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Unluhizarci K, Urhan E. Epidemiology and risk factors for hypopituitarism due to traumatic brain injury. Best Pract Res Clin Endocrinol Metab 2025:101997. [PMID: 40274450 DOI: 10.1016/j.beem.2025.101997] [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] [Indexed: 04/26/2025]
Abstract
During the last two decades traumatic brain injury (TBI) was also found as an important cause of hypopituitarism. Although the most common causes of TBI are traffic accidents and falls, others such as blast-related injuries, acts of violence and combative sports are also considered in the etiology. TBI may lead to transient or permanent pituitary dysfunction. The definition of TBI-induced hypopituitarism cover alterations in pituitary hormone levels which may occur even after five years of injury and characterised by hormonal deficiencies but rarely recovery of some hormones during the course of the disease. It has been shown that between 5 % and 70 % of the TBI patients suffer from hypopituitarism. This large variation in the prevalence may be explained by diverse diagnostic criteria used in different studies, different time points of interventions after TBI, severity of trauma etc. Patients with advanced age, low Glasgow Coma Scale, needing intensive care unit stay, presence of skull fractures, brain edema are particularly make patients vulnerable to TBI-induced hypopituitarism.
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Affiliation(s)
- Kursad Unluhizarci
- Department of Endocrinology, Erciyes University Medical School, Kayseri, Türkiye.
| | - Emre Urhan
- Department of Endocrinology, Erciyes University Medical School, Kayseri, Türkiye.
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Xing MW, Zhang Y, Zhu HT, Liu C, Geng ZY, Song LL, Wang DX. Intraoperative isotonic balanced versus hypotonic crystalloids on postoperative sodium homeostasis in small children undergoing major neurosurgery: a randomized controlled trial. BMC Pediatr 2025; 25:195. [PMID: 40089683 PMCID: PMC11909862 DOI: 10.1186/s12887-025-05543-6] [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: 11/14/2024] [Accepted: 02/25/2025] [Indexed: 03/17/2025] Open
Abstract
BACKGROUND Whether intraoperative isotonic balanced maintenance fluid is associated with less variation in sodium homeostasis in small children undergoing major neurosurgery remains unknown. METHODS Patients aged up to 6 years undergoing major neurosurgery were randomly assigned to receive either isotonic balanced solution (IB) or 0.2% hypotonic solution (H) as intraoperative maintenance fluid. Serum electrolyte levels were measured from preoperative baseline to 6 d following surgery. RESULTS Eighty patients were included in the primary analysis. Serum sodium change was significantly less in the IB patients from the end of surgery continuing to 24 h following surgery (at the end of surgery: -1.4 ± 3.6 versus - 4.6 ± 3.5 mmol/l, P < 0.001; 24 h post: -1.2 ± 4.8 versus - 3.4 ± 2.5 mmol/l, P = 0.028). Twenty (50%) of the IB patients and 25 (63%) of the H patients had serum sodium change > 2.5 mmol/l 24 h following surgery (6.0 ± 3.4 versus 4.8 ± 2.1 mmol/l), with 13 (33%) of the IB patients and 25 (63%) of the H patients having sodium decrease > 2.5 mmol/l (6.4 ± 3.7 versus 4.8 ± 2.1 mmol/l) (P = 0.007). Seven patients in group IB experienced an increase in blood sodium levels exceeding 2.5 mmol/l (median, 4.1 [range 2.7 ∼ 9.2] mmol/l). Notably, 10 (25%) of the IB patients and 6 (15%) of the H patients had sodium variation > 5 mmol/l (median, 8.5 [range 5.1 ∼ 14.6] versus 7.2 [range 5.5 ∼ 11.1] mmol/l). Immediately following surgery till 24 h postoperatively, hyponatremia was less observed in the IB patients compared with that in the H patients. The IB patients had higher hemoglobin levels and less diuresis 48 h postoperatively. No symptoms including altered mental status, seizure, and circulatory overload were observed in all patients. CONCLUSION Intraoperative isotonic balanced solution infusion resulted in statistically but not clinically minimal variation of sodium homeostasis and hemoglobin level postoperatively in small children undergoing major neurosurgery, compared to the use hypotonic solution. Potentially excessive sodium fluctuation following isotonic balanced maintenance fluid infusion should be cautioned, even for a brief period of infusion. TRIAL REGISTRATION Chinese Clinical Trial Registry ( http://www.chictr.org.cn/ ). REGISTRATION NUMBER ChiCTR2100046539. Registration date: May 21, 2021. Principal investigator: Lin-Lin Song.
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Affiliation(s)
- Mao-Wei Xing
- Department of Anesthesiology, Peking University First Hospital, Beijing, China
- Department of Anesthesiology, Beijing Friendship Hospital of Capital Medical University, Beijing, China
| | - Yue Zhang
- Department of Anesthesiology, Peking University First Hospital, Beijing, China
| | - Hui-Ting Zhu
- Department of Anesthesiology, Peking University First Hospital, Beijing, China
| | - Chang Liu
- Pediatric epilepsy center, Peking University First Hospital, Beijing, China
| | - Zhi-Yu Geng
- Department of Anesthesiology, Peking University First Hospital, Beijing, China
| | - Lin-Lin Song
- Department of Anesthesiology, Peking University First Hospital, Beijing, China.
| | - Dong-Xin Wang
- Department of Anesthesiology, Peking University First Hospital, Beijing, China
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Petria I, Indirli R, Mantovani B, Lanzi V, Mantovani G, Ferrante E. Recurrent hyponatremia due to syndrome of inappropriate antidiuresis after traumatic brain injury: two case reports. Front Endocrinol (Lausanne) 2025; 16:1536247. [PMID: 40115742 PMCID: PMC11922699 DOI: 10.3389/fendo.2025.1536247] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/28/2024] [Accepted: 02/17/2025] [Indexed: 03/23/2025] Open
Abstract
Background Transient hyponatremia due to syndrome of inappropriate antidiuresis (SIAD) is a frequent (20-50%) complication of traumatic brain injury (TBI), but it rarely persists or recurs. There are only few published reports of patients suffering from non-transient hyponatremia due to chronic SIAD after TBI. We report two more cases with this condition. Case 1 A 36-year-old woman suffering from major depression and treated with olanzapine reported severe TBI after a severe fall. Following head injury, she developed severe hyponatremia, which was managed with fluid restriction and salt supplementation. Upon hospital discharge, 7 months after trauma, mild hyponatremia was still reported (Na 134 mmol/L), which dropped to severe hyponatremia in a week despite continuation of treatment, and spontaneously returned to normal. Two months later, the patient presented one more episode of moderate hyponatremia without clear triggering events. Pituitary hormones were normal and urinary sodium and urinary and plasma osmolality supported the diagnosis of SIAD. Therefore, tolvaptan 7.5 mg daily was started, with sustained normalization of sodium levels. When olanzapine was stopped, discontinuation of tolvaptan was attempted. However, serum sodium dropped again and tolvaptan had to be resumed, with natremia remaining within normal range at follow-up. Consistently, olanzapine-related hyponatremia could be ruled out and post-traumatic SIAD confirmed. Case 2 A 37-year-old man experienced TBI with diffuse axonal injury falling during a mountain trip. Over the following year, he presented two episodes of tonic-clonic seizures accompanied by the biochemical finding of moderate-severe hyponatremia. Hyponatremia resolved following hypertonic (3% NaCl) saline infusion, and valproate treatment was started after the second episode. In the following outpatient visits, a progressive decrease of serum sodium from 141 mmol/L to 132 mmol/L was observed, with other tests consistent with SIAD. Therefore, considering the high risk of recurrent seizures as well as the concomitant treatment with valproate, tolvaptan 7.5 mg every other day was started and normal sodium levels have been maintained since then. Conclusions We report two cases of recurrent SIAD following TBI, with multiple hyponatremic episodes after initial presentation. This highlights the importance of long-term follow-up of electrolyte abnormalities after head injury.
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Affiliation(s)
- Iulia Petria
- Endocrinology Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
- Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy
| | - Rita Indirli
- Endocrinology Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
- Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy
| | - Beatrice Mantovani
- Endocrinology Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Valeria Lanzi
- Endocrinology Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
- Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy
| | - Giovanna Mantovani
- Endocrinology Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
- Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy
| | - Emanuele Ferrante
- Endocrinology Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
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Sharma B, Jiang W, Hasan MM, Agriantonis G, Bhatia ND, Shafaee Z, Twelker K, Whittington J. Natremia Significantly Influences the Clinical Outcomes in Patients with Severe Traumatic Brain Injury. Diagnostics (Basel) 2025; 15:125. [PMID: 39857008 PMCID: PMC11764417 DOI: 10.3390/diagnostics15020125] [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: 12/10/2024] [Revised: 12/23/2024] [Accepted: 12/30/2024] [Indexed: 01/27/2025] Open
Abstract
Objective: Fluctuations in sodium levels (SLs) may increase mortality, severity, and prolonged length of stay (LOS) in critically ill patients. We aim to study the effect of SL on various clinical outcomes in patients with severe traumatic brain injury (TBI). Methods: This is a single-center, retrospective study of patients with severe TBI from 1 January 2020 to 31 December 2023, inclusive. Patients were identified using Abbreviated Injury Severity (AIS) scores and International Classification of Diseases (ICD) injury descriptions. Result: Variations in hospital (H) admission SLs were statistically significant across four age ranges (pediatric, young adult, older adults, and elderly). Intensive care unit (ICU) admission, H discharge, and death also showed significance. A statistical difference was noted in ICU discharge levels while comparing blunt versus penetrating injury. We found statistically significant differences in SLs at H admission, ICU admission, and ICU discharge when compared to the Injury Severity Score (ISS) and the Glasgow Coma Scale (GCS) at admission. A linear regression analysis revealed a statistically significant positive correlation between ICU admission SLs and ISS. We discovered statistically significant differences when comparing ICU admission levels to H LOS, ventilator days, and mortality. Conclusions: SL upon ICU admission is correlated with ISS, GCS, and mortality rates. The elevated admission SL was linked to adverse hospital outcomes, including prolonged LOS at the H, ICU, and mechanical ventilation. Moreover, variability in serum SLs is independently associated with mortality throughout the hospital stay, irrespective of the absolute serum sodium concentration.
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Affiliation(s)
- Bharti Sharma
- Elmhurst Hospital Center, Trauma Unit, Department of Surgery, NYC Health & Hospitals, New York, NY 11373, USA; (W.J.); (M.M.H.); (G.A.); (N.D.B.); (Z.S.); (K.T.); (J.W.)
- Trauma Unit, Department of Surgery, Icahn School of Medicine at Mount Sinai Hospital, New York, NY 10029, USA
| | - Winston Jiang
- Elmhurst Hospital Center, Trauma Unit, Department of Surgery, NYC Health & Hospitals, New York, NY 11373, USA; (W.J.); (M.M.H.); (G.A.); (N.D.B.); (Z.S.); (K.T.); (J.W.)
- Trauma Unit, Department of Surgery, Icahn School of Medicine at Mount Sinai Hospital, New York, NY 10029, USA
| | - Munirah M. Hasan
- Elmhurst Hospital Center, Trauma Unit, Department of Surgery, NYC Health & Hospitals, New York, NY 11373, USA; (W.J.); (M.M.H.); (G.A.); (N.D.B.); (Z.S.); (K.T.); (J.W.)
- Trauma Unit, Department of Surgery, Icahn School of Medicine at Mount Sinai Hospital, New York, NY 10029, USA
| | - George Agriantonis
- Elmhurst Hospital Center, Trauma Unit, Department of Surgery, NYC Health & Hospitals, New York, NY 11373, USA; (W.J.); (M.M.H.); (G.A.); (N.D.B.); (Z.S.); (K.T.); (J.W.)
- Trauma Unit, Department of Surgery, Icahn School of Medicine at Mount Sinai Hospital, New York, NY 10029, USA
| | - Navin D. Bhatia
- Elmhurst Hospital Center, Trauma Unit, Department of Surgery, NYC Health & Hospitals, New York, NY 11373, USA; (W.J.); (M.M.H.); (G.A.); (N.D.B.); (Z.S.); (K.T.); (J.W.)
- Trauma Unit, Department of Surgery, Icahn School of Medicine at Mount Sinai Hospital, New York, NY 10029, USA
| | - Zahra Shafaee
- Elmhurst Hospital Center, Trauma Unit, Department of Surgery, NYC Health & Hospitals, New York, NY 11373, USA; (W.J.); (M.M.H.); (G.A.); (N.D.B.); (Z.S.); (K.T.); (J.W.)
- Trauma Unit, Department of Surgery, Icahn School of Medicine at Mount Sinai Hospital, New York, NY 10029, USA
| | - Kate Twelker
- Elmhurst Hospital Center, Trauma Unit, Department of Surgery, NYC Health & Hospitals, New York, NY 11373, USA; (W.J.); (M.M.H.); (G.A.); (N.D.B.); (Z.S.); (K.T.); (J.W.)
- Trauma Unit, Department of Surgery, Icahn School of Medicine at Mount Sinai Hospital, New York, NY 10029, USA
| | - Jennifer Whittington
- Elmhurst Hospital Center, Trauma Unit, Department of Surgery, NYC Health & Hospitals, New York, NY 11373, USA; (W.J.); (M.M.H.); (G.A.); (N.D.B.); (Z.S.); (K.T.); (J.W.)
- Trauma Unit, Department of Surgery, Icahn School of Medicine at Mount Sinai Hospital, New York, NY 10029, USA
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Breuler C, Lynn JV, Buchman L, Matusko N, Makar K, Ranganathan K, Mouch C, Muraszko K, Buchman SR. Low Prevalence of Clinically Significant Hyponatremia following Cranial Vault Reconstruction for Single-Suture Craniosynostosis. Plast Reconstr Surg 2024; 153:1379-1386. [PMID: 38810163 DOI: 10.1097/prs.0000000000010852] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/31/2024]
Abstract
BACKGROUND Patients are commonly monitored for hyponatremia after intracranial procedures, yet the prevalence of hyponatremia after cranial vault reconstruction (CVR) remains unclear. The purpose of this study is to define the prevalence, risk factors, and complications of hyponatremia after CVR to optimize postoperative sodium surveillance protocols. METHODS Patients with nonsyndromic, single-suture craniosynostosis who underwent primary CVR between 2009 and 2020 at Michigan Medicine were included (n = 231). Demographic, intraoperative, and postoperative characteristics were compared by postoperative hyponatremia status at P < 0.05 significance. Hyponatremia was defined as mild (<135 mEq/L), moderate (<130 mEq/L), or severe (<125 mEq/L) based on the lowest postoperative laboratory draw. RESULTS Twenty-three patients (10.0%) developed mild postoperative hyponatremia. No patient developed moderate or severe postoperative hyponatremia. On multivariable regression, decreased preoperative sodium level (P = 0.03) and decreased preoperative weight (P = 0.02) were significantly associated with mild postoperative hyponatremia. No patient developed complications or required hospital readmission because of hyponatremia. CONCLUSIONS This large retrospective cohort study of patients with nonsyndromic single-suture craniosynostosis demonstrated a 10% prevalence of mild, clinically inconsequential hyponatremia and 0% prevalence of moderate or severe, clinically significant hyponatremia after primary CVR. Patients with low preoperative sodium level or weight were at increased risk for developing mild postoperative hyponatremia. The results suggest that patients with preoperative sodium greater than 140 mEq/L or preoperative weight greater than 10 kg may be candidates for limited postoperative sodium surveillance; however, future prospective studies are warranted before implementation. CLINICAL QUESTION/LEVEL OF EVIDENCE Risk, III.
