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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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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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Choudhary A, Kumar A, Sharma R, Khurana L, Jain S, Sharma S, Kumar D, Sharma S. Optimal vitamin D level ameliorates neurological outcome and quality of life after traumatic brain injury: a clinical perspective. Int J Neurosci 2023; 133:417-425. [PMID: 33930999 DOI: 10.1080/00207454.2021.1924706] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
BACKGROUND Deficiency of vitamin D along with traumatic brain injury (TBI) augments the risk of injury severity. This possibly affects the therapeutic regimen prescribed for TBI which may pessimistically affects its outcome. METHODS Studies literature search was conducted in Google Scholar and PubMed. The inclusions were studies performed clinically on both male and female. All included studies' references were also reviewed to find any additional relevance related to this review. Studies published in English were considered for this review. This review focuses upon the incidence of vitamin D deficiency in TBI and how it affects the Quality of life of the sufferer. RESULTS A total of 176 studies were reviewed and 58 were thoroughly focussed for review as they met inclusion criteria. These studies demonstrate that levels of vitamin D influence the recovery outcome after TBI. Vitamin D deficiency has been found to cause more deterioration in severe TBI than in patients with mild TBI. CONCLUSION Paucity of vitamin D significantly affects the outcome after brain injury. This clearly validates the necessity for screening of vitamin D levels in neurological deficit in order to reduce the risk of morbidity in terms of neurocognitive disorder.
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Affiliation(s)
- Ajay Choudhary
- Department of Neurosurgery, PGIMER, Dr. R.M.L. Hospital, New Delhi, India
| | - Ashok Kumar
- Department of Pharmacy, Banasthali Vidyapith, Banasthali, Rajasthan, India
| | - Rajesh Sharma
- Department of Neurosurgery, PGIMER, Dr. R.M.L. Hospital, New Delhi, India
| | - Lipika Khurana
- Institute of Obstetrics and Gynaecology, Sir Ganga Ram Hospital, New Delhi, India
| | - Smita Jain
- Department of Pharmacy, Banasthali Vidyapith, Banasthali, Rajasthan, India
| | - Shallu Sharma
- Department of Pharmacy, Banasthali Vidyapith, Banasthali, Rajasthan, India
| | - Deepak Kumar
- Department of Physical Medicine and Rehabilitation, PGIMER, Dr. R.M.L. Hospital, New Delhi, India
| | - Swapnil Sharma
- Department of Pharmacy, Banasthali Vidyapith, Banasthali, Rajasthan, India
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Wexler TL, Reifschneider K, Backeljauw P, Cárdenas JF, Hoffman AR, Miller BS, Yuen KCJ. Growth Hormone Deficiency following Traumatic Brain Injury in Pediatric and Adolescent Patients: Presentation, Treatment, and Challenges of Transitioning from Pediatric to Adult Services. J Neurotrauma 2023. [PMID: 36825511 DOI: 10.1089/neu.2022.0384] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/25/2023] Open
Abstract
Traumatic brain injury (TBI) is increasingly recognized, with an incidence of approximately 110 per 100,000 in pediatric populations and 618 per 100,000 in adolescent and adult populations. TBI often leads to cognitive, behavioral, and physical consequences, including endocrinopathies. Deficiencies in anterior pituitary hormones (e.g., adrenocorticotropic hormone, thyroid-stimulating hormone, gonadotropins, and growth hormone [GH]) can negatively impact health outcomes and quality of life post-TBI. This review focuses on GH deficiency (GHD), the most common post-TBI pituitary hormone deficiency. GHD is associated with abnormal body composition, lipid metabolism, bone mineral density, executive brain functions, behavior, and height outcomes in pediatric, adolescent, and transition-age patients. Despite its relatively frequent occurrence, post-TBI GHD has not been well studied in these patients; hence, diagnostic and treatment recommendations are limited. Here, we examine the occurrence and diagnosis of TBI, retrospectively analyze post-TBI hypopituitarism and GHD prevalence rates in pediatric and adolescent patients, and discuss appropriate GHD testing strategies and GH dosage recommendations for these patients. We place particular emphasis on the ways in which testing and dosage recommendations may change during the transition phase. We conclude with a review of the challenges faced by transition-age patients and how these may be addressed to improve access to adequate healthcare. Little information is currently available to help guide patients with TBI and GHD through the transition phase and there is a risk of interrupted care; therefore, a strength of this review is its emphasis on this critical period in a patient's healthcare journey.
