Medicine of University of Southern California, Los Angeles, California
| | - Martin J Rutkowski
- 1Department of Neurosurgery, USC Pituitary Center, Keck School of Medicine of University of Southern California, Los Angeles, California
| | - Alexander Micko
- 1Department of Neurosurgery, USC Pituitary Center, Keck School of Medicine of University of Southern California, Los Angeles, California.,2Department of Neurosurgery, Medical University of Vienna, Austria
| | - Mark Shiroishi
- 3Department of Radiology, Division of Neuroradiology, Keck School of Medicine of University of Southern California
| | - Chia-Shang Jason Liu
- 3Department of Radiology, Division of Neuroradiology, Keck School of Medicine of University of Southern California
| | - Bozena Wrobel
- 5Department of Otolaryngology, Keck School of Medicine of University of Southern California, Los Angeles, California
| | - John Carmichael
- 1Department of Neurosurgery, USC Pituitary Center, Keck School of Medicine of University of Southern California, Los Angeles, California.,4Department of Medicine, Division of Endocrinology and Diabetes, Keck School of Medicine of University of Southern California; and
| | - Gabriel Zada
- 1Department of Neurosurgery, USC Pituitary Center, Keck School of Medicine of University of Southern California, Los Angeles, California
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Zeng J, Qiu X, Shi S, Bian X. Forensic human image identification using medical indicators. Forensic Sci Res 2021; 7:808-814. [PMID: 36817237 PMCID: PMC9930830 DOI: 10.1080/20961790.2020.1838252] [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] [Indexed: 10/22/2022] Open
Abstract
Diseases not only bring troubles to people's body functions and mind but also influence the appearances and behaviours of human beings. Similarly, we can analyse the diseases from people's appearances and behaviours and use the personal medical history for human identification. In this article, medical indicators presented in abnormal changes of human appearances and behaviours caused by physiological or psychological diseases were introduced, and were applied in the field of forensic identification of human images, which we called medical forensic identification of human images (mFIHI). The proposed method analysed the people's medical signs by studying the appearance and behaviour characteristics depicted in images or videos, and made a comparative examination between the medical indicators of the questioned human images and the corresponding signs or medical history of suspects. Through a conformity and difference analysis on medical indicators and their indicated diseases, it would provide an important information for human identification from images or videos. A case study was carried out to demonstrate and verify the feasibility of the proposed method of mFIHI, and our results showed that it would be important contents and angles for forensic expert manual examination in forensic human image identification.
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Affiliation(s)
- Jinhua Zeng
- Shanghai Key Laboratory of Forensic Medicine, Shanghai Forensic Service Platform, Academy of Forensic Science, Ministry of Justice, Shanghai, China,CONTACT Jinhua Zeng
| | - Xiulian Qiu
- Shanghai Key Laboratory of Forensic Medicine, Shanghai Forensic Service Platform, Academy of Forensic Science, Ministry of Justice, Shanghai, China
| | - Shaopei Shi
- Shanghai Key Laboratory of Forensic Medicine, Shanghai Forensic Service Platform, Academy of Forensic Science, Ministry of Justice, Shanghai, China
| | - Xinwei Bian
- Shanghai Key Laboratory of Forensic Medicine, Shanghai Forensic Service Platform, Academy of Forensic Science, Ministry of Justice, Shanghai, China
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Rotermund R, Mader MM, Burkhardt T, Matschke J, Aberle J, Krajewski K, Flitsch J, Rahvar AH. Real-life analysis of 280 patients with surgically treated acromegaly: a single-center experience from 2008 to 2015. Neurosurg Focus 2020; 48:E9. [DOI: 10.3171/2020.3.focus2061] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2020] [Accepted: 03/03/2020] [Indexed: 11/06/2022]
Abstract
OBJECTIVEThe purpose of this study was to analyze the clinical and biochemical outcome of consecutive patients with acromegaly after microscopic transsphenoidal surgery (MTS) at a single center over an 8-year period.METHODSA retrospective analysis of patients with acromegaly treated via MTS between 2008 and 2015 at the authors’ center was performed. The mean follow-up was 29 months (range 1–120 months). Parameters investigated included tumor size, pre- and postoperative insulin-like growth factor–I, growth hormone levels, pretreatment, perioperative complications, and clinical outcome.RESULTSA total of 280 patients with acromegaly were treated surgically at the authors’ center over the abovementioned time frame and were included in analyses. For 231 of these patients, complete follow-up data were available for evaluation. One hundred eighty-eight patients (81%) showed remission initially according to current criteria. So far, 23 of these patients relapsed in the further course, so that on follow-up 165 patients (71%) demonstrated full remission by surgery alone. Most patients in whom remission after surgery failed were treated with somatostatin receptor ligands and/or dopamine agonists as second-line treatment. The main postoperative complications included transient hyponatremia and diabetes insipidus (13/280; 4.6%). CSF leakage only occurred in 2 cases (2/280; 0.7%). No surgery-related death occurred.CONCLUSIONSThe data underline the effectiveness of MTS in acromegaly. Many patients with recurrent disease or incomplete tumor resection can be successfully managed pharmacologically.
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Affiliation(s)
| | | | - Till Burkhardt
- 4Department of Neurosurgery, Friedrich-Ebert-Krankenhaus, Neumuenster; and
| | - Jakob Matschke
- 3Institute of Neuropathology, University Medical Center Hamburg-Eppendorf, Hamburg
| | | | - Kara Krajewski
- 5Department of Neurosurgery, University Clinic Schleswig-Holstein, Campus Lübeck, Germany
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Park KH, Lee EJ, Seo GH, Ku CR. Risk for Acromegaly-related Comorbidities by Sex in Korean Acromegaly. J Clin Endocrinol Metab 2020; 105:5696792. [PMID: 31903478 DOI: 10.1210/clinem/dgz317] [Citation(s) in RCA: 27] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/06/2019] [Accepted: 01/02/2020] [Indexed: 11/19/2022]
Abstract
CONTEXT Reports on the incidence, characteristics, and comorbidity in Asian patients with acromegaly are scarce. OBJECTIVE To evaluate the incidence of acromegaly and the risk of comorbidities in East Asia, especially South Korea. DESIGN This nationwide population-based cohort study using the Korean Health Insurance Review and Assessment claims database evaluated the incidence of acromegaly, initially diagnosed from 2010 to 2013. We identified comorbidities during, before, and 2 years after diagnosis. Acromegaly and control cases (718 and 7180, respectively) were included in the analysis. SETTING A longitudinal case-control study using a nationwide population cohort. RESULTS The mean annual incidence rate of acromegaly was 3.57 cases per 1 000 000. Malignancies occurred in 61 patients with acromegaly (8.5%) during the study period and thyroid cancer was the most common malignancy (n = 38). In the acromegaly group, the overall risk of malignancy was higher: hazard ratio (HR), 2.82 (95% confidence interval [CI]: 2.12-3.74). Malignancy risk was more pronounced in females, with increased risk from the prediagnosis period that is sustained until the postdiagnosis period. Prevalence of diabetes mellitus (DM) and heart failure increased significantly in acromegalic patients. Over the entire period, DM developed in 51.1% and 57.0% of male and female acromegalic patients, respectively. Mortality risk was higher (HR 1.65, 95%; CI: 1.13-2.41) and statistically significant in females (HR 1.75, 95%; CI: 1.07-2.84). CONCLUSION Comorbidities associated with acromegaly differed by sex in Korean subjects. High malignancy and mortality risk should be considered in female patients when managing acromegaly in Korea.
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Affiliation(s)
- Kyeong Hye Park
- Division of Endocrinology and Metabolism, Department of Internal Medicine, National Health Insurance Service Ilsan Hospital, Goyang, Gyeonggi, Republic of Korea
| | - Eun Jig Lee
- Endocrinology, Institute of Endocrine Research, Department of Internal Medicine, Severance Hospital Pituitary Tumor Center, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Gi Hyeon Seo
- Health Insurance Review and Assessment Service, Seoul, Republic of Korea
| | - Cheol Ryong Ku
- Endocrinology, Institute of Endocrine Research, Department of Internal Medicine, Severance Hospital Pituitary Tumor Center, Yonsei University College of Medicine, Seoul, Republic of Korea
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17
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Bano G. Somatotroph adenomas: histological subtypes and predicted response to treatment. INTERNATIONAL JOURNAL OF ENDOCRINE ONCOLOGY 2020. [DOI: 10.2217/ije-2020-0002] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022] Open
Affiliation(s)
- Gul Bano
- Department of Endocrinology & Diabetes, Thomas Addison Unit, St George's Hospital, Blackshaw road, London, SW17 0QT, UK
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18
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Meng T, Guo X, Lian W, Deng K, Gao L, Wang Z, Huang J, Wang X, Long X, Xing B. Identifying Facial Features and Predicting Patients of Acromegaly Using Three-Dimensional Imaging Techniques and Machine Learning. Front Endocrinol (Lausanne) 2020; 11:492. [PMID: 32849283 PMCID: PMC7403213 DOI: 10.3389/fendo.2020.00492] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/28/2019] [Accepted: 06/22/2020] [Indexed: 11/13/2022] Open
Abstract
Objective: Facial changes are common among nearly all acromegalic patients. As they develop slowly, patients often fail to notice such changes before they become obvious. Consequently, diagnosis and treatment are often delayed. So far, convenient and accurate early detection of this disease is still unavailable. This study is designed to combine the use of 3D imaging and machine learning techniques in facial feature analysis and identification of acromegalic patients, in an effort to ascertain how both techniques performed in terms of applicability and value in the early detection of the disease. Methods: One hundred and twenty-four participants including 62 patients with acromegaly and 62 matched controls were enrolled. Using three-dimensional imaging techniques, 58 facial parameters were measured on each face. A two-way analysis of variance (ANOVA) and a post-hoc t-tests were conducted to examine the variations of these parameters with disease status and gender. Using linear discriminant analysis (LDA), we further distinguished patients from controls, characterized what combinations of the parameters could best predict disease state and their relative contributions. Results: Patients are significantly different from normal subjects in many variables, and facial changes of male patients are more significant than female ones. Both male and female patients present following major changes: the increase of facial length and breadth, the widening and elevation of the nose, the thickening of vermilion and the enlargement of the mandible. Facial variables which strongly related to the pathological states can be used to predict the morbid state with high accuracy (prediction accuracies 92.86% in females, p < 0.0001 and 75% in males, p < 0.001). We have further testified that only a few variables play a vital role in disease prediction and the vital combination of variables vary with gender. Conclusions: Three-dimensional imaging enables comprehensive and accurate quantification of facial characteristics, which makes it a promising technique to investigate facial features of acromegalic patients. In combination with machine learning technique, patients can be accurately identified and predicted by their facial variables. This approach might be beneficial for the early detection of acromegalic patients and timely consultation to improve their outcomes.