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Ebrahimi F, Andereggen L, Christ ER. Morbidities and mortality among hospitalized patients with hypopituitarism: Prevalence, causes and management. Rev Endocr Metab Disord 2024; 25:599-608. [PMID: 38802643 PMCID: PMC11162375 DOI: 10.1007/s11154-024-09888-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 03/15/2024] [Indexed: 05/29/2024]
Abstract
Hypopituitarism is a highly heterogeneous multisystem disorder that can have a major impact on long-term morbidity and mortality, but even more so during acute medical conditions requiring hospitalization. Recent studies suggest a significant in-hospital burden with prolonged length of stay, increased rate of intensive care unit (ICU) admission, and initiation of mechanical ventilation - all of which may lead to an increased risk of in-hospital mortality. On the one hand, patients with hypopituitarism are often burdened by metabolic complications, including obesity, hypertension, dyslipidemia, and hyperglycemia, which alone, or in combination, are known to significantly alter relevant physiological mechanisms, including metabolism, innate and adaptive immune responses, coagulation, and wound healing, thereby contributing to adverse in-hospital outcomes. On the other hand, depending on the extent and the number of pituitary hormone deficiencies, early recognition of hormone deficiencies and appropriate management and replacement strategy within a well-organized multidisciplinary team are even stronger determinants of short-term outcomes during acute hospitalization in this vulnerable patient population. This review aims to provide an up-to-date summary of recent advances in pathophysiologic understanding, clinical implications, and recommendations for optimized multidisciplinary management of hospitalized patients with hypopituitarism.
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Affiliation(s)
- Fahim Ebrahimi
- Department of Endocrinology, Diabetes and Metabolism, University Hospital Basel, Basel, Switzerland.
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, 17177, Stockholm, Sweden.
- Department of Gastroenterology and Hepatology, Clarunis University Center for Gastrointestinal and Liver Diseases, Basel, Switzerland.
| | - Lukas Andereggen
- Department of Neurosurgery, Cantonal Hospital Aarau, Aarau, Switzerland
- Faculty of Medicine, University of Bern, Bern, Switzerland
| | - Emanuel R Christ
- Department of Endocrinology, Diabetes and Metabolism, University Hospital Basel, Basel, Switzerland
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Magyar-Sumegi ZD, Stankovics L, Lendvai-Emmert D, Czigler A, Hegedus E, Csendes M, Toth L, Ungvari Z, Buki A, Toth P. Acute neuroendocrine changes after traumatic brain injury. BRAIN & SPINE 2024; 4:102830. [PMID: 38764890 PMCID: PMC11101905 DOI: 10.1016/j.bas.2024.102830] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/04/2024] [Revised: 04/26/2024] [Accepted: 05/06/2024] [Indexed: 05/21/2024]
Abstract
Introduction Post-traumatic hypopituitarism (PTHP) is a significant, but often neglected consequence of traumatic brain injury (TBI). Research question We aimed to provide a comprehensive overview of epidemiology, pathophysiology, clinical features and diagnostic approaches of PTHP. Materials and methods MEDLINE, EMBASE, Cochrane Library and Web of Science were searched. 45 articles of human studies evaluating acute endocrine changes following mild, moderate and severe TBI were selected. Results Severity of TBI seems to be the most important risk factor of PTHP. Adrenal insufficiency (AI) was present in 10% of TBI patients (prevalence can be as high as 50% after severe TBI), and hypocortisolemia is a predictor of mortality and long-term hypopituitarism. Suppression of the thyroid axis in 2-33% of TBI patients may be an independent predictor of adverse neurological outcome, as well. 9-36% of patients with severe TBI exhibit decreased function of the somatotrophic axis with a divergent effect on the central nervous system. Arginine-Vasopressin (AVP) deficiency is present in 15-51% of patients, associated with increased mortality and unfavorable outcome. Due to shear and injury of the stalk hyperprolactinemia is relatively common (2-50%), but it bears little clinical significance. Sex hormone levels remain within normal values. Discussion and conclusion PTHP occurs frequently after TBI, affecting various axis and determining patients' outcome. However, evidence is scarce regarding exact epidemiology, diagnosis, and effective clinical application of hormone substitution. Future studies are needed to identify patients at-risk, determine the optimal timing for endocrine testing, and refine diagnostic and treatment approaches to improve outcome.
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Affiliation(s)
- Zsofia Dina Magyar-Sumegi
- Department of Neurosurgery, Medical School, University of Pecs, Pecs, Hungary
- Department of Psychiatry and Psychotherapy, Medical School, University of Pecs, Pecs, Hungary
- Doctoral School of Clinical Neurosciences, Medical School, University of Pecs, Pecs, Hungary
| | - Levente Stankovics
- Department of Neurosurgery, Medical School, University of Pecs, Pecs, Hungary
| | | | - Andras Czigler
- Department of Neurosurgery, Medical School, University of Pecs, Pecs, Hungary
| | - Emoke Hegedus
- Doctoral School of Clinical Neurosciences, Medical School, University of Pecs, Pecs, Hungary
- Department of Anaesthesiology and Intensive Therapy, Medical School, University of Pecs, Pecs, Hungary
| | - Mark Csendes
- Department of Neurosurgery, Medical School, University of Pecs, Pecs, Hungary
- Doctoral School of Clinical Neurosciences, Medical School, University of Pecs, Pecs, Hungary
| | - Luca Toth
- Department of Neurosurgery, Medical School, University of Pecs, Pecs, Hungary
| | - Zoltan Ungvari
- Department of Neurosurgery, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA
- International Training Program in Geroscience, Doctoral School of Basic and Translational Medicine/Department of Public Health, Semmelweis University, Budapest, Hungary
| | - Andras Buki
- Department of Neurosurgery, Faculty of Medicine and Health, Orebro University, Orebro, Sweden
| | - Peter Toth
- Department of Neurosurgery, Medical School, University of Pecs, Pecs, Hungary
- Department of Neurosurgery, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA
- International Training Program in Geroscience, Doctoral School of Basic and Translational Medicine/Department of Public Health, Semmelweis University, Budapest, Hungary
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Fernández Rodriguez E, Villar Taibo R, Bernabeu I. Hypopituitarism after traumatic brain injury in adults: Clinical guidelines of the neuroendocrinology area of the Spanish Society of Endocrinology and Nutrition (SEEN). ENDOCRINOL DIAB NUTR 2023; 70:584-591. [PMID: 37977921 DOI: 10.1016/j.endien.2023.11.002] [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: 06/12/2023] [Accepted: 07/20/2023] [Indexed: 11/19/2023]
Abstract
Traumatic brain injury (TBI) is associated with hypopituitarism with a variable incidence, depending on the time and methods used to diagnosis, and on factors related to the trauma, such as its severity, its anatomical location and the drugs used in the acute phase. The pituitary gland can be damaged directly by the impact or secondary to factors such as ischemia, inflammation, excitotoxicity or immunity. In acute phases ACTH deficiency is the most relevant, since failure to detect and treat it can compromise the patient's life. Clinical manifestations are typical of each hormone deficient axes, although the combination hypopituitarism-trauma has been associated with cognitive deterioration, worse metabolic profile and greater impairment of quality of life. One of the clinical challenges is to determine which patients benefit from a systematic hormonal evaluation, and therefore from hormone replacement, and what is the appropriate time to do so and the most suitable diagnostic methods.
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Affiliation(s)
- Eva Fernández Rodriguez
- Servicio de Endocrinología y Nutrición, Complejo Hospitalario Universitario de Ourense, Ourense, Spain
| | - Rocío Villar Taibo
- Servicio de Endocrinología y Nutrición, Complejo Hospitalario Universitario de Santiago de Compostela, Santiago de Compostela, A Coruña, Spain
| | - Ignacio Bernabeu
- Servicio de Endocrinología y Nutrición, Complejo Hospitalario Universitario de Santiago de Compostela, Santiago de Compostela, A Coruña, Spain.
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Azam H, Tuch B. A rare case of isolated ACTH deficiency associated with a Rathke's Cleft Cyst and a review of the literature. Clin Case Rep 2023; 11:e8026. [PMID: 37822479 PMCID: PMC10562649 DOI: 10.1002/ccr3.8026] [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] [Received: 08/10/2023] [Revised: 09/13/2023] [Accepted: 09/19/2023] [Indexed: 10/13/2023] Open
Abstract
A 78-year-old man was referred to clinic due to a 5-year history of weight loss, lethargy, and pathology showing hyponatremia. In the year prior, he had a hospital admission for symptomatic hyponatremia. MRI brain during that admission showed a 1-2 mm pituitary lesion of unknown significance. Testing during this presentation revealed hypocortisolism with ACTH deficiency. Progress MRI brain revealed the presence of a Rathke's Cleft Cyst (RC). Medical management with glucocorticoids resulted in symptomatic and biochemical parameter improvement. To our knowledge this is the first reported case of isolated ACTH deficiency in the setting of a RC.
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Affiliation(s)
- Hamza Azam
- Liverpool HospitalLiverpoolNew South WalesAustralia
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Abstract
PURPOSE OF REVIEW This article reviews hypopituitarism after TBI, the importance of pituitary hormones, and related controversies, concluding with a suggested patient approach. RECENT FINDINGS While earlier studies focused on increased pituitary deficiencies after moderate-severe TBI, recent studies have focused on deficiencies after mild TBI. There has been increasing focus on the role of growth hormone after injury; growth hormone is the most frequent reported deficiency at 1 year post-TBI, and an area with unresolved questions. While more research is needed to quantify the risk of deficiencies in special populations, and establish the natural history, increasing data indicate an increase in hypopituitarism after other acquired brain injuries; the potential role of pituitary hormone deficiencies after stroke and after COVID-19 infection is an area of active inquiry. Given the negative health effects of untreated hypopituitarism and the opportunity to intervene via hormone replacement, it is important to recognize the role of pituitary hormone deficiencies after TBI.
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Affiliation(s)
- Tamara L Wexler
- Department of Rehabilitation Medicine, NYU Grossman School of Medicine, 240 E 38th St 15th Floor, New York, NY, 10016, USA.
- Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
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Tabor J, La P, Kline G, Wang M, Bonfield S, Machan M, Wynne-Edwards K, Emery C, Debert C. Saliva Cortisol as a Biomarker of Injury in Youth Sport-Related Concussion. J Neurotrauma 2023; 40:296-308. [PMID: 35906800 DOI: 10.1089/neu.2022.0190] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023] Open
Abstract
Increasing rates of sport-related concussion (SRC) in youth impose a significant burden on public health systems and the lives of young athletes. Accurate prediction for those likely to develop persistent post-concussion symptomology (PPCS) using a fluid biomarker, reflecting both acute injury and recovery processes, would provide the opportunity for early intervention. Cortisol, a stress hormone released through the hypothalamic-pituitary-adrenal (HPA) axis following injury, may provide a missing physiological link to clinical recovery. This cohort study investigated the change in saliva cortisol following SRC and the association between cortisol and symptom burden in pediatric ice hockey players. Further, the association between cortisol levels and medical clearance to return to play was explored. In total, cortisol samples from 233 players were included; 165 athletes (23.6% female) provided pre-injury saliva and 68 athletes (19.1% female) provided post-SRC saliva samples for cortisol analysis. Quantile (median) regressions were used to compare cortisol between pre-injury and post-SRC groups, and the association between total symptoms (/22) and symptom severity scores (/132) reported on the Sport Concussion Assessment Tool (SCAT)3/SCAT5 and post-SRC cortisol (adjusting for age, sex, history of concussion, and time from injury to sample collection). Results demonstrated significantly lower saliva cortisol in post-SRC athletes compared with the pre-injury group (β = -0.62, 95% confidence interval [CI; -1.08, -0.16], p = 0.009). Post-SRC cortisol was not significantly associated with the SCAT3/SCAT5 symptom totals or symptom severity scores; however, females were found to report more symptoms (β = 6.95, 95% CI [0.35, 13.55], p = 0.040) and greater symptom severity (β = 23.87, 95% CI [9.58, 38.15], p = 0.002) compared with males. Exploratory time-to-event analysis revealed a point estimate suggesting a potential association between low cortisol levels and days to medical clearance to return to play. Although preliminary, these findings suggest that the HPA axis may be dysregulated post-SRC. Further, our exploratory analysis and case presentation of post-injury outliers highlight the need to further research cortisol as a prognostic biomarker to inform individualized sex-specific care after SRC.