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Affiliation(s)
- Tamara L Wexler
- Department of Rehabilitation Medicine, NYU Langone Health, New York, New York, USA
- Division of Endocrinology, Diabetes, and Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Kent Reifschneider
- Children's Hospital of The King's Daughters, Eastern Virginia Medical Center, Norfolk, Virginia, USA
| | - Philippe Backeljauw
- Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA
| | - Javier F Cárdenas
- Barrow Concussion and Brain Injury Center, Barrow Neurological Institute, University of Arizona College of Medicine and Creighton School of Medicine, Phoenix, Arizona, USA
| | - Andrew R Hoffman
- Department of Medicine, Division of Endocrinology, Metabolism and Gerontology, Stanford University School of Medicine, Stanford, California, USA
| | - Bradley S Miller
- Department of Pediatrics, Division of Pediatric Endocrinology, University of Minnesota Medical School, M Health Fairview Masonic Children's Hospital, Minneapolis, Minnesota, USA
| | - Kevin C J Yuen
- Barrow Pituitary Center, Barrow Neurological Institute, University of Arizona College of Medicine and Creighton School of Medicine, Phoenix, Arizona, 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: 4] [Impact Index Per Article: 2.0] [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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Vlad RM, Albu AI, Nicolaescu ID, Dobritoiu R, Carsote M, Sandru F, Albu D, Păcurar D. An Approach to Traumatic Brain Injury-Related Hypopituitarism: Overcoming the Pediatric Challenges. Diagnostics (Basel) 2023; 13:diagnostics13020212. [PMID: 36673021 PMCID: PMC9857786 DOI: 10.3390/diagnostics13020212] [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: 11/30/2022] [Revised: 12/30/2022] [Accepted: 01/01/2023] [Indexed: 01/09/2023] Open
Abstract
Traumatic brain injury (TBI)-related hypopituitarism is a rare polymorphic complication of brain injury, with very little data, particularly concerning children and teenagers. This is a comprehensive review of the literature regarding this pathology, starting from a new pediatric case. The research was conducted on PubMed and included publications from the last 22 years. We identified nine original studies on the pediatric population (two case reports and seven studies; only four of these seven were prospective studies). TBI-related hypopituitarism is associated with isolated hormonal deficits ranging from 22.5% to 86% and multiple hormonal deficiencies from 5.9% to 50% in the studied pediatric population. Growth hormone (GH) deficiency is most often found, including the form with late occurrence after TBI; it was described as persistent in half of the studies. Thyroid-stimulating hormone (TSH) deficiency is identified as a distant complication following TBI; in all three studies, we identified this complication was found to be permanent. Adrenocorticotropic hormone (ACTH) deficiency did not relate to a certain type of brain trauma, and it was transient in reported cases. Hyperprolactinemia was the most frequent hormonal finding, also occurring late after injury. Central diabetes insipidus was encountered early post-TBI, typically with a transient pattern and did not relate to a particular type of injury. TBI-related hypopituitarism, although rare in children, should be taken into consideration even after a long time since the trauma. A multidisciplinary approach is needed if the patient is to safely overcome any acute condition.
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Affiliation(s)
- Raluca Maria Vlad
- Department of Pediatrics, “Grigore Alexandrescu” Emergency Children’s Hospital, 011743 Bucharest, Romania
- Faculty of Medicine, “Carol Davila” University of Medicine and Pharmacy, 020021 Bucharest, Romania
- Correspondence: (R.M.V.); (A.I.A.); Tel.: +40-722451462 (R.M.V.); +40-723886967 (A.I.A.)
| | - Alice Ioana Albu
- Department of Endocrinology, “Carol Davila” University of Medicine and Pharmacy, 020021 Bucharest, Romania
- “Elias” Emergency Clinical Hospital, 011461 Bucharest, Romania
- Correspondence: (R.M.V.); (A.I.A.); Tel.: +40-722451462 (R.M.V.); +40-723886967 (A.I.A.)
