The Development of Neuroendocrine Disturbances over Time: Longitudinal Findings in Patients after Traumatic Brain Injury and Subarachnoid Hemorrhage.

Previous reports suggest that neuroendocrine disturbances in patients with traumatic brain injury (TBI) or aneurysmal subarachnoid hemorrhage (SAH) may still develop or resolve months or even years after the trauma. We investigated a cohort of n = 168 patients (81 patients after TBI and 87 patients after SAH) in whom hormone levels had been determined at various time points to assess the course and pattern of hormonal insufficiencies. Data were analyzed using three different criteria: (1) patients with lowered basal laboratory values; (2) patients with lowered basal laboratory values or the need for hormone replacement therapy; (3) diagnosis of the treating physician. The first hormonal assessment after a median time of three months after the injury showed lowered hormone laboratory test results in 35% of cases. Lowered testosterone (23.1% of male patients), lowered estradiol (14.3% of female patients) and lowered insulin-like growth factor I (IGF-I) values (12.1%) were most common. Using Criterion 2, a higher prevalence rate of 55.6% of cases was determined, which correlated well with the prevalence rate of 54% of cases using the physicians' diagnosis as the criterion. Intraindividual changes (new onset insufficiency or recovery) were predominantly observed for the somatotropic axis (12.5%), the gonadotropic axis in women (11.1%) and the corticotropic axis (10.6%). Patients after TBI showed more often lowered IGF-I values at first testing, but normal values at follow-up (p < 0.0004). In general, most patients remained stable. Stable hormone results at follow-up were obtained in 78% (free thyroxine (fT4) values) to 94.6% (prolactin values).

Effects of growth hormone replacement within the KIMS survey on estimated cardiovascular risk and predictors of risk reduction in patients with growth hormone deficiency.

OBJECTIVE: There is growing evidence for an increased cardiovascular (CV) risk in untreated growth hormone deficiency of adults (GHD). We aimed at estimating CV risk with established algorithms before and during GH replacement in GHD and in healthy controls and at identifying predictors of risk reduction. DESIGN: A prospective, nested case-control study. PATIENTS: We included 344 patients (44·7 ± 14·9 years) from the German Pfizer (formerly Kabi) International Metabolic Database (KIMS) cohort and included a healthy sex- and age-matched control group from a primary care cohort. MEASUREMENTS: We calculated Framingham, Prospective Cardiovascular Münster Heart Study (PROCAM) and European Society of Cardiology (ESC) Score algorithms at all time points. In multivariate analyses, we analysed potential predictors of 2-year reduction in CV risk, defined as a higher than median reduction in risk. RESULTS: In KIMS, the estimated 10-year risks of CV events or CV mortality calculated with Framingham, PROCAM and ESC Score algorithms at baseline were 4·6%, 6·0% and 2·3%, respectively. These dropped to 2·4%, 4·8% and 0·8%, respectively, after 2 years of GH replacement (all P < 0·001 vs baseline) and returned to baseline levels after four years of GH replacement. In controls, the Framingham risk estimates were lower than in KIMS at baseline. All risk estimates increased during follow-up and were significantly higher than in KIMS after four years (all P < 0·01). In backward-selection models, high total cholesterol, low high-density lipoprotein (HDL) cholesterol and male sex were significant predictors of response in most scores. CONCLUSION: Two years of GH replacement decreased CV risk estimates approximately by half. Male sex, high total and low HDL cholesterol levels are potential predictors of good response.

Prevalence of low male testosterone levels in primary care in Germany: cross-sectional results from the DETECT study.

