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3- Pituitary insufficiency after traumatic brain injury. J Clin Neurosci.  2009; 16(2):202-8. Wachter D; Gündling K; Oertel MF; Stracke H; Böker DK. Department of Neurosurgery, University Hospital, Giessen-Marburg, Klinikstrasse 29, 35385 Giessen, Germany.

After traumatic brain injury (TBI), patients present with psychological disorders that may be explained by post-traumatic pituitary insufficiency (PI). The goal of this study was to determine the relationship between hypopituitarism, neuropsychological changes and findings on CT scans after TBI. Hospital charts of 55 TBI patients were screened for age, Glasgow Coma Scale (GSC) score, hypoxia or hypotension. The first two CT scans were analyzed for hemorrhagic lesions. Basal levels of the following hormones were recorded: cortisol, prolactin, estradiol, testosterone, insulin-like growth factor 1 and free thyroxine. Hormonal stimulation tests were performed either if the basal hormone screening revealed an abnormality or if the patient answered "yes" to at least one question in the non-evaluated neuropsychological questionnaire. Overall, 14 out of 55 patients (25.4%) presented with PI; one of them with two hormonal deficits. Growth hormone deficit, hypothyroidism and hypocortisolism were found in one, one and two patients, respectively. Neuropsychological complaints were present in 67% of the patients and were associated with intracerebral hemorrhagic lesions and not PI. Neuropsychological complaints after TBI are more frequent than PI. Brain tissue damage is most important than PI in the development of psychological changes after TBI.

Neurobehavioral and quality of life changes associated with growth hormone insufficiency after complicated mild, moderate, or severe traumatic brain injury. J Neurotrauma.  2006; 23(6):928-2.  DF ; McArthur DL ; Levin H ; Swimmer S ; Dusick JR ; Cohan P ; Wang C ; Swerdloff R Division of Neurosurgery, and Gonda Diabetes Center, UCLA School of Medicine, Los Angeles, California, and Los Angeles Biomedical Research Institute, Torrance, California, USA.