| | | | - Ruxandra Dobritoiu
- Department of Pediatrics, “Grigore Alexandrescu” Emergency Children’s Hospital, 011743 Bucharest, Romania
| | - Mara Carsote
- Department of Endocrinology, “Carol Davila” University of Medicine and Pharmacy, 020021 Bucharest, Romania
- “C. I. Parhon” National Institute of Endocrinology, 011863 Bucharest, Romania
| | - Florica Sandru
- Department of Dermatovenerology, “Carol Davila” University of Medicine and Pharmacy, 020021 Bucharest, Romania
- “Elias” University Emergency Hospital, 011461 Bucharest, Romania
| | - Dragos Albu
- 2nd Clinical Department Obstetrics Gynecology, Faculty of Dentistry, “Carol Davila” University of Medicine and Pharmacy, 020021 Bucharest, Romania
| | - Daniela Păcurar
- Department of Pediatrics, “Grigore Alexandrescu” Emergency Children’s Hospital, 011743 Bucharest, Romania
- Faculty of Medicine, “Carol Davila” University of Medicine and Pharmacy, 020021 Bucharest, Romania
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Yuen KCJ, Masel B, Jaffee MS, O'Shanick G, Wexler TL, Reifschneider K, Urban RJ, Hoang S, Kelepouris N, Hoffman AR. A consensus on optimization of care in patients with growth hormone deficiency and mild traumatic brain injury. Growth Horm IGF Res 2022; 66:101495. [PMID: 35933894 DOI: 10.1016/j.ghir.2022.101495] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/11/2022] [Revised: 07/01/2022] [Accepted: 07/20/2022] [Indexed: 11/24/2022]
Abstract
OBJECTIVE/DESIGN Approximately 2.9 million children and adults in the US experience traumatic brain injuries (TBIs) annually, most of which are considered mild. TBI can induce varying consequences on pituitary function, with growth hormone deficiency (GHD) among the more commonly reported conditions. Panels of pediatric and adult endocrinologists, neurologists, physical medicine and rehabilitation specialists, and neuropsychologists convened in February and October 2020 to discuss ongoing challenges and provide strategies for detection and optimal management of patients with mild TBI and GHD. RESULTS Difficulties include a low rate of seeking medical attention in the population, suboptimal screening tools, cost and complexity of GHD testing, and a lack of consensus regarding when to test or retest for GHD. Additionally, referrals to endocrinologists from other specialists are uncommon. Recommendations from the panels for managing such patients included multidisciplinary guidelines on the diagnosis and management of post-TBI GHD and additional education on long-term metabolic and probable cognitive benefits of GH replacement therapy. CONCLUSION As patients of all ages with mild TBI may develop GHD and/or other pituitary deficiencies, a multidisciplinary approach to provide education to endocrinologists, neurologists, neurosurgeons, traumatologists, and other providers and guidelines for the early identification and management of persistent mild TBI-related GHD are urgently needed.
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Affiliation(s)
- Kevin C J Yuen
- Barrow Pituitary Center, Barrow Neurological Institute, University of Arizona College of Medicine and Creighton School of Medicine, Phoenix, AZ, USA
| | - Brent Masel
- Department of Neurology, University of Texas Medical Branch, Galveston, TX, USA
| | - Michael S Jaffee
- Department of Neurology, University of Florida, Gainesville, FL, USA
| | | | - Tamara L Wexler
- Rusk Rehabilitation, NYU Langone Health, New York, NY, USA; University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA
| | - Kent Reifschneider
- Division of Endocrinology, Children's Hospital of The King's Daughters, Norfolk, VA, USA
| | - Randall J Urban
- Institute for Translational Sciences, University of Texas Medical Branch, Galveston, TX, USA
| | | | | | - Andrew R Hoffman
- Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA
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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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9
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Drummond JB, Soares BS, Pedrosa W, Ribeiro-Oliveira A. Revisiting peak serum cortisol response to insulin-induced hypoglycemia in children. J Endocrinol Invest 2021; 44:1291-1299. [PMID: 32959333 DOI: 10.1007/s40618-020-01427-x] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/31/2020] [Accepted: 09/14/2020] [Indexed: 01/16/2023]
Abstract
PURPOSE To evaluate factors that could potentially affect the hypothalamic-pituitary adrenal (HPA) axis response to insulin-induced hypoglycemia in children without history or symptoms of adrenal insufficiency and to propose a cut-off value to define a normal response in this population. METHODS Exploratory single-center study involving 78 children that prospectively underwent insulin tolerance test (ITT) for suspected growth hormone (GH) deficiency. METHODS Glucose, cortisol, GH, adrenocorticotrophic hormone (ACTH), epinephrine and norepinephrine levels were measured at baseline and after insulin-induced hypoglycemia. Serum cortisol was measured using Access automated immunoassay. RESULTS Mean (range) basal morning serum cortisol of 8 (2.2-19.5) µg/dL/222 (61-542) nmol/L increased after hypoglycemia to 20.5 (14.6-29.5) µg/dL/570 nmol/L (405-819) nmol/L. Peak serum cortisol levels of 14.6 µg/dL (405 nmol/L) and 15.4 µg/dL (428 nmol/L) corresponded to the 2.5th and 5th percentiles, respectively. Peak serum cortisol correlated with peak plasma epinephrine (r = 0.367; P = 0.0014) but did not correlate with age, BMI-SD or peak serum GH. Children with intact and abnormal GH responses presented similar mean peak serum cortisol levels (20.0 vs. 20.6 µg/dL/555 vs. 572 nmol/L; P = 0.21). CONCLUSION Our data indicate that the current cut-off to define normal HPA axis response in children after insulin-induced hypoglycemia warrants reevaluation to avoid over-diagnosis of adrenal insufficiency. Our results suggest that peak serum cortisol levels ≥ 15.4 µg/dL (428 nmol/L) in children undergoing ITT might represent a normal cortisol response to stress, regardless of age, BMI or GH secretory capacity.