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Affiliation(s)
- Tian Meng
- Department of Plastic and Aesthetic Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
| | - Xiaopeng Guo
- Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
- China Pituitary Disease Registry Center, Beijing, China
- China Pituitary Adenoma Specialist Council, Beijing, China
| | - Wei Lian
- Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
- China Pituitary Disease Registry Center, Beijing, China
- China Pituitary Adenoma Specialist Council, Beijing, China
| | - Kan Deng
- Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
- China Pituitary Disease Registry Center, Beijing, China
- China Pituitary Adenoma Specialist Council, Beijing, China
| | - Lu Gao
- Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
- China Pituitary Disease Registry Center, Beijing, China
- China Pituitary Adenoma Specialist Council, Beijing, China
| | - Zihao Wang
- Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
- China Pituitary Disease Registry Center, Beijing, China
- China Pituitary Adenoma Specialist Council, Beijing, China
| | - Jiuzuo Huang
- Department of Plastic and Aesthetic Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
| | - Xiaojun Wang
- Department of Plastic and Aesthetic Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
| | - Xiao Long
- Department of Plastic and Aesthetic Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
- *Correspondence: Xiao Long
| | - Bing Xing
- Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
- China Pituitary Disease Registry Center, Beijing, China
- China Pituitary Adenoma Specialist Council, Beijing, China
- Bing Xing
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The Clinicopathological Spectrum of Acromegaly. J Clin Med 2019; 8:jcm8111962. [PMID: 31766255 PMCID: PMC6912315 DOI: 10.3390/jcm8111962] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2019] [Revised: 11/08/2019] [Accepted: 11/11/2019] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Acromegaly results from a persistent excess in growth hormone with clinical features that may be subtle or severe. The most common cause of acromegaly is a pituitary tumor that causes excessive production of growth hormone (GH), and rare cases are due to an excess of the GH-releasing hormone (GHRH) or the ectopic production of GH. OBJECTIVE Discuss the different diseases that present with manifestations of GH excess and clinical acromegaly, emphasizing the distinct clinical and radiological characteristics of the different pathological entities. METHODS We performed a narrative review of the published clinicopathological information about acromegaly. An English-language search for relevant studies was conducted on PubMed from inception to 1 August 2019. The reference lists of relevant studies were also reviewed. RESULTS Pituitary tumors that cause GH excess have several variants, including pure somatotroph tumors that can be densely or sparsely granulated, or plurihormonal tumors that include mammosomatotroph, mixed somatotroph-lactotroph tumors and mature plurihomonal Pit1-lineage tumors, acidophil stem cell tumors and poorly-differentiated Pit1-lineage tumors. Each tumor type has a distinct pathophysiology, resulting in variations in clinical manifestations, imaging and responses to therapies. CONCLUSION Detailed clinicopathological information will be useful in the era of precision medicine, in which physicians tailor the correct treatment modality to each patient.
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Chen Y, Liu Z, Lin Z, Shi X. Eye Signs in Pituitary Disorders. Neurol India 2019; 67:979-982. [PMID: 31512618 DOI: 10.4103/0028-3886.266265] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022]
Abstract
The eye is a vital sense organ and plays a vital role in conveying the underlying physical and mental state of wellbeing of an individual. A comprehensive examination of the eye is often required in patients presenting with systemic complaints. Many endocrine disorders have characteristic manifestations pertaining to the eye, the classical being the exophthalmos in thyrotoxicosis. However, a cursory eye evaluation may lead to the identification of early features that can help in the diagnosis of other endocrine disorders. This is more common in cases of pituitary mass lesions, who often present with the functional hormonal alterations rather than the visual symptoms. The definitive therapy during the late stages of the disease leads to persisting visual disabilities and affects the quality of life. Hence, the endocrinologists and ophthalmologists need to be aware of various ophthalmic features in the pituitary disorders. In this review, we highlight the eye signs in pituitary disorders, along with a brief description of uncommon ocular-pituitary syndromes.
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Affiliation(s)
- Yan Chen
- Department of Ophthalmology, The Affiiated Hospital to Changchun University of Chinese Medicine, Changchun, Jilin, China
| | - Zhihong Liu
- Department of Ophthalmology, The Affiiated Hospital to Changchun University of Chinese Medicine, Changchun, Jilin, China
| | - Zhihui Lin
- Department of Ophthalmology, The Affiiated Hospital to Changchun University of Chinese Medicine, Changchun, Jilin, China
| | - Xiaozhe Shi
- Department of Ophthalmology, The Affiiated Hospital to Changchun University of Chinese Medicine, Changchun, Jilin, China
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Feng J, Wang J, Liu Q, Li J, Zhang Q, Zhuang Z, Yao X, Liu C, Li Y, Cao L, Li C, Gong L, Li D, Zhang Y, Gao H. DAPT, a γ-Secretase Inhibitor, Suppresses Tumorigenesis, and Progression of Growth Hormone-Producing Adenomas by Targeting Notch Signaling. Front Oncol 2019; 9:809. [PMID: 31508369 PMCID: PMC6718711 DOI: 10.3389/fonc.2019.00809] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2018] [Accepted: 08/07/2019] [Indexed: 01/04/2023] Open
Abstract
Advances in the understanding of growth hormone-producing adenomas (GHomas) are ongoing, but current therapy is limited by moderate and variable efficacy and in need of life-long treatment. In this study, the molecular signaling pathway related to GHoma was investigated by proteomics and transcriptomics. The differentially expressed proteins and genes were significantly enriched in Extracellular Matrix-Receptor Interactions, Notch Signaling, Basal Cell Carcinoma Signaling, JAK-STAT3, Wnt Signaling, and Glioblastoma Multiforme Signaling by Ingenuity Pathway Analysis. Furthermore, the Notch2/Delta-like canonical Notch ligand (DLL) signaling pathway was identified to be associated with tumorigenesis and invasiveness of GHoma. In 76 patients, Notch2 and DLL3 were upregulated in invasive compared to those in non-invasive GHoma (p < 0.05). Disease-free survival was significantly longer in patients with low, compared with high, DLL3 expression (p = 0.027). Notch 2 knockdown inhibited cell migration in both GH3 cells and primary GHoma cells, along with downregulation of the mRNA expression of related genes. DAPT, a γ-secretase inhibitor, inhibited tumor growth and invasion in vivo and in vitro and suppressed the release of growth hormone in primary GHoma cells. The involvement of Notch2/DLL3 signaling in GHoma progression warrants additional study of Notch inhibitor, DAPT, as a potential GHoma treatment.
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Affiliation(s)
- Jie Feng
- Key Laboratory of Central Nervous System Injury Research, Center of Brain Tumor of Beijing Institute for Brain Disorders, Beijing Neurosurgical Institute, Capital Medical University, Beijing, China
| | - Jianpeng Wang
- The Affiliated Hospital of Medical College, Qingdao University, Qingdao, China
| | - Qian Liu
- Key Laboratory of Central Nervous System Injury Research, Center of Brain Tumor of Beijing Institute for Brain Disorders, Beijing Neurosurgical Institute, Capital Medical University, Beijing, China
| | - Jiye Li
- Key Laboratory of Central Nervous System Injury Research, Center of Brain Tumor of Beijing Institute for Brain Disorders, Beijing Neurosurgical Institute, Capital Medical University, Beijing, China
| | - Qi Zhang
- Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, United States
| | - Zhengping Zhuang
- Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, United States
| | - Xiaohui Yao
- Neurosurgery, Shanxi Provincial People's Hospital, Taiyuan, China
| | - Chunhui Liu
- Key Laboratory of Central Nervous System Injury Research, Center of Brain Tumor of Beijing Institute for Brain Disorders, Beijing Neurosurgical Institute, Capital Medical University, Beijing, China
| | - Yangfang Li
- Key Laboratory of Central Nervous System Injury Research, Center of Brain Tumor of Beijing Institute for Brain Disorders, Beijing Neurosurgical Institute, Capital Medical University, Beijing, China
| | - Lei Cao
- Key Laboratory of Central Nervous System Injury Research, Center of Brain Tumor of Beijing Institute for Brain Disorders, Beijing Neurosurgical Institute, Capital Medical University, Beijing, China
| | - Chuzhong Li
- Key Laboratory of Central Nervous System Injury Research, Center of Brain Tumor of Beijing Institute for Brain Disorders, Beijing Neurosurgical Institute, Capital Medical University, Beijing, China
| | - Lei Gong
- Key Laboratory of Central Nervous System Injury Research, Center of Brain Tumor of Beijing Institute for Brain Disorders, Beijing Neurosurgical Institute, Capital Medical University, Beijing, China
| | - Dan Li
- Key Laboratory of Central Nervous System Injury Research, Center of Brain Tumor of Beijing Institute for Brain Disorders, Beijing Neurosurgical Institute, Capital Medical University, Beijing, China
| | - Yazhuo Zhang
- Key Laboratory of Central Nervous System Injury Research, Center of Brain Tumor of Beijing Institute for Brain Disorders, Beijing Neurosurgical Institute, Capital Medical University, Beijing, China
| | - Hua Gao
- Key Laboratory of Central Nervous System Injury Research, Center of Brain Tumor of Beijing Institute for Brain Disorders, Beijing Neurosurgical Institute, Capital Medical University, Beijing, China
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Caputo M, Ucciero A, Mele C, De Marchi L, Magnani C, Cena T, Marzullo P, Barone-Adesi F, Aimaretti G. Use of administrative health databases to estimate incidence and prevalence of acromegaly in Piedmont Region, Italy. J Endocrinol Invest 2019; 42:397-402. [PMID: 30069856 DOI: 10.1007/s40618-018-0928-7] [Citation(s) in RCA: 27] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/04/2018] [Accepted: 07/25/2018] [Indexed: 11/26/2022]
Abstract
PURPOSE Recent studies from national registries have described changing patterns in epidemiology of acromegaly. Our retrospective study used administrative databases to estimate prevalence and incidence of acromegaly in the Piedmont Region, Italy. METHODS This study was conducted in Piedmont between 2012 and 2016 on administrative health databases for inpatients and outpatients of any age. Enrollees were included if claims suggestive of acromegaly were identified in at least two of the following databases: Drug Claims Registry, Hospital Information System, Co-payment Exemption Registry and Outpatient Specialist Service Information System. RESULTS 369 individuals (M = 146, F = 223) met our criteria. Overall incidence was 5.3 per million person years (95% CI 4.2-6.7), and prevalence was 83 cases per million inhabitants (95% CI 75-92). Mean age was 50.9 years. Both incidence and prevalence were slightly higher among women (rate ratio 1.08, prevalence ratio 1.43). Age-specific incidence was similar between sexes up to 39 years and diverged thereafter, with an increasing trend recorded among men. Prevalence was higher in women aged 40-79 years, and increased continuously up to 79 years in both sexes. CONCLUSIONS This is the first population-based study conducted in Italy to estimate incidence and prevalence of acromegaly and results show a higher prevalence than previously reported. Although our algorithm requires proper validation, it constitutes a promising tool to describe the epidemiology of acromegaly.
