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Acute neuro-endocrine profile and prediction of outcome after severe brain injury
Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience.
Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience.
2013 (English)In: Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine, ISSN 1757-7241, E-ISSN 1757-7241, Vol. 21, no 33Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
2013. Vol. 21, no 33
Keyword [en]
Severe traumatic brain injury, Hypopituitarism, Outcome, ICP targeted therapy, Hypothalamic-pituitary dysfunction, Prostacyclin
National Category
Neurosciences
Identifiers
URN: urn:nbn:se:umu:diva-73085DOI: 10.1186/1757-7241-21-33ISI: 000318597100002OAI: oai:DiVA.org:umu-73085DiVA: diva2:629523
Available from: 2013-06-17 Created: 2013-06-17 Last updated: 2017-12-06Bibliographically approved
In thesis
1. Hormones, biomarkers, genetics and prognostication of patients suffering severe traumatic brain injury
Open this publication in new window or tab >>Hormones, biomarkers, genetics and prognostication of patients suffering severe traumatic brain injury
2014 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Severe traumatic brain injury (sTBI) is a significant cause of mortality and mobidity worldwide. In Umeå University Hospital, at the department of Neurosurgery, patients with sTBI are treated by the Lund concept, which can be characterized as an intracranial pressure (ICP) targeted therapy.

In recent decades, there has been an increasing interest in trying to understand why some patients recover better and survive after sTBI, and why some do not. Also, improving the instruments of prognostication is becoming increasingly important both for relocating health resources and for the benefit of patients and relatives.

The main goal of the work described in this thesis was to explore factors influencing clinical outcome and improve the prognostication of outcome after sTBI. The ultimate goal is to improve the clinical outcome in patients suffering sTBI.

It has been proposed that the outcome after sTBI is influenced by genetic variability, including variability in apolipoprotein E (APOE). We therefore examined the relationship between the presence of APOE ε4 allele and the outcome. Except for 1 dichotomization of Glasgow outcome scale (GOS) at 3 months, the presence of the allele did not influence the outcome.

The biochemical markers of brain injury, S-100B and NSE, can be used to quantify the tissue lesion in sTBI. We investigated whether the levels of the biomarkers were associated with the APOE ε4 allele. Patients expressing the APOEε4 allele had significantly higher levels of S-100B than non-ε4 subjects. The temporal course of S-100B differed between the APOE groups. Similar, but not statistically significant results were observed for NSE. The results suggest that variations in genetics have to be considered when interpreting the biochemical markers.

We also found that serum levels of S-100B and NSE were correlated with ICPmax, CPPmin and radiological findings on brain CT quanttified by CT scoring systems and that S-100B and NSE (max and bulk release) may predict mortality.

The pituitary gland is vulnerable for traumatic events. This may be reflected in acute hormonal deviations, which can influence the clinical outcome. We found dynamic changes in hormone levels after sTBI. A large number of the patients had low cortisol levels, which were not however associated with an unfavourable outcome. We also found that a preserved capacity to a mutable hormonal response, i.e. fast and strong repression of the pituitary-gonadal axis and a capacity to re-establish activity in the pituitary-thyroid axis, was associated with less severe injury according to CT-findings and to a more favourable outcome after sTBI.

It is concluded that the presence of the APOEε4 allele did not indicate worse long-term outcome in our patient group. Patients expressing the APOEε4 allele, had significantly higher levels of S-100B than non-ε4 subjects, indicating that in some cases the genetics have to be considered when interpreting the biochemical markers. The biomarkers were also correlated to intracranial pressure and radiological findings, and may predict for mortality at 3 months. Profound hormonal changes in the acute phase occur. However, low levels of cortisol are not associated with a worse clinical outcome.

 

 

 

 

 

Place, publisher, year, edition, pages
Umeå: Umeå universitet, 2014. 60 p.
Series
Umeå University medical dissertations, ISSN 0346-6612 ; 1624
National Category
Surgery
Research subject
Neurosurgery
Identifiers
urn:nbn:se:umu:diva-85845 (URN)978-91-7459-790-5 (ISBN)
Public defence
2014-03-07, sal E04, Norrlands universitetssjukhus, Umeå, 09:00 (Swedish)
Opponent
Supervisors
Available from: 2014-02-14 Created: 2014-02-11 Last updated: 2014-02-14Bibliographically approved

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