Adult-onset growth hormone deficiency (GHD) has been associated with reduced quality of life (QOL) and neurobehavioral (NB) deficits. This prospective study tested the hypothesis that traumatic brain injury (TBI) patients with GHD or GH insufficiency (GHI) would exhibit greater NB/QOL impairment than patients without GHD/GHI. Complicated mild, moderate, and severe adult TBI patients (GCS score 3-14) had pituitary function and NB/QOL testing performed 6-9 months postinjury. GH-secretory capacity was assessed with a GHRH-arginine stimulation test and GHD and GHI were defined as peak GH<6 or <or=12 ng/mL (5th and 10th percentiles of healthy control subjects, respectively). Of 44 patients (mean age, 32+/-18 years; median GCS, 7), one (2%) was GHD, seven (16%) were GHI, and 36 (82%) were GH-sufficient at 6-9 months post-injury. Mean peak GH was 8.2+/-2.1 ng/mL in the GHD/GHI group versus 45.7+/-29 ng/mL in the GH sufficient group. The two groups were well-matched in injury characteristics, except that one patient with GHD had central hypogonadism treated with testosterone prior to NB/QOL testing. At 6-9 months postinjury, patients with GHD/GHI had higher rates of at least one marker of depression, and reduced QOL  in the domains of limitations due to physical health, energy and fatigue, emotional well-being, pain, and general health . Chronic GHI develops in approximately 18% of patients with complicated mild, moderate, or severe TBI, and is associated with depression and diminished QOL. The impact of GH replacement therapy on NB function and QOL in these TBI patients is being tested in a randomized placebo-controlled trial.
Cognitive deterioration due to GH deficiency in patients with Traumatic Brain Injury: A preliminary report. Brain Injury, July 2007; 21(8): 871–875. J. Leon-Carrion et al 1Department of Experimental Psychology, Human Neuropsychology Laboratory, University of Seville, Spain, Division of Endocrinology, Critical Care and Emergency Department, University Hospital Virgen del Rocio, Seville, Spain, and Center for Brain Injury Rehabilitation (CRECER), Seville, Spain Primary objective: To determine whether cognitive and behavioral disorders observed in TBI patients are due to hormonal deficits or to the brain injury itself.Methods and procedures: Studied 22 severe TBI patients (GCS<8): 11 had isolated GH deficiency and 11 did not. Prepared detailed clinical reports on patients and performed physical examinations, standard biochemical and full blood count analysis. Patients underwent neuropsychological assessment and hormonal evaluation 6 months after TBI diagnosis.Results: TBI patients with GH deficiency show greater deficits in attention, executive functioning, memory and emotion than those without GH deficiency.Conclusions: Results show GH-related cognitive impairment in patients who develop GH deficiency after TBI and suggest that treatment of GH deficiency would improve cognition. The clinical importance of these findings should be established to better understand the nature, magnitude and meaning of GH-related cognitive impairment in patients who develop GH deficiency after TBI.
Neuroendocrine dysfunction in the acute phase of traumatic brain injury. Clinical Endocrinology (2004) 60 , 584–591. Amar Agha, et al., Academic Department of Endocrinology, Department of Neurosurgery and Department of Clinical Chemistry, Beaumont Hospital, Dublin, Ireland. Pituitary hormone abnormalities have been reported in up to 50% of survivors of traumatic brain injury (TBI) who were investigated several months or longer following the event. The frequency of pituitary dysfunction in the early post-TBI period is unknown.OBJECTIVE: Evaluate the prevalence of anterior and posterior pituitary dysfunction in the early phase TBI.SUBJECTS: Fifty consecutive patients admitted to the neurosurgical unit with severe or moderate TBI [initial Glasgow Coma Scale (GCS) score 3–13], and 31 matched healthy control volunteers were studied.METHODS: The glucagon stimulation test (GST) was performed at a median of 12 days (range 7–20) following TBI. Baseline thyroid function, PRL, IGF-1, gonadotrophins, testosterone or oestradiol, plasma sodium, plasma and urine osmolalities or the standard observed water deprivation test were performed. The control subjects underwent the GST for GH and cortisol responses; other parameters were compared to locally derived reference ranges.RESULTS: Control data indicated that peak serum GH of > 5 ng/ml and cortisol > 450 nmol/l following glucagon stimulation should be taken as normal. Nine TBI patients (18%) had GH response < 5 ng/ml (12 mU/l). Eight patients (16%) had peak cortisol responses < 450 nmol/l. Compared to controls, basal cortisol values were significantly lower in patients with subnormal cortisol responses to glucagon and significantly higher in (26%) had cranial diabetes insipidus (DI) and seven (14%) had syndrome of inappropriate ADH secretion.CONCLUSION: Our data show that post-traumatic neuroendocrine abnormalities occur early and with high frequency, which may have significant implications for recovery and rehabilitation of TBI patients.
Effect of recombinant growth hormone replacement in a growth hormone deficient subject recovering from mild traumatic brain injury: A case report. Brain Injury, March 2010; 24(3): 560–567  Vinita Bhagia,  et al. University of Texas Medical Branch, Galveston, TX, USA, 2Marquette University, Milwaukee, WI, USA, Transitional Learning Center, Galveston, TX, USA, and University of Kentucky, Lexington, KY, USA. Objective: To assess the effects of growth hormone (GH) replacement in an individual who sustained mild traumatic brain injury (mTBI) as an adult and was found to have GH deficiency by glucagon stimulation testing.Participant: A 43-year old woman who sustained a mild TBI at age 37 years. She was 6.8 years post-injury when she began supplementation.Intervention: Recombinant human GH (rhGH) subcutaneously per day for 1 year. Main outcome measures: Single fiber muscle function was evaluated from muscle biopsies. Body composition, muscle strength and peak aerobic capacity was also measured. In addition, neuropsychological tests of memory, processing speed and motor dexterity and speed, as well as a self-report depression inventory were administered. All assessments were performed at baseline and after 6 and 12 months of rhGH replacement therapy.Results: Single muscle fiber changes were greatest at 6 months. Body composition showed continuous improvement. Muscle strength improved for knee extension. Peak oxygen consumption increased at 6 months and total work and ventilatory equivalents continued to improve at 12 months. Significant improvements in neuropsychological test performance were not found, with the exception of performance on a test of motor dexterity and speed.Conclusion: rhGH replacement in a subject with GH deficiency after mild TBI improves muscle force production, body composition and aerobic capacity. Reliable improvements on tests of cognition were not found in this subject.
The Effects of Growth Hormone Replacement Therapy on Cognition after TBI. J Neurotrauma, 27, 1565-1575. 2010. Brent E. Masel, M.D.*, Dennis J. Zgaljardic, Ph.D.  Transitional Learning Center at Galveston. Galveston, Texas 77550  Although traumatic brain injury (TBI) is a major public health issue, medical science has little to offer for the persistent symptoms that prevent many of these individuals from fully re-entering society. Post traumatic hypopituitarism and specifically, Growth Hormone Deficiency (GHD) has been found in a large percentage of individuals with chronic moderate to severe TBIs, yet presently, there are no published treatment studies of hormone replacement in this population. In this study, eighty-three subjects with chronic TBIs were screened for hypopituitarism. Forty-two subjects were found to have either GHD or GH insufficiency (GHI) of which twenty-three agreed to be randomized to either a year of GH replacement or placebo. All subjects completed the study with no untoward side effects from treatment. A battery of neuropsychological tests and functional measures were administered before and after treatment. Improvement was seen on the following tests: Dominant Hand Finger Tapping Test, Wechsler Adult Intelligence Scale III - Information Processing Speed Index, California Verbal Learning Test II and the Wisconsin Card Sorting Test (executive functioning). The findings of this pilot study provide preliminary evidence suggesting that some of the cognitive impairments observed in persons who are GHD/GHI after TBI may be partially reversible with appropriate GH replacement therapy.

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