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Affiliation(s)
- J B Drummond
- Laboratory of Endocrinology, Federal University of Minas Gerais, Av. Alfredo Balena, 190, Belo Horizonte, Minas Gerais, 30130-100, Brazil
- Hermes Pardini Institute, Belo Horizonte, Minas Gerais, Brazil
| | - B S Soares
- Laboratory of Endocrinology, Federal University of Minas Gerais, Av. Alfredo Balena, 190, Belo Horizonte, Minas Gerais, 30130-100, Brazil
| | - W Pedrosa
- Hermes Pardini Institute, Belo Horizonte, Minas Gerais, Brazil
| | - A Ribeiro-Oliveira
- Laboratory of Endocrinology, Federal University of Minas Gerais, Av. Alfredo Balena, 190, Belo Horizonte, Minas Gerais, 30130-100, Brazil.
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10
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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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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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Ntali G, Tsagarakis S. Traumatic brain injury induced neuroendocrine changes: acute hormonal changes of anterior pituitary function. Pituitary 2019; 22:283-295. [PMID: 30746590 DOI: 10.1007/s11102-019-00944-0] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
PURPOSE It is estimated that approximately 69 million individuals worldwide will sustain a TBI each year, which accounts for substantial morbidity and mortality in both children and adults. TBI may lead to significant neuroendocrine changes, if the delicate pituitary is ruptured. In this review, we focus on the anterior pituitary hormonal changes in the acute post-TBI period and we present the evidence supporting the need for screening of anterior pituitary function in the early post-TBI time along with current suggestions regarding the endocrine assessment and management of these patients. METHODS Original systematic articles with prospective and/or retrospective design studies of acute TBI were included, as were review articles and case series. RESULTS Although TBI may motivate an acute increase of stress hormones, it may also generate a wide spectrum of anterior pituitary hormonal deficiencies. The frequency of post-traumatic anterior hypopituitarism (PTHP) varies according to the severity, the type of trauma, the time elapsed since injury, the study population, and the methodology used to diagnose pituitary hormone deficiency. Early neuroendocrine abnormalities may be transient, but additional late ones may also appear during the course of rehabilitation. CONCLUSIONS Acute hypocortisolism should be diagnosed and managed promptly, as it can be life-threatening, but currently there is no evidence to support treatment of acute GH, thyroid hormones or gonadotropins deficiencies. However, a more comprehensive assessment of anterior pituitary function should be undertaken both in the early and in the post-acute phase, since ongoing hormone deficiencies may adversely affect the recovery and quality of life of these patients.
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Affiliation(s)
- Georgia Ntali
- Department of Endocrinology and Diabetes, Evangelismos Hospital, Athens, Greece
| | - Stylianos Tsagarakis
- Department of Endocrinology and Diabetes, Evangelismos Hospital, Athens, Greece.
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De Bellis A, Bellastella G, Maiorino MI, Costantino A, Cirillo P, Longo M, Pernice V, Bellastella A, Esposito K. The role of autoimmunity in pituitary dysfunction due to traumatic brain injury. Pituitary 2019; 22:236-248. [PMID: 30847776 DOI: 10.1007/s11102-019-00953-z] [Citation(s) in RCA: 10] [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] [Indexed: 12/11/2022]
Abstract
PURPOSE Traumatic brain injury (TBI) is one of the most common causes of mortality and long-term disability and it is associated with an increased prevalence of neuroendocrine dysfunctions. Post-traumatic hypopituitarism (PTHP) results in major physical, psychological and social consequences leading to impaired quality of life. PTHP can occur at any time after traumatic event, evolving through various ways and degrees of deficit, requiring appropriate screening for early detection and treatment. Although the PTHP pathophysiology remains to be elucitated, on the basis of proposed hypotheses it seems to be the result of combined pathological processes, with a possible role played by hypothalamic-pituitary autoimmunity (HPA). This review is aimed at focusing on this possible role in the development of PTHP and its potential clinical consequences, on the basis of the data so far appeared in the literature and of some results of personal studies on this issue. METHODS Scrutinizing the data so far appeared in literature on this topic, we have found only few studies evaluating the autoimmune pattern in affected patients, searching in particular for antipituitary and antihypothalamus autoantibodies (APA and AHA, respectively) by simple indirect immunofluorescence. RESULTS The presence of APA and/or AHA at high titers was associated with an increased risk of onset/persistence of PTHP. CONCLUSIONS HPA seems to contribute to TBI-induced pituitary damage and related PTHP. However, further prospective studies in a larger cohort of patients are needed to define etiopathogenic and diagnostic role of APA/AHA in development of post-traumatic hypothalamic/pituitary dysfunctions after a TBI.
