Search

Objective: Assessment of posttraumatic hypothalamic-pituitary dysfunctions is expected to be the most relevant assessment to offer patients with severe intracranial affection. In this study, we aim to investigate the prevalence of hypopituitarism in patients with severe acquired traumatic brain injury (TBI) compared with nontraumatic brain injury (NTBI) and to relate pituitary insufficiency to functional and patient-reported outcomes., Design: This is a prospective study., Methods: We included patients admitted for inpatient neurorehabilitation after severe TBI (N = 42) and NTBI (N = 18). The patients underwent a pituitary function assessment at a mean of 2.4 years after the injury. Functional outcome was assessed by using Functional Independence Measure and Glasgow Outcome Scale-Extended (both 1 year after discharge from neurorehabilitation) and patient-reported outcome was assessed by using Multiple Fatigue Inventory-20 and EQ-5D-3L., Results: Hypopituitarism was reported in 10/42 (24%) patients with TBI and 7/18 (39%) patients with NTBI (P = .23). Insufficiencies affected 1 axis in 14/17 (82%) patients (13 hypogonadotropic hypogonadism and 1 growth hormone [GH] deficiency) and 2 axes in 3/17 (18%) patients (1 hypogonadotropic hypogonadism and GH deficiency, and 2 hypogonadotropic hypogonadism and arginin vasopressin deficiency). None had central hypoadrenalism or central hypothyroidism. In patients with both TBI and NTBI, pituitary status was unrelated to functioning and ability scores at 1 year and to patient-reported outcome scores at a mean of 2.4 years after the injury., Conclusion: Patients with severe acquired brain injury may develop long-term hypothalamus-pituitary insufficiency, with an equal occurrence in patients with TBI and NTBI. In both types of patients, mainly isolated deficiencies, most commonly affecting the gonadal axis, were seen. Insufficiencies were unrelated to functional outcomes and patient-reported outcomes, probably reflecting the complexity and heterogeneous manifestations in both patient groups., Competing Interests: Conflict of interest: none declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of European Society of Endocrinology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Objective: Posttraumatic pituitary hormone deficiency is often suggested. The impact of these predominantly mild and often irreproducible deficiencies on outcome is less clear. The aim of the present study was to describe patient reported outcome in a national a priori unselected cohort of patients with traumatic brain injury (TBI) in relation to deficiencies identified upon pituitary assessment., Design and Methods: We conducted a nationwide population-based cohort study. Participants were Danish patients with a head trauma diagnosis recorded in the Danish Board of Health diagnostic code registry; 439 patients (and 124 healthy controls) underwent assessment of anterior pituitary function 2.5 years (median) after TBI. Questionnaires on health-related quality of life (QoL) (SF36, EuroQoL-5D, QoL assessment of GH deficiency in adults) and fatigue (MFI-20) were completed in parallel to pituitary assessment., Results: Patients with TBI had significant detriments in QoL. Impairment (mainly physical scales) related to pituitary deficiency, although only partially confirmed after adjustment for demographic differences. Hypogonadotropic hypogonadism related to several QoL scores. Increasing impairments were observed with declining total testosterone concentrations (men), but not free testosterone concentrations or any other hormone concentrations. Total testosterone was not independently related to impaired QoL and fatigue, after adjustment for demographics, and treatment with antidiabetics, opioids, antidepressants, and anticonvulsants., Conclusions: Only a very limited relationship between pituitary hormone deficiencies and QoL/fatigue was demonstrated. Due to the dominating influence of concurrent comorbidities, pituitary deficiencies were not independently related to QoL/fatigue. Causality is still to be shown, and whether substitution therapy could be of additional relevance in selected patients needs to be proven., (© 2015 European Society of Endocrinology.)

Objective: Severe brain injury may increase the risk of developing acute and chronic hypopituitarism. Pituitary hormone alterations developed in the early recovery phase after brain injury may have implications for long-term functional recovery. The objective of the present study was to assess the pattern and prevalence of pituitary hormone alterations 3 months after a severe brain injury with relation to functional outcome at a 1-year follow-up., Design: Prospective study at a tertiary university referral centre., Methods: A total of 163 patients admitted to neurorehabilitation after severe traumatic brain injury (TBI, n=111) or non-TBI (n=52) were included. The main outcome measures were endocrine alterations 3.3 months (median) after the brain injury and their relationship to the functioning and ability of the patients at a 1-year follow-up, as measured by the Functional Independence Measure and the Glasgow Outcome Scale-Extended., Results: Three months after the injury, elevated stress hormones (i.e. 30 min stimulated cortisol, prolactin and/or IGF1) and/or suppressed gonadal or thyroid hormones were recorded in 68 and 32% of the patients respectively. At 1 year after the injury, lower functioning level (Functional Independence Measure) and lower capability of performing normal life activities (Glasgow Outcome Scale-Extended) were related to both the elevated stress hormones (P≤0.01) and the reduced gonadal and/or thyroid hormones (P≤0.01) measured at 3 months., Conclusion: The present study suggests that brain injury-related endocrine alterations that mimic secondary hypogonadism and hypothyroidism and that occur with elevated stress hormones most probably reflect a prolonged stress response 2-5 months after severe brain injury, rather than pituitary insufficiency per se. These endocrine alterations thus seem to reflect a more severe disease state and relate to 1-year functional outcome., (© 2015 European Society of Endocrinology.)