OBJECTIVE: Low testosterone levels in men occur with increasing age and are associated with increased morbidity, particularly metabolic syndrome, and mortality. As the prevalence of hypogonadal testosterone levels has not been assessed in the primary care setting in Europe, we aimed to investigate the prevalence of low testosterone levels in this setting, and the patient characteristics and comorbidities associated with this finding. DESIGN: A cross-sectional, epidemiological study (the Diabetes Cardiovascular Risk-Evaluation: Targets and Essential Data for Commitment of Treatment (DETECT) study). PATIENTS: A total of 2719 male primary care patients (age 58.7 +/- 13.4 years) were included. MEASUREMENTS: Testosterone was measured in all patients. Information on diseases, risk conditions and treatments was documented by the primary care physicians. A large set of laboratory parameters was measured in a central laboratory. We calculated univariate and multivariate logistic regression models to assess the associations of low testosterone levels with different health and life style factors. RESULTS: A total of 19.3% of all men had hypogonadism as defined by testosterone levels < 3.0 ng/ml. Stepwise logistic regression analysis revealed that obesity, metabolic syndrome, cancer, intake of six or more drugs, acute inflammation and nonsmoking were associated with hypogonadal testosterone levels. Higher age, liver diseases, and cancer were associated with very low testosterone levels (< 1.0 ng/ml). CONCLUSIONS: Hypogonadal testosterone levels are common in primary care, particularly in patients with the above conditions.

Prevalence of mental disorders in acromegaly: a cross-sectional study in 81 acromegalic patients.

OBJECTIVE: Emotional and behavioural alterations have been described in acromegalic patients. However, the nature and psychopathological value of these changes remained unclear. We examined whether acromegalic patients have an increased prevalence of comorbid DSM-IV (Diagnostic and Statistical Manual of Mental Disorders, 4th Version) mental disorders in comparison to subjects with or without chronic somatic disorders. DESIGN/PATIENTS: A cross-sectional study was conducted at the Max-Planck Institute of Psychiatry and the Ludwig-Maximilians-University Munich. Eighty-one acromegalic patients were enrolled. Control subjects with (n = 3281) and without chronic somatic (n = 430) disorders were drawn from a representative sample of the German adult general population as part of the Mental Health Supplement of the German Health Interview and Examination Survey. Lifetime and 12-month prevalences of DSM-IV mental disorders were assessed with face-to-face interviews using the standardized German computer-assisted version of the Composite International Diagnostic Interview. RESULTS: Acromegalic patients had increased lifetime rates of affective disorders of 34.6% compared to 21.4% in the group with chronic somatic disorders (OR = 2.0, 95% CI 1.2-3.2) and to 11.1% in the group without chronic somatic disorders (OR = 4.4, 95% CI 2.3-8.7). Affective disorders that occurred significantly more often than in the control groups began during the putative period of already present GH excess. Higher rates of DSM-IV mental disorders were reported in those patients with additional treatment after surgery. CONCLUSION: Acromegaly is associated with an increased prevalence and a specific pattern of affective disorders. Greater emphasis on diagnosing and treatment of mental disorders in acromegalic patients might improve the disease management.

Computer Vision Technology in the Differential Diagnosis of Cushing's Syndrome.

OBJECTIVE: Cushing's syndrome is a rare disease characterized by clinical features that show morphological similarity with the metabolic syndrome. Distinguishing these diseases in clinical practice is challenging. We have previously shown that computer vision technology can be a potentially useful diagnostic tool in Cushing's syndrome. In this follow-up study, we addressed the described problem by increasing the sample size and including controls matched by body mass index. METHODS: We enrolled 82 patients (22 male, 60 female) and 98 control subjects (32 male, 66 female) matched by age, gender and body-mass-index. The control group consisted of patients with initially suspected, but biochemically excluded Cushing's syndrome. Standardized frontal and profile facial digital photographs were acquired. The images were analyzed using specialized computer vision and classification software. A grid of nodes was semi-automatically placed on disease-relevant facial structures for analysis of texture and geometry. Classification accuracy was calculated using a leave-one-out cross-validation procedure with a maximum likelihood classifier. RESULTS: The overall correct classification rates were 10/22 (45.5%) for male patients and 26/32 (81.3%) for male controls, and 34/60 (56.7%) for female patients and 43/66 (65.2%) for female controls. In subgroup analyses, correct classification rates were higher for iatrogenic than for endogenous Cushing's syndrome. CONCLUSION: Regarding the advanced problem of detecting Cushing's syndrome within a study sample matched by body mass index, we found moderate classification accuracy by facial image analysis. Classification accuracy is most likely higher in a larger sample with healthy control subjects. Further studies might pursue a more advanced analysis and classification algorithm.