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Affiliation(s)
- Annamaria De Bellis
- Department of Advanced Medical and Surgical Sciences, University of Campania "Luigi Vanvitelli", Naples, Italy.
| | - Giuseppe Bellastella
- Department of Advanced Medical and Surgical Sciences, University of Campania "Luigi Vanvitelli", Naples, Italy
| | - Maria Ida Maiorino
- Department of Advanced Medical and Surgical Sciences, University of Campania "Luigi Vanvitelli", Naples, Italy
| | - Angela Costantino
- Department of Advanced Medical and Surgical Sciences, University of Campania "Luigi Vanvitelli", Naples, Italy
| | - Paolo Cirillo
- Department of Advanced Medical and Surgical Sciences, University of Campania "Luigi Vanvitelli", Naples, Italy
| | - Miriam Longo
- Department of Advanced Medical and Surgical Sciences, University of Campania "Luigi Vanvitelli", Naples, Italy
| | - Vlenia Pernice
- Department of Advanced Medical and Surgical Sciences, University of Campania "Luigi Vanvitelli", Naples, Italy
| | - Antonio Bellastella
- Department of Advanced Medical and Surgical Sciences, University of Campania "Luigi Vanvitelli", Naples, Italy
| | - Katherine Esposito
- Department of Advanced Medical and Surgical Sciences, University of Campania "Luigi Vanvitelli", Naples, Italy
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Briet C, Braun K, Lefranc M, Toussaint P, Boudailliez B, Bony H. Should We Assess Pituitary Function in Children After a Mild Traumatic Brain Injury? A Prospective Study. Front Endocrinol (Lausanne) 2019; 10:149. [PMID: 30941101 PMCID: PMC6433821 DOI: 10.3389/fendo.2019.00149] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/19/2018] [Accepted: 02/20/2019] [Indexed: 01/07/2023] Open
Abstract
Objective: The aim of this study was to evaluate the frequency of hypopituitarism following TBI in a cohort of children who had been hospitalized for mild TBI and to identify the predictive factors for this deficiency. Design: A prospective study was conducted on children between 2 and 16 years of age who had been hospitalized for mild TBI according to the Glasgow Coma Scale between September 2009 and June 2013. Clinical parameters, basal pituitary hormone assessment at 0, 6, and 12 months, as well as a dynamic testing (insulin tolerance test) 12 months after TBI were performed. Results: The study included 109 children, the median age was 8.5 years. Patients were examined 6 months (n = 99) and 12 months (n = 96) after TBI. Somatotropic deficiency (defined by a GH peak <20 mUI/l in two tests, an IGF-1 <-1SDS and a delta height <0SDS) were confirmed in 2 cases. One case of gonadotrophic deficiency occurred 1 year after TBI among 13 pubertal children. No cases of precocious puberty, 5 cases of low prolactin level, no cases of corticotropic insufficiency (cortisol peak <500 nmol/l) and no cases diabetes insipidus were recorded. Conclusion: Pituitary insufficiency was present 1year after mild TBI in about 7% of children. Based on our results, we suggest testing children after mild TBI in case of clinical abnormalities. i.e., for GH axis, IGF-1, which should be assessed in children with a delta height <0 SDS, 6 to 12 months after TBI, and a dynamic GH testing (preferentially by an ITT) should be performed in case of IGF-1 <-1SDS, with a GH threshold at 20 mUI/L. However, if a systematic pituitary assessment is not required for mild TBI, physicians should monitor children 1 year after mild TBI with particular attention to growth and weight gain.
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Affiliation(s)
- Claire Briet
- Department of Pediatrics, University Medical Center, Amiens, France
- Department of Endocrinology, Diabetology and Nutrition, Institut MITOVASC, INSERM U1083, Angers University, University Medical Center, Angers, France
- *Correspondence: Claire Briet
| | - Karine Braun
- Department of Pediatrics, University Medical Center, Amiens, France
| | - Michel Lefranc
- Department of Neurosurgery, University Medical Center, Amiens, France
- Department of Medicine, University of Picardie Jules Verne, Amiens, France
| | - Patrick Toussaint
- Department of Neurosurgery, University Medical Center, Amiens, France
- Department of Medicine, University of Picardie Jules Verne, Amiens, France
| | - Bernard Boudailliez
- Department of Pediatrics, University Medical Center, Amiens, France
- Department of Medicine, University of Picardie Jules Verne, Amiens, France
| | - Hélène Bony
- Department of Pediatrics, University Medical Center, Amiens, France
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Fan E, Skippen PW, Sargent MA, Cochrane DD, Chanoine JP. Central adrenal insufficiency following traumatic brain injury: a missed diagnosis in the critically injured. Childs Nerv Syst 2017; 33:2205-2207. [PMID: 28721596 DOI: 10.1007/s00381-017-3536-5] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/04/2017] [Accepted: 07/06/2017] [Indexed: 10/19/2022]
Abstract
BACKGROUND High-dose steroid administration is no longer recommended in the treatment of acute traumatic brain injury (TBI) as it failed to prove beneficial in improving patients' outcome. However, a masked benefit of steroid administration in TBI management was that it provided corticosteroid replacement therapy in patients with TBI-related central adrenal insufficiency. CASE PRESENTATION We report the case of a 12-year-old boy who suffered a severe TBI from a motor vehicle accident that resulted in complete deficiency of anterior pituitary function. Central adrenal insufficiency was not ruled out by a near normal response to a low-dose ACTH test performed on D11. CONCLUSION Consideration should be given to the empirical treatment of TBI pediatric patients with stress doses of corticosteroids if injury to the hypothalamus or pituitary gland is possible until a formal assessment of the hypothalamic-pituitary-adrenal axis can be made.
