Einleitung: Eine größere Zahl von Studien hat gezeigt, dass eine Hypophyseninsuffizienz nach Schädel-Hirn-Trauma (SHT) oder Subarachnoidalblutung (SAB) relativ häufig ist (Schneider HJ et al 2007). So wurde in einer eigenen prospektiven Studie (n=78) 3 Monate nach SHT bei 56% und 12 Monate nach SHT bei 36% eine Störung mindestens einer hypophysären Hormonachse gefunden (Schneider HJ et al., 2006). Aufgrund dieser Ergebnisse wurden an unserer Klinik ein Routinescreening und der Insulin-Hypoglykämie-Test (IHT) etabliert, Erfahrungen damit und Ergebnisse werden hier dargestellt. Methoden: Bei allen ab Januar 2007 in der Neurologischen Klinik Bad Aibling aufgenommenen Patienten im Alter von 18a bis 65a mit SHT oder SAB wurden 1 bis 14 Tage nach Aufnahme folgende basale Hormone bestimmt: fT4, Cortisol, Prolaktin, Östradiol (Frauen) bzw. Testosteron (Männer) und IGF-1. Patienten, die sich nach Aufklärung schriftlich einverstanden erklärten, wurden ferner einem Stimulationstest unterzogen (IHT, bei Epilepsie alternativ GHRH/Arginin + ACTH-Kurztest). Für die Auswertung des maximalen Wachstumshormonanstiegs wurden die BMI-adaptierten Richtwerte nach Corneli (2007) angewendet. Ergebnisse: Insgesamt wurden bislang 403 Patienten (mittleres Alter 44 Jahre, 146 Frauen, 257Männer) gescreent, von diesen hatten 273 ein SHT und 130 eine SAB erlitten. 85 Patienten nahmen an der Stimulationstestung teil, davon erhielten 54 Patienten einen IHT und 31 Patienten einen GHRH/Arginin + ACTH-Kurztest. In der Screening-Untersuchung zeigten 129 von 401 Patienten eine hormonelle Störung. Am häufigsten waren gonadotrope Insuffizienzen zu verzeichnen (38% der Männer). Im GHRH-L-Arginin-Test und ACTH-Kurztest wurden 13% corticotrope Insuffizienzen und keine somatotrope Insuffizienzen diagnostiziert. Im IHT wurden 39% corticotrope Insuffizienzen und 33% somatotrope Insuffizienzen nachgewiesen. Dabei zeigte sich, dass die Lagerung des Patienten (sitzend/liegend) für die Art der Hypoglykämiesymptome sowie den max. Hormonanstieg und damit für die Reliabilität des Tests von wesentlicher Bedeutung ist. Interessanterweise wurde trotz z.T. ausgeprägter Hirnschädigung bei keinem der 54 Patienten im IHT ein epileptischer Anfall beobachtet. Diskussion: Die Ergebnisse bestätigen die Notwendigkeit einer screening-Untersuchung bei Patienten nach einer SAB oder einem SHT. Obwohl epileptische Anfälle als Komplikation eines IHT möglich sind, wurden bei unseren hirngeschädigten Patienten keine epileptischen Anfälle verzeichnet. Die häufig anzutreffende Zurückhaltung gegenüber der Verwendung dieses Tests an hirngeschädigten Patienten ist, zumindest bei anfallsfreien Patienten, möglicherweise nicht gerechtfertigt.

Background Several studies have reported a high prevalence of hypopituitarism after traumatic brain injury (TBI). Risk stratification is a prerequisite for cost-effective hormonal screening of these patients. However, it is still unclear which risk factors predispose patients to develop anterior hypopituitarism after TBI.Objective To assess clinical and radiological risk factors for post-traumatic hypopituitarism.Patients and methods Seventy-eight consecutive patients (52 men, 26 women; mean age 36.0 years, range 18-65 years) with mild, moderate or severe TBI were studied. Endocrine and clinical parameters were assessed 3 and 12 months after TBI.Results We found diffuse axonal injury, basal skull fracture and older age to be major risk factors of post-traumatic hypopituitarism.Conclusions We have defined specific risk factors for the development of post-traumatic hypopituitarism that are consistent with pathophysiological considerations. These findings might help to identify at-risk patients.