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Affiliation(s)
- M Caputo
- Endocrinology, Department of Translational Medicine, Università del Piemonte Orientale, Novara, Italy
| | - A Ucciero
- Department of Translational Medicine, Università del Piemonte Orientale, Novara, Italy
| | - C Mele
- Endocrinology, Department of Translational Medicine, Università del Piemonte Orientale, Novara, Italy
| | - L De Marchi
- Endocrinology, Department of Translational Medicine, Università del Piemonte Orientale, Novara, Italy
| | - C Magnani
- Department of Translational Medicine, Università del Piemonte Orientale, Novara, Italy
| | - T Cena
- Department of Translational Medicine, Università del Piemonte Orientale, Novara, Italy
| | - P Marzullo
- Endocrinology, Department of Translational Medicine, Università del Piemonte Orientale, Novara, Italy
| | - F Barone-Adesi
- Department of Pharmaceutical Sciences, Università del Piemonte Orientale, Novara, Italy
| | - G Aimaretti
- Endocrinology, Department of Translational Medicine, Università del Piemonte Orientale, Novara, Italy.
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Abstract
Pituitary diseases are rare conditions with severe chronic multiorgan and multisystemic morbidity requiring complex multidisciplinary treatment and usually life-long drug treatment. Most cases are caused by functioning or non-functioning pituitary adenoma. From the patient's perspective, the burden of disease is caused by the tumour itself and associated compression symptoms, interventions, hormone excess and deficiencies, systemic manifestations of these endocrine abnormalities and general psychosocial issues that can manifest in patients with a chronic condition. In this review, patient burden is classified according to classic endocrine syndromes, with burden at diagnosis and after long-term remission, and also within the framework of value-based health care and the conceptual model of wellbeing. The recently developed patient-reported outcome measurement tool that helps to evaluate burden of patients is also discussed.
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Affiliation(s)
- Nienke R Biermasz
- Leiden University Medical Center, Department of Medicine, Division of Endocrinology, Center of Endocrine Tumors Leiden, Albinusdreef 2, 2333 ZA, Leiden, the Netherlands.
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Abstract
Acromegaly is characterized by increased release of growth hormone and, consequently, insulin-like growth factor I (IGF1), most often by a pituitary adenoma. Prolonged exposure to excess hormone leads to progressive somatic disfigurement and a wide range of systemic manifestations that are associated with increased mortality. Although considered a rare disease, recent studies have reported an increased incidence of acromegaly owing to better disease awareness, improved diagnostic tools and perhaps a real increase in prevalence. Acromegaly treatment approaches, which include surgery, radiotherapy and medical therapy, have changed considerably over time owing to improved surgical procedures, development of new radiotherapy techniques and availability of new medical therapies. The optimal use of these treatments will reduce mortality in patients with acromegaly to levels in the general population. Medical therapy is currently an important treatment option and can even be the first-line treatment in patients with acromegaly who will not benefit from or are not suitable for first-line neurosurgical treatment. Pharmacological treatments include somatostatin receptor ligands (such as octreotide, lanreotide and pasireotide), dopamine agonists and the growth hormone receptor antagonist pegvisomant. In this Primer, we review the main aspects of acromegaly, including scientific advances that underlie expanding knowledge of disease pathogenesis, improvements in disease management and new medical therapies that are available and in development to improve disease control.
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Affiliation(s)
- Annamaria Colao
- Dipartimento di Medicina Clinica e Chirurgia, Sezione di Endocrinologia, University Federico II, Naples, Italy.
| | - Ludovica F S Grasso
- Dipartimento di Medicina Clinica e Chirurgia, Sezione di Endocrinologia, University Federico II, Naples, Italy
| | - Andrea Giustina
- Chair of Endocrinology, San Raffaele Vita-Salute University, Milano, Italy
| | - Shlomo Melmed
- Pituitary Center, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA
| | - Philippe Chanson
- Assistance Publique-Hôpitaux de Paris, Service d'Endocrinologie et des Maladies de la Reproduction, Centre de Référence des Maladies Endocriniennes Rares de la Croissance, Hôpital Bicêtre, Paris, France.,UMR S-1185, Faculté de Médecine Paris-Sud 11, Université Paris-Sud, Université Paris-Saclay, Paris, France
| | - Alberto M Pereira
- Department of Medicine, Division of Endocrinology and Center for Endocrine Tumors, Leiden University Medical Center, Leiden, The Netherlands
| | - Rosario Pivonello
- Dipartimento di Medicina Clinica e Chirurgia, Sezione di Endocrinologia, University Federico II, Naples, Italy
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25
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Malaysian Consensus Statement for the Diagnosis and Management of Acromegaly. J ASEAN Fed Endocr Soc 2019; 34:8-14. [PMID: 33442131 PMCID: PMC7784186 DOI: 10.15605/jafes.034.01.03] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2019] [Accepted: 05/14/2019] [Indexed: 12/17/2022] Open
Abstract
In Malaysia, acromegaly is under-recognised with only 10-15% of the expected number of cases from prevalence estimates, having been diagnosed and managed in established endocrine centres with access to multidisciplinary care. This is mainly due to lack of awareness and standardised approach in diagnosing this disease resulting in delay in diagnosis and management with suboptimal treatment outcomes. This first Malaysian consensus statement on the diagnosis and management of acromegaly addresses these issues and is based on current best practices and latest available evidence so as to reduce the disease burden on acromegaly patients managed in the Malaysian healthcare system.
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26
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Tsiberkin AI, Tsoy UA, Cherebillo VY, Polezhaev AV, Gussarova NV, Grineva EN. [Evaluation of transsphenoidal adenomectomy outcomes in acromegaly using different remission criteria]. ZHURNAL VOPROSY NEIROKHIRURGII IMENI N. N. BURDENKO 2019; 83:98-104. [PMID: 30900693 DOI: 10.17116/neiro20198301198] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/09/2023]
Abstract
UNLABELLED For a long time, surgical removal of somatotropinoma using the transsphenoidal approach has been the first stage of treatment in most acromegaly patients. For the past decades, the efficacy criteria for surgical treatment of acromegaly have significantly changed, which requires appropriate correction. PURPOSE We aimed to evaluate the results of transsphenoidal adenomectomy in acromegaly patients using various criteria for disease remission. MATERIAL AND METHODS The study included patients with newly diagnosed acromegaly who underwent transnasal transsphenoidal endoscopic adenomectomy performed by a single neurosurgeon. The surgical treatment outcomes were evaluated 6 months after operative intervention based on levels of IGF-1, OGTT, and GH. The obtained data were analyzed using different threshold values for the level of GH nadir during OGTT: criteria A <2.0 ng/ml, criteria B <1.0 ng/ml, and criteria C <0.4 ng/ml to assess acromegaly remission, along with matching of the IGF-1 level to the reference range for a given gender and age. RESULTS The study included 70 patients (52 females and 18 males) with a mean age of 52.2±11.5 years (29 to 73 years). The baseline IGF-1 level exceeded the upper limit of the reference range 3.3±1.4 (1.1-7.3)-fold, on average. The baseline mean basal GH level was 34.2±41.7 (1.2-192.0) ng/ml. The mean pituitary adenoma size was 16.7±8.6 (4.3-46.0) mm; 18 (26%) out of 70 patients had pituitary microadenoma, and 52 (74%) patients had macroadenoma. Six months after surgery, acromegaly remission met criteria A in 47 (67%) patients, criteria B in 28 (40%) patients, and criteria C in 18 (26%) patients. CONCLUSION Our findings demonstrate that evaluation of transsphenoidal adenomectomy outcomes in treatment of acromegaly patients depends on the criteria chosen for assessing remission. This feature should be considered when comparing outcomes of surgical treatment for acromegaly in different years. Probably, introduction of the 2010 criteria should be accompanied by revision of the previous remission indicators.
