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 GHsecretion 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.

PURPOSE OF REVIEW:

This article attempts to summarize findings of recent publications addressing the prevalence, effects, and treatment of pituitary hormone deficiency following traumatic brain injury (TBI).

RECENT FINDINGS:

A number of recent studies of TBI victims offer larger samples and much longer follow-up times. However, the prevalence of pituitary hormone deficiency continues to vary widely, underscoring the influence of patient selection, differences in endocrine testing, and patient’s comorbidities and age. Growth hormone deficiency (GHD) continues to be the most frequently detected type of pituitary dysfunction. Several reports show the influence of GHD on functional outcomes of TBI victims beyond what is predicted by traumaseverity. Emerging data support the notion growth hormone (GH) replacement as a useful intervention to improve symptomatology and functional outcomes among adequately selected GH-deficient patients recovering from TBI.

SUMMARY:

Pituitary dysfunction is prevalent following TBI. Pituitary dysfunction seems to influence functional outcomes in some patients recovering from brain injury. Adequately selected patients could benefit from hormonal replacement.

Growth hormone (GH) is a pleiotropic hormone that exerts important functions in the control of braindevelopment as well as in the regulation neuronal differentiation and function, together with several behavioral and psychological effects that have been linked to its modulatory actions on brain neurotransmitters. In addition, the possibility that GH may play a role on brain repair after injury has been also envisaged, and a number of reports have shown that GH administration following injury confers neuroprotection and accelerates the recovery of some neural functions. In this review we have analyzed the state of the art of GHadministration in several neural diseases. Though more studies are still necessary in order to completely understand the importance of GH in these processes, the promising results obtained so far, together with the absence of untoward effects during GH therapy, encourages the development of clinical assays in order to further support the use GH treatment in neural diseases in which neuroprotection and/or neuroregeneration are involved.

Copyright © 2013. Published by Elsevier Ireland Ltd.

OBJECT:

The aim of the study was to evaluate the early changes in pituitary hormone levels after severe traumatic brain injury (sTBI) and compare hormone levels to basic neuro-intensive care data, a systematic scoring of the CT-findings and to evaluate whether hormone changes are related to outcome.

METHODS:

Prospective study, including consecutive patients, 15-70 years, with sTBI, Glasgow Coma Scale (GCS) score ≤ 8, initial cerebral perfusion pressure > 10 mm Hg, and arrival to our level one trauma university hospital within 24 hours after head trauma (n = 48). Serum samples were collected in the morning (08-10 am) day 1 and day 4 after sTBI for analysis of cortisol, growth hormone (GH), prolactin, insulin-like growth factor 1 (IGF-1), thyroid-stimulating hormone (TSH), free triiodothyronine (fT3), free thyroxine (fT4), follicular stimulating hormone (FSH), luteinizing hormone (LH), testosterone and sex hormone-binding globulin (SHBG) (men). Serum for cortisol and GH was also obtained in the evening (17-19 pm) at day 1 and day 4. The first CT of the brain was classified according to Marshall. Independent staff evaluated outcome at 3 months using GOS-E.

RESULTS:

Profound changes were found for most pituitary-dependent hormones in the acute phase after sTBI, i.e. low levels of thyroid hormones, strong suppression of the pituitary-gonadal axis and increased levels of prolactin. The main findings of this study were: 1) A large proportion (54% day 1 and 70% day 4) of the patients showed morning s-cortisol levels below the proposed cut-off levels for critical illness related corticosteroid insufficiency (CIRCI), i.e. <276 nmol/L (=10 ug/dL), 2) Low s-cortisol was not associated with higher mortality or worse outcome at 3 months, 3) There was a significant association between early (day 1) and strong suppression of the pituitary-gonadal axis and improved survival and favorable functional outcome 3 months after sTBI, 4) Significantly lower levels of fT3 and TSH at day 4 in patients with a poor outcome at 3 months. 5) A higher Marshall CT score was associated with higher day 1 LH/FSH- and lower day 4 TSH levels 6) In general no significant correlation between GCS, ICP or CPP and hormone levels were detected. Only ICPmax and LH day 1 in men was significantly correlated.

CONCLUSION:

Profound dynamic changes in hormone levels are found in the acute phase of sTBI. This is consistent with previous findings in different groups of critically ill patients, most of which are likely to be attributed to physiological adaptation to acute illness. Low cortisol levels were a common finding, and not associated with unfavorable outcome. A retained ability to a dynamic hormonal response, i.e. fast and strong suppression of the pituitary-gonadal axis (day 1) and ability to restore activity in the pituitary-thyroid axis (day 4) was associated with less severe injury according to CT-findings and favorable outcome.