Aims: Recent studies show that traumatic brain injury (TBI) and aneurysmal subarachnoid hemorrhage (SAH) are frequent causes of long-term disturbances of hypothalamo-pituitary function. Still, little is known about risk factors and clinical characteristics of pituitary impairment after brain damage. This study aims to address these questions on a larger scale by establishing a national registry of these patients. Methods: Several large trauma centers in Germany treating patients with TBI or SAH and performing endocrine assessments include patients in this on-going investigation. Data are collected using a structured, internet-based study sheet, obtaining information on clinical, radiological and hormonal parameters. Results: To date, 1112 patients (725 TBI, age 43.5±19.7 years; 378 SAH, 49.7±11.8 years) have been included. Stimulation tests for the corticotropic and somatotropic axes were performed in 26% and 22% of the patients, respectively. In patients with known pituitary function, hypopituitarism was reported in 28% and 27% after TBI and SAH, respectively. According to the frequency of impairment, pituitary hormone secretion was impaired the following sequence: ACTH, LH/FSH, GH, and TSH. Conclusions: Our data confirm that hypopituitarism is a common complication of TBI and SAH, also when using data obtained from a large and unselected patient cohort. However, we can not exclude a certain selection bias for performing endocrine stimulation tests only in more severely traumatized patients.

Recent evidence suggests that patients with traumatic brain injury (TBI) are at substantial risk of hypopituitarism. The pathomechanisms, however, are not completely understood yet. Little is known about the association of morphological changes in the sella region with pituitary function in TBI. In this study, we assessed morphological abnormalities of the sella region in patients with TBI and their relation to endocrine function. We studied magnetic resonance (MR) or computed tomography (CT) scans of 22 patients with TBI [17 men, 5 women, age (mean±SD) 43.5±10.6 yr, time after trauma 17.4 ±15.0 yr]. Of these, 15 patients had some degree of hypopituitarism. We found abnormalities of the sella region in 80% of the patients with hypopituitarism and 29% of those without hypopituitarism (Fisher’s exact test, p=0.032). The most common abnormality was loss of volume or empty sella, followed by native signal inhomogeneities, perfusion deficit, and lack of neurohypophyseal signal. Our results indicate that pituitary imaging abnormalities are more common in TBI patients with hypopituitarism than those without. Both immediate trauma-induced pathology as necrosis and hemorrhage as well as multifactorial mid- to long-term changes may underlie these abnormalities.

Einleitung: Aufgrund der Verbesserung der Intensivmedizin und der Ausbildung im Bereich Laienreanimation nimmt die Anzahl der überlebenden Patienten nach Reanimation, aber auch der Patienten mit hypoxischer Encephalopathie stetig zu. Eine Reihe von Untersuchungen haben gezeigt, dass es regional verschiedene Vulnerabilitäten für Schädigungen bei Anoxie gibt. Der Hirnstamm ist vergleichweise unempfindlich gegenüber einer Minderversorgung mit Sauerstoff. Ist die Hypoxie jedoch so gravierend, dass es auch in diesem Bereich zu Gewebeschäden kommt, so ist eine Reanimation in der Regel nicht mehr erfolgreich.

OBJECTIVE Patients with traumatic brain injury (TBI) are at moderate risk of GH deficiency (GHD), requiring a diagnostic test with high specificity. The GHRH + arginine (GHRH + ARG) test has been recommended as a reliable alternative to the insulin-tolerance test (ITT) as a standard test with a cutoff level of 9 ng/ml. However, it has recently been questioned for its low specificity in obese subjects, and now BMI-dependent cut-off levels are available. In this study, we compared the ITT and GHRH + ARG test in patients with TBI. DESIGN A cross-sectional study METHODS We performed an ITT and a GHRH + ARG test in 21 patients with TBI (6 women, 15 men; mean age 40.2 +/- 12.1 years; BMI 30.7 +/- 6.2). The number of patients classified discordantly as GH deficient by the ITT and the GHRH + ARG test with both classical and BMI-dependent cut-off levels was assessed. RESULTS Using the GHRH + ARG test with the classical cut-off ( 3 ng/ml), and one patient as GH sufficient who had a blunted GH response to ITT (discordance rate 61.9%). All patients discordantly classified as GH deficient by the GHRH + ARG test had a BMI of >or= 28. With the BMI-dependent cut-offs (4.2, 8.0, and 11.5 ng/ml in obese, overweight, and lean subjects respectively), only 3 of the 21 patients were discordantly classified (discordance rate 14.3%). CONCLUSIONS Our results discourage the use of a cut-off level of 9 ng/ml for the GHRH + ARG test in obese subjects. The diagnostic reliability of this test is improved with the BMI-dependent cut-offs.