Context: Recent international guidelines suggest pituitary screening in patients with moderate and severe traumatic brain injury (TBI). Predominantly isolated GH deficiency (GHD) was reported in the literature, raising the question of potential methodological bias., Objective: Our objective was to assess the prevalence of GHD in patients admitted in 2008 with TBI, with concurrent assessment of methodological bias., Design and Setting: We conducted a nationwide population-based cohort study at tertiary referral university hospitals., Participants: Participants were Danish patients with a head trauma diagnosis from the Danish Board of Health diagnostic code registry; 439 patients and 124 healthy controls underwent dynamic assessment of GH secretion 2.5 years (median) after TBI., Main Outcome: We evaluated the prevalence of GHD given use of 1) local versus guideline cutoffs, 2) insulin tolerance test (ITT), pyridostigmine (PD)-GHRH or GHRH-arginine (arg) test, 3) single versus repeated testing, and 4) GH assessment by assays with different isoform specificities., Results: The prevalence of GHD was lower by local than by guideline cutoffs (12% vs 19% [PD-GHRH/GHRH-arg, P<.001]; 4.5% vs 5% [ITT, P=.9]), and by ITT than by PD-GHRH/GHRH-arg (P=.006 [local cutoffs]; P<.001 [guideline cutoffs]). Only 1% of patients had GHD according to 2 tests. GH assessment by the Immulite or iSYS assay caused no significant diagnostic differences., Conclusions: The study confirmed a high risk of bias in the management of pituitary testing of patients with TBI and stresses the importance of a proper control group and stringent GH testing including confirmatory testing in cohorts with low a priori likelihood of GHD such as in TBI. Our results question the evidence for newly introduced recommendations for routine pituitary assessment in TBI.

Traumatic brain injury (TBI)-induced hypopituitarism remains a relevant medical problem, because it may affect a significant proportion of the population. In the last decade important studies have been published investigating pituitary dysfunction after TBI. Recently, a group of experts gathered and revisited the topic of TBI-induced hypopituitarism. During the 2-day meeting, the main issues of this topic were presented and discussed, and current understanding and management of TBI-induced hypopituitarism are summarized here.

Several studies have reported a close association between traumatic brain injury (TBI) and pituitary dysfunction, and expert panels have recently proposed recommendations for hormone assessment and replacement for pituitary insufficiency after TBI. Given the high incidence of TBI, identification of reliable predictors is of utmost importance in order to secure a cost-effective screening strategy. It has not yet been possible to identify early hormone alterations as a useful tool for the prediction of long-term post-traumatic hypopituitarism, whereas indicators of increased trauma severity have been reported as predictive in an increasing number of studies. Outcome studies have moreover indicated that post-traumatic hypopituitarism is of clinical significance, which may justify introduction of neuroendocrine screening in TBI. Much larger cohorts are, however, still needed for further evaluation and confirmation of reliable screening markers, and future studies should be designed to ensure a high diagnostic robustness for proper identification of reliable predictors, as the results may be highly dependent on diagnostic pitfalls.

Objective: Our objective was to describe body composition, lipid profile, and health-related quality of life (HRQL) in patients with traumatic brain injury (TBI) in relation to the development of posttraumatic hypopituitarism., Design: This is a cross-sectional evaluation with a nested prospective substudy., Patients: The cross-sectional cohort included 104 hospitalized patients with TBI [26 females/78 males; median age 41 yr (range 18-64); body mass index (BMI) 25 kg/m(2) (range 17-39); and severity, mild (Glasgow Coma Scale score (GCS) 13-15) n = 44, moderate (GCS 9-12) n = 20, and severe (GCS <9) n = 40)]. A nested cohort of 46 patients was followed prospectively., Measurements: BMI, waist circumference, lipid profile, total- and regional-fat mass were assessed 3 and 12 months (prospective) or only 12 months (cross-sectional) posttraumatically. HRQL questionnaires (Nottingham Health Profile, EuroQoL-5D, and the GH deficiency (GHD) specific instrument, Quality of Life Assessment of GHD in Adults) were completed "pre-traumatically," 3 and 12 months (prospective), or only 12 months (cross-sectional) posttraumatically., Results: Patients with posttraumatic hypopituitarism had higher age-, gender-, and BMI-adjusted 12-month low-density lipoprotein-cholesterol, waist circumference, and total fat mass (P < 0.05 in all cases), and a higher increase in total cholesterol (P = 0.01) during follow-up compared with sufficient patients. These findings were unrelated to 12-month IGF-I and IGF-I sd scores. Hypopituitary patients also had worse age, BMI, and TBI severity adjusted overall EuroQoL-5D visual analog scale (P = 0.03) and Quality of Life Assessment of GHD in Adults (P = 0.01) scores, and worse Nottingham Health Profile dimension scores of sleep (P = 0.03), energy (P = 0.02), and social isolation (P = 0.04), compared with patients with an intact pituitary function., Conclusion: Posttraumatic hypopituitarism was an independent predictor of the classical phenotypical features of hypopituitarism, including an unfavorable lipid and body composition profile, as well as worsened HRQL.