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Affiliation(s)
- Jason Tabor
- Sport Injury Prevention Research Centre, Faculty of Kinesiology, University of Calgary, Calgary, Alberta, Canada.,Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada.,Alberta Children's Hospital Research Institute, University of Calgary, Calgary, Alberta, Canada
| | - Parker La
- Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada.,Alberta Children's Hospital Research Institute, University of Calgary, Calgary, Alberta, Canada.,Departments of Pediatrics and Community Health Sciences, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
| | - Gregory Kline
- Division of Endocrinology, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
| | - Meng Wang
- Department of Clinical Neurosciences, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
| | - Stephan Bonfield
- Sport Injury Prevention Research Centre, Faculty of Kinesiology, University of Calgary, Calgary, Alberta, Canada
| | - Matthew Machan
- Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada
| | - Katherine Wynne-Edwards
- Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada.,Faculty of Veterinary Medicine, University of Calgary, Calgary, Alberta, Canada
| | - Carolyn Emery
- Sport Injury Prevention Research Centre, Faculty of Kinesiology, University of Calgary, Calgary, Alberta, Canada.,Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada.,Alberta Children's Hospital Research Institute, University of Calgary, Calgary, Alberta, Canada.,Departments of Pediatrics and Community Health Sciences, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
| | - Chantel Debert
- Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada.,Alberta Children's Hospital Research Institute, University of Calgary, Calgary, Alberta, Canada.,Departments of Pediatrics and Community Health Sciences, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.,Department of Clinical Neurosciences, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
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12
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Das L, Dutta P. Approach to a case with an unusual cause of hypopituitarism. J Clin Endocrinol Metab 2022; 108:1488-1504. [PMID: 36573291 DOI: 10.1210/clinem/dgac747] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/15/2022] [Indexed: 12/29/2022]
Abstract
Hypopituitarism refers to insufficiency of one or more hormones of the pituitary and can be due to myriad causes. The clinical and radiological spectrum of the condition is heterogeneous, based on the age, gender, clinical setting and/or other past medical history. Hypopituitarism includes central hypocortisolism, hypothyroidism, hypogonadism and growth hormone deficiency. Both hypo- and hyperprolactinemia can be associated with hypopituitarism, with low prolactin signifying more extensive pituitary damage. Posterior pituitary insufficiency (arginine vasopressin deficiency), occurs either in isolation or with anterior pituitary hormone deficiency. Clinical symptomatology of hypopituitarism is usually non-specific and insidious in onset and progression. Overall, the most common cause of hypopituitarism is a pituitary adenoma and/or its management (surgery, radiotherapy, pharmacotherapy or a combination of these). However, it is this subset of patients which is more likely to be identified and managed timely, possibly alleviating the premature mortality associated with hypopituitarism. What is more challenging is the recognition of hypopituitarism in less common settings, which may be either due to direct involvement of the pituitary (infection, traumatic brain injury, or infiltrative causes) or indirectly as a consequence of the primary process (thalassemia, vasculotoxic snakebite, subarachnoid hemorrhage). These entities are often under-recognised, and increased awareness can help in greater recognition of the problem burden. Further, pituitary insufficiency in most of these settings is dynamic, which may progress, or rarely, show recovery of function. This renders complexity to the problem, but makes it even more imperative to suspect, screen and appropriately manage patients with less common causes of hypopituitarism.
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Affiliation(s)
- Liza Das
- Department of Endocrinology, Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh
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13
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Tomkins M, Lawless S, Martin-Grace J, Sherlock M, Thompson CJ. Diagnosis and Management of Central Diabetes Insipidus in Adults. J Clin Endocrinol Metab 2022; 107:2701-2715. [PMID: 35771962 PMCID: PMC9516129 DOI: 10.1210/clinem/dgac381] [Citation(s) in RCA: 42] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/28/2022] [Indexed: 11/19/2022]
Abstract
Central diabetes insipidus (CDI) is a clinical syndrome which results from loss or impaired function of vasopressinergic neurons in the hypothalamus/posterior pituitary, resulting in impaired synthesis and/or secretion of arginine vasopressin (AVP). AVP deficiency leads to the inability to concentrate urine and excessive renal water losses, resulting in a clinical syndrome of hypotonic polyuria with compensatory thirst. CDI is caused by diverse etiologies, although it typically develops due to neoplastic, traumatic, or autoimmune destruction of AVP-synthesizing/secreting neurons. This review focuses on the diagnosis and management of CDI, providing insights into the physiological disturbances underpinning the syndrome. Recent developments in diagnostic techniques, particularly the development of the copeptin assay, have improved accuracy and acceptability of the diagnostic approach to the hypotonic polyuria syndrome. We discuss the management of CDI with particular emphasis on management of fluid intake and pharmacological replacement of AVP. Specific clinical syndromes such as adipsic diabetes insipidus and diabetes insipidus in pregnancy as well as management of the perioperative patient with diabetes insipidus are also discussed.
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Affiliation(s)
- Maria Tomkins
- Academic Department of Endocrinology, Beaumont Hospital and Royal College of Surgeons in Ireland, Dublin, Ireland
| | - Sarah Lawless
- Academic Department of Endocrinology, Beaumont Hospital and Royal College of Surgeons in Ireland, Dublin, Ireland
| | - Julie Martin-Grace
- Academic Department of Endocrinology, Beaumont Hospital and Royal College of Surgeons in Ireland, Dublin, Ireland
| | - Mark Sherlock
- Academic Department of Endocrinology, Beaumont Hospital and Royal College of Surgeons in Ireland, Dublin, Ireland
| | - Chris J Thompson
- Correspondence: Chris Thompson, Academic Department of Endocrinology, Beaumont Hospital and Royal College of Surgeons in Ireland, Dublin, Ireland.
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14
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Dilrukshi MDSA, Vickars M, May CJH, Makaya T, Ryan F, Jafar-Mohammadi B, Wass JAH, Pal A, Garrahy A. Management of cranial diabetes insipidus: clinical outcomes and patient perception of care. Eur J Endocrinol 2022; 187:489-495. [PMID: 35900310 DOI: 10.1530/eje-22-0187] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/14/2022] [Accepted: 07/04/2022] [Indexed: 11/08/2022]
Abstract
OBJECTIVE There is growing recognition of morbidity and mortality that can occur in patients with cranial diabetes insipidus (CDI) during hospitalisation, due to prescribing errors and dysnatraemia, often related to confusion between CDI and diabetes mellitus among non-specialists. We aimed to investigate this. METHODS Data for each hospitalisation in patients with CDI attending Oxford University Hospital (OUH) were collected retrospectively. The same cohort were invited to complete a questionnaire by telephone. RESULTS One hundred and nine patients were included, median age was 42 (range: 6-80) years. Route of desmopressin was tablet, melt and nasal spray in 74%, 7% and 17% of patients, respectively, while two patients used a combination of tablet and nasal spray. There were 85 admissions to OUH by 38 patients between 2012 and 2021. Daily measurement of serum sodium was performed in 39% of admissions; hyponatraemia and hypernatraemia occurred in 44 and 15% of admissions, respectively. Endocrine consultation was sought in 63% of admissions post-2018. Forty-five of 78 patients (58%) self-reported ≥1 admission to any hospital since diagnosis. Of these, 53% felt their medical team did not have a good understanding of the management of CDI during hospital admission. Twenty-four per cent reported delay in administration of desmopressin, while 44% reported confusion between CDI and diabetes mellitus, often leading to unnecessary blood glucose monitoring. CONCLUSION Dysnatraemia is common in hospitalised patients with CDI. More than half of patients perceived their medical team's understanding of CDI to be poor when admitted with intercurrent illness. A coordinated approach, including early consultation of specialists, frequent serum sodium monitoring, and education of hospital specialists is needed to address this.
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Affiliation(s)
- M D S A Dilrukshi
- Department of Endocrinology, Oxford Centre for Diabetes, Endocrinology and Metabolism
| | - Marcus Vickars
- Department of Endocrinology, Oxford Centre for Diabetes, Endocrinology and Metabolism
| | - Christine J H May
- Department of Endocrinology, Oxford Centre for Diabetes, Endocrinology and Metabolism
| | - Taffy Makaya
- Department of Paediatric Endocrinology, Oxford University Hospitals Trust, Oxford, UK
| | - Fiona Ryan
- Department of Paediatric Endocrinology, Oxford University Hospitals Trust, Oxford, UK
| | | | - John A H Wass
- Department of Endocrinology, Oxford Centre for Diabetes, Endocrinology and Metabolism
| | - Aparna Pal
- Department of Endocrinology, Oxford Centre for Diabetes, Endocrinology and Metabolism
| | - Aoife Garrahy
- Department of Endocrinology, Oxford Centre for Diabetes, Endocrinology and Metabolism
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15
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Aungkawattanapong N, Jakchai K, Tempark T, Bongsebandhu-Phubhakdi C. Recurrent hypoglycemic seizure as a presenting symptom of post-TBI hypopituitarism in children: a case report, review and proposed protocol. J Pediatr Endocrinol Metab 2022; 35:1078-1088. [PMID: 35860974 DOI: 10.1515/jpem-2022-0129] [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: 01/09/2022] [Accepted: 06/18/2022] [Indexed: 11/15/2022]
Abstract
OBJECTIVES Post-traumatic brain injury hypopituitarism is a common unrecognized condition in children after head injury. Due to its similarity of clinical symptoms with those of head trauma, clinical diagnosis of post-TBI hypopituitarism is challenging. To date, there is no standardized screening protocol for children with history of brain injury. This article demonstrates a case of 14-year-old boy with severe head trauma who developed refractory seizures with episodic hypoglycemia and weight loss. We aimed to focus on the prevalence, clinical courses and clinical implementations of each hormonal axis in children with post-traumatic brain injury hypopituitarism. We also aim to raise awareness of this condition to pediatricians in light of enhancing patient care. METHODS We have searched for original articles, published in English between year 2000 and 2021. There are 20 related articles, authors reviewed all the articles independently. RESULTS Prevalence of post-traumatic hypopituitarism ranges from 5-57% in children. Growth hormone is the most commonly affected hormone. The highest prevalence is 42.3% at more than 12 months after the brain injury. The symptoms and severity range from asymptomatic to requiring long-term hormonal therapy. Although normalization of pituitary function is demonstrated at various times after the injury, hormone replacement therapy is still required in some patients. CONCLUSIONS This is the first report that demonstrates a presenting symptom of hypopituitarism mimic traumatic brain symptoms which result in it being overlooked. This case emphasizes the need to develop pituitary function screening protocols for children with TBI. We have proposed our pituitary screening protocol for children with TBI in this article.
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Affiliation(s)
- Nadvadee Aungkawattanapong
- Division of Ambulatory, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Bangkok, Thailand
| | - Ketsuda Jakchai
- Department of Radiology, King Chulalongkorn Memorial Hospital, The Thai Red Cross Society, Bangkok, Thailand
| | - Therdpong Tempark
- Division of Ambulatory, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Bangkok, Thailand
| | - Chansuda Bongsebandhu-Phubhakdi
- Division of Ambulatory, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Bangkok, Thailand.,Division of Pediatric Endocrinology, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
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16
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Ono M, Fukuda I, Nagao M, Tomiyama K, Okazaki-Hada M, Shuto Y, Kobayashi S, Yamaguchi Y, Nagamine T, Nakajima Y, Inagaki-Tanimura K, Sugihara H. HLA analysis of immune checkpoint inhibitor-induced and idiopathic isolated ACTH deficiency. Pituitary 2022; 25:615-621. [PMID: 35653047 DOI: 10.1007/s11102-022-01231-1] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 05/09/2022] [Indexed: 10/18/2022]
Abstract
PURPOSE Isolated adrenocorticotropic hormone deficiency is a rare disease; however, since immune check point inhibitors (ICIs) have become widely used, many more cases have been reported. In this study, we compared the human leukocyte antigen (HLA) signatures between ICI-induced isolated adrenocorticotropic hormone deficiency (IAD) and idiopathic IAD (IIAD). DESIGN AND METHODS Clinical features and HLA frequencies were compared among 13 patients with ICI-induced IAD, 8 patients with IIAD, and healthy controls. HLA frequencies of healthy controls were adopted from a HLA database of Japanese population. RESULTS Age and body mass index were higher, while the rate of weight loss was lower, in patients with ICI-induced IAD than in those with IIAD. No HLA alleles had a significantly higher frequency in patients with ICI-induced IAD than in healthy controls, whereas the frequencies of HLA-DRB1*09:01, HLA-DQA1*03:02, and DQB1*03:03 were significantly higher in patients with IIAD than in healthy controls. CONCLUSIONS ICI-induced IAD and IIAD were different in terms of HLA frequencies. There were no specific HLAs related to ICI-induced IAD, whereas several HLAs in strong linkage disequilibrium were associated with IIAD. This might suggest that the two diseases have different pathological mechanisms. HLAs unique to IIAD may be helpful in predicting its pathophysiology.
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Affiliation(s)
- Mayo Ono
- Department of Endocrinology, Diabetes and Metabolism, Graduate School of Medicine, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, 113-8603, Tokyo, Japan
| | - Izumi Fukuda
- Department of Endocrinology, Diabetes and Metabolism, Graduate School of Medicine, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, 113-8603, Tokyo, Japan.
| | - Mototsugu Nagao
- Department of Endocrinology, Diabetes and Metabolism, Graduate School of Medicine, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, 113-8603, Tokyo, Japan
| | - Keiko Tomiyama
- Department of Endocrinology, Diabetes and Metabolism, Graduate School of Medicine, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, 113-8603, Tokyo, Japan
| | - Mikiko Okazaki-Hada
- Department of Endocrinology, Diabetes and Metabolism, Graduate School of Medicine, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, 113-8603, Tokyo, Japan
| | - Yuki Shuto
- Department of Endocrinology, Diabetes and Metabolism, Graduate School of Medicine, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, 113-8603, Tokyo, Japan
| | - Shunsuke Kobayashi
- Department of Endocrinology, Diabetes and Metabolism, Graduate School of Medicine, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, 113-8603, Tokyo, Japan
| | - Yuji Yamaguchi
- Department of Endocrinology, Diabetes and Metabolism, Graduate School of Medicine, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, 113-8603, Tokyo, Japan
| | - Tomoko Nagamine
- Department of Endocrinology, Diabetes and Metabolism, Graduate School of Medicine, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, 113-8603, Tokyo, Japan
| | - Yasushi Nakajima
- Department of Endocrinology, Diabetes and Metabolism, Graduate School of Medicine, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, 113-8603, Tokyo, Japan
| | - Kyoko Inagaki-Tanimura
- Department of Endocrinology, Diabetes and Metabolism, Graduate School of Medicine, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, 113-8603, Tokyo, Japan
| | - Hitoshi Sugihara
- Department of Endocrinology, Diabetes and Metabolism, Graduate School of Medicine, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, 113-8603, Tokyo, Japan
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17
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Zhang XC, Sun Y. Hypopituitary syndrome with pituitary crisis in a patient with traumatic shock: A case report. World J Clin Cases 2022; 10:7029-7036. [PMID: 36051123 PMCID: PMC9297421 DOI: 10.12998/wjcc.v10.i20.7029] [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: 11/14/2021] [Revised: 04/01/2022] [Accepted: 05/22/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Shock is among the most common conditions that clinicians face in intensive care unit (ICU), of which hypovolemic shock is encountered most frequently; some patients instead suffer from neurogenic, cardiogenic, or infectious forms of shock. However, there are additional types of shock from unusual causes that are often undiagnosed. Here, we report the case of a patient who was initially misdiagnosed with hypovolemic shock, but exhibited persistent hypotension because of continuous fluid replacement and vasoactive drug administration, and was eventually diagnosed with hypopituitarism with crisis.