Hypopituitarism.

Incidence and prevalence of hypopituitarism are estimated to be 4.2 per 100,000 per year and 45.5 per 100,000, respectively. Although the clinical symptoms of this disorder are usually unspecific, it can cause life-threatening events and lead to increased mortality. Current research has refined the diagnosis of hypopituitarism. Identification of growth hormone and corticotropin deficiency generally requires a stimulation test, whereas other deficiencies can be detected by basal hormones in combination with clinical judgment. Newly developed formulations of replacement hormones are convenient and physiological. Work has shown that many patients with brain damage--such as traumatic brain injury or aneurysmal subarachnoid haemorrhage--are at high risk of (sometimes unrecognised) hypopituitarism. Thus, a much increased true prevalence of this disorder needs to be assumed. As a result, hypopituitarism is not a rare disease and should be recognised by the general practitioner.

Insulin-like growth factor-1 in plasma and brain: regulation in health and disease.

IGF-1 was first described as a growth mediating factor regulated in the context of the somatotrophic axis. During the last decade, it has gained much attention for its role in the regulation of lifespan, brain function, cell growth, and metabolism. Associations of plasma IGF-1 levels in physiological and pathological conditions such as aging, cardiovascular disease, metabolic disorders, dementia, and neurodegenerative disorders, and its potential as a neurotrophic agent, have been intensively studied. Acromegaly due to jGH and IGF-1 excess and growth hormone deficiency with decreased GH and IGF-1 might serve as models to study IGF-1 function, but the effects of GH and IGF-1 in these conditions are often indistinguishable. Due to this overlap, this article will only briefly mention pathophysiological implications in acromegaly and growth hormone deficiency. It will focus on IGF-1 and give an overview of the vast literature on the role and regulation of IGF-1 in plasma and brain, its alteration in health and disease and its possible therapeutical applications.

Efficacy of a polyethylene glycol marker system in urine drug screening in an opiate substitution program.

AIMS: Screening for concomitant drug consumption is necessary in opiate substitution therapy of opiate-dependent patients. Adulteration of samples is a common problem in this setting. A recently developed polyethylene glycol marker system allows reliable identification of urine samples. In this study, we aimed to compare the rates of drug detection in conventional and marker urine samples. DESIGN: This cross-sectional evaluation was performed in an ambulatory opiate substitution program. We studied 55 opiate-dependent patients (32 men, 23 women). In all patients we compared the rates of drugs detected in the marker urine with the most recent conventional urine control. Additionally we assessed the rate of marker urine manipulation. FINDINGS: In the conventional urine controls, opiates and benzodiazepines were found in 3.6 and 27%, respectively, whereas in the marker urine controls, these rates were 33 and 40%, respectively. Signs of urine manipulation were present in 35%. The rates of concomitant consumption and urine manipulation were higher among the patients without than among those with take-home substitution. CONCLUSIONS: With the marker urine, an unexpectedly high prevalence of concomitant consumption can be found. Marker urine testing has a significantly higher sensitivity for the detection of concomitant drug use.

Enantio-selective effects of clenbuterol in cultured neurons and astrocytes, and in a mouse model of cerebral ischemia.