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Affiliation(s)
- A I Tsiberkin
- Almazov National Medical Research Center, St. Petersburg, Russia
| | - U A Tsoy
- Almazov National Medical Research Center, St. Petersburg, Russia
| | - V Yu Cherebillo
- Almazov National Medical Research Center, St. Petersburg, Russia
| | - A V Polezhaev
- Almazov National Medical Research Center, St. Petersburg, Russia
| | - N V Gussarova
- Almazov National Medical Research Center, St. Petersburg, Russia
| | - E N Grineva
- Almazov National Medical Research Center, St. Petersburg, Russia
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27
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Hage M, Kamenický P, Chanson P. Growth Hormone Response to Oral Glucose Load: From Normal to Pathological Conditions. Neuroendocrinology 2019; 108:244-255. [PMID: 30685760 DOI: 10.1159/000497214] [Citation(s) in RCA: 26] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/27/2018] [Accepted: 01/24/2019] [Indexed: 11/19/2022]
Abstract
The exact physiological basis of acute growth hormone (GH) suppression by oral glucose is not fully understood. Glucose-mediated increase in hypothalamic somatostatin seems to be the most plausible explanation. Attempts to better understand its underlying mechanisms are compromised by species disparities in the response of GH to glucose load. While in humans, glucose inhibits GH release, the acute elevation of circulating glucose levels in rats has either no effect on GH secretion or may be stimulatory. Likewise, chronic hyperglycemia alters GH release in both humans and rats nonetheless in opposite directions. Several factors influence nadir GH concentrations including, age, gender, body mass index, pubertal age, and the type of assay used. Besides the classical suppressive effects of glucose on GH release, a paradoxical GH increase to oral glucose may be observed in around one third of patients with acromegaly as well as in various other disorders. Though its pathophysiology is poorly characterized, an altered interplay between somatostatin and GH-releasing hormone has been suggested and a link with pituitary ectopic expression of glucose-dependent insulinotropic polypeptide receptor has been recently demonstrated. A better understanding of the dynamics mediating GH response to glucose may allow a more optimal use of the OGTT as a diagnostic tool in various conditions, especially acromegaly.
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Affiliation(s)
- Mirella Hage
- Assistance Publique-Hôpitaux de Paris, Hôpital de Bicêtre, Service d'Endocrinologie et des Maladies de la Reproduction, Centre de Référence des Maladies Rares de l'Hypophyse, Institut National de la Santé et de la Recherche Médicale (Inserm) U1185, Université Paris-Sud, Université Paris-Saclay, Le Kremlin-Bicêtre, France
| | - Peter Kamenický
- Assistance Publique-Hôpitaux de Paris, Hôpital de Bicêtre, Service d'Endocrinologie et des Maladies de la Reproduction, Centre de Référence des Maladies Rares de l'Hypophyse, Institut National de la Santé et de la Recherche Médicale (Inserm) U1185, Université Paris-Sud, Université Paris-Saclay, Le Kremlin-Bicêtre, France
| | - Philippe Chanson
- Assistance Publique-Hôpitaux de Paris, Hôpital de Bicêtre, Service d'Endocrinologie et des Maladies de la Reproduction, Centre de Référence des Maladies Rares de l'Hypophyse, Institut National de la Santé et de la Recherche Médicale (Inserm) U1185, Université Paris-Sud, Université Paris-Saclay, Le Kremlin-Bicêtre, France,
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28
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Ribeiro de Oliveira Longo Schweizer J, Ribeiro-Oliveira A, Bidlingmaier M. Growth hormone: isoforms, clinical aspects and assays interference. Clin Diabetes Endocrinol 2018; 4:18. [PMID: 30181896 PMCID: PMC6114276 DOI: 10.1186/s40842-018-0068-1] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/01/2018] [Accepted: 08/19/2018] [Indexed: 11/11/2022] Open
Abstract
The measurement of circulating concentrations of growth hormone (GH) is an indispensable tool in the diagnosis of both GH deficiency and GH excess. GH is a heterogeneous protein composed of several molecular isoforms, but the physiological role of these different isoforms has not yet been fully understood. The 22KD GH (22 K-GH) is the main isoform in circulation, followed by 20KD GH (20 K-GH) and other rare isoforms. Studies have been performed to better understand the biological actions of the different isoforms as well as their importance in pathological conditions. Generally, the non-22 K- and 20 K-GH isoforms are secreted in parallel to 22 K-GH, and only very moderate changes in the ratio between isoforms have been described in some pituitary tumors or during exercise. Therefore, in a diagnostic approach, concentrations of 22 K-GH accurately reflect total GH secretion. On the other hand, the differential recognition of GH isoforms by different GH immunoassays used in clinical routine contributes to the known discrepancy in results from different GH assays. This makes the application of uniform decision limits problematic. Therefore, the worldwide efforts to standardize GH assays include the recommendation to use 22 K-GH specific GH assays calibrated against the pure 22 K-GH reference preparation 98/574. Adoption of this recommendation might lead to improvement in diagnosis and follow-up of pathological conditions, and facilitate the comparison of results from different laboratories.
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Affiliation(s)
| | - Antônio Ribeiro-Oliveira
- 1Endocrinology Laboratory of Federal University of Minas Gerais. Alfredo Balena, 190, Santa Efigênia, Belo Horizonte, 30130-100 Brazil
| | - Martin Bidlingmaier
- 2Endocrine Laboratory, Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, Ziemssenstraße 1, 80336 Munich, Germany
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29
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Abstract
Acromegaly is an uncommon, chronic disease, characterized by hypersecretion of a pituitary growth hormone by somatotroph adenomas, along with increased levels of insulin-like growth factor-1. Although acromegaly presents a wide array of clinical manifestations, the salient symptoms include acral and soft tissue enlargement, joint pain, heart and respiratory failure, diabetes mellitus, and hypertension, leading to increased morbidity and mortality. Hence, early diagnosis of the disease is critical to enhance life expectancy and quality of life. New approaches are being developed for diagnosis and surveillance (both screening and follow-up), including sensitive biochemical assays and the use of MRI to visualize extremely small tumors, and are helpful in the early diagnosis of acromegaly, subsequent treatment, and disease control. This mini-review summarizes the most common and effective tools used in the diagnosis of acromegaly.
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Affiliation(s)
- Salma AlDallal
- Haematology & Blood Bank Department, Amiri Hospital, Kuwait Ministry of Health, Sharq, Kuwait,
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30
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Shan X, Liu Q, Li Z, Li C, Gao H, Zhang Y. Epithelial–Mesenchymal Transition Induced by SMAD4 Activation in Invasive Growth Hormone-Secreting Adenomas. OPEN CHEM 2018. [DOI: 10.1515/chem-2018-0061] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Abstract
AbstractBackgroundThe detection and treatment of invasive growth hormone-secreting pituitary adenoma (GHPA) remains challenging. Several transcription factors promoting the epithelial–mesenchymal transition (EMT) can act as cofactors for the transforming growth factor-beta (TGF-ß)/SMAD4. The goal of this study was to investigate the association of SMAD4 expression and clinicopathologic features using a tissue microarray analysis (TMA). The levels of SMAD4 and the related genes of EMT in GHPAs were analyzed by q-PCR and western blot. SMAD4 was strongly expressed in 15/19 cases (78.9%) of invasive GHPA and 10/42 cases (23.8%) of noninvasive GHPA (χ2=10.887,p=0.000). In the high SMAD4 group, a headache was reported in 16/25 cases (64%) compared with 13/36 cases (36.1%) in the low SMAD4 group (χ2=4.565,p=0.032). The progression-free survival (PFS) in the high group was lower than that in the low group (p=0.026). qRT-PCR and western blot analysis further revealed a significant downregulation of E-cadherin and upregulation of N-cadherin and vimentin in the invasive GHPA group. SMAD4 was associated with increased levels of invasion of GH3 cells, as determined by a transwell test. SMAD4 downregulated E-cadherin levels and increased the levels of N-cadherin and vimentin. Our data provide evidence that SMAD4 is a potential prognosis biomarker and a therapeutic target for patients with invasive GHPA.
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Affiliation(s)
- Xiaosong Shan
- Beijing Neurosurgical Institute, Capital Medical University, Beijing, China
| | - Qian Liu
- Beijing Neurosurgical Institute, Capital Medical University, Beijing, China
| | - Zhenye Li
- Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
| | - Chuzhong Li
- Beijing Neurosurgical Institute, Capital Medical University, Beijing, China
| | - Hua Gao
- Beijing Neurosurgical Institute, Capital Medical University, Beijing, China
- Beijing Institute for Brain Disorders, Brain Tumor Center, Beijing, China National Clinical Research Center for Neurological Diseases, Beijing, China
| | - Yazhuo Zhang
- Beijing Neurosurgical Institute, Capital Medical University, Beijing, China
- Beijing Institute for Brain Disorders, Brain Tumor Center, Beijing, China National Clinical Research Center for Neurological Diseases, Beijing, China
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31
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Perry A, Graffeo CS, Marcellino C, Pollock BE, Wetjen NM, Meyer FB. Pediatric Pituitary Adenoma: Case Series, Review of the Literature, and a Skull Base Treatment Paradigm. J Neurol Surg B Skull Base 2018; 79:91-114. [PMID: 29404245 DOI: 10.1055/s-0038-1625984] [Citation(s) in RCA: 51] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022] Open
Abstract
Background Pediatric pituitary adenoma is a rare skull base neoplasm, accounting for 3% of all intracranial neoplasms in children and 5% of pituitary adenomas. Compared with pituitary tumors in adults, secreting tumors predominate and longer disease trajectories are expected due to the patient age resulting in a natural history and treatment paradigm that is complex and controversial. Objectives The aims of this study were to describe a large, single-institution series of pediatric pituitary adenomas with extensive long-term follow-up and to conduct a systematic review examining outcomes after pituitary adenoma surgery in the pediatric population. Methods The study cohort was compiled by searching institutional pathology and operative reports using diagnosis and site codes for pituitary and sellar pathology, from 1956 to 2016. Systematic review of the English language literature since 1970 was conducted using PubMed, MEDLINE, Embase, and Google Scholar. Results Thirty-nine surgically managed pediatric pituitary adenomas were identified, including 15 prolactinomas, 14 corticotrophs, 7 somatotrophs, and 4 non-secreting adenomas. All patients underwent transsphenoidal resection (TSR) as the initial surgical treatment. Surgical cure was achieved in 18 (46%); 21 experienced recurrent/persistent disease, with secondary treatments including repeat surgery in 10, radiation in 14, adjuvant pharmacotherapy in 11, and bilateral adrenalectomy in 3. At the last follow-up (median 87 months, range 3-581), nine remained with recurrent/persistent disease (23%). Thirty-seven publications reporting surgical series of pediatric pituitary adenomas were included, containing 1,284 patients. Adrenocorticotropic hormone (ACTH)-secreting tumors were most prevalent (43%), followed by prolactin (PRL)-secreting (37%), growth hormone (GH)-secreting (12%), and nonsecreting (7%). Surgical cure was reported in 65%. Complications included pituitary insufficiency (23%), permanent visual dysfunction (6%), chronic diabetes insipidus (DI) (3%), and postoperative cerebrospinal fluid (CSF) leak (4%). Mean follow-up was 63 months (range 0-240), with recurrent/persistent disease reported in 18% at the time of last follow-up. Conclusion Pediatric pituitary adenomas are diverse and challenging tumors with complexities far beyond those encountered in the management of routine adult pituitary disease, including nuanced decision-making, a technically demanding operative environment, high propensity for recurrence, and the potentially serious consequences of hypopituitarism with respect to fertility and growth potential in a pediatric population. Optimal treatment requires a high degree of individualization, and patients are most likely to benefit from consolidated, multidisciplinary care in highly experienced centers.
