Cortisol and adrenocorticotropic hormone dynamics in the acute phase of subarachnoid haemorrhage

Department of Neuroscience, Section of Neurosurgery, Uppsala University Hospital, Sweden.
British Journal of Neurosurgery (Impact Factor: 0.96). 12/2011; 25(6):684-92. DOI: 10.3109/02688697.2011.584638
Source: PubMed


An adequate response of hypothalamic-pituitary-adrenal (HPA) axis is important for survival and recovery after a severe disease. The hypothalamus and the pituitary glands are at risk of damage after subarachnoid haemorrhage (SAH). A better understanding of the hormonal changes would be valuable for optimising care in the acute phase of SAH.
Fifty-five patients with spontaneous SAH were evaluated regarding morning concentrations of serum (S)-cortisol and P-adrenocorticotropic hormone (ACTH) 7 days after the bleeding. In a subgroup of 20 patients, the diurnal changes of S-cortisol and P-ACTH were studied and urine (U)-cortisol was measured. The relationships of hormone concentrations to clinical and radiological parameters and to outcome were assessed.
S-cortisol and P-ACTH were elevated the day of SAH. S-cortisol concentrations below reference range were uncommon. Early global cerebral oedema was associated with higher S-cortisol concentrations at admission and a worse World Federation of Neurological Surgeons (WFNS) and Reaction Level Scale 85 grade. Global cerebral oedema