Neuroprotective effects of the lipophilic beta(2)-adrenoceptor agonist clenbuterol have been established in neuronal cultures and in various rodent models of stroke. In previous studies, however, clenbuterol was always applied as a racemate, while it has not been established whether the enantiomers differ in their neuroprotective activities. Here, we demonstrate that R,S-clenbuterol and S(+)-clenbuterol, but not the R(-)-enantiomer protect cultured neurons against glutamate-mediated excitotoxicity and staurosporine-induced apoptosis. Similar to previous findings with clenbuterol racemate, the neuroprotective effect of S(+)-clenbuterol correlated well with morphological changes of astrocytes which transformed into dense stellate cells with dendritic processes indicating beta(2)-adrenoceptor-mediated activation. Most importantly, the S(+)-enantiomer but not R(-)-clenbuterol reduced ischemic brain damage similar to the effect of the racemate. The selective beta(2)-adrenoceptor antagonist butoxamine blocked this neuroprotective effect of S(+)-clenbuterol. In addition, S(+)-clenbuterol significantly reduced blood pressure, enhanced blood glucose levels and increased glucocorticoid levels compared to vehicle-or R(-)-clenbuterol-treated controls. These results clearly demonstrate that S(+)-clenbuterol is the eutomer that mediates neuroprotective effects of the beta(2)-adrenoceptor agonist but also according changes of physiological parameters.

Hypothalamopituitary dysfunction following traumatic brain injury and aneurysmal subarachnoid hemorrhage: a systematic review.

CONTEXT: Neuroendocrine dysfunction following traumatic brain injury and aneurysmal subarachnoid hemorrhage may occur with a much higher prevalence than previously suspected. This sequela is a potentially serious but treatable complication of brain injury. OBJECTIVE: To review research on hypothalamopituitary dysfunction as an underdiagnosed consequence of traumatic brain injury and subarachnoid hemorrhage, the natural history of this complication, and the potential clinical and public health implications of posttraumatic hypopituitarism. EVIDENCE ACQUISITION: The MEDLINE database was searched for articles published between 2000 and 2007 using any combination of the terms traumatic brain injury or subarachnoid hemorrhage with pituitary, hypopituitarism, growth hormone deficiency, hypogonadism, hypocortisolism, hypothyroidism, or diabetes insipidus. The reference lists of articles identified by this search strategy were also searched. All articles reporting original data on endocrine outcomes after traumatic brain injury or aneurysmal subarachnoid hemorrhage in peer-reviewed journals with regard to prevalence, pathogenesis, risk factors, outcomes, and clinical course were selected. We pooled data and calculated prevalence rates and 95% confidence intervals (CIs). RESULTS: We identified 19 studies including 1137 patients. The pooled prevalences of hypopituitarism in the chronic phase after traumatic brain injury and aneurysmal subarachnoid hemorrhage were 27.5% (95% confidence interval [CI], 22.8%-28.9%) and 47% (95% CI, 37.4%-56.8%), respectively. The pooled prevalence of hypopituitarism was greater in patients with severe compared with those with mild or moderate traumatic brain injury. Early neuroendocrine abnormalities were transient in some patients while, less commonly, hypopituitarism evolved over time in others. Patients with posttraumatic hypopituitarism showed an impaired quality of life and an adverse metabolic profile. CONCLUSION: Hypopituitarism is a common complication of both traumatic brain injury and aneurysmal subarachnoid hemorrhage and might contribute to morbidity and poor recovery after brain injury.

Opposite associations of age-dependent insulin-like growth factor-I standard deviation scores with nutritional state in normal weight and obese subjects.