CASE SUMMARY A 73-year-old Chinese man was admitted to the neurosurgery department following injury caused by a heavy object with symptoms of anemia and high fever. He was transferred to the ICU on the fourth day after hospitalization because of hypotension and unconsciousness. Blood analysis indicated that the patient was suffering from anemia and thrombocytopenia. Ultrasonography showed that there was no apparent abnormality in the cardiac structure but there was mild tricuspid regurgitation. Computed tomography revealed that there were signs of hemorrhage at the right basal ganglia; accordingly, hypovolemic shock, possibly septic shock, was initially considered. Even after routine treatment for shock, the hypotension remained severe. The patient was again thoroughly examined to investigate the underlying cause. The antishock therapy was supplemented with corticosteroids to counter potential hypopituitarism. The patient made a full recovery, and the blood pressure returned to normal.
CONCLUSION A case of pituitary adenoma with multiple injuries was identified. Because of hypopituitarism, functionality of the corresponding endocrine system was restricted, with the most pronounced manifestation being unstable blood circulation requiring hormone replacement therapy. Such cases are relatively rare but may occur if multiple injuries are sustained. The present case represents a reference for the clinical treatment of patients with multiple injuries.
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Affiliation(s)
- Xing-Cheng Zhang
- Department of Critical Care Medicine, The Second Affiliated Hospital, Anhui Medical University, Hefei 230601, Anhui Province, China
| | - Yun Sun
- Department of Critical Care Medicine, The Second Affiliated Hospital, Anhui Medical University, Hefei 230601, Anhui Province, China
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18
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Weil ZM, White B, Whitehead B, Karelina K. The role of the stress system in recovery after traumatic brain injury: A tribute to Bruce S. McEwen. Neurobiol Stress 2022; 19:100467. [PMID: 35720260 PMCID: PMC9201063 DOI: 10.1016/j.ynstr.2022.100467] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2021] [Revised: 05/25/2022] [Accepted: 06/02/2022] [Indexed: 11/21/2022] Open
Abstract
Traumatic brain injury (TBI) represents a major public health concern. Although the majority of individuals that suffer mild-moderate TBI recover relatively quickly, a substantial subset of individuals experiences prolonged and debilitating symptoms. An exacerbated response to physiological and psychological stressors after TBI may mediate poor functional recovery. Individuals with TBI can suffer from poor stress tolerance, impairments in the ability to evaluate stressors, and poor initiation (and cessation) of neuroendocrine stress responses, all of which can exacerbate TBI-mediated dysfunction. Here, we pay tribute to the pioneering neuroendocrinologist Dr. Bruce McEwen by discussing the ways in which his work on stress physiology and allostatic loading impacts the TBI patient population both before and after their injuries. Specifically, we will discuss the modulatory role of hypothalamic-pituitary-adrenal axis responses immediately after TBI and later in recovery. We will also consider the impact of stressors and stress responses in promoting post-concussive syndrome and post-traumatic stress disorders, two common sequelae of TBI. Finally, we will explore the role of early life stressors, prior to brain injuries, as modulators of injury outcomes.
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Affiliation(s)
- Zachary M. Weil
- Department of Neuroscience and Rockefeller Neuroscience Institute, West Virginia University, 108 Biomedical Rd, Morgantown, WV, 26506, USA
| | - Brishti White
- Department of Neuroscience and Rockefeller Neuroscience Institute, West Virginia University, 108 Biomedical Rd, Morgantown, WV, 26506, USA
| | - Bailey Whitehead
- Department of Neuroscience and Rockefeller Neuroscience Institute, West Virginia University, 108 Biomedical Rd, Morgantown, WV, 26506, USA
| | - Kate Karelina
- Department of Neuroscience and Rockefeller Neuroscience Institute, West Virginia University, 108 Biomedical Rd, Morgantown, WV, 26506, USA
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19
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Akira M, Yuichi T, Tomotaka U, Takaaki K, Kenichi M, Chimi M. The Outcome of Neurorehabilitation Efficacy and Management of Traumatic Brain Injury. Front Hum Neurosci 2022; 16:870190. [PMID: 35814948 PMCID: PMC9256961 DOI: 10.3389/fnhum.2022.870190] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2022] [Accepted: 05/31/2022] [Indexed: 11/13/2022] Open
Abstract
For public health professionals, traumatic brain injury (TBI) and its possible protracted repercussions are a significant source of worry. In opposed to patient neurorehabilitation with developed brain abnormalities of different etiologies, neurorehabilitation of affected persons has several distinct features. The clinical repercussions of the various types of TBI injuries will be discussed in detail in this paper. During severe TBI, the medical course frequently follows a familiar first sequence of coma, accompanied by disordered awareness, followed by agitation and forgetfulness, followed by return of function. Clinicians must be aware of common medical issues that might occur throughout the various stages of neurorehabilitation, for example, posttraumatic hydrocephalus, paroxysmal sympathetic hyperactivity and posttraumatic neuroendocrine disorders, at each step of the process. Furthermore, we address problems about the scheduling of various rehabilitation programs as well as the availability of current data for comprehensive rehabilitative neuropsychology techniques.
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Affiliation(s)
- Miyamoto Akira
- Faculty of Rehabilitation Sciences, Nishikyushu University, Kanzaki, Japan
| | - Takata Yuichi
- Faculty of Human Science, Hokkaido Bunkyo University, Eniwa, Japan
| | - Ueda Tomotaka
- Faculty of Rehabilitation Sciences, Nishikyushu University, Kanzaki, Japan
| | - Kubo Takaaki
- Division of Physical Therapy, Department of Rehabilitation, Faculty of Health Science, Kumamoto Health Science University, Kumamoto, Japan
| | - Mori Kenichi
- Omote Orthopedic Osteoporosis Clinic, Toyonaka, Japan
| | - Miyamoto Chimi
- Department of Occupational Therapy, Faculty of Health Science, Aino University, Ibaraki, Japan
- *Correspondence: Miyamoto Chimi,
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20
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Lawless SJ, Thompson C, Garrahy A. The management of acute and chronic hyponatraemia. Ther Adv Endocrinol Metab 2022; 13:20420188221097343. [PMID: 35586730 PMCID: PMC9109487 DOI: 10.1177/20420188221097343] [Citation(s) in RCA: 8] [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: 01/06/2022] [Accepted: 04/11/2022] [Indexed: 11/15/2022] Open
Abstract
Hyponatraemia is the most common electrolyte abnormality encountered in clinical practice; despite this, the work-up and management of hyponatraemia remain suboptimal and varies among different specialist groups. The majority of data comparing hyponatraemia treatments have been observational, up until recently. The past two years have seen the publication of several randomised control trials investigating hyponatraemia treatments, both for chronic and acute hyponatraemia. In this article, we aim to provide a background to the physiology, cause and impact of hyponatraemia and summarise the most recent data on treatments for acute and chronic hyponatraemia, highlighting their efficacy, tolerability and adverse effects.
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Affiliation(s)
- Sarah Jean Lawless
- Academic Department of Endocrinology, Beaumont
Hospital/RCSI Medical School, Dublin, Ireland
| | - Chris Thompson
- Academic Department of Endocrinology, Beaumont
Hospital/RCSI Medical School, Dublin, Ireland
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21
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Săcărescu A, Turliuc MD, Brănișteanu DD. Role of copeptin in the diagnosis of traumatic neuroendocrine dysfunction. Neuropeptides 2021; 89:102167. [PMID: 34175655 DOI: 10.1016/j.npep.2021.102167] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/13/2021] [Revised: 06/08/2021] [Accepted: 06/20/2021] [Indexed: 11/22/2022]
Abstract
Traumatic neuroendocrine dysfunction may present with diabetes insipidus (DI) or with the syndrome of inappropriate antidiuretic hormone secretion (SIADH). Both these pathologies involve a disturbance in the antidiuretic hormone (ADH) secretion, causing dysnatremias. Diagnosis of posttraumatic ADH dysfunction is hampered by technical difficulties in ADH assessment, and relies mostly on non-specific serum sodium, serum and urine osmolality and diuresis, often leading to misdiagnosis in the acute care setting. Research now focuses on the diagnostic role of copeptin, a peptide secreted together with ADH in an equimolar fashion, and which can be accurately evaluated. Recent studies identified cut-off values of 2.6 pmol/L for baseline copeptin and of 4.9 and 3.8 pmol/L for hypertonic saline infusion and arginine infusion stimulated copeptin, respectively, for the diagnosis of DI in patients with polyuria-polydipsia syndrome. Although SIADH is more difficult to be explored due to its heterogeneity, a ratio of copeptin to urinary sodium below 30 pmol/mmol identifies euvolemic hyponatremia. Exploring the role of copeptin assessment in patients with traumatic brain injury (TBI) in the acute phase may improve their diagnosis accuracy, management and outcome.
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Affiliation(s)
- Alina Săcărescu
- Department of Medical Specialties II, "Grigore T. Popa" University of Medicine and Pharmacy, 16 Universitatii, Iasi 700115, Romania; Department of Neurology, Clinical Rehabilitation Hospital, 14 Pantelimon Halipa, Iasi 700661, Romania.
| | - Mihaela-Dana Turliuc
- Department of Surgery II, "Grigore T. Popa" University of Medicine and Pharmacy, 16 Universitatii, Iasi 700115, Romania; Department of Neurosurgery II, "Prof. Dr. N. Oblu" Clinical Emergency Hospital, 2 Ateneului, Iasi 700309, Romania
| | - Dumitru D Brănișteanu
- Department of Medical Specialties II, "Grigore T. Popa" University of Medicine and Pharmacy, 16 Universitatii, Iasi 700115, Romania; Department of Endocrinology, "Sf. Spiridon" Clinical County Emergency Hospital", 1 Independentei, Iasi 700111, Romania
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22
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Edalatfar M, Piri SM, Mehrabinejad MM, Mousavi MS, Meknatkhah S, Fattahi MR, Kavyani Z, Hajighadery A, Kaveh M, Aryannejad A, Ghafouri M, Jamshidi E, Rezwanifar MM, Sadeghi-Naini M, Bari A, Sharif-Alhoseini M. Biofluid Biomarkers in Traumatic Brain Injury: A Systematic Scoping Review. Neurocrit Care 2021; 35:559-572. [PMID: 33403583 DOI: 10.1007/s12028-020-01173-1] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2020] [Accepted: 12/01/2020] [Indexed: 02/05/2023]
Abstract
Emerging evidence suggests that biofluid-based biomarkers have diagnostic and prognostic potential in traumatic brain injuries (TBI). However, owing to the lack of a conceptual framework or comprehensive review, it is difficult to visualize the breadth of materials that might be available. We conducted a systematic scoping review to map and categorize the evidence regarding biofluid-based biochemical markers of TBI. A comprehensive search was undertaken in January 2019. Of 25,354 records identified through the literature search, 1036 original human studies were included. Five hundred forty biofluid biomarkers were extracted from included studies and classified into 19 distinct categories. Three categories of biomarkers including cytokines, coagulation tests, and nerve tissue proteins were investigated more than others and assessed in almost half of the studies (560, 515, and 502 from 1036 studies, respectively). S100 beta as the most common biomarker for TBI was tested in 21.2% of studies (220 articles). Cortisol was the only biomarker measured in blood, cerebrospinal fluid, urine, and saliva. The most common sampling time was at admission and within 24 h of injury. The included studies focused mainly on biomarkers from blood and central nervous system sources, the adult population, and severe and blunt injuries. The most common outcome measures used in studies were changes in biomarker concentration level, Glasgow coma scale, Glasgow outcome scale, brain computed tomography scan, and mortality rate. Biofluid biomarkers could be clinically helpful in the diagnosis and prognosis of TBI. However, there was no single definitive biomarker with accurate characteristics. The present categorization would be a road map to investigate the biomarkers of the brain injury cascade separately and detect the most representative biomarker of each category. Also, this comprehensive categorization could provide a guiding framework to design combined panels of multiple biomarkers.
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Affiliation(s)
- Maryam Edalatfar
- Sina Trauma and Surgery Research Center, Tehran University of Medical Sciences, Sina Hospital, Hassan-Abad Square, Imam Khomeini Ave, Tehran, 11365-3876, Iran
| | - Seyed Mohammad Piri
- Sina Trauma and Surgery Research Center, Tehran University of Medical Sciences, Sina Hospital, Hassan-Abad Square, Imam Khomeini Ave, Tehran, 11365-3876, Iran
| | - Mohammad-Mehdi Mehrabinejad
- Sina Trauma and Surgery Research Center, Tehran University of Medical Sciences, Sina Hospital, Hassan-Abad Square, Imam Khomeini Ave, Tehran, 11365-3876, Iran
- Department of Radiology, Advanced Diagnostic and Interventional Radiology Research Center (ADIR), Tehran University of Medical Sciences, Tehran, Iran
| | - Monireh-Sadat Mousavi
- Laboratory of Neuro-Organic Chemistry, Institute of Biochemistry and Biophysics (IBB), University of Tehran, Tehran, Iran
| | - Sogol Meknatkhah
- Laboratory of Neuro-Organic Chemistry, Institute of Biochemistry and Biophysics (IBB), University of Tehran, Tehran, Iran
| | - Mohammad-Reza Fattahi
- Sina Trauma and Surgery Research Center, Tehran University of Medical Sciences, Sina Hospital, Hassan-Abad Square, Imam Khomeini Ave, Tehran, 11365-3876, Iran
- Department of Sports and Exercise Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Zeinab Kavyani
- Maternal-Fetal and Neonatal Research Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Abdolkarim Hajighadery
- Sina Trauma and Surgery Research Center, Tehran University of Medical Sciences, Sina Hospital, Hassan-Abad Square, Imam Khomeini Ave, Tehran, 11365-3876, Iran
| | - Meysam Kaveh
- Sina Trauma and Surgery Research Center, Tehran University of Medical Sciences, Sina Hospital, Hassan-Abad Square, Imam Khomeini Ave, Tehran, 11365-3876, Iran
| | - Armin Aryannejad
- Sina Trauma and Surgery Research Center, Tehran University of Medical Sciences, Sina Hospital, Hassan-Abad Square, Imam Khomeini Ave, Tehran, 11365-3876, Iran
| | - Mohammad Ghafouri
- Sina Trauma and Surgery Research Center, Tehran University of Medical Sciences, Sina Hospital, Hassan-Abad Square, Imam Khomeini Ave, Tehran, 11365-3876, Iran
| | - Elham Jamshidi
- Student Research Committee, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mohamad Mehdi Rezwanifar
- Sina Trauma and Surgery Research Center, Tehran University of Medical Sciences, Sina Hospital, Hassan-Abad Square, Imam Khomeini Ave, Tehran, 11365-3876, Iran
| | - Mohsen Sadeghi-Naini
- Department of Neurosurgery, Imam Hossein Hospital, Shahid Beheshti University of Medical Science, Tehran, Iran
| | - Ausaf Bari
- Department of Neurosurgery, David Geffen School of Medicine, University of California, Los Angeles, USA
| | - Mahdi Sharif-Alhoseini
- Sina Trauma and Surgery Research Center, Tehran University of Medical Sciences, Sina Hospital, Hassan-Abad Square, Imam Khomeini Ave, Tehran, 11365-3876, Iran.