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Affiliation(s)
- Avital Perry
- Department of Neurologic Surgery, Mayo Clinic, Rochester Minnesota, United States
| | | | | | - Bruce E Pollock
- Department of Neurologic Surgery, Mayo Clinic, Rochester Minnesota, United States
| | - Nicholas M Wetjen
- Department of Neurologic Surgery, Mayo Clinic, Rochester Minnesota, United States
| | - Fredric B Meyer
- Department of Neurologic Surgery, Mayo Clinic, Rochester Minnesota, United States
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Automatic Detection of Acromegaly From Facial Photographs Using Machine Learning Methods. EBioMedicine 2017; 27:94-102. [PMID: 29269039 PMCID: PMC5828367 DOI: 10.1016/j.ebiom.2017.12.015] [Citation(s) in RCA: 52] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2017] [Revised: 12/06/2017] [Accepted: 12/14/2017] [Indexed: 01/30/2023] Open
Abstract
BACKGROUND Automatic early detection of acromegaly is theoretically possible from facial photographs, which can lessen the prevalence and increase the cure probability. METHODS In this study, several popular machine learning algorithms were used to train a retrospective development dataset consisting of 527 acromegaly patients and 596 normal subjects. We firstly used OpenCV to detect the face bounding rectangle box, and then cropped and resized it to the same pixel dimensions. From the detected faces, locations of facial landmarks which were the potential clinical indicators were extracted. Frontalization was then adopted to synthesize frontal facing views to improve the performance. Several popular machine learning methods including LM, KNN, SVM, RT, CNN, and EM were used to automatically identify acromegaly from the detected facial photographs, extracted facial landmarks, and synthesized frontal faces. The trained models were evaluated using a separate dataset, of which half were diagnosed as acromegaly by growth hormone suppression test. RESULTS The best result of our proposed methods showed a PPV of 96%, a NPV of 95%, a sensitivity of 96% and a specificity of 96%. CONCLUSIONS Artificial intelligence can automatically early detect acromegaly with a high sensitivity and specificity.
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Ribeiro-Oliveira A, Barkan A. Biochemical diagnosis of acromegaly without a typical clinical phenotype: what are the concerns? ARCHIVES OF ENDOCRINOLOGY AND METABOLISM 2017; 61:414-415. [PMID: 29166453 PMCID: PMC10522247 DOI: 10.1590/2359-3997000000301] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/21/2017] [Accepted: 10/21/2017] [Indexed: 06/07/2023]
Affiliation(s)
- Antonio Ribeiro-Oliveira
- Laboratory of EndocrinologyFederal University of Minas GeraisBelo HorizonteMGBrazilLaboratory of Endocrinology, Federal University of Minas Gerais (UFMG), Belo Horizonte, MG, Brazil
| | - Ariel Barkan
- Department of MedicineDepartment of NeurosurgeryUniversity of MichiganAnn ArborMIUSADepartment of Medicine, Division of MEND, and Department of Neurosurgery, University of Michigan, Ann Arbor, MI, USA
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Rosario PW, Calsolari MR. Long-term follow-up of patients with elevated IGF-1 and nadir GH > 0.4 µg/L but < 1 µg/L. ARCHIVES OF ENDOCRINOLOGY AND METABOLISM 2017; 61:426-431. [PMID: 28977166 PMCID: PMC10522245 DOI: 10.1590/2359-3997000000295] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/08/2016] [Accepted: 06/11/2017] [Indexed: 11/22/2022]
Abstract
OBJECTIVE To report the results of initial investigation and after 5 years of patients with a suspicious clinical scenario for acromegaly, elevated IGF-1, and nadir GH during an oral glucose tolerance test (OGTT) > 0.4 µg/L but < 1 µg/L. SUBJECTS AND METHODS Seventeen patients who had elevated IGF-1 (outside puberty and pregnancy) in two measurements and GH between 0.4 and 1 µg/L during OGTT were selected. RESULTS During initial assessment, only one patient had microadenoma on magnetic resonance imaging (MRI) of the pituitary. In this patient, IGF-1 returned to normal spontaneously after 5 years. In the remaining 16 patients, spontaneous normalization of IGF-1 was observed in four and IGF-1 continued to be elevated in 12 after 5 years. None of the latter patients developed a phenotype of acromegaly, changes in physiognomy or increase in IGF-1 and no tumor was detected by imaging methods. Two patients had nadir GH < 0.4 µg/L, while the nadir GH remained between 0.4 and 1 µg/L in 10 patients. CONCLUSION In patients (notably young adult or adult women) without a typical phenotype in whom IGF-1 is measured due to a suspicious clinical scenario and is found to be slightly elevated, even if confirmed and in the absence of other causes, a nadir GH cut-off value of 0.4 µg/L instead of 1 µg/L in the OGTT might be inadequate for the diagnosis.
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Affiliation(s)
- Pedro Weslley Rosario
- Santa Casa de Belo HorizonteMGBrasilServiço de Endocrinologia, Santa Casa de Belo Horizonte, MG, Brasil
| | - Maria Regina Calsolari
- Santa Casa de Belo HorizonteMGBrasilServiço de Endocrinologia, Santa Casa de Belo Horizonte, MG, Brasil
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35
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Duan L, Zhu H, Xing B, Gu F. Prolonged preoperative treatment of acromegaly with Somatostatin analogs may improve surgical outcome in patients with invasive pituitary macroadenoma (Knosp grades 1-3): a retrospective cohort study conducted at a single center. BMC Endocr Disord 2017; 17:55. [PMID: 28874187 PMCID: PMC5585918 DOI: 10.1186/s12902-017-0205-3] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/08/2017] [Accepted: 08/29/2017] [Indexed: 02/01/2023] Open
Abstract
BACKGROUND This study aimed to investigate preoperative somatostatin analogs (SSAs) treatment on the surgical outcome in patients with acromegaly. METHODS An analysis of 358 patients with acromegaly was conducted. The preoperative medical therapy group (81 patients) received SSA treatment for at least 3 months prior to surgery, while the primary surgery group (277 patients) underwent transsphenoidal surgery directly. Follow-up duration was ≥3 months. Tumor invasion was evaluated by magnetic resonance imaging (MRI) and classified according to the Knosp grading system. RESULTS Most patients were diagnosed with macroadenoma. Among all patients (Knosp grades 0-4), preoperative SSA therapy did not significantly improve the curative effect of surgery, according to the levels of growth hormone (GH) and/or insulin-like growth factor 1 (IGF-1) markers. In patients with macroadenoma (Knosp grades 1-3), the remission rates were significantly higher in the SSA group compared to the surgery group when considering GH (56.4% vs. 37.3%, P = 0.048) and IGF-1 (43.2% vs. 17.6%, P = 0.004). In the preoperative medical therapy group, long-term use of SSAs (>6 months) led to higher remission rates (GH, 72.2% vs. 51.0%; and IGF-1, 61.1% vs. 29.8%; P = 0.12 and 0.02, respectively]. CONCLUSIONS The long-term preoperative SSAs treatment may improve the surgical curative rate in acromegalic patients with invasive macroadenomas (Knosp grades 1-3).
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Affiliation(s)
- Lian Duan
- Key Laboratory of Endocrinology, Ministry of Health; Department of Endocrinology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, 100730 China
| | - Huijuan Zhu
- Key Laboratory of Endocrinology, Ministry of Health; Department of Endocrinology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, 100730 China
| | - Bing Xing
- Department of Neurosurgery, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, 100730 China
| | - Feng Gu
- Key Laboratory of Endocrinology, Ministry of Health; Department of Endocrinology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, 100730 China
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Abstract
Acromegaly, a rare disease due to growth hormone (GH) hypersecretion by a pituitary adenoma, is associated with severe comorbidity and premature death if not adequately treated. The usual first-line treatment is surgery. Various drugs, including somatostatin receptor ligands, dopamine agonists and GH receptor antagonists, are now available for use if surgery fails to suppress GH/IGF-I hypersecretion. Cabergoline, now the preferred dopamine agonist for treating hyperprolactinemia, is also used off-label for treating acromegaly. Cabergoline monotherapy is reported to normalize IGF-I levels in more than one-third of patients with acromegaly. When a somatostatin receptor ligand proves ineffective, cabergoline add-on therapy normalizes the IGF-I level in 40-50% of patients. Finally, when combined with the GH receptor antagonist pegvisomant in patients with mild uncontrolled disease, cabergoline helps to achieve normal IGF-I levels while avoiding the need for high-dose pegvisomant. Cabergoline is also inexpensive and well tolerated; in particular, it does not appear to promote heart valve disease.