OBJECTIVE: Insulin-like growth factor-I (IGF-I) has been suggested to be a prognostic marker for the development of cancer and, more recently, cardiovascular disease. These diseases are closely linked to obesity, but reports of the association of IGF-I with measures of obesity are divergent. In this study, we assessed the association of age-dependent IGF-I standard deviation scores with body mass index (BMI) and intra-abdominal fat accumulation in a large population. DESIGN: A cross-sectional, epidemiological study. METHODS: IGF-I levels were measured with an automated chemiluminescence assay system in 6282 patients from the DETECT study. Weight, height, and waist and hip circumference were measured according to the written instructions. Standard deviation scores (SDS), correcting IGF-I levels for age, were calculated and were used for further analyses. RESULTS: An inverse U-shaped association of IGF-I SDS with BMI, waist circumference, and the ratio of waist circumference to height was found. BMI was positively associated with IGF-I SDS in normal weight subjects, and negatively associated in obese subjects. The highest mean IGF-I SDS were seen at a BMI of 22.5-25 kg/m2 in men (+0.08), and at a BMI of 27.5-30 kg/m2 in women (+0.21). Multiple linear regression models, controlling for different diseases, medications and risk conditions, revealed a significant negative association of BMI with IGF-I SDS. BMI contributed most to the additional explained variance to the other health conditions. CONCLUSIONS: IGF-I standard deviation scores are decreased in obesity and underweight subjects. These interactions should be taken into account when analyzing the association of IGF-I with diseases and risk conditions.

[Prevalence, drug treatment and metabolic control of diabetes mellitus in primary care]. / Prävalenz, medikamentöse Behandlung und Einstellung des Diabetes mellitus in der Hausarztpraxis.

BACKGROUND AND PURPOSE: The primary care sector is of key importance for the management of patients with diabetes mellitus. The authors investigated (a) the prevalence of diabetes mellitus type 1 and type 2, (b) the type and frequency of non-drug and drug treatment and its association with the presence of diabetic complications, and (c) the quality of metabolic control by HbA1c. METHODS: Using a nationwide probability sample of 3,188 general practices (response rate [RR] 50.6%), a total of 55,518 (RR 93.5%) patients were assessed in a prospective cross-sectional study by their physicians in September 2003 in a standardized manner using questionnaires, physician interview, and laboratory assessments. In addition to diabetes mellitus, 28 diseases were explicitly screened for, among them typical macrovascular (coronary heart disease, cerebrovascular disease, peripheral arterial disease) and microvascular disease (neuropathy, nephropathy, retinopathy, diabetic foot) complications. RESULTS: The prevalence of diabetes mellitus was 0.5% (type 1) and 14.7% (type 2), respectively. 49.5% (type 1) and 50.2% (type 2) of patients had micro- or macrovascular complications. 6.8% did not receive any treatment, 13.5% received non-drug treatment, and 75.3% received oral antidiabetic drugs and/or insulin (26.6% a combination of two or more). Compared to diabetics without any complications, treatment intensity was significantly higher in patients with microvascular complications (odds ratio [OR] 3.02), but not in those with macrovascular complications only (OR 0.98). An HbA1c value>or=7.0% was recorded in 39.6% of patients. CONCLUSION: Compared to previous studies in this setting, the proportion of diabetics with drug treatment has increased. More patients receive antidiabetic drug combinations. Quality of blood sugar control appears to have improved as well.

Neuroendocrine Disturbances One to Five or More Years after Traumatic Brain Injury and Aneurysmal Subarachnoid Hemorrhage: Data from the German Database on Hypopituitarism.

Neuroendocrine disturbances are common after traumatic brain injury (TBI) and aneurysmal subarachnoid hemorrhage (SAH), but only a few data exist on long-term anterior pituitary deficiencies after brain injury. We present data from the Structured Data Assessment of Hypopituitarism after TBI and SAH, a multi-center study including 1242 patients. We studied a subgroup of 351 patients, who had sustained a TBI (245) or SAH (106) at least 1 year before endocrine assessment (range 1-55 years) in a separate analysis. The highest prevalence of neuroendocrine disorders was observed 1-2 years post-injury, and it decreased over time only to show another maximum in the long-term phase in patients with brain injury occurring ≥5 years prior to assessment. Gonadotropic and somatotropic insufficiencies were most common. In the subgroup from 1 to 2 years after brain injury (n = 126), gonadotropic insufficiency was the most common hormonal disturbance (19%, 12/63 men) followed by somatotropic insufficiency (11.5%, 7/61), corticotropic insufficiency (9.2%, 11/119), and thyrotropic insufficiency (3.3%, 4/122). In patients observed ≥ 5 years after brain injury, the prevalence of somatotropic insufficiency increased over time to 24.1%, whereas corticotropic and thyrotrophic insufficiency became less frequent (2.5% and 0%, respectively). The prevalence differed regarding the diagnostic criteria (laboratory values vs. physician`s diagnosis vs. stimulation tests). Our data showed that neuroendocrine disturbances are frequent even years after TBI or SAH, in a cohort of patients who are still on medical treatment.