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Affiliation(s)
- Eileen Fan
- Endocrinology and Diabetes Unit, British Columbia Children's Hospital and University of British Columbia, 4480 Oak Street, Vancouver, BC, V6H 3V4, Canada
| | - Peter W Skippen
- Pediatric Intensive Care Unit, British Columbia Children's Hospital and University of British Columbia, 4480 Oak Street, Vancouver, BC, V6H 3V4, Canada
| | - Michael A Sargent
- Department of Radiology, British Columbia Children's Hospital and University of British Columbia, 4480 Oak Street, Vancouver, BC, V6H 3V4, Canada
| | - David D Cochrane
- Division of Neurosurgery, British Columbia Children's Hospital and University of British Columbia, 4480 Oak Street, Vancouver, BC, V6H 3V4, Canada.
| | - Jean-Pierre Chanoine
- Endocrinology and Diabetes Unit, British Columbia Children's Hospital and University of British Columbia, 4480 Oak Street, Vancouver, BC, V6H 3V4, Canada
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16
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Ergul AB, Ozcan A, Bas VN, Aslaner H, Kurtoglu S, Altuner Torun Y, Koc A. A rare cause of refractory hyponatremia after traumatic brain injury: Acute post-traumatic hypopituitarism due to pituitary stalk transection. J Acute Med 2016. [DOI: 10.1016/j.jacme.2016.09.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
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Aylanç H, Tütüncüler F, Süt N. Evaluation of pituitary function in cases with the diagnosis of pediatric mild traumatic brain injury: Cross-sectional study. J Neurosci Rural Pract 2016; 7:537-543. [PMID: 27695233 PMCID: PMC5006465 DOI: 10.4103/0976-3147.185509] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
Abstract
BACKGROUND This study was to determine whether pituitary dysfunction occurs after head trauma in children or not and which axis is affected more; to define the association of pituitary dysfunction with the severity of head trauma and duration time after the diagnosis of head trauma. MATERIALS AND METHODS In this study, 24 children who were diagnosed with head trauma were evaluated regarding pituitary dysfunction. In all cases, after 12 h fasting, serum cortisol, fT3, fT4, thyroid-stimulating hormone, prolactin, insulin-like growth factor-1, serum sodium, urine density, follicle-stimulating hormone, luteinizing hormone, in female cases E2, in male cases, TT levels were determined. RESULTS Mean age of children was 9.5 ± 3.1 years, 14 children (58.3%) had mild, 9 children (37.5%) had moderate, and 1 children (4.2%) had severe head trauma according to the Glasgow coma scale. Mean duration time after head trauma was 29.4 ± 9.8 months. In all cases, no pathologic condition was determined in the pituitary hormonal axis. In one children (4.2%), low basal cortisol level was found. There were no children with hormonal deficiency in this study. CONCLUSION Although pituitary dysfunction after head trauma may develop in the early period, some may present in the late period; therefore, all cases should be followed up at outpatient clinics for a longer period.