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23
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Almalki MH, Ahmad MM, Brema I, Almehthel M, AlDahmani KM, Mahzari M, Beshyah SA. Management of Diabetes Insipidus following Surgery for Pituitary and Suprasellar Tumours. Sultan Qaboos Univ Med J 2021; 21:354-364. [PMID: 34522399 PMCID: PMC8407907 DOI: 10.18295/squmj.4.2021.010] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2020] [Revised: 08/14/2020] [Accepted: 08/09/2020] [Indexed: 12/03/2022] Open
Abstract
Central diabetes insipidus (CDI) is a common complication after pituitary surgery. However, it is most frequently transient. It is defined by the excretion of an abnormally large volume of dilute urine with increasing serum osmolality. The reported incidence of CDI after pituitary surgery ranges from 0–90%. Large tumour size, gross total resection and intraoperative cerebrospinal fluid leak usually pose an increased risk of CDI as observed with craniopharyngioma and Rathke’s cleft cysts. CDI can be associated with high morbidity and mortality if not promptly recognised and treated on time. It is also essential to rule out other causes of postoperative polyuria to avoid unnecessary pharmacotherapy and iatrogenic hyponatremia. Once the diagnosis of CDI is established, close monitoring is required to evaluate the response to treatment and to determine whether the CDI is transient or permanent. This review outlines the evaluation and management of patients with CDI following pituitary and suprasellar tumour surgery to help recognise the diagnosis, consider the differential diagnosis, initiate therapeutic interventions and guide monitoring and long-term management.
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Affiliation(s)
- Mussa H Almalki
- Obesity, Endocrine and Metabolism Centre, King Fahad Medical City, Riyadh, Saudi Arabia.,Faculty of Medicine, King Saud Bin Abdul Aziz University of Health Sciences, Riyadh, Saudi Arabia
| | - Maswood M Ahmad
- Obesity, Endocrine and Metabolism Centre, King Fahad Medical City, Riyadh, Saudi Arabia
| | - Imad Brema
- Obesity, Endocrine and Metabolism Centre, King Fahad Medical City, Riyadh, Saudi Arabia
| | - Mohammed Almehthel
- Obesity, Endocrine and Metabolism Centre, King Fahad Medical City, Riyadh, Saudi Arabia.,Division of Endocrinology, University of British Columbia, Vancouver, Canada
| | - Khaled M AlDahmani
- Division of Endocrinology, Tawam Hospital, Al Ain, United Arab Emirates.,Department of Medicine, United Arab Emirates University, Al Ain, United Arab Emirates
| | - Moeber Mahzari
- Faculty of Medicine, King Saud Bin Abdul Aziz University of Health Sciences, Riyadh, Saudi Arabia.,Department of Medicine, Ministry of National Guard Health Affair, Riyadh, Saudi Arabia
| | - Salem A Beshyah
- Department of Medicine, Dubai Medical College, Dubai, United Arab Emirates.,Department of Endocrinology, Mediclinic Airport Road, Abu Dhabi, United Arab Emirates
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24
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Christ-Crain M, Hoorn EJ, Sherlock M, Thompson CJ, Wass J. ENDOCRINOLOGY IN THE TIME OF COVID-19-2021 UPDATES: The management of diabetes insipidus and hyponatraemia. Eur J Endocrinol 2021; 185:G35-G42. [PMID: 34292875 PMCID: PMC8428073 DOI: 10.1530/eje-21-0596] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/08/2021] [Accepted: 07/22/2021] [Indexed: 11/08/2022]
Abstract
COVID-19 has changed the nature of medical consultations, emphasizing virtual patient counselling, with relevance for patients with diabetes insipidus (DI) or hyponatraemia. The main complication of desmopressin treatment in DI is dilutional hyponatraemia. Since plasma sodium monitoring is not always possible in times of COVID-19, we recommend to delay the desmopressin dose once a week until aquaresis occurs allowing excess retained water to be excreted. Patients should measure their body weight daily. Patients with DI admitted to the hospital with COVID-19 have a high risk for mortality due to volume depletion. Specialists must supervise fluid replacement and dosing of desmopressin. Patients after pituitary surgery should drink to thirst and measure their body weight daily to early recognize the development of postoperative SIAD. They should know hyponatraemia symptoms. Hyponatraemia in COVID-19 is common with a prevalence of 20-30% and is mostly due to SIAD or hypovolaemia. It mirrors disease severity and is an early predictor of mortality. Hypernatraemia may also develop in COVID-19 patients, with a prevalence of 3-5%, especially in ICU, and derives from different multifactorial reasons, for example, due to insensible water losses from pyrexia, increased respiration rate and use of diuretics. Hypernatraemic dehydration may contribute to the high risk of acute kidney injury in COVID-19. IV fluid replacement should be administered with caution in severe cases of COVID-19 because of the risk of pulmonary oedema.
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Affiliation(s)
- Mirjam Christ-Crain
- Division of Endocrinology, Diabetes and Metabolism, Department of Clinical
Research, University Hospital Basel, University of Basel, Basel, Switzerland
- Correspondence should be addressed to M Christ-Crain;
| | - Ewout J Hoorn
- Division of Nephrology and Transplantation, Department of Internal Medicine,
Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands
| | - Mark Sherlock
- Academic Department of Endocrinology, Beaumont Hospital/RCSI Medical
School, Dublin, Ireland
| | - Chris J Thompson
- Academic Department of Endocrinology, Beaumont Hospital/RCSI Medical
School, Dublin, Ireland
| | - John Wass
- Department of Endocrinology, Oxford Centre for Diabetes, Endocrinology and
Metabolism, Churchill Hospital, Oxford, UK
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25
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Christ-Crain M, Winzeler B, Refardt J. Diagnosis and management of diabetes insipidus for the internist: an update. J Intern Med 2021; 290:73-87. [PMID: 33713498 DOI: 10.1111/joim.13261] [Citation(s) in RCA: 45] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/07/2020] [Revised: 12/18/2020] [Accepted: 01/08/2021] [Indexed: 12/26/2022]
Abstract
Diabetes insipidus is a disorder characterized by excretion of large amounts of hypotonic urine. Four entities have to be differentiated: central diabetes insipidus resulting from a deficiency of the hormone arginine vasopressin (AVP) in the pituitary gland or the hypothalamus, nephrogenic diabetes insipidus resulting from resistance to AVP in the kidneys, gestational diabetes insipidus resulting from an increase in placental vasopressinase and finally primary polydipsia, which involves excessive intake of large amounts of water despite normal AVP secretion and action. Distinguishing between the different types of diabetes insipidus can be challenging. A detailed medical history, physical examination and imaging studies are needed to detect the aetiology of diabetes insipidus. Differentiation between the various forms of hypotonic polyuria is then done by the classical water deprivation test or the more recently developed hypertonic saline or arginine stimulation together with copeptin (or AVP) measurement. In patients with idiopathic central DI, a close follow-up is needed since central DI can be the first sign of an underlying pathology. Treatment of diabetes insipidus or primary polydipsia depends on the underlying aetiology and differs in central diabetes insipidus, nephrogenic diabetes insipidus and primary polydipsia. This review will discuss issues and newest developments in diagnosis, differential diagnosis and treatment, with a focus on central diabetes insipidus.
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Affiliation(s)
- M Christ-Crain
- From the, Clinic for Endocrinology, Diabetes and Metabolism, University Hospital Basel, University of Basel, Basel, Switzerland
| | - B Winzeler
- From the, Clinic for Endocrinology, Diabetes and Metabolism, University Hospital Basel, University of Basel, Basel, Switzerland
| | - J Refardt
- From the, Clinic for Endocrinology, Diabetes and Metabolism, University Hospital Basel, University of Basel, Basel, Switzerland
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26
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Ha J, Baek H, Jeong C, Yeo M, Lee SH, Cho JH, Baek KH, Kang MI, Lim DJ. Heart Rate Variability in Postoperative Patients with Nonfunctioning Pituitary Adenoma. Endocrinol Metab (Seoul) 2021; 36:678-687. [PMID: 34107675 PMCID: PMC8258319 DOI: 10.3803/enm.2021.978] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/28/2021] [Accepted: 03/29/2021] [Indexed: 12/03/2022] Open
Abstract
BACKGROUND Decreased heart rate variability (HRV) has been reported to be associated with cardiac autonomic dysfunction. Hypopituitarism in nonfunctioning pituitary adenoma (NFPA) is often linked to increased cardiovascular mortality. We therefore hypothesized that postoperative NFPA patients with hormone deficiency have an elevated risk of HRV alterations indicating cardiac autonomic dysfunction. METHODS A total of 22 patients with NFPA were enrolled in the study. Between 3 and 6 months after surgery, a combined pituitary function test (CPFT) was performed, and HRV was measured. The period of sleep before the CPFT was deemed the most stable period, and the hypoglycemic period that occurred during the CPFT was defined as the most unstable period. Changes in HRV parameters in stable and unstable periods were observed and compared depending on the status of hormone deficiencies. RESULTS In patients with adrenocorticotropic hormone (ACTH) deficiency with other pituitary hormone deficiencies, the low frequency to high frequency ratio, which represents overall autonomic function and is increased in the disease state, was higher (P=0.005). Additionally, the standard deviation of the normal-to-normal interval, which decreases in the autonomic dysfunction state, was lower (P=0.030) during the hypoglycemic period. In panhypopituitarism, the low frequency to high frequency ratio during the hypoglycemic period was increased (P=0.007). CONCLUSION HRV analysis during CPFT enables estimation of cardiac autonomic dysfunction in patients with NFPA who develop ACTH deficiency with other pituitary hormone deficiencies or panhypopituitarism after surgery. These patients may require a preemptive assessment of cardiovascular risk.
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Affiliation(s)
- Jeonghoon Ha
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul,
Korea
| | - Hansang Baek
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul,
Korea
| | - Chaiho Jeong
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul,
Korea
| | - Minsoo Yeo
- Digital Healthcare Research Center, Taewoong Medical Co. Ltd., Gimpo,
Korea
| | - Seung-Hwan Lee
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul,
Korea
| | - Jae Hyoung Cho
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul,
Korea
| | - Ki-Hyun Baek
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Yeouido St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul,
Korea
| | - Moo Il Kang
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul,
Korea
| | - Dong-Jun Lim
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul,
Korea
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27
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Sabet N, Soltani Z, Khaksari M. Multipotential and systemic effects of traumatic brain injury. J Neuroimmunol 2021; 357:577619. [PMID: 34058510 DOI: 10.1016/j.jneuroim.2021.577619] [Citation(s) in RCA: 36] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2021] [Revised: 05/07/2021] [Accepted: 05/24/2021] [Indexed: 02/06/2023]
Abstract
Traumatic brain injury (TBI) is one of the leading causes of disability and mortality of people at all ages. Biochemical, cellular and physiological events that occur during primary injury lead to a delayed and long-term secondary damage that can last from hours to years. Secondary brain injury causes tissue damage in the central nervous system and a subsequent strong and rapid inflammatory response that may lead to persistent inflammation. However, this inflammatory response is not limited to the brain. Inflammatory mediators are transferred from damaged brain tissue to the bloodstream and produce a systemic inflammatory response in peripheral organs, including the cardiovascular, pulmonary, gastrointestinal, renal and endocrine systems. Complications of TBI are associated with its multiple and systemic effects that should be considered in the treatment of TBI patients. Therefore, in this review, an attempt was made to examine the systemic effects of TBI in detail. It is hoped that this review will identify the mechanisms of injury and complications of TBI, and open a window for promising treatment in TBI complications.
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Affiliation(s)
- Nazanin Sabet
- Endocrinology and Metabolism Research Center, Institute of Basic and Clinical Physiology Sciences, Faculty of Medicine, Kerman University of Medical Sciences, Kerman, Iran; Department of Physiology and Pharmacology, Afzalipour Faculty of Medicine, Kerman University of Medical Sciences, Kerman, Iran
| | - Zahra Soltani
- Endocrinology and Metabolism Research Center, Institute of Basic and Clinical Physiology Sciences, Faculty of Medicine, Kerman University of Medical Sciences, Kerman, Iran; Department of Physiology and Pharmacology, Afzalipour Faculty of Medicine, Kerman University of Medical Sciences, Kerman, Iran.
| | - Mohammad Khaksari
- Physiology Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran
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28
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Neuroinflammation and Hypothalamo-Pituitary Dysfunction: Focus of Traumatic Brain Injury. Int J Mol Sci 2021; 22:ijms22052686. [PMID: 33799967 PMCID: PMC7961958 DOI: 10.3390/ijms22052686] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2021] [Revised: 02/28/2021] [Accepted: 03/04/2021] [Indexed: 12/17/2022] Open
Abstract
The incidence of traumatic brain injury (TBI) has increased over the last years with an important impact on public health. Many preclinical and clinical studies identified multiple and heterogeneous TBI-related pathophysiological mechanisms that are responsible for functional, cognitive, and behavioral alterations. Recent evidence has suggested that post-TBI neuroinflammation is responsible for several long-term clinical consequences, including hypopituitarism. This review aims to summarize current evidence on TBI-induced neuroinflammation and its potential role in determining hypothalamic-pituitary dysfunctions.