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Affiliation(s)
- Emmanuelle Kuhn
- Assistance Publique-Hôpitaux de Paris, Hôpital Bicêtre Service d'Endocrinologie et des Maladies de la Reproduction, 78 rue du Général Leclerc, 94275, Le Kremlin-Bicêtre, France
- Faculté de Médecine Paris-Sud, Université Paris-Sud, Orsay, France
- Unité Mixte de Recherche-S1185, 94276, Le Kremlin Bicêtre, France
- Institut National de la Santé et de la Recherche Médicale (INSERM) U1185, 94276, Le Kremlin Bicêtre, France
| | - Philippe Chanson
- Assistance Publique-Hôpitaux de Paris, Hôpital Bicêtre Service d'Endocrinologie et des Maladies de la Reproduction, 78 rue du Général Leclerc, 94275, Le Kremlin-Bicêtre, France.
- Faculté de Médecine Paris-Sud, Université Paris-Sud, Orsay, France.
- Unité Mixte de Recherche-S1185, 94276, Le Kremlin Bicêtre, France.
- Institut National de la Santé et de la Recherche Médicale (INSERM) U1185, 94276, Le Kremlin Bicêtre, France.
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Endoscopic Endonasal versus Microsurgical Transsphenoidal Approach for Growth Hormone–Secreting Pituitary Adenomas—Systematic Review and Meta-Analysis. World Neurosurg 2017; 97:398-406. [DOI: 10.1016/j.wneu.2016.10.029] [Citation(s) in RCA: 42] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2016] [Revised: 10/01/2016] [Accepted: 10/04/2016] [Indexed: 12/26/2022]
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Grasso LFS, Auriemma RS, Pivonello R, Colao A. Somatostatin analogs, cabergoline and pegvisomant: comparing the efficacy of medical treatment for acromegaly. Expert Rev Endocrinol Metab 2017; 12:73-85. [PMID: 30058878 DOI: 10.1080/17446651.2016.1222899] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
Therapies for acromegaly aim at normalizing hormonal excess and controlling tumor growth . Therapeutic approaches are surgery, pharmacotherapy and radiotherapy. Area covered: This review focuses on the role of medical therapy of acromegaly, comparing the efficacy of somatostatin analogues (SSA), dopamine-agonists (DA) and pegvisomant (PEG), the three available drug classes for treating acromegaly. To clarify the difference in response rates reported in the literature for these therapies, we performed a search for original articles published in PubMed. SSA represent the first-line approach to medical treatment. This therapy is effective in controlling acromegaly in about 40% of patients, however there are great differences in the reported hormonal efficacy of SSA in the different series. In patients partially resistant to SSA, cabergoline can be added when hormonal levels are close to normalization, resulting effective in control IGF-I levels in 43% of patients. In patients with higher hormonal levels PEG is indicated, normalizing IGF-I levels in 79.8% and 80.6% of cases when used in monotherapy or in combination with SSA. Pasireotide, the newly developed SSA multi-ligand receptor, represents a new option in SSA resistant patients. Expert commentary: Medical therapy represents an important therapeutic option resulting safe and effective in controlling acromegaly in a high percentage of patients. The best treatment should be individually tailored for each patient, taking into account sex, age, comorbidities, tumor characteristics and hormonal levels.
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Affiliation(s)
- Ludovica F S Grasso
- a Dipartimento di Medicina Clinica e Chirurgia, Sezione di Endocrinologia , 'Federico II' University of Naples , Naples , Italy
| | - Renata S Auriemma
- a Dipartimento di Medicina Clinica e Chirurgia, Sezione di Endocrinologia , 'Federico II' University of Naples , Naples , Italy
| | - Rosario Pivonello
- a Dipartimento di Medicina Clinica e Chirurgia, Sezione di Endocrinologia , 'Federico II' University of Naples , Naples , Italy
| | - Annamaria Colao
- a Dipartimento di Medicina Clinica e Chirurgia, Sezione di Endocrinologia , 'Federico II' University of Naples , Naples , Italy
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Chanson P. Diagnosis of acromegaly: black, white… and sometimes gray! ARCHIVES OF ENDOCRINOLOGY AND METABOLISM 2016; 60:505-506. [PMID: 27982196 PMCID: PMC10522171 DOI: 10.1590/2359-3997000000231] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/10/2016] [Accepted: 11/28/2016] [Indexed: 11/21/2022]
Affiliation(s)
- Philippe Chanson
- Hôpitaux Universitaires Paris-SudLe Kremlin BicêtreFrance Assistance Publique-Hôpitaux de Paris (P.C.), Hôpitaux Universitaires Paris-Sud, Hôpital de Bicêtre, Service d’Endocrinologie et des Maladies de la Reproduction, Le Kremlin Bicêtre, France
- Fac Med Paris SudUniv Paris-SudFrance Inserm 1185, Fac Med Paris Sud, Univ Paris-Sud,
- Université Paris-SaclayLe Kremlin-BicêtreFranceUniversité Paris-Saclay, Le Kremlin-Bicêtre, France
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Rosario PW, Calsolari MR. Elevated IGF-1 with GH suppression after an oral glucose overload: incipient acromegaly or false-positive IGF-1? ARCHIVES OF ENDOCRINOLOGY AND METABOLISM 2016; 60:510-514. [PMID: 27982199 PMCID: PMC10522166 DOI: 10.1590/2359-3997000000193] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/15/2015] [Accepted: 03/07/2016] [Indexed: 11/21/2022]
Abstract
OBJECTIVE To report the evolution of patients with a suggestive clinical scenario and elevated serum insulin-like growth factor-1 (IGF-1), but growth hormone (GH) suppression in the oral glucose tolerance test (OGTT), in whom acromegaly was not initially excluded. SUBJECTS AND METHODS Forty six patients with a suggestive clinical scenario, who had elevated IGF-1 (outside puberty and pregnancy) in two measurements, but GH < 0.4 µg/L in the OGTT, were selected. Five years after initial evaluation, the patients were submitted to clinical and laboratory (serum IGF-1) reassessment. Patients with persistently elevated IGF-1 were submitted to a new GH suppression test and magnetic resonance imaging (MRI) of the pituitary. RESULTS Four patients were lost to follow-up. During reassessment, 42 patients continued to show no "typical phenotype" or changes in physiognomy. Fifteen of the 42 patients had normal IGF-1. Among the 27 patients with persistently elevated IGF-1 and who were submitted to a new OGTT, GH suppression was confirmed in all. Two patients exhibited a lesion suggestive of microadenoma on pituitary MRI. In our interpretation of the results, acromegaly was ruled out in 40 patients and considered "possible" in only 2. CONCLUSION Our results show that even in patients with a suggestive clinical scenario and elevated IGF-1, confirmed in a second measurement and without apparent cause, acromegaly is very unlikely in the case of GH suppression in the OGTT.
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Affiliation(s)
- Pedro W. Rosario
- Santa Casa de Belo HorizonteBelo HorizonteMGBrazilPrograma de Pós-Graduação e Serviço de Endocrinologia, Santa Casa de Belo Horizonte, Belo Horizonte, MG, Brazil
| | - Maria R. Calsolari
- Santa Casa de Belo HorizonteBelo HorizonteMGBrazilPrograma de Pós-Graduação e Serviço de Endocrinologia, Santa Casa de Belo Horizonte, Belo Horizonte, MG, Brazil
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41
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Abreu A, Tovar AP, Castellanos R, Valenzuela A, Giraldo CMG, Pinedo AC, Guerrero DP, Barrera CAB, Franco HI, Ribeiro-Oliveira A, Vilar L, Jallad RS, Duarte FG, Gadelha M, Boguszewski CL, Abucham J, Naves LA, Musolino NRC, de Faria MEJ, Rossato C, Bronstein MD. Challenges in the diagnosis and management of acromegaly: a focus on comorbidities. Pituitary 2016; 19:448-57. [PMID: 27279011 PMCID: PMC4935749 DOI: 10.1007/s11102-016-0725-2] [Citation(s) in RCA: 94] [Impact Index Per Article: 10.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/14/2023]
Abstract
INTRODUCTION Acromegaly is a rare, insidious disease resulting from the overproduction of growth hormone (GH) and insulin-like growth factor 1 (IGF-1), and is associated with a range of comorbidities. The extent of associated complications and mortality risk is related to length of exposure to the excess GH and IGF-1, thus early diagnosis and treatment is imperative. Unfortunately, acromegaly is often diagnosed late, when patients already have a wide range of comorbidities. The presence of comorbid conditions contributes significantly to patient morbidity/mortality and impaired quality of life. METHODS We conducted a retrospective literature review for information relating to the diagnosis of acromegaly, and its associated comorbidities using PubMed. The main aim of this review is to highlight the issues of comorbidities in acromegaly, and to reinforce the importance of early diagnosis and treatment. FINDINGS AND CONCLUSIONS Successful management of acromegaly goes beyond treating the disease itself, since many patients are diagnosed late in disease evolution, they present with a range of comorbid conditions, such as cardiovascular disease, diabetes, hypertension, and sleep apnea. It is important that patients are screened carefully at diagnosis (and thereafter), for common associated complications, and that biochemical control does not become the only treatment goal. Mortality and morbidities in acromegaly can be reduced successfully if patients are treated using a multimodal approach with comprehensive comorbidity management.
