H. J. Schneider

Predictors of anterior pituitary insufficiency after traumatic brain injury

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.

Pituitary imaging abnormalities in patients with and without hypopituitarism after traumatic brain injury

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.

Is there a neuroendocrinological rationale for testosterone as a therapeutic option in depression

Abstract Depression is a disease of growing incidence and economic burden worldwide. In view of increasing treatment resistance, new therapeutic approaches are urgently needed. In addition to its gonadal functions, testosterone has many effects on the central nervous system. An association between testosterone levels and depressive symptoms has been proposed. Many hormones and neurotransmitters are involved in the aetiology and the course of depression including serotonin, dopamine, noradrenaline, vasopressin and cortisol. Testosterone is known to interact with them. Preclinical data suggest that testosterone has antidepressant potential. However, the data from clinical studies have been inconsistent. This review provides a critical overview on the currently available preclinical and clinical literature and concludes with clinical recommendations.

Expert meeting: hypopituitarism after traumatic brain injury and subarachnoid haemorrhage

Pl€ockinger U (Campus Virchow-Klinikum, Charit e, Berlin): Endocrine deficiencies after traumatic brain injury and their possible relevance to the clinical course of rehabilitation from the endocrinologist’s perspective Schneider HJ (Clinical Neuroendocrinology Group, Max Planck Institute of Psychiatry, Munich): Hypopituitarism after traumatic brain injury; Endocrine deficiencies in the acute phase after traumatic brain injury; Possible pathophysiological explanations for hypopituitarism after traumatic brain injury

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.

The German Database on Hypopituitarism after Traumatic Brain Injury and Aneurysmal Subarachnoid Hemorrhage - Description, Objectives and Design

Within the last years, a number of clinical studies have addressed the topic of hypothalamo-pituitary dysfunction following traumatic brain injury (TBI) and aneurysmal subarachnoid hemorrhage (SAH). Clinical studies oftentimes reflect the investigation of highly selective patient groups, very standardized test procedures and may be influenced by a publication bias. Epidemiological data on the prevalence and incidence of hypopituitarism after TBI and SAH in the general population still do not exist. Moreover, very little is known about risk factors and clinical characteristics of pituitary impairment after brain damage. Epidemiologic surveys which aggregate information of many different treatment centers become an increasingly important means of bridging the gap between standardized study situations and clinical practice. Therefore, a multi-center, structured data assessment to create a national registry of TBI and SAH patients has been established in 2005. The Structured Data Assessment of Hypopituitarism after TBI and SAH is coordinated by the Department of Endocrinology, Max-Planck-Institute in Munich with participation of at present 13 neurosurgical, rehabilitation and endocrinological centers in Germany and one Austrian center. Within this database, a large scope of very detailed, clinical, endocrine and outcome information is collected. It also offers the possibility of long-term follow up of the recorded patients. This is the first report of the registry describing goals, organization, methodology, funding and the descriptive data of the first 1,242 patients entered until November 20th, 2008.

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).

Change of symptoms and perceived health in acromegalic patients on pegvisomant therapy: a retrospective cohort study within the German Pegvisomant Observational Study (GPOS).

Objective  This study aimed at investigating how symptoms and perceived health changes in acromegalic patients during pegvisomant treatment in respect to IGF‐1 levels and disease characteristics.

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.

Differences in the insulin tolerance test in patients with brain damage depending on posture.

OBJECTIVE The insulin tolerance test (ITT) is the gold standard for the diagnosis of GH deficiency (GHD) and hypocortisolism. As hypopituitarism is a common disorder after traumatic brain injury (TBI) and subarachnoid hemorrhage (SAH), the test is increasingly used in patients with pre-existing brain damage. DESIGN A cross-sectional, observational study. METHODS Fifty-six patients (41 TBI and 15 SAH) were tested with the ITT (0.15 IE/kg body weight, mean glucose 33 mg/dl). In 38 patients, the test was performed in a supine position; the other 18 patients were in a sitting position during the ITT. RESULTS Hypocortisolism and GHD were more often diagnosed in a supine than in a sitting position (hypocortisolism: 55.3% supine versus 0% sitting, P<0.0001; GHD: 42.1% supine versus 11.1% sitting, P=0.03). Patients in a sitting position suffered more often from symptoms such as tachycardia (61.1% sitting versus 15.8% supine, P=0.001), trembling (22.2 vs 7.9%, NS), and sweating (66.7 vs 28.9%, P=0.007). There were no significant differences between the groups in drowsiness (72.2% sitting versus 65.8% supine, NS), dizziness (44.4 vs 44.7%, NS), and fatigue (33.3 vs 15.8%, NS). Because of somnolence, the hypoglycemic state could only be stopped with i.v. administration of glucose in 25 supine patients (66%). In contrast, none of the 18 patients (0%) tested in a sitting position got somnolent or was in need of i.v. application of glucose (P<0.001). CONCLUSIONS In patients with brain injury, posture might affect rates of diagnosing GHD and hypocortisolism and sympathetic symptoms in the ITT. These findings are exploratory and need replication in a standardized setting.