A number of studies, in animals and humans, describe the positive effects of the growth hormone (GH) treatment combined with rehabilitation on brain reparation after brain injury. We examined the effect of GHtreatment and rehabilitation in adult rats with severe frontal motor cortex ablation. Thirty-five male rats were trained in the paw-reaching-for-food task and the preferred forelimb was recorded. Under anesthesia, the motor cortex contralateral to the preferred forelimb was aspirated or sham-operated. Animals were then treated with GH (0.15 mg/kg/day, s.c) or vehicle during 5 days, commencing immediately or 6 days post-lesion. Rehabilitation was applied at short- and long-term after GH treatment. Behavioral data were analized by ANOVA following Bonferroni post hoc test. After sacrifice, immunohistochemical detection of glial fibrillary acid protein (GFAP) and nestin were undertaken in the brain of all groups. Animal group treated with GHimmediately after the lesion, but not any other group, showed a significant improvement of the motor impairment induced by the motor lesion, and their performances in the motor test were no different from sham-operated controls. GFAP immunolabeling and nestin immunoreactivity were observed in the perilesional area in all injured animals; nestin immunoreactivity was higher in GH-treated injured rats (mainly in animals GH-treated 6 days post-lesion). GFAP immunoreactivity was similar among injured rats. Interestingly, nestin re-expression was detected in the contralateral undamaged motor cortex only in GH-treated injured rats, being higher in animals GH-treated immediately after the lesion than in animals GH-treated 6 days post-lesion. EarlyGH treatment induces significant recovery of the motor impairment produced by frontal cortical ablation. GHeffects include increased neurogenesis for reparation (perilesional area) and for increased brain plasticity (contralateral motor area).

Copyright © 2013 Elsevier B.V. All rights reserved.

BACKGROUND:

Somatotropic and thyroid hormones are probably important for the recovery after acute braininjury. Still, the dynamics of these hormones after spontaneous subarachnoid haemorrhage (SAH) is not well described. The purpose of this study was to investigate the relation between somatotropic and thyroid hormones and clinical factors after SAH.

METHODS:

Twenty patients with spontaneous SAH were included prospectively. Serum concentrations of TSH, fT4, T3, IGF-1 and GH were measured once a day for 7 days after SAH. Hormone patterns and serum concentrations were compared to the severity of SAH, neurological condition at admission, clinical course and outcome of the patients.

RESULTS:

During the first week after SAH, all patients showed increased GH and IGF-1 concentrations. In the whole group, concentrations of TSH increased, whereas T3 and fT4 decreased. There were no relations of serum concentrations of IGF-1 or GH to clinical condition at admission, clinical course or outcome of the patients. Half of the patients showed low T3 serum concentrations. A complicated course was associated with a deeper fall in TSH and T3 concentrations. There were negative correlations for mean concentrations of TSH and T3 versus WFNS grade and a positive correlation for T3 versus GOS after 6 months, indicating that low concentrations of TSH and T3 were connected to worse SAH grade and poor outcome.

CONCLUSIONS:

All patients showed increased GH and IGF-1 concentrations irrespective of the grade of SAH or clinical course. Patients with a complicated clinical course showed a more pronounced fall in TSH and T3 concentrations and low serum T3 concentrations were related to a more serious SAH and poor patient outcome. These results need to be studied further and they may contribute to the accumulated knowledge needed to understand the complex mechanisms influencing the unpredictable clinical course after SAH.

OBJECTIVE:

To compare neurocognition and quality-of-life (QoL) in a group of children and adolescents with or without growth hormone deficiency (GHD) following moderate-to-severe traumatic brain injury (TBI).

STUDY DESIGNS:

Thirty-two children and adolescents were recruited from the TBI clinic at a children’s hospital. Growth hormone (GH) was measured by both spontaneous overnight testing and following arginine/glucagon stimulation administration. Twenty-nine subjects participated in extensive neuropsychological assessment.

RESULTS:

GHD as measured on overnight testing was significantly associated with a variety of neurocognitive and QoL measures. Specifically, subjects with GHD had significantly (p”‰<”‰0.05) lower scores on measures of visual memory and health-related quality-of-life. These scores were not explained by severity of injury or IQ (p”‰>”‰0.05). GHD noted in response to provocative testing was not associated with any neurocognitive or QoL measures.

CONCLUSIONS:

GHD following TBI is common in children and adolescents. Deficits in neurocognition and QoL impact recovery after TBI. It is important to assess potential neurocognitive and QoL changes that may occur as a result of GHD. It is also important to consider the potential added benefit of overnight GH testing as compared to stimulation testing in predicting changes in neurocognition or QoL.