Night sleep EEG and daytime sleep propensity in adult hypopituitary patients with growth hormone deficiency before and after six months of growth hormone replacement.

BACKGROUND: Hypopituitary patients with growth hormone deficiency (GHD) complain of reduced vitality, general fatigue, lack of concentration, irritability and reduced alertness during daytime. It is unclear whether these symptoms are primarily due to GH-deficiency and/or secondary to GHD related sleep impairments. Bi-directional interactions between the somatotropic system and human sleep patterns are well established. However, data on the effect of GH either in subjects without GHD or in patients with GHD under GH replacement therapy on the sleep electroencephalogram (EEG) are controversial. No reports exist about objective measures of daytime sleepiness in GH deficient patients before and during GH-therapy. OBJECTIVE: To assess the effects of GH on nocturnal and daytime sleep in adult patients with GHD before and during recombinant human GH (rhGH, Somatropin) replacement therapy. METHODS: Eighteen adult patients with GHD (4 women and 14 men) participated in the study. Mean age at the beginning of the study was 48.5 years (range 27-64 years). Ten patients were recruited from a double-blind, randomized placebo controlled trial over 6 months, followed by an open treatment period of 6 additional months (Group I). In all patients from this group, only the effects of the first 6 months of GH treatment were assessed. Eight additional patients were treated in an open study design for 6 months (Group II). Nocturnal sleep recordings and daytime sleep EEGs with a multiple sleep latency test were performed at baseline and after 6 months of additional GH replacement therapy. RESULTS: One patient dropped out due to side effects and was not included in sleep analysis. IGF-1 levels were increased in all patients, partially in a supraphysiologic range. Side effects were mainly mild but in one patient (from group II), general muscle pain led to interruption of the study. Therefore sleep analysis was only done in 17 patients. Sleep parameters were comparable to healthy control groups from the literature. GH substitution over 6 months did neither affect total sleep time nor times spent in different sleep stages. REM sleep density was also not changed. Daytime sleep propensity as measured by the multiple sleep latency test was not influenced by GH treatment. CONCLUSIONS: GH replacement does neither affect night sleep nor daytime sleep propensity in GH deficient hypopituitary adults. GH substitution has no sleep disturbing effect.

Anterior pituitary hormone abnormalities following traumatic brain injury.

Traumatic brain injury (TBI) leads to approximately 100 hospitalizations per 100,000/year. Whereas diabetes insipidus is a well-known complication of TBI, anterior hypopituitarism as a consequence of TBI has been regarded as rare. More recent studies, however, suggest a prevalence of at least 30% of anterior pituitary dysfunction after TBI. Clinical signs of anterior hypopituitarism are often subtle and may be masked by sequalae of TBI. Therefore, post-traumatic anterior pituitary dysfunction may remain undiagnosed and, possibly, aggravate symptoms of brain injury. Moreover it may, if undiagnosed, lead to potentially fatal endocrine crises. This review updates clinical researchers, physicians, and other healthcare providers on the relationship between TBI and subsequent anterior pituitary insufficiency.

Pituitary dysfunction after traumatic brain injury: a clinical and pathophysiological approach.