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Affiliation(s)
- Alin Abreu
- Endocrinology Unit, Centro Médico Imbanaco Cali, Cali, Colombia
| | - Alejandro Pinzón Tovar
- Internal Medicine Department, Hospital of Neiva, University Surcolombiana, Neiva, Colombia
| | - Rafael Castellanos
- Internal Medicine Department, University Industrial of Santander, Bucaramanga, Colombia
| | - Alex Valenzuela
- Department of Internal Medicine, Endocrinology Fundación Cardio-Infantil, Instituto de Cardiología, Universidad del Rosario, Bogotá, Colombia
| | | | | | - Doly Pantoja Guerrero
- Endocrinology Unit, Hospital Universitario Departamental de Nariño, CENTRO de Endocrinologia CENDOO, Universidad Nacional de Colombia, Pasto, Colombia
| | - Carlos Alfonso Builes Barrera
- Endocrinology Department, Hospital Universitario San Vicente Fundación, Universidad de Antioquia, Medellín, Colombia
| | | | | | - Lucio Vilar
- Endocrinology and Chair, Division of Endocrinology, Hospital das Clínicas, Pernambuco Federal University Medical School, Recife, Brazil
| | - Raquel S Jallad
- Neuroendocrine Unit, Division of Endocrinology and Metabolism, Hospital das Clínicas, University of São Paulo Medical School, Av. Dr. Eneas de Carvalho, 255, 7ºandar, sala 7037, São Carlos, SP, CEP 05403-000, Brazil
| | - Felipe Gaia Duarte
- Neuroendocrine Unit, Division of Endocrinology and Metabolism, Hospital das Clínicas, University of São Paulo Medical School, Av. Dr. Eneas de Carvalho, 255, 7ºandar, sala 7037, São Carlos, SP, CEP 05403-000, Brazil
| | - Mônica Gadelha
- Endocrine Section, Medical School and Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
| | - Cesar Luiz Boguszewski
- Department of Internal Medicine, Endocrine Division (SEMPR), Federal University of Paraná, Curitiba, Brazil
| | - Julio Abucham
- Neuroendocrine Unit, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, SP, Brazil
| | - Luciana A Naves
- Department of Endocrinology, Faculty of Medicine, University of Brasilia, Brasília, Brazil
| | - Nina Rosa C Musolino
- Neuroendocrine Unit, Division of Neurosurgery, Hospital das Clínicas, University of Sao Paulo School of Medicine, São Paulo, SP, Brazil
| | - Maria Estela Justamante de Faria
- Department of Odontology, Central Unit, Hospital das Clínicas, University of Sao Paulo School of Medicine, São Paulo, SP, Brazil
| | - Ciliana Rossato
- Department of Odontology, Central Unit, Hospital das Clínicas, University of Sao Paulo School of Medicine, São Paulo, SP, Brazil
| | - Marcello D Bronstein
- Neuroendocrine Unit, Division of Endocrinology and Metabolism, Hospital das Clínicas, University of São Paulo Medical School, Av. Dr. Eneas de Carvalho, 255, 7ºandar, sala 7037, São Carlos, SP, CEP 05403-000, Brazil.
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Acromegaly in a patient with a pulmonary neuroendocrine tumor: case report and review of current literature. BMC Res Notes 2016; 9:326. [PMID: 27349224 PMCID: PMC4924317 DOI: 10.1186/s13104-016-2132-1] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2015] [Accepted: 06/18/2016] [Indexed: 12/16/2022] Open
Abstract
Background Pulmonary neuroendocrine tumors (NET) form a heterogeneous group of rare diseases. In these tumors, paraneoplastic syndromes have been described to drive the course of the disease, among them acromegaly induced by paraneoplastic secretion of growth hormone-releasing hormone (GHRH). Case presentation We report the case of a 43 years old patient initially diagnosed with acromegaly accompanied by weight gain and acral enlargement. Subsequently, further diagnostic work-up identified a solitary pulmonary neuroendocrine tumor (NET). Laboratory tests revealed markedly increased growth hormone (GH) and insulin-like growth factor 1 (IGF-1) without GHRH elevation in the absence of pituitary pathologies confirming the paraneoplastic origin of clinical presentation with acromegaly. Curative surgery was performed leading to normalization of the elevated hormone levels and improvement of the clinical symptoms. Immunohistochemically, a typical carcinoid (TC) was seen with low proliferation index and abundant IGF-1 expression. Conclusions The association of acromegaly and pulmonary NET has only rarely been reported. We present an individual case of paraneoplastic GH- and IGF-1 secretion in a patient with pulmonary NET. Based on their rarity, the knowledge of paraneoplastic syndromes occurring in patients with pulmonary NET such as acromegaly due to paraneoplastic GH- and IGF-1 secretion is mandatory to adequately diagnose and treat these patients.
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Fletcher JM, Scudder CJ, Kiupel M, Pipe-Martin HN, Kenny PJ, Mantis P, Fenn J, Smith K, Blair RV, Granger LA, Niessen SJM. Hypersomatotropism in 3 Cats without Concurrent Diabetes Mellitus. J Vet Intern Med 2016; 30:1216-21. [PMID: 27255700 PMCID: PMC5089606 DOI: 10.1111/jvim.14360] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2016] [Revised: 05/12/2016] [Accepted: 05/16/2016] [Indexed: 11/30/2022] Open
Affiliation(s)
- J M Fletcher
- Department of Veterinary Clinical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA, 70810
| | - C J Scudder
- Department of Clinical Science and Services, The Royal Veterinary College, University of London, North Mymms, AL9 7TA, Herts, UK
| | - M Kiupel
- Department of Pathobiology and Diagnostic Investigation, Diagnostic Center for Population and Animal Health, Michigan State University, Lansing, MI, 48910
| | - H N Pipe-Martin
- Department of Veterinary Clinical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA, 70810
| | - P J Kenny
- Department of Clinical Science and Services, The Royal Veterinary College, University of London, North Mymms, AL9 7TA, Herts, UK
| | - P Mantis
- Department of Clinical Science and Services, The Royal Veterinary College, University of London, North Mymms, AL9 7TA, Herts, UK
| | - J Fenn
- Department of Clinical Science and Services, The Royal Veterinary College, University of London, North Mymms, AL9 7TA, Herts, UK
| | - K Smith
- Department of Pathology and Pathogen Biology, The Royal Veterinary College, University of London, North Mymms, AL9 7TA, Herts, UK
| | - R V Blair
- Department of Pathobiological Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA, 70810
| | - L A Granger
- Department of Veterinary Clinical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA, 70810
| | - S J M Niessen
- Department of Clinical Science and Services, The Royal Veterinary College, University of London, North Mymms, AL9 7TA, Herts, UK
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Melmed S. Pituitary Medicine From Discovery to Patient-Focused Outcomes. J Clin Endocrinol Metab 2016; 101:769-77. [PMID: 26908107 PMCID: PMC4803158 DOI: 10.1210/jc.2015-3653] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/09/2015] [Accepted: 12/27/2015] [Indexed: 12/14/2022]
Abstract
CONTEXT This perspective traces a pipeline of discovery in pituitary medicine over the past 75 years. OBJECTIVE To place in context past advances and predict future changes in understanding pituitary pathophysiology and clinical care. DESIGN Author's perspective on reports of pituitary advances in the published literature. SETTING Clinical and translational Endocrinology. OUTCOMES Discovery of the hypothalamic-pituitary axis and mechanisms for pituitary control, have culminated in exquisite understanding of anterior pituitary cell function and dysfunction. Challenges facing the discipline include fundamental understanding of pituitary adenoma pathogenesis leading to more effective treatments of inexorably growing and debilitating hormone secreting pituitary tumors as well as medical management of non-secreting pituitary adenomas. Newly emerging pituitary syndromes include those associated with immune-targeted cancer therapies and head trauma. CONCLUSIONS Novel diagnostic techniques including imaging genomic, proteomic, and biochemical analyses will yield further knowledge to enable diagnosis of heretofore cryptic syndromes, as well as sub classifications of pituitary syndromes for personalized treatment approaches. Cost effective personalized approaches to precision therapy must demonstrate value, and will be empowered by multidisciplinary approaches to integrating complex subcellular information to identify therapeutic targets for enabling maximal outcomes. These goals will be challenging to attain given the rarity of pituitary disorders and the difficulty in conducting appropriately powered prospective trials.
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Affiliation(s)
- Shlomo Melmed
- Cedars-Sinai Medical Center, Los Angeles, California 90048
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Giustina A, Bevan JS, Bronstein MD, Casanueva FF, Chanson P, Petersenn S, Thanh XMT, Sert C, Houchard A, Guillemin I, Melmed S. SAGIT®: clinician-reported outcome instrument for managing acromegaly in clinical practice--development and results from a pilot study. Pituitary 2016; 19:39-49. [PMID: 26377024 PMCID: PMC4710645 DOI: 10.1007/s11102-015-0681-2] [Citation(s) in RCA: 43] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Abstract
PURPOSE The SAGIT instrument is a comprehensive clinician-reported outcome instrument assessing key features of acromegaly: signs and symptoms, associated comorbidities; growth hormone levels; insulin-like growth factor-1 levels; and tumor profile. The SAGIT instrument has been designed to assist endocrinologists managing acromegaly in practice. Here, we report on pre-testing (to assess ease of understanding and acceptability) and a pilot study (to assess relevance, ease of use, and utility in real-life conditions) (NCT02231593). METHODS For pre-testing, 11 endocrinologists completed the SAGIT instrument using patient medical records and were also interviewed. They subsequently completed a PRAgmatic Content and face validity Test (PRAC-Test(©)) to report their experiences using SAGIT, and feedback was used to revise the instrument. In the pilot study, nine endocrinologists completed the SAGIT instrument in real-time with patients belonging to three different categories (stable/controlled, active/uncontrolled acromegaly, treatment-naïve), while four completed the instrument based on medical-record review. All participants then completed the PRAC-Test(©) and their feedback was used to update the instrument. RESULTS The SAGIT instrument was well accepted by endocrinologists, with most indicating that it was concise, practical, easy to understand, useful for assessing treatment response, and valuable as a component of the patient's medical record. The pilot study confirmed the instrument's acceptability, utility, and ease of use, and indicated its potential for distinguishing acromegaly clinical stages. CONCLUSIONS The SAGIT instrument is promising as a tool for use by endocrinologists in everyday practice to assess the status and evolution of disease in patients with acromegaly and to guide treatment decision-making.