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29
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Jacob JJ. Traumatic brain injuries- How can Endocrinologists help? Indian J Endocrinol Metab 2021; 25:73-75. [PMID: 34660233 PMCID: PMC8477735 DOI: 10.4103/2230-8210.325715] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
Affiliation(s)
- Jubbin J. Jacob
- Department of Endocrinology, Christian Medical College and Hospital, Ludhiana, Punjab, India
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30
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Loggini A, Tangonan R, El Ammar F, Mansour A, Kramer CL, Lazaridis C, Goldenberg FD. Neuroendocrine Dysfunction in the Acute Setting of Penetrating Brain Injury: A Systematic Review. World Neurosurg 2021; 147:172-180.e1. [PMID: 33346052 DOI: 10.1016/j.wneu.2020.12.058] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2020] [Revised: 12/09/2020] [Accepted: 12/10/2020] [Indexed: 11/20/2022]
Abstract
BACKGROUND Data on neuroendocrine dysfunction (NED) in the acute setting of penetrating brain injury (PBI) are scarce, and the clinical approach to diagnosis and treatment remains extrapolated from the literature on blunt head trauma. METHODS Three databases were searched (PubMed, Scopus, and Cochrane). Risk of bias was computed using the Newcastle-Ottawa Scale, or the methodological quality of case series and case reports, as indicated. This systematic review was registered in PROSPERO (42020172163). RESULTS Six relevant studies involving 58 patients with PBI were included. Two studies were prospective cohort analyses, whereas 4 were case reports. The onset of NED was acute in all studies, by the first postinjury day. Risk factors for NED included worse injury severity and the presence of cerebral edema on imaging. Dysfunction of the anterior hypophysis involved the hypothalamic-pituitary-thyroid axis, treated with hormonal replacement, and hypocortisolism, treated with hydrocortisone. The prevalence of central diabetes insipidus was up to 41%. Most patients showed persistent NED months after injury. In separate reports, diabetes insipidus and hypocortisolism showed an association with higher mortality. The available literature for this review is poor, and the studies included had overall low quality with high risk of bias. CONCLUSIONS NED seems to be prevalent in the acute phase of PBI, equally involving both anterior and posterior hypophysis. Despite a potential association between NED and mortality, data on the optimal management of NED are limited. This situation defines the need for prospective studies to better characterize the clinical features and optimal therapeutic interventions for NED in PBI.
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Affiliation(s)
- Andrea Loggini
- Neuroscience Intensive Care Unit, Department of Neurology, University of Chicago Medical Center, Chicago, Illinois, USA.
| | - Ruth Tangonan
- Neuroscience Intensive Care Unit, Department of Neurology, University of Chicago Medical Center, Chicago, Illinois, USA
| | - Faten El Ammar
- Neuroscience Intensive Care Unit, Department of Neurology, University of Chicago Medical Center, Chicago, Illinois, USA
| | - Ali Mansour
- Neuroscience Intensive Care Unit, Department of Neurology, University of Chicago Medical Center, Chicago, Illinois, USA
| | - Christopher L Kramer
- Neuroscience Intensive Care Unit, Department of Neurology, University of Chicago Medical Center, Chicago, Illinois, USA
| | - Christos Lazaridis
- Neuroscience Intensive Care Unit, Department of Neurology, University of Chicago Medical Center, Chicago, Illinois, USA
| | - Fernando D Goldenberg
- Neuroscience Intensive Care Unit, Department of Neurology, University of Chicago Medical Center, Chicago, Illinois, USA
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31
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Prodam F, Caputo M, Mele C, Marzullo P, Aimaretti G. Insights into non-classic and emerging causes of hypopituitarism. Nat Rev Endocrinol 2021; 17:114-129. [PMID: 33247226 DOI: 10.1038/s41574-020-00437-2] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 10/19/2020] [Indexed: 12/11/2022]
Abstract
Hypopituitarism is defined as one or more partial or complete pituitary hormone deficiencies, which are related to the anterior and/or posterior gland and can have an onset in childhood or adulthood. The most common aetiology is a sellar or suprasellar lesion, often an adenoma, which causes hypopituitarism due to tumour mass effects, or the effects of surgery and/or radiation therapy. However, other clinical conditions, such as traumatic brain injury, and autoimmune and inflammatory diseases, can result in hypopituitarism, and there are also genetic causes of hypopituitarism. Furthermore, the use of immune checkpoint inhibitors to treat cancer is increasing the risk of hypopituitarism, with a pattern of hormone defects that is different from the classic patterns and depends on mechanisms that are specific for each drug. Moreover, autoantibody production against the pituitary and hypothalamus has been demonstrated in studies investigating the development or worsening of some cases of hypopituitarism. Finally, evidence suggests that posterior pituitary damage can affect oxytocin secretion. The aim of this Review is to summarize current knowledge on non-classic and emerging causes of hypopituitarism, so as to help clinicians improve early identification, avoid life-threatening events and improve the clinical care and quality of life of patients at risk of hypopituitarism.
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Affiliation(s)
- Flavia Prodam
- Endocrinology, Department of Translational Medicine, Università del Piemonte Orientale, Novara, Italy
- Department of Health Sciences, Università del Piemonte Orientale, Novara, Italy
| | - Marina Caputo
- Endocrinology, Department of Translational Medicine, Università del Piemonte Orientale, Novara, Italy
- Department of Health Sciences, Università del Piemonte Orientale, Novara, Italy
| | - Chiara Mele
- Endocrinology, Department of Translational Medicine, Università del Piemonte Orientale, Novara, Italy
| | - Paolo Marzullo
- Endocrinology, Department of Translational Medicine, Università del Piemonte Orientale, Novara, Italy
- Division of General Medicine, I.R.C.C.S. Istituto Auxologico Italiano, Ospedale San Giuseppe, Verbania, Italy
| | - Gianluca Aimaretti
- Endocrinology, Department of Translational Medicine, Università del Piemonte Orientale, Novara, Italy.
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32
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Chua M, Tay DYK, Ng YS, Rajasoorya C. Adipsic diabetes insipidus and SGLT2 inhibitor: A perplexing conundrum. ANNALS OF THE ACADEMY OF MEDICINE, SINGAPORE 2021; 50:181-183. [PMID: 33733264 DOI: 10.47102/annals-acadmedsg.2020418] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/12/2023]
Affiliation(s)
- Marvin Chua
- Department of General Medicine, Sengkang General Hospital, Singapore
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33
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Gasco V, Cambria V, Bioletto F, Ghigo E, Grottoli S. Traumatic Brain Injury as Frequent Cause of Hypopituitarism and Growth Hormone Deficiency: Epidemiology, Diagnosis, and Treatment. Front Endocrinol (Lausanne) 2021; 12:634415. [PMID: 33790864 PMCID: PMC8005917 DOI: 10.3389/fendo.2021.634415] [Citation(s) in RCA: 26] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/27/2020] [Accepted: 02/16/2021] [Indexed: 12/12/2022] Open
Abstract
Traumatic brain injury (TBI)-related hypopituitarism has been recognized as a clinical entity for more than a century, with the first case being reported in 1918. However, during the 20th century hypopituitarism was considered only a rare sequela of TBI. Since 2000 several studies strongly suggest that TBI-mediated pituitary hormones deficiency may be more frequent than previously thought. Growth hormone deficiency (GHD) is the most common abnormality, followed by hypogonadism, hypothyroidism, hypocortisolism, and diabetes insipidus. The pathophysiological mechanisms underlying pituitary damage in TBI patients include a primary injury that may lead to the direct trauma of the hypothalamus or pituitary gland; on the other hand, secondary injuries are mainly related to an interplay of a complex and ongoing cascade of specific molecular/biochemical events. The available data describe the importance of GHD after TBI and its influence in promoting neurocognitive and behavioral deficits. The poor outcomes that are seen with long standing GHD in post TBI patients could be improved by GH treatment, but to date literature data on the possible beneficial effects of GH replacement therapy in post-TBI GHD patients are currently scarce and fragmented. More studies are needed to further characterize this clinical syndrome with the purpose of establishing appropriate standards of care. The purpose of this review is to summarize the current state of knowledge about post-traumatic GH deficiency.
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Rachfalska N, Putowski Z, Krzych ŁJ. Distant Organ Damage in Acute Brain Injury. Brain Sci 2020; 10:E1019. [PMID: 33371363 PMCID: PMC7767338 DOI: 10.3390/brainsci10121019] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2020] [Revised: 12/15/2020] [Accepted: 12/18/2020] [Indexed: 02/07/2023] Open
Abstract
Acute brain injuries pose a great threat to global health, having significant impact on mortality and disability. Patients with acute brain injury may develop distant organ failure, even if no systemic diseases or infection is present. The severity of non-neurologic organs' dysfunction depends on the extremity of the insult to the brain. In this comprehensive review we sought to describe the organ-related consequences of acute brain injuries. The clinician should always be aware of the interplay between central nervous system and non-neurological organs, that is constantly present. Cerebral injury is not only a brain disease, but also affects the body as whole, and thus requires holistic therapeutical approach.
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Affiliation(s)
| | | | - Łukasz J. Krzych
- Department of Anaesthesiology and Intensive Care, Faculty of Medical Sciences in Katowice, Medical University of Silesia, 40-055 Katowice, Poland; (N.R.); (Z.P.)
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Garrahy A, Galloway I, Hannon AM, Dineen R, O'Kelly P, Tormey WP, O'Reilly MW, Williams DJ, Sherlock M, Thompson CJ. Fluid Restriction Therapy for Chronic SIAD; Results of a Prospective Randomized Controlled Trial. J Clin Endocrinol Metab 2020; 105:5900862. [PMID: 32879954 DOI: 10.1210/clinem/dgaa619] [Citation(s) in RCA: 29] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/18/2020] [Accepted: 08/31/2020] [Indexed: 01/23/2023]
Abstract
CONTEXT Fluid restriction (FR) is the recommended first-line treatment for syndrome of inappropriate antidiuresis (SIAD), despite the lack of prospective data to support its efficacy. DESIGN A prospective nonblinded randomized controlled trial of FR versus no treatment in chronic SIAD. INTERVENTIONS AND OUTCOME A total of 46 patients with chronic asymptomatic SIAD were randomized to either FR (1 liter/day) or no specific hyponatremia treatment (NoTx) for 1 month. The primary endpoints were change in plasma sodium concentration (pNa) at days 4 and 30. RESULTS Median baseline pNa was similar in the 2 groups [127 mmol/L (interquartile range [IQR] 126-129) FR and 128 mmol/L (IQR 126-129) NoTx, P = 0.36]. PNa rose by 3 mmol/L (IQR 2-4) after 3 days FR, compared with 1 mmol/L (IQR 0-3) NoTx, P = 0.005. There was minimal additional rise in pNa by day 30; median pNa increased from baseline by 4 mmol/L (IQR 2-6) in FR, compared with 1 mmol/L (IQR 0-1) NoTx, P = 0.04. After 3 days, 17% of FR had a rise in pNa of ≥5 mmol/L, compared with 4% NoTx, RR 4.0 (95% CI 0.66-25.69), P = 0.35. After 3 days, 61% of FR corrected pNa to ≥130 mmol/L, compared with 39% of NoTx, RR 1.56 (95% CI 0.87-2.94), P = 0.24. CONCLUSION FR induces a modest early rise in pNa in patients with chronic SIAD, with minimal additional rise thereafter, and it is well-tolerated. More than one-third of patients fail to reach a pNa ≥130 mmol/L after 3 days of FR, emphasizing the clinical need for additional therapies for SIAD in some patients.
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Affiliation(s)
- Aoife Garrahy
- Academic Department of Endocrinology, RCSI Medical School and Beaumont Hospital, Dublin, Ireland
| | - Iona Galloway
- Academic Department of Endocrinology, RCSI Medical School and Beaumont Hospital, Dublin, Ireland
| | - Anne Marie Hannon
- Academic Department of Endocrinology, RCSI Medical School and Beaumont Hospital, Dublin, Ireland
| | - Rosemary Dineen
- Academic Department of Endocrinology, RCSI Medical School and Beaumont Hospital, Dublin, Ireland
| | - Patrick O'Kelly
- Department of Medical Statistics, Beaumont Hospital, Dublin, Ireland
| | - William P Tormey
- Department of Chemical Pathology, Beaumont Hospital, Dublin, Ireland
| | - Michael W O'Reilly
- Academic Department of Endocrinology, RCSI Medical School and Beaumont Hospital, Dublin, Ireland
| | - David J Williams
- Department of Geriatric and Stroke Medicine, RCSI Medical School and Beaumont Hospital, Dublin, Ireland
| | - Mark Sherlock
- Academic Department of Endocrinology, RCSI Medical School and Beaumont Hospital, Dublin, Ireland
| | - Chris J Thompson
- Academic Department of Endocrinology, RCSI Medical School and Beaumont Hospital, Dublin, Ireland
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West AN, Diaz-Thomas AM, Shafi NI. Evidence Limitations in Determining Sexually Dimorphic Outcomes in Pediatric Post-Traumatic Hypopituitarism and the Path Forward. Front Neurol 2020; 11:551923. [PMID: 33324312 PMCID: PMC7726201 DOI: 10.3389/fneur.2020.551923] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2020] [Accepted: 09/16/2020] [Indexed: 11/21/2022] Open
Abstract
Neuroendocrine dysfunction can occur as a consequence of traumatic brain injury (TBI), and disruptions to the hypothalamic-pituitary axis can be especially consequential to children. The purpose of our review is to summarize current literature relevant to studying sex differences in pediatric post-traumatic hypopituitarism (PTHP). Our understanding of incidence, time course, and impact is constrained by studies which are primarily small, are disadvantaged by significant methodological challenges, and have investigated limited temporal windows. Because hormonal changes underpin the basis of growth and development, the timing of injury and PTHP testing with respect to pubertal stage gains particular importance. Reciprocal relationships among neuroendocrine function, TBI, adverse childhood events, and physiological, psychological and cognitive sequelae are underconsidered influencers of sexually dimorphic outcomes. In light of the tremendous heterogeneity in this body of literature, we conclude with the common path upon which we must collectively arrive in order to make progress in understanding PTHP.