OBJECTIVE:Cross-sectional studies report a high prevalence of hypopituitarism after traumatic brain injury (TBI); however, no longitudinal studies on time of manifestation and reversibility exist. This study was conducted to assess hypopituitarism 3 and 12 months after TBI. DESIGN:This was a prospective, longitudinal, diagnostic study. METHODS:Seventy-eight patients (52 men, 26 women, mean age 36.0 years) with TBI grades I-III and 38 healthy subjects (25 men, 13 women, mean age 36.4 years) as a control group for the GHRH + arginine test were studied. The prevalence of hypopituitarism was assessed 3 and 12 months after TBI by GHRH + arginine test, short adrenocorticotropic hormone (ACTH) test, and basal hormone measurements in patients. RESULTS:After 3 months, 56% of all patients had impairments of at least one pituitary axis with axes being affected as follows: gonadotropic 32%, corticotropic 19%, somatotropic 9% and thyrotropic 8%. After 12 months, fewer patients were affected, but in some cases new impairments occurred; 36% still had impairments. The axes were affected as follows after 12 months: gonadotropic 21%, somatotropic 10%, corticotropic 9% and thyrotropic 3%. CONCLUSIONS:Hypopituitarism occurs often in the post-acute phase after TBI and may normalize later, but may also develop after the post-acute phase of TBI.

Several studies report a high prevalence of hypopituitarism after traumatic brain injury (TBI). However, it is still not clear which risk factors predispose patients to develop anterior hypopituitarism after TBI. In this study we wanted to assess clinical and radiographical risk factors for the development of hypopituitarism. Seventy-eight patients (52 men, 26 women, mean age 36.0 years) with TBI °I-III were studied prospectively. We evaluated initial CT scans and clinical status and complications from clinical records. Additionally, we assessed endocrine and clinical parameters 3 and 12 months after TBI. To this end, basal hormone values, a GHRH+arginine and an ACTH test were done and the modified Rankin Scale was assessed in all patients. We evaluated the association of several potential clinical and radiological predictors with the presence of pituitary impairment at different time points. The rate of hypopituitarism (impairment of at least one pituitary axis) at at least one time point was significantly higher in patients with diffuse axonal injury (DAI). Secondary hypogonadism was significantly more common in patients with severe TBI, DAI, history of transient diabetes insipidus, hypoxia, external ventricular drain, and polytrauma. Impairment of at least one of the hormones ACTH, GH, TSH was significantly more frequent in patients with basal skull fracture. Logistic regression analysis showed DAI and higher age to be associated with hypopituitarism and basal skull fracture to be associated to presence of ACTH, GH, or TSH deficiency. Cranial vault fracture was associated with a decreased frequency of hypopituitarism. DAI and basal skull fractures are independent predictors of post-traumatic hypopituitarism. Particular care should be taken to screen for hormone deficiencies in these patients. Unlike the other pituitary hormone axes, the gonadotropic axis is associated with the severity of TBI.

Several recent studies have pointed to a substantial prevalence of hypopituitarism in defined groups of patients with traumatic brain injury (TBI) and aneurysmal subarachnoid hemorrhage (SAH). However, epidemiological data on the prevalence and incidence of hypopituitarism after TBI and SAH in the general population do not exist. Moreover, very little is known about risk factors and clinical characteristics of pituitary impairment after brain damage. To address these questions we are establishing a multi-center, structured data assessment to create a national registry of these patients. It is planned to include 600–1000 patients per year. Data will be collected using a structured, internet-based study sheet, collecting information on clinical, radiological and hormonal parameters. The study aims to connect clinical information on trauma and presence and type of hypopituitarism.