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Affiliation(s)
- Andrea Giustina
- Chair of Endocrinology, University of Brescia, Brescia, Italy.
| | | | | | - Felipe F Casanueva
- Department of Medicine, Santiago de Compostela University - CIBER de Fisiopatología de la Obesidad y Nutrición (CIBERobn), Instituto Salud Carlos III, Santiago de Compostela, Spain
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Abstract
The currently available somatostatin receptor ligands (SRLs) and growth hormone (GH) antagonists are used to control levels of GH and insulin-like growth factor 1 (IGF-1) in patients with acromegaly. However, these therapies are limited by wide variations in efficacy, associated adverse effects and the need for frequent injections. A phase III trial of oral octreotide capsules demonstrated that this treatment can safely sustain suppressed levels of GH and IGF-1 and reduce the severity of symptoms in patients with acromegaly previously controlled by injectable SRL therapy, with the added benefit of no injection-site reactions. Phase I and phase II trials of the pan-selective SRL DG3173, the liquid crystal octreotide depot CAM2029 and an antisense oligonucleotide directed against the GH receptor have shown that these agents can be used to achieve biochemical suppression in acromegaly and have favourable safety profiles. This Review outlines the need for new therapeutic agents for patients with acromegaly, reviews clinical trial data of investigational agents and considers how these therapies might best be integrated into clinical practice.
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Affiliation(s)
- Shlomo Melmed
- Pituitary Center, Department of Medicine, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Room 2015, Los Angeles, California 90048, USA
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47
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Haliloglu O, Kuruoglu E, Ozkaya HM, Keskin FE, Gunaldi O, Oz B, Gazioglu N, Kadioglu P, Tanriover N. Multidisciplinary Approach for Acromegaly: A Single Tertiary Center's Experience. World Neurosurg 2016; 88:270-276. [PMID: 26806060 DOI: 10.1016/j.wneu.2015.12.092] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2015] [Revised: 12/25/2015] [Accepted: 12/26/2015] [Indexed: 11/16/2022]
Abstract
BACKGROUND Acromegaly is a multisystemic disease that requires a multidisciplinary approach. The aim of this study was to determine early and late remissions of patients who underwent surgery at our center and to evaluate relations between pathologic and radiologic properties of adenoma and medical and radiosurgical treatments with remissions. METHODS The medical records of 103 patients with acromegaly who underwent endoscopic endonasal transsphenoidal surgery in Cerrahpasa Medical Faculty, Istanbul University, between 2007 and 2014 were reviewed. Clinical, biochemical, radiologic, and pathologic properties were determined. RESULTS The total median follow-up time was 38 months [interquartile range: 24-53.5 months]. Thirty-two percent of the adenomas were microadenomas and 68% were macroadenomas The early remission rate was 51.5% and late remission was 75.2%. The sellar floor invasion was significantly lower in patients with early and late remissions (P = 0.01 and P = 0.009, respectively). The initial growth hormone (GH; P < 0.001), first-day GH (P = 0.03), 3-month GH (P = 0.001), insulin-like growth factor-1 (P = 0.004), and 6-month insulin-like growth factor-1 (P = 0.02) levels were significantly greater in patients with sellar floor invasion. The late remission rates (P = 0.004) were greter and reoperation needs (P = 0.05) were lower in patients with Ki-67 <3% than in patients with ≥3%. Seventy (68.6%) patients needed medical therapy during follow-up. CONCLUSIONS Late remission was achieved using a multidiciplinary approach in 75.2% of 103 patients with acromegaly, and young age, male sex, high Ki-67 and mitosis indices, and cavernous sinus and sellar-floor invasion had negative effects on clinical and biochemical control of the disease.
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Affiliation(s)
- Ozlem Haliloglu
- Division of Endocrinology-Metabolism and Diabetes, Department of Internal Medicine, Cerrahpasa Medical Faculty, Istanbul University, Istanbul, Turkey
| | - Enis Kuruoglu
- Department of Neurosurgery, Cerrahpasa Medical Faculty, Istanbul University, Istanbul, Turkey
| | - Hande Mefkure Ozkaya
- Division of Endocrinology-Metabolism and Diabetes, Department of Internal Medicine, Cerrahpasa Medical Faculty, Istanbul University, Istanbul, Turkey
| | - Fatma Ela Keskin
- Division of Endocrinology-Metabolism and Diabetes, Department of Internal Medicine, Cerrahpasa Medical Faculty, Istanbul University, Istanbul, Turkey
| | - Omur Gunaldi
- Department of Neurosurgery, Cerrahpasa Medical Faculty, Istanbul University, Istanbul, Turkey
| | - Buge Oz
- Department of Pathology, Cerrahpasa Medical Faculty, Istanbul University, Istanbul, Turkey
| | - Nurperi Gazioglu
- Department of Neurosurgery, Cerrahpasa Medical Faculty, Istanbul University, Istanbul, Turkey
| | - Pinar Kadioglu
- Division of Endocrinology-Metabolism and Diabetes, Department of Internal Medicine, Cerrahpasa Medical Faculty, Istanbul University, Istanbul, Turkey
| | - Necmettin Tanriover
- Department of Neurosurgery, Cerrahpasa Medical Faculty, Istanbul University, Istanbul, Turkey.
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Chanson P. Medical Treatment of Acromegaly with Dopamine Agonists or Somatostatin Analogs. Neuroendocrinology 2016; 103:50-8. [PMID: 25677539 DOI: 10.1159/000377704] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/05/2014] [Accepted: 02/04/2015] [Indexed: 11/19/2022]
Abstract
Treatment of acromegaly aims to correct (or prevent) tumor compression of surrounding tissues by excising the disease-causing lesion and reduce growth hormone (GH) and IGF-1 levels to normal values. When surgery (the usual first-line treatment) fails to correct GH/IGF-1 hypersecretion, medical treatment with dopamine agonists (DAs; particularly cabergoline) or somatostatin analogs (SAs) can be used. The GH receptor antagonist pegvisomant is helpful in patients who are totally or partially resistant to SAs and can be given in association with both SAs and/or DAs. Thanks to this multistep therapeutic strategy, adequate hormonal disease control is achieved in most patients, giving them normal life expectancy. Comorbidities associated with acromegaly generally improve after treatment, but persistent sequelae may nonetheless impair quality of life.
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Affiliation(s)
- Philippe Chanson
- Service d'Endocrinologie et des Maladies de la Reproduction and Centre de Référence des Maladies Endocriniennes Rares de la Croissance, Hôpital Bicêtre, Assistance Publique-Hôpitaux de Paris, and Inserm 1185, Fac Med Paris Sud, Université Paris-Saclay, Le Kremlin-Bicêtre, France
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Zhang JJ, Nellesen D, Ludlam WH, Neary MP. Budget impact of pasireotide LAR for the treatment of acromegaly, a rare endocrine disorder. J Med Econ 2016; 19:374-85. [PMID: 26629745 DOI: 10.3111/13696998.2015.1127816] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Abstract
BACKGROUND Acromegaly is a rare disorder characterized by the over-production of growth hormone (GH). Patients often experience a range of chronic comorbidities including hypertension, cardiac dysfunction, diabetes, osteoarthropathy, and obstructive sleep apnea. Untreated or inadequately controlled patients incur substantial healthcare costs, while normalization of GH levels may reduce morbidity and mortality rates to be comparable to the general population. OBJECTIVE To assess the 3-year budget impact of pasireotide LAR on a US managed care health plan following pasireotide LAR availability. METHODS Two separate economic models were developed: one from the perspective of an entire health plan and another from the perspective of a pharmacy budget. The total budget impact model includes costs of drug therapies and other costs for treatment, monitoring, management of adverse events, and comorbidities. The pharmacy cost calculator only considers drug costs. RESULTS The total estimated budget impact associated with the introduction of pasireotide LAR is 0.31 cents ($0.0031) per member per month (PMPM) in the first year, 0.78 cents ($0.0078) in the second year, and 1.42 cents ($0.0142) in the third year following FDA approval. Costs were similar or lower from a pharmacy budget impact perspective. For each patient achieving disease control, cost savings from reduced comorbidities amounted to $10,240 per year. LIMITATIONS Published data on comorbidities for acromegaly are limited. In the absence of data on acromegaly-related costs for some comorbidities, comorbidity costs for the general population were used (may be under-estimates). CONCLUSIONS The budget impact of pasireotide LAR is expected to be modest, with an expected increase of 1.42 cents PMPM on the total health plan budget in the third year after FDA approval. The efficacy of pasireotide LAR in acromegaly, as demonstrated in head-to-head trials compared with currently available treatment options, is expected to be associated with a reduction of the prevalence of comorbidities.
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Affiliation(s)
- J J Zhang
- a a Analysis Group, Inc. , Menlo Park , CA , USA
| | - D Nellesen
- a a Analysis Group, Inc. , Menlo Park , CA , USA
| | - W H Ludlam
- b b Novartis Pharmaceuticals Corporation , East Hanover , NJ , USA
| | - M P Neary
- b b Novartis Pharmaceuticals Corporation , East Hanover , NJ , USA
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50
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Molecular Characterization of Growth Hormone-producing Tumors in the GC Rat Model of Acromegaly. Sci Rep 2015; 5:16298. [PMID: 26549306 PMCID: PMC4637865 DOI: 10.1038/srep16298] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2015] [Accepted: 10/08/2015] [Indexed: 12/14/2022] Open
Abstract
Acromegaly is a disorder resulting from excessive production of growth hormone (GH) and consequent increase of insulin-like growth factor 1 (IGF-I), most frequently caused by pituitary adenomas. Elevated GH and IGF-I levels results in wide range of somatic, cardiovascular, endocrine, metabolic, and gastrointestinal morbidities. Subcutaneous implantation of the GH-secreting GC cell line in rats leads to the formation of tumors. GC tumor-bearing rats develop characteristics that resemble human acromegaly including gigantism and visceromegaly. However, GC tumors remain poorly characterized at a molecular level. In the present work, we report a detailed histological and molecular characterization of GC tumors using immunohistochemistry, molecular biology and imaging techniques. GC tumors display histopathological and molecular features of human GH-producing tumors, including hormone production, cell architecture, senescence activation and alterations in cell cycle gene expression. Furthermore, GC tumors cells displayed sensitivity to somatostatin analogues, drugs that are currently used in the treatment of human GH-producing adenomas, thus supporting the GC tumor model as a translational tool to evaluate therapeutic agents. The information obtained would help to maximize the usefulness of the GC rat model for research and preclinical studies in GH-secreting tumors.
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