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Affiliation(s)
- Hakan Aylanç
- Department of Pediatrics, School of Medicine, Trakya University, Edirne, Turkey
| | - Filiz Tütüncüler
- Department of Pediatric Endocrinology, School of Medicine, Trakya University, Edirne, Turkey
| | - Necdet Süt
- Department of Biostatistics and Medical Informatics, School of Medicine, Trakya University, Edirne, Turkey
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Agrawal S, Branco RG. Neuroprotective measures in children with traumatic brain injury. World J Crit Care Med 2016; 5:36-46. [PMID: 26855892 PMCID: PMC4733454 DOI: 10.5492/wjccm.v5.i1.36] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/29/2015] [Revised: 12/01/2015] [Accepted: 01/08/2016] [Indexed: 02/06/2023] Open
Abstract
Traumatic brain injury (TBI) is a major cause of death and disability in children. Severe TBI is a leading cause of death and often leads to life changing disabilities in survivors. The modern management of severe TBI in children on intensive care unit focuses on preventing secondary brain injury to improve outcome. Standard neuroprotective measures are based on management of intracranial pressure (ICP) and cerebral perfusion pressure (CPP) to optimize the cerebral blood flow and oxygenation, with the intention to avoid and minimise secondary brain injury. In this article, we review the current trends in management of severe TBI in children, detailing the general and specific measures followed to achieve the desired ICP and CPP goals. We discuss the often limited evidence for these therapeutic interventions in children, extrapolation of data from adults, and current recommendation from paediatric guidelines. We also review the recent advances in understanding the intracranial physiology and neuroprotective therapies, the current research focus on advanced and multi-modal neuromonitoring, and potential new therapeutic and prognostic targets.
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19
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Masel BE, Urban R. Chronic Endocrinopathies in Traumatic Brain Injury Disease. J Neurotrauma 2015; 32:1902-10. [DOI: 10.1089/neu.2014.3526] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023] Open
Affiliation(s)
- Brent E. Masel
- Transitional Learning Center at Galveston, Galveston, Texas
| | - Randy Urban
- Department of Internal Medicine, University of Texas Medical Branch, Galveston, Texas
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20
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Karaca Z, Tanrıverdi F, Ünlühızarcı K, Kelestimur F. GH and Pituitary Hormone Alterations After Traumatic Brain Injury. PROGRESS IN MOLECULAR BIOLOGY AND TRANSLATIONAL SCIENCE 2015; 138:167-91. [PMID: 26940391 DOI: 10.1016/bs.pmbts.2015.10.010] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Traumatic brain injury (TBI) is a crucially important public health problem around the world, which gives rise to increased mortality and is the leading cause of physical and psychological disability in young adults, in particular. Pituitary dysfunction due to TBI was first described 95 years ago. However, until recently, only a few papers have been published in the literature and for this reason, TBI-induced hypopituitarism has been neglected for a long time. Recent studies have revealed that TBI is one of the leading causes of hypopituitarism. TBI which causes hypopituitarism may be characterized by a single head injury such as from a traffic accident or by chronic repetitive head trauma as seen in combative sports including boxing, kickboxing, and football. Vascular damage, hypoxic insult, direct trauma, genetic predisposition, autoimmunity, and neuroinflammatory changes may have a role in the development of hypopituitarism after TBI. Because of the exceptional structure of the hypothalamo-pituitary vasculature and the special anatomic location of anterior pituitary cells, GH is the most commonly lost hormone after TBI, and the frequency of isolated GHD is considerably high. TBI-induced pituitary dysfunction remains undiagnosed and therefore untreated in most patients because of the nonspecific and subtle clinical manifestations of hypopituitarism. Treatment of TBI-induced hypopituitarism depends on the deficient anterior pituitary hormones. GH replacement therapy has some beneficial effects on metabolic parameters and neurocognitive dysfunction. Patients with TBI without neuroendocrine changes and those with TBI-induced hypopituitarism share the same clinical manifestations, such as attention deficits, impulsion impairment, depression, sleep abnormalities, and cognitive disorders. For this reason, TBI-induced hypopituitarism may be neglected in TBI victims and it would be expected that underlying hypopituitarism would aggravate the clinical picture of TBI itself. Therefore, the diagnosis and treatment of unrecognized hypopituitarism due to TBI are very important not only to decrease morbidity and mortality due to hypopituitarism but also to alleviate the chronic sequelae caused by TBI.
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Affiliation(s)
- Züleyha Karaca
- Department of Endocrinology, Erciyes University Medical School, Kayseri, Turkey
| | - Fatih Tanrıverdi
- Department of Endocrinology, Erciyes University Medical School, Kayseri, Turkey
| | - Kürşad Ünlühızarcı
- Department of Endocrinology, Erciyes University Medical School, Kayseri, Turkey
| | - Fahrettin Kelestimur
- Department of Endocrinology, Erciyes University Medical School, Kayseri, Turkey.