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Affiliation(s)
- Alina Nico West
- Division of Critical Care Medicine, Department of Pediatrics, University of Tennessee Health Science Center, Memphis, TN, United States
| | - Alicia M Diaz-Thomas
- Division of Endocrinology, Department of Pediatrics, University of Tennessee Health Science Center, Memphis, TN, United States
| | - Nadeem I Shafi
- Division of Critical Care Medicine, Department of Pediatrics, University of Tennessee Health Science Center, Memphis, TN, United States
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Zhang B, Bai M, Xu X, Yang M, Niu F, Gao F, Liu B. Corticosteroid receptor rebalancing alleviates critical illness-related corticosteroid insufficiency after traumatic brain injury by promoting paraventricular nuclear cell survival via Akt/CREB/BDNF signaling. J Neuroinflammation 2020; 17:318. [PMID: 33100225 PMCID: PMC7586672 DOI: 10.1186/s12974-020-02000-2] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2020] [Accepted: 10/16/2020] [Indexed: 12/30/2022] Open
Abstract
BACKGROUND We previously found that high-dose methylprednisolone increased the incidence of critical illness-related corticosteroid insufficiency (CIRCI) and mortality in rats with traumatic brain injury (TBI), whereas low-dose hydrocortisone but not methylprednisolone exerted protective effects. However, the receptor-mediated mechanism remains unclear. This study investigated the receptor-mediated mechanism of the opposite effects of different glucocorticoids on the survival of paraventricular nucleus (PVN) cells and the incidence of CIRCI after TBI. METHODS Based on controlled cortical impact (CCI) and treatments, male SD rats (n = 300) were randomly divided into the sham, CCI, CCI + GCs (methylprednisolone 1 or 30 mg/kg/day; corticosterone 1 mg/kg/day), CCI + methylprednisolone+RU486 (RU486 50 mg/kg/day), and CCI + corticosterone+spironolactone (spironolactone 50 mg/kg/day) groups. Blood samples were collected 7 days before and after CCI. Brain tissues were collected on postinjury day 7 and processed for histology and western blot analysis. RESULTS We examined the incidence of CIRCI, mortality, apoptosis in the PVN, the receptor-mediated mechanism, and downstream signaling pathways on postinjury day 7. We found that methylprednisolone and corticosterone exerted opposite effects on the survival of PVN cells and the incidence of CIRCI by activating different receptors. High-dose methylprednisolone increased the nuclear glucocorticoid receptor (GR) level and subsequently increased cell loss in the PVN and the incidence of CIRCI. In contrast, low-dose corticosterone but not methylprednisolone played a protective role by upregulating mineralocorticoid receptor (MR) activation. The possible downstream receptor signaling mechanism involved the differential effects of GR and MR on the activity of the Akt/CREB/BDNF pathway. CONCLUSION The excessive activation of GR by high-dose methylprednisolone exacerbated apoptosis in the PVN and increased CIRCI. In contrast, refilling of MR by corticosterone protects PVN neurons and reduces the incidence of CIRCI by promoting GR/MR rebalancing after TBI.
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Affiliation(s)
- Bin Zhang
- Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
| | - Miao Bai
- Department of Neurology, Tangdu Hospital, Fourth Military Medical University, Xi'an, China
| | - Xiaojian Xu
- Beijing Neurosurgical Institute, Capital Medical University, Beijing, China
| | - Mengshi Yang
- Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
| | - Fei Niu
- Beijing Neurosurgical Institute, Capital Medical University, Beijing, China
| | - Fei Gao
- Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
| | - Baiyun Liu
- Beijing Key Laboratory of Central Nervous System Injury and Department of Neurosurgery, Beijing Neurosurgical Institute and Beijing Tiantan Hospital, Capital Medical University, No.119 South Fourth Ring West Road, Fengtai District, Beijing, 100070, People's Republic of China.
- Nerve Injury and Repair Center of Beijing Institute for Brain Disorders, Beijing, China.
- China National Clinical Research Center for Neurological Diseases, Beijing, China.
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Variability in Serum Sodium Concentration and Prognostic Significance in Severe Traumatic Brain Injury: A Multicenter Observational Study. Neurocrit Care 2020; 34:899-907. [PMID: 33009658 DOI: 10.1007/s12028-020-01118-8] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2020] [Accepted: 09/15/2020] [Indexed: 10/23/2022]
Abstract
BACKGROUND/OBJECTIVE Dysnatremia is common in severe traumatic brain injury (TBI) patients and may contribute to mortality. However, serum sodium variability has not been studied in TBI patients. We hypothesized that such variability would be independently associated with mortality. METHODS We collected 6-hourly serum sodium levels for the first 7 days of ICU admission from 240 severe TBI patients in 14 neurotrauma ICUs in Europe and Australia. We evaluated the association between daily serum sodium standard deviation (dNaSD), an index of variability, and 28-day mortality. RESULTS Patients were 46 ± 19 years of age with a median initial GCS of 6 [4-8]. Overall hospital mortality was 28%. Hypernatremia and hyponatremia occurred in 64% and 24% of patients, respectively. Over the first 7 days in ICU, serum sodium standard deviation was 2.8 [2.0-3.9] mmol/L. Maximum daily serum sodium standard deviation (dNaSD) occurred at a median of 2 [1-4] days after admission. There was a significant progressive decrease in dNaSD over the first 7 days (coefficient - 0.15 95% CI [- 0.18 to - 0.12], p < 0.001). After adjusting for baseline TBI severity, diabetes insipidus, the use of osmotherapy, the occurrence of hypernatremia, and hyponatremia and center, dNaSD was significantly independently associated with 28-day mortality (HR 1.27 95% CI (1.01-1.61), p = 0.048). CONCLUSIONS Our study demonstrates that daily serum sodium variability is an independent predictor of 28-day mortality in severe TBI patients. Further prospective investigations are necessary to confirm the significance of sodium variability in larger cohorts of TBI patients and test whether attenuating such variability confers outcome benefits to such patients.
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Abstract
The treatment of central diabetes insipidus has not changed significantly in recent decades, and dDAVP and replacement of free water deficit remain the cornerstones of treatment. Oral dDAVP has replaced nasal dDAVP as a more reliable mode of treatment for chronic central diabetes insipidus. Hyponatraemia is a common side effect, occurring in one in four patients, and should be avoided by allowing a regular break from dDAVP to allow a resultant aquaresis. Hypernatraemia is less common, and typically occurs during hospitalization, when access to water is restricted, and in cases of adipsic DI. Management of adipsic DI can be challenging, and requires initial inpatient assessment to establish dose of dDAVP, daily fluid prescription, and eunatraemic weight which can guide day-to-day fluid targets in the long-term.
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Affiliation(s)
- Aoife Garrahy
- Academic Department of Endocrinology, Beaumont Hospital/RCSI Medical School, Dublin, Ireland.
| | - Christopher J Thompson
- Academic Department of Endocrinology, Beaumont Hospital/RCSI Medical School, Dublin, Ireland.
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Ntali G, Tsagarakis S. Pituitary dysfunction after traumatic brain injury: prevalence and screening strategies. Expert Rev Endocrinol Metab 2020; 15:341-354. [PMID: 32967470 DOI: 10.1080/17446651.2020.1810561] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/14/2020] [Accepted: 08/12/2020] [Indexed: 12/11/2022]
Abstract
INTRODUCTION Pituitary gland is vulnerable to traumatic brain injury (TBI). As a result a series of neuroendocrine changes appear after head injury; in many occasions they reverse with time, while occasionally new late onset changes may develop. AREAS COVERED In this review, we focus on the prevalence of anterior and posterior pituitary hormonal changes in the acute and chronic post-TBI period in both children and adults. Moreover, we present evidence supporting the need for evaluating pituitary function along with the current suggestions for the most appropriate screening strategies. We attempted to identify all published literature and we conducted an online search of PubMed, from January 1970 to June 2020. EXPERT OPINION Adrenal insufficiency and water metabolism disorders are medical emergencies and should be promptly recognized. Awareness for long-term hormonal derangements is necessary, as they may lead to a series of chronic health issues and compromise quality of life. There is a need for well-designed prospective long-term studies that will estimate pituitary function during the acute and chronic phase after head injury.
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Affiliation(s)
- Georgia Ntali
- Department of Endocrinology, Diabetes and Metabolism, Evangelismos Hospital , Athens, Greece
| | - Stylianos Tsagarakis
- Department of Endocrinology, Diabetes and Metabolism, Evangelismos Hospital , Athens, Greece
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Christ-Crain M, Hoorn EJ, Sherlock M, Thompson CJ, Wass JAH. ENDOCRINOLOGY IN THE TIME OF COVID-19: Management of diabetes insipidus and hyponatraemia. Eur J Endocrinol 2020; 183:G9-G15. [PMID: 32380474 PMCID: PMC7938013 DOI: 10.1530/eje-20-0338] [Citation(s) in RCA: 36] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/09/2020] [Accepted: 04/24/2020] [Indexed: 01/08/2023]
Abstract
COVID-19 has changed the nature of medical consultations, emphasizing virtual patient counseling, with relevance for patients with diabetes insipidus (DI) or hyponatraemia. The main complication of desmopressin treatment in DI is dilutional hyponatraemia. Since plasma sodium monitoring is not always possible in times of COVID-19, we recommend to delay the desmopressin dose once a week until aquaresis occurs allowing excess retained water to be excreted. Patients should measure their body weight daily. Patients with DI admitted to the hospital with COVID-19 have a high risk for mortality due to volume depletion. Specialists must supervise fluid replacement and dosing of desmopressin. Patients after pituitary surgery should drink to thirst and measure their body weight daily to early recognize the development of the postoperative syndrome of inappropriate antidiuresis (SIAD). They should know hyponatraemia symptoms. The prevalence of hyponatraemia in patients with pneumonia due to COVID-19 is not yet known, but seems to be low. In contrast, hypernatraemia may develop in COVID-19 patients in ICU, from different multifactorial reasons, for example, due to insensible water losses from pyrexia, increased respiration rate and use of diuretics. Hypernatraemic dehydration may contribute to the high risk of acute kidney injury in COVID-19. IV fluid replacement should be administered with caution in severe cases of COVID-19 because of the risk of pulmonary oedema.
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Affiliation(s)
- Mirjam Christ-Crain
- Division of Endocrinology, Diabetes and Metabolism, Department of Internal Medicine and Department of Clinical Research, University Hospital Basel, University of Basel, Basel, Switzerland
- Correspondence should be addressed to M Christ-Crain;
| | - Ewout J Hoorn
- Division of Nephrology and Transplantation, Department of Internal Medicine, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands
| | - Mark Sherlock
- Academic Department of Endocrinology, Beaumont Hospital/RCSI Medical School, Dublin, Ireland
| | - Chris J Thompson
- Academic Department of Endocrinology, Beaumont Hospital/RCSI Medical School, Dublin, Ireland
| | - John A H Wass
- Department of Endocrinology, Oxford Centre for Diabetes, Endocrinology and Metabolism, Churchill Hospital, Oxford, UK
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Gilis-Januszewska A, Kluczyński Ł, Hubalewska-Dydejczyk A. Traumatic brain injuries induced pituitary dysfunction: a call for algorithms. Endocr Connect 2020; 9:R112-R123. [PMID: 32412425 PMCID: PMC7274553 DOI: 10.1530/ec-20-0117] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/08/2020] [Accepted: 04/21/2020] [Indexed: 12/13/2022]
Abstract
Traumatic brain injury affects many people each year, resulting in a serious burden of devastating health consequences. Motor-vehicle and work-related accidents, falls, assaults, as well as sport activities are the most common causes of traumatic brain injuries. Consequently, they may lead to permanent or transient pituitary insufficiency that causes adverse changes in body composition, worrisome metabolic function, reduced bone density, and a significant decrease in one's quality of life. The prevalence of post-traumatic hypopituitarism is difficult to determine, and the exact mechanisms lying behind it remain unclear. Several probable hypotheses have been suggested. The diagnosis of pituitary dysfunction is very challenging both due to the common occurrence of brain injuries, the subtle character of clinical manifestations, the variable course of the disease, as well as the lack of proper diagnostic algorithms. Insufficiency of somatotropic axis is the most common abnormality, followed by presence of hypogonadism, hypothyroidism, hypocortisolism, and diabetes insipidus. The purpose of this review is to summarize the current state of knowledge about post-traumatic hypopituitarism. Moreover, based on available data and on our own clinical experience, we suggest an algorithm for the evaluation of post-traumatic hypopituitarism. In addition, well-designed studies are needed to further investigate the pathophysiology, epidemiology, and timing of pituitary dysfunction after a traumatic brain injury with the purpose of establishing appropriate standards of care.
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Affiliation(s)
- Aleksandra Gilis-Januszewska
- Chair and Department of Endocrinology, Jagiellonian University Medical College, Krakow, Poland
- Endocrinology Department, University Hospital in Krakow, Krakow, Poland
| | - Łukasz Kluczyński
- Chair and Department of Endocrinology, Jagiellonian University Medical College, Krakow, Poland
- Endocrinology Department, University Hospital in Krakow, Krakow, Poland
- Correspondence should be addressed to Ł Kluczyński:
| | - Alicja Hubalewska-Dydejczyk
- Chair and Department of Endocrinology, Jagiellonian University Medical College, Krakow, Poland
- Endocrinology Department, University Hospital in Krakow, Krakow, Poland
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Hacioglu A, Kelestimur F, Tanriverdi F. Long-term neuroendocrine consequences of traumatic brain injury and strategies for management. Expert Rev Endocrinol Metab 2020; 15:123-139. [PMID: 32133881 DOI: 10.1080/17446651.2020.1733411] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/15/2019] [Accepted: 02/19/2020] [Indexed: 12/15/2022]
Abstract
Introduction: Traumatic brain injuries (TBI) are reported to cause neuroendocrine impairment with a prevalence of 15% with confirmatory testing. Pituitary dysfunction (PD) may have detrimental effects on vital parameters as well as on body composition, cardiovascular functions, cognition, and quality of life. Therefore, much effort has been made to identify predictive factors for post-TBI PD and various screening strategies have been offered.Areas covered: We searched PubMed and reviewed the recent data on clinical perspectives and long-term outcomes as well as predictive factors and screening modalities of post-TBI PD. Inconsistencies in the literature are overviewed and new areas of research are discussed.Expert opinion: Studies investigating biomarkers that will accurately predict TBI patients with a high risk of PD are generally pilot studies with a small number of participants. Anti-pituitary and anti-hypothalamic antibodies, neural proteins, micro-RNAs are promising in this field. As severity of TBI has been the most commonly associated risk factor for post-TBI PD, we suggest prospective screening based on severity of head trauma until new evidence emerges. There is also a need for more studies investigating the clinical effects of hormone replacement in TBI patients with PD.