Objective: To assess the prevalence of hypopituitarism following traumatic brain injury (TBI), describe the time-course and assess the association with trauma-related parameters and early post-traumatic hormone alterations., Design: A 12-month prospective study., Patients: Forty-six consecutive patients with TBI (mild: N = 22; moderate: N = 9; severe: N = 15)., Measurements: Baseline and stimulated hormone concentrations were assessed in the early phase (0-12 days post-traumatically), and at 3, 6 and 12 months postinjury. Pituitary tests included the Synacthen-test (acute +6 months) and the insulin tolerance test (ITT) or the GHRH + arginine test if the ITT was contraindicated (3 + 12 months). Insufficiencies were confirmed by retesting., Results: Early post-traumatic hormone alterations mimicking central hypogonadism or hypothyroidism were present in 35 of the 46 (76%) patients. Three months post-traumatically, 6 of the 46 patients failed anterior pituitary testing. At 12 months, one patient had recovered, whereas none developed new insufficiencies. All insufficient patients had GH deficiency (5 out of 46), followed by ACTH- (3 out of 46), TSH- (1 out of 46), LH/FSH- (1 out of 46) and ADH deficiency (1 out of 46). Hypopituitary patients had more frequently been exposed to severe TBI (4 out of 15) than to mild or moderate TBI (1 out of 31) (P = 0.02). Early endocrine alterations including lowered thyroid and gonadal hormones, and increased total cortisol, free cortisol and copeptin were positively associated to TBI severity (P < 0.05), but not to long-term development of hypopituitarism (P > 0.1), although it was indicative in some., Conclusion: Long-term hypopituitarism was frequent only in severe TBI. During the 3-12 months follow-up, recovery but no new insufficiencies were recorded, indicating manifest hypothalamic or pituitary damage already a few months postinjury. Very early hormone alterations were not associated to long-term post-traumatic hypopituitarism. Clinicians should, nonetheless, be aware of potential ACTH deficiency in the early post-traumatic period.

Objective: To estimate the prevalence and predictive factors of hypopituitarism following traumatic brain injury (TBI)., Design: A cross-sectional cohort study., Patients: One hundred and four hospitalized TBI patients (26F/78M), median age 41 (range 18-64) years, body mass index (BMI) 25 (17-39) kg/m(2); severity: mild [Glasgow Coma Scale (GCS) score 13-15) n = 44, moderate (GCS 9-12) n = 20, severe (GCS < 9) n = 40]., Measurements: Patients were evaluated 13 (10-27) months post-injury, with measurement of baseline (0800-1000 h) and post-stimulatory hormonal levels during an insulin tolerance test (ITT) (86%) or, if contraindicated, an arginine(arg)-GHRH test + Synacthen test (14%). Insufficiencies were confirmed by retesting., Results: Hypopituitarism was found in 16 (15%) patients, affecting one axis in 10, two axes in four and more than two axes in two patients. The GH axis was most frequently affected (15%), followed by secondary hypoadrenalism (5%), hypogonadism (2%), hypothyroidism (2%) and diabetes insipidus (2%). The risk of pituitary insufficiency was increased in patients with severe TBI as opposed to mild TBI [odds ratio (OR) 10.1, 95% confidence interval (CI) 2.1-48.4, P = 0.004], and in those patients with increased intracerebral pressure [OR 6.5, 95% CI 1.0-42.2, P = 0.03]. Patients with only one affected axis were all GH deficient; 60% (n = 6) of these were overweight or obese., Conclusion: The prevalence of hypopituitarism was estimated at 16%. Although high, this value was lower than previously reported, and may still be overestimated because of well-known confounding factors, such as obesity. Indicators of increased TBI severity were predictive of hypopituitarism, with a high negative predictive value. Neuroendocrine evaluation should therefore be considered in patients with severe TBI, and in particular in those with increased intracerebral pressure (ICP).