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Javed Z, Qamar U, Sathyapalan T. Pituitary and/or hypothalamic dysfunction following moderate to severe traumatic brain injury: Current perspectives. Indian J Endocrinol Metab 2015; 19:753-63. [PMID: 26693424 PMCID: PMC4673802 DOI: 10.4103/2230-8210.167561] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/07/2023] Open
Abstract
There is an increasing deliberation regarding hypopituitarism following traumatic brain injury (TBI) and recent data have suggested that pituitary dysfunction is very common among survivors of patients having moderate-severe TBI which may evolve or resolve over time. Due to high prevalence of pituitary dysfunction after moderate-severe TBI and its association with increased morbidity and poor recovery and the fact that it can be easily treated with hormone replacement, it has been suggested that early detection and treatment is necessary to prevent long-term neurological consequences. The cause of pituitary dysfunction after TBI is still not well understood, but evidence suggests few possible primary and secondary causes. Results of recent studies focusing on the incidence of hypopituitarism in the acute and chronic phases after TBI are varied in terms of severity and time of occurrence. Although the literature available does not show consistent values and there is difference in study parameters and diagnostic tests used, it is clear that pituitary dysfunction is very common after moderate to severe TBI and patients should be carefully monitored. The exact timing of development cannot be predicted but has suggested regular assessment of pituitary function up to 1 year after TBI. In this narrative review, we aim to explore the current evidence available regarding the incidence of pituitary dysfunction in acute and chronic phase post-TBI and recommendations for screening and follow-up in these patients. We will also focus light over areas in this field worthy of further investigation.
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Affiliation(s)
- Zeeshan Javed
- Department of Academic Endocrinology, Diabetes and Metabolism, Hull York Medical School, University of Hull, Hull and East Yorkshire NHS Trust, Hull, UK
| | - Unaiza Qamar
- The Children's Hospital and Institute of Child Health, Department of Clinical Pathology, Punjab Health Department, Lahore, Pakistan
| | - Thozhukat Sathyapalan
- Department of Academic Endocrinology, Diabetes and Metabolism, Hull York Medical School, University of Hull, Hull and East Yorkshire NHS Trust, Hull, UK
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Hypothalamic-Pituitary Autoimmunity and Traumatic Brain Injury. J Clin Med 2015; 4:1025-35. [PMID: 26239463 PMCID: PMC4470214 DOI: 10.3390/jcm4051025] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2015] [Revised: 04/25/2015] [Accepted: 05/04/2015] [Indexed: 01/31/2023] Open
Abstract
Background: Traumatic brain injury (TBI) is a leading cause of secondary hypopituitarism in children and adults, and is responsible for impaired quality of life, disabilities and compromised development. Alterations of pituitary function can occur at any time after the traumatic event, presenting in various ways and evolving during time, so they require appropriate screening for early detection and treatment. Although the exact pathophysiology is unknown, several mechanisms have been hypothesized, including hypothalamic-pituitary autoimmunity (HP-A). The aim of this study was to systematically review literature on the association between HP-A and TBI-induced hypopituitarism. Major pitfalls related to the HP-A investigation were also discussed. Methods: The PubMed database was searched with a string developed for this purpose, without temporal or language limits, for original articles assessing the association of HP-A and TBI-induced hypopituitarism. Results: Three articles from the same group met the inclusion criteria. Anti-pituitary and anti-hypothalamic antibodies were detected using indirect immunofluorescence in a significant number of patients with acute and chronic TBI. Elevated antibody titer was associated with an increased risk of persistent hypopituitarism, especially somatotroph and gonadotroph deficiency, while no correlations were found with clinical parameters. Conclusion: HPA seems to contribute to TBI-induced pituitary damage, although major methodological issues need to be overcome and larger studies are warranted to confirm these preliminary data.
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Neuroendocrine Disturbances after Brain Damage: An Important and Often Undiagnosed Disorder. J Clin Med 2015; 4:847-57. [PMID: 26239451 PMCID: PMC4470202 DOI: 10.3390/jcm4050847] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2015] [Revised: 04/13/2015] [Accepted: 04/20/2015] [Indexed: 01/21/2023] Open
Abstract
Traumatic brain injury (TBI) is a common and significant public health problem all over the world. Until recently, TBI has been recognized as an uncommon cause of hypopituitarism. The studies conducted during the last 15 years revealed that TBI is a serious cause of hypopituitarism. Although the underlying pathophysiology has not yet been fully clarified, new data indicate that genetic predisposition, autoimmunity and neuroinflammatory changes may play a role in the development of hypopituitarism. Combative sports, including boxing and kickboxing, both of which are characterized by chronic repetitive head trauma, have been shown as new causes of neuroendocrine abnormalities, mainly hypopituitarism, for the first time during the last 10 years. Most patients with TBI-induced pituitary dysfunction remain undiagnosed and untreated because of the non-specific and subtle clinical manifestations of hypopituitarism. Replacement of the deficient hormones, of which GH is the commonest hormone lost, may not only reverse the clinical manifestations and neurocognitive dysfunction, but may also help posttraumatic disabled patients resistant to classical treatment who have undiagnosed hypopituitarism and GH deficiency in particular. Therefore, early diagnosis, which depends on the awareness of TBI as a cause of neuroendocrine abnormalities among the medical community, is crucially important.
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