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Affiliation(s)
- Aysa Hacioglu
- Department of Endocrinology and Metabolism, Erciyes University Medical School, Kayseri, Turkey
| | - Fahrettin Kelestimur
- Department of Endocrinology and Metabolism, Yeditepe University Medical Faculty, Istanbul, Turkey
| | - Fatih Tanriverdi
- Department of Endocrinology and Metabolism, Memorial Kayseri Hospital, Kayseri, Turkey
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Adrenal insufficiency: Physiology, clinical presentation and diagnostic challenges. Clin Chim Acta 2020; 505:78-91. [PMID: 32035851 DOI: 10.1016/j.cca.2020.01.029] [Citation(s) in RCA: 53] [Impact Index Per Article: 10.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2019] [Revised: 01/24/2020] [Accepted: 01/27/2020] [Indexed: 12/21/2022]
Abstract
Adrenal insufficiency (AI) is a serious condition, which can arise from pathology affecting the adrenal gland itself (primary adrenal insufficiency, PAI), hypothalamic or pituitary pathology (secondary adrenal insufficiency, SAI), or as a result of suppression of the hypothalamic-pituitaryadrenal (HPA) axis by exogenous glucocorticoid therapy (tertiary adrenal insufficiency, TAI). AI is associated with an increase in morbidity and mortality and a reduction in quality of life. In addition, the most common cause of PAI, autoimmune adrenalitis, may be associated with a variety of other autoimmune disorders. Untreated AI can present with chronic fatigue, weight loss and vulnerability to infection. The inability to cope with acute illness or infection can precipitate life-threatening adrenal crisis. It is therefore a critical diagnosis to make in a timely fashion, in order to institute appropriate management, aimed at reversing chronic ill health, preventing acute crises, and restoring quality of life. In this review, we will describe the normal physiology of the HPA axis and explain how knowledge of the physiology of this axis helps us understand the clinical presentation of AI, and forms the basis for the biochemical investigations which lead to the diagnosis of AI.
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Zhang B, Zhu X, Wang L, Hou Z, Hao S, Yang M, Gao F, Liu B. Inadequate Expression and Activation of Mineralocorticoid Receptor Aggravates Spatial Memory Impairment after Traumatic Brain Injury. Neuroscience 2019; 424:1-11. [PMID: 31734415 DOI: 10.1016/j.neuroscience.2019.10.026] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2019] [Revised: 09/27/2019] [Accepted: 10/17/2019] [Indexed: 12/31/2022]
Abstract
The administration of glucocorticoids (GCs) for the treatment of traumatic brain injury (TBI) is controversial. Both protective and deleterious effects of GCs on the brain have been reported in previous studies, while the mechanisms are unclear. Most experimental studies have reported glucocorticoid receptor (GR)-mediated deleterious effects after TBI. Sufficient mineralocorticoid receptor (MR) activation was reported to be indispensable for normal function and survival of hippocampal neurons, but changes in MR expression and activation and the roles of MRs in the survival of neurons after TBI remain unclear. We hypothesized that inadequate MR expression and activation caused by TBI aggravates posttraumatic hippocampal apoptosis but that restoration by restoring MRs promotes the survival of neurons. Using a rat controlled cortical impact model, we examined plasma corticosterone, MR expression and activation, neuronal apoptosis in the hippocampus, and spatial memory on day 3 after injury with and without fludrocortisone (1 mg/kg) treatment. Plasma corticosterone levels were significantly reduced after TBI. In addition, both MR expression and activation were inhibited. Fludrocortisone treatment significantly increased both the expression and activation of MRs, reduced the number of apoptotic neurons and cell loss in the ipsilateral hippocampus, and subsequently improved spatial memory. Its protective effects were counteracted by the MR antagonist spironolactone. The results suggest that adequate expression and activation of MRs is crucial for the survival of neurons after TBI and that fludrocortisone protects hippocampal neurons via promoting MR expression and activation.
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Affiliation(s)
- Bin Zhang
- Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
| | - Xueli Zhu
- Department of Ultrasound, Beijing Tian Tan Hospital, Capital Medical University, Beijing, China
| | - Liang Wang
- Department of Neurosurgery, Tianjin Fifth Center Hospital, Tianjin, China
| | - Zonggang Hou
- Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
| | - Shuyu Hao
- Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
| | - Mengshi Yang
- Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
| | - Fei Gao
- Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
| | - Baiyun Liu
- Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China; Beijing Key Laboratory of Central Nervous System Injury, Beijing Neurosurgical Institute, Capital Medical University, Beijing, China; Nerve Injury and Repair Center of Beijing Institute for Brain Disorders, Beijing, China; China National Clinical Research Center for Neurological Diseases, Beijing, China.
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Emelifeonwu JA, Flower H, Loan JJ, McGivern K, Andrews PJD. Prevalence of Anterior Pituitary Dysfunction Twelve Months or More following Traumatic Brain Injury in Adults: A Systematic Review and Meta-Analysis. J Neurotrauma 2019; 37:217-226. [PMID: 31111791 DOI: 10.1089/neu.2018.6349] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/03/2023] Open
Abstract
The objective of this study is to systematically review clinical studies that have reported on the prevalence of chronic post-traumatic brain injury anterior pituitary dysfunction (PTPD) 12 months or more following traumatic brain injury (TBI). We searched Medline, Embase, and PubMed up to April 2017 and consulted bibliographies of narrative reviews. We included cohort, case-control, and cross-sectional studies enrolling at least five adults with primary TBI in whom at least one anterior pituitary axis was assessed at least 12 months following TBI. We excluded studies in which other brain injuries were indistinguishable from TBI. Study quality was assessed using the Newcastle-Ottawa Scale (NOS) score. We also considered studies that determined growth hormone deficiency and adrenocorticotrophic hormone reserve using provocation test to be at low risk of bias. Data were extracted by four independent reviewers and assessed for risk of bias using a data extraction form. We performed meta-analyses using random effect models and assessed heterogeneity using the I2 index. We identified 58 publications, of which 29 (2756 participants) were selected for meta-analysis. Twelve of these were deemed to be at low risk of bias and therefore "high-quality," as they had NOS scores greater than 8 and had used provocation tests. The overall prevalence of at least one anterior pituitary hormone dysfunction for all 29 studies was 32% (95% confidence interval [CI] 25-38%). The overall prevalence in the 12 high-quality studies was 34% (95% CI 27-42%). We observed significant heterogeneity that was not solely explained by the risk of bias. Studies with a higher proportion of participants with mild TBI had a lower prevalence of PTPD. Our results show that approximately one-third of TBI sufferers have persistent anterior pituitary dysfunction 12 months or more following trauma. Future research on PTPD should differentiate between mild and moderate/severe TBI.
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Affiliation(s)
- John A Emelifeonwu
- Department of Neurosurgery, University of Edinburgh and NHS Lothian Western General Hospital, Edinburgh, United Kingdom.,Center for Clinical Brain Sciences, University of Edinburgh and NHS Lothian Western General Hospital, Edinburgh, United Kingdom
| | - Hannah Flower
- School of Medicine, University of Edinburgh, Edinburgh, United Kingdom
| | - Jamie J Loan
- Department of Neurosurgery, NHS Lothian Western General Hospital, Edinburgh, United Kingdom
| | - Kieran McGivern
- Institute of Neurological Sciences, Queen Elizabeth University Hospital, Glasgow, United Kingdom
| | - Peter J D Andrews
- Center for Clinical Brain Sciences, University of Edinburgh and NHS Lothian Western General Hospital, Edinburgh, United Kingdom
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Weil ZM, Karelina K. Lifelong consequences of brain injuries during development: From risk to resilience. Front Neuroendocrinol 2019; 55:100793. [PMID: 31560884 PMCID: PMC6905510 DOI: 10.1016/j.yfrne.2019.100793] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/25/2019] [Revised: 08/23/2019] [Accepted: 09/23/2019] [Indexed: 10/26/2022]
Abstract
Traumatic brain injuries in children represent a major public health issue and even relatively mild injuries can have lifelong consequences. However, the outcomes from these injuries are highly heterogeneous, with most individuals recovering fully, but a substantial subset experiencing prolonged or permanent disabilities across a number of domains. Moreover, brain injuries predispose individuals to other kinds of neuropsychiatric and somatic illnesses. Critically, the severity of the injury only partially predicts subsequent outcomes, thus other factors must be involved. In this review, we discuss the psychological, social, neuroendocrine, and autonomic processes that are disrupted following traumatic brain injury during development, and consider the mechanisms the mediate risk or resilience after traumatic brain injury in this vulnerable population.
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Affiliation(s)
- Zachary M Weil
- Department of Neuroscience, Group in Behavioral Neuroendocrinology, Center for Brain and Spinal Cord Repair, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA.
| | - Kate Karelina
- Department of Neuroscience, Group in Behavioral Neuroendocrinology, Center for Brain and Spinal Cord Repair, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA
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Zhang B, Xu X, Niu F, Mao X, Dong J, Yang M, Gao F, Liu B. Corticosterone Replacement Alleviates Hippocampal Neuronal Apoptosis and Spatial Memory Impairment Induced by Dexamethasone via Promoting Brain Corticosteroid Receptor Rebalance after Traumatic Brain Injury. J Neurotrauma 2019; 37:262-272. [PMID: 31436134 DOI: 10.1089/neu.2019.6556] [Citation(s) in RCA: 25] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
The balance of mineralocorticoid receptor (MR) and glucocorticoid receptor (GR) is indispensable for maintaining the normal function and structure of the hippocampus. However, changes in GR/MR and their effect on the survival of hippocampal neurons after traumatic brain injury (TBI) are still unclear. Previous studies have indicated that high-dose glucocorticoids (GC) aggravate hippocampal neuronal damage after TBI. We hypothesize that the imbalance of GR/MR expression and activation caused by injury and irrational use of dexamethasone (DEX) aggravates post-traumatic hippocampal apoptosis and spatial memory dysfunction, but that restoration by refilling MR and inhibiting GR promotes the survival of neurons. Using rat controlled cortical impact model, we examined the plasma corticosterone (CORT), corticosteroid receptor expression, apoptosis, and cell loss in the hippocampus, and, accordingly, the spatial memory after TBI and GC treatment within 7 days. Plasma CORT, MR, and GR expression level were significantly reduced at 2 days after TBI. Accordingly, the number of apoptotic cells also peaked at 2 days. Compared with the TBI control group, DEX treatment (5 mg/kg) significantly reduced plasma CORT, upregulated GR expression, and increased the number of apoptotic cells and cell loss, whereas CORT replacement (0.3 mg/kg) upregulated MR expression, inhibited apoptosis, and improved spatial memory. The deleterious and protective effects of DEX and CORT were counteracted by spironolactone and mifepristone respectively. The results suggest that inhibition of GR by RU486 or the refilling of MR by CORT protects hippocampal neurons and alleviates spatial memory impairment via promoting GR/MR rebalancing after TBI.
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Affiliation(s)
- Bin Zhang
- Department of Neurosurgery, Beijing Tian Tan Hospital, Capital Medical University, Beijing, China
| | - Xiaojian Xu
- Beijing Key Laboratory of Central Nervous System Injury, Beijing Neurosurgical Institute, Capital Medical University, Beijing, China
| | - Fei Niu
- Beijing Key Laboratory of Central Nervous System Injury, Beijing Neurosurgical Institute, Capital Medical University, Beijing, China
| | - Xiang Mao
- Department of Neurosurgery, The First Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Jinqian Dong
- Department of Neurosurgery, Beijing Tian Tan Hospital, Capital Medical University, Beijing, China
| | - Mengshi Yang
- Department of Neurosurgery, Beijing Tian Tan Hospital, Capital Medical University, Beijing, China
| | - Fei Gao
- Department of Neurosurgery, Beijing Tian Tan Hospital, Capital Medical University, Beijing, China
| | - Baiyun Liu
- Department of Neurosurgery, Beijing Tian Tan Hospital, Capital Medical University, Beijing, China.,Beijing Key Laboratory of Central Nervous System Injury, Beijing Neurosurgical Institute, Capital Medical University, Beijing, China.,Nerve Injury and Repair Center of Beijing Institute for Brain Disorders, Beijing, China.,China National Clinical Research Center for Neurological Diseases, Beijing, China
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Growth Hormone Deficiency Following Traumatic Brain Injury. Int J Mol Sci 2019; 20:ijms20133323. [PMID: 31284550 PMCID: PMC6651180 DOI: 10.3390/ijms20133323] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2019] [Revised: 06/28/2019] [Accepted: 07/04/2019] [Indexed: 02/06/2023] Open
Abstract
Traumatic brain injury (TBI) is fairly common and annually affects millions of people worldwide. Post traumatic hypopituitarism (PTHP) has been increasingly recognized as an important and prevalent clinical entity. Growth hormone deficiency (GHD) is the most common pituitary hormone deficit in long-term survivors of TBI. The pathophysiology of GHD post TBI is thought to be multifactorial including primary and secondary mechanisms. An interplay of ischemia, cytotoxicity, and inflammation post TBI have been suggested, resulting in pituitary hormone deficits. Signs and symptoms of GHD can overlap with those of TBI and may delay rehabilitation/recovery if not recognized and treated. Screening for GHD is recommended in the chronic phase, at least six months to a year after TBI as GH may recover in those with GHD in the acute phase; conversely, it may manifest in those with a previously intact GH axis. Dynamic testing is the standard method to diagnose GHD in this population. GHD is associated with long-term poor medical outcomes. Treatment with recombinant human growth hormone (rhGH) seems to ameliorate some of these features. This review will discuss the frequency and pathophysiology of GHD post TBI, its clinical consequences, and the outcomes of treatment with GH replacement.
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Successful Treatment of Transient Central Diabetes Insipidus following Traumatic Brain Injury in a Dog. Case Rep Vet Med 2019; 2019:3563675. [PMID: 31179153 PMCID: PMC6507253 DOI: 10.1155/2019/3563675] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2019] [Revised: 03/15/2019] [Accepted: 04/07/2019] [Indexed: 12/30/2022] Open
Abstract
An 11-year-old female spayed Maltese presented comatose, half an hour after vehicular trauma, and was treated for traumatic brain injury and pulmonary contusions. The dog developed severe hypernatremia within six hours of presentation, which responded poorly to the administration of five percent dextrose in water. As central diabetes insipidus was suspected, desmopressin was trialled and resolution of hypernatremia was achieved six days later. Transient trauma-induced central diabetes insipidus has been described previously in two dogs; in the first, serum sodium concentrations were evaluated three days after injury and the other developed hypernatremia seven days after injury. To the authors' knowledge, this is the first report of rapid onset, transient, and trauma-induced central diabetes insipidus in a dog that encompasses the complete clinical progression of the syndrome from shortly after injury through to resolution.
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