Traumatic brain injury (TBI) is a growing public health problem worldwide and is a leading cause of death and disability. The causes of TBI include motor vehicle accidents, which are the most common cause, falls, acts of violence, sports-related head traumas, and war accidents including blast-related brain injuries. Recently, pituitary dysfunction has also been described in boxers and kickboxers. Neuroendocrine dysfunction due to TBI was described for the first time in 1918. Only case reports and small case series were reported until 2000, but since then pituitary function in TBI victims has been investigated in more detail. The frequency of hypopituitarism after TBI varies widely among different studies (15-50% of the patients with TBI in most studies). The estimates of persistent hypopituitarism decrease to 12% if repeated testing is applied. GH is the most common hormone lost after TBI, followed by ACTH, gonadotropins (FSH and LH), and TSH. The underlying mechanisms responsible for pituitary dysfunction after TBI are not entirely clear; however, recent studies have shown that genetic predisposition and autoimmunity may have a role. Hypopituitarism after TBI may have a negative impact on the pace or degree of functional recovery and cognition. What is not clear is whether treatment of hypopituitarism has a beneficial effect on specific function. In this review, the current data related to anterior pituitary dysfunction after TBI in adult patients are updated, and guidelines for the diagnosis, follow-up strategies, and therapeutic approaches are reported.

Central effects of the somatotropic system.

The somatotropic axis interacts with the central nervous system (CNS) on several levels. Growth hormone (GH) and insulin-like growth factor-I (IGF-I) receptors are expressed in many brain areas including the hippocampus, pituitary and hypothalamus. GH and IGF-I can pass the blood-brain barrier by an as yet not completely understood mechanism. They can also be produced in the brain and thus act via paracrine/autocrine mechanisms. GH and IGF-I are important factors in the development and differentiation of the CNS and have protective properties in dementia, and in traumatic and ischemic injury of the CNS. An improvement in cognitive functioning in GH-deficient patients by GH substitution has been shown. Significant results could, however, only be achieved with supraphysiological doses. In some studies, a correlation between IGF-I and cognitive function in the elderly has been found. GH has an important impact on mood and well-being with GH secretory capacity being reduced in depression. Pulsatile GH secretion is closely related to slow wave sleep (SWS) with SWS being stimulated by GH releasing hormone and rapid eye movement (REM) sleep by GH.

Screening for hypopituitarism in 509 patients with traumatic brain injury or subarachnoid hemorrhage.

We performed a screening on patients with traumatic brain injury (TBI) or subarachnoid hemorrhage (SAH) to determine the prevalence of post-traumatic hypopituitarism in neurorehabilitation in a cross-sectional, observational single-center study. In addition, the therapeutic consequences of our screening were analyzed retrospectively. From February 2006 to August 2009, patients between 18 and 65 years (n=509) with the diagnosis of TBI (n=340) or SAH (n=169) were screened within two weeks of admittance to neurorehabilitation as clinical routine. Blood was drawn to determine fasting cortisol, free thyroxine (fT4), prolactin, testosterone or estradiol, and insulin-like growth factor I (IGF-I). Patients with abnormalities in the screening or clinical signs of hypopituitarism received further stimulation tests: growth hormone releasing hormone -L-arginine-test and adrenocorticotrophic hormone (ACTH)-test (n=36); ACTH-test alone (n=26); or insulin tolerance test (n=56). In our screening of 509 patients, 28.5% showed lowered values in at least one hormone of the hypothalamus-pituitary axis and 4.5% in two or more axes. The most common disturbance was a decrease of testosterone in 40.7% of all men (in the following 13/131 men were given substitution therapy). Low fT4 was detected in 5.9% (n=3 were given substitution therapy). Low IGF-I was detected in 5.8%, low cortisol in 1.4%, and low prolactin in 0.2%; none were given substitution therapy. Further stimulation tests revealed growth hormone deficiency in 20.7% (n=19/92) and hypocortisolism in 23.7% (n=28/118). Laboratory values possibly indicating hypopituitarism (33%) were common but did not always implicate post-traumatic hypopituitarism. Laboratory values possibly indicating hypopituitarism were common in our screening but most patients were clinically not diagnosed as pituitary insufficient and did not receive hormone replacement therapy. A routine screening of all patients in neurorehabilitation without considering the time since injury, the severity of illness and therapeutic consequences seems not useful.