Acute neuro-endocrine profile and prediction of outcome after severe brain injury

Abstract

ObjectThe 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.MethodsProspective 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.ResultsProfound 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.ConclusionProfound 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.

The pıtuıtary-gonadal-thyroıd and lactotroph axes ın crıtıcally ıll patıents

“…Elevated aromatisation of adrenal androgens to E 2 mediated by cytokines is proven to result in increased serum E 2 levels [23,25]. PRL also increases in response to acute illness [6,22,26]. We showed that male and female critically ill patients had high PRL levels compared to controls, and correlations between admission PRL and mortality and disease severity were observed that were new findings compared to the literature.…”

Analytical challenges for measuring steroid responses to stress, neurodegeneration and injury in the central nervous system

“…Thus, the decrease in brain progesterone may result from a reduction in plasma levels. Pituitary dysfunction and alterations of the hypothalamopituitary gonadal and hypothalamo-pituitary-adrenal axes are indeed a well-known consequence of TBI [227,228]. Noteworthy, brain progesterone levels, but not its plasma levels, showed a positive correlation with neurological recovery, consistent with a protective role [226].…”

Preoperative low tri-iodothyronine concentration is associated with worse health status and shorter five year survival of primary brain tumor patients

“…Our findings suggest that greater reduction of triiodothyronine concentration might reflect more aggressive brain tumor biology and greater health status impairment imposed by brain tumor. High prevalence of the Low triiodothyronine syndrome was also reported in other critical illnesses, such as sepsis (65%) [17] and severe traumatic brain injury (60%) [8]. Impaired peripheral tissue 5’-deiodination and reduced hypothalamic and pituitary TRH and TSH secretion are the chief mechanisms responsible for development of the Low triiodothyronine syndrome [6, 9].…”