Several studies have shown a high prevalence of anterior pituitary dysfunctions after traumatic brain injury. However, data on possible predictors, which would facilitate diagnostic decisions, remains sparse. In a prospective study on prevalence and time-course of posttraumatic hypopituitarism we also evaluated possible predictors. Methods: 79 Patients (52 men, 26 women, mean age 36.4 years) of a neurologic rehabilitation unit, with TBI, severity grades I-III according to post-resuscitation Glasgow-Coma-Scale. Basal hormone measurements (sexual hormones, thyroid hormones, IGF-1, cortisol basal and prolactin) and stimulation tests (GHRH-L-Arginine-Test, short ACTH-Test) at 3 and 12 month after TBI. Analysis of clinical data and neuroimaging. Results: 62% of patients showed hormonal deficiencies at least at one point of time. Of all clinical parameters, only the presence of diffuse axonal injury reached a level of significance (p=0,02, Fisher exact test); initial hypotension or hypoxia, optic nerve lesion, hydrocephalus and transient diabetes insipidus showed only a tendency to correlate with posttraumatic pituitary deficiencies, but correlations were not significant. Conclusion: Diffuse axonal injury seems to be a predictor of posttraumatic anterior hypopituitarism. Other possible risk factors, derived from pathophysiological and neuroanatomic considerations, showed at least some correlation. Further studies should focus on these risk factors as diagnostic stratifying of patient groups will be essential for the cost-effectiveness of screening programs.

In Germany, traumatic brain injury (TBI) has an annual incidence of approximately 200000. In contrast to earlier assumptions, pituitary insufficiency is a common complication of TBI, with a prevalence of 30-50%. Since thesymptoms are often nonspecific and may be masked by the sequelae of head injury, it may go unrecognized and may possibly aggravate the symptomatology of such injury. It is therefore to be recommended that patients who suffer a head injury should be examined to exclude pituitary gland insufficiency, by measuring the basal hormone level - where necessary in combination with stimulation tests.

Hypopituitarism has been described as a complication of traumatic brain injury (TBI). Due to unspecific symptomatology and masking by TBI sequalae hypoptituitarism often remains unrecognized and may lead to aggravation of TBI symptoms. Adequate diagnosis and treatment of hypopituitarism is important, first, to prevent life threatening hormonal crisis, and, second, because hormone replacement might have beneficial effects on rehabilitation after TBI. We have studied pituitary function in 72 patients three months after TBI. In all patients a GHRH + arginine test, a 30-minute ACTH test and basal assessments of thyroid hormones, gonadotrophins, sex steroids, prolactin, and IGF-1 were performed. Impairment of at least one axis of the pituitary have been found in 43% of the patients. In most patients with hypopituitarism only one axis was impaired. The somatotrophic axis was affected in 10%, the gonadotrophic in 15%, the corticoptrophic in 18% and thyreotrophic in 8% of patients. Transient but not persistent diabetes insipidus was present in 9 patients. Peak GH levels in the GHRH + arginine test did not correlate with IGF-1 levels but correlated negatively with BMI. Hyperprolactinemia often occurred in combination with drugs that may elevate prolactin levels. These results show that hypopituitarism is a common finding after TBI. Mostly only one axis is concerned. These findings strongly suggest that assessment of pituitary function should be performed on a regular basis after TBI. Further studies to evaluate natural course and effects of hormone substitution in posttraumatic hypopituitarism are needed.

Hypopituitarism has been described as a complication of traumatic brain injury (TBI). Often, however, these disturbances remain unrecognised, due to unspecific symptomatology and masking by TBI sequalae. However, adequate diagnosis and treatment of hypopituitarism is important, first, to prevent life threatening hormonal crisis, and, second, because hormone replacement might have beneficial effects on rehabilitation after TBI. We have studied pituitary function in 26 patients (13 females, mean age 35,5±14,4 years) three months after TBI. In all patients a GHRH + arginine test, a 30-minute ACTH test and basal assessments of thyroid hormones, gonadotrophins, sex steroids, prolactin, and IGF-1 were performed. Some degree of hypopituitarism was present in 13 patients (50%). In most cases, impairment of one axis was observed (12 patients=46%) and only in one patient (4%) two axes were impaired (gonadotroph and somatotroph axis). Corticotroph insufficiency has been found in 5 patients (19%) in the ACTH stimulation test (cortisol cut-off 500 nmol/l). In 4 patients (15%) signs of secondary hypothyroidism were present. 2/13 (15%) males had low testosterone and gonadotrophin levels and 10/12 (75%) premenopausal women reported secondary amenorrhea. Complete GH deficiency (GH cut-off 9 ng/ml) was found in 3/25 patients (12%). Peak GH after GHRH + arginine stimulation showed a significant negative correlation with body mass index but not with IGF-1. These results show that hypopituitarism is a common finding after TBI. Mostly only one axis is concerned. These preliminary findings strongly suggest that assessment of pituitary function should be performed on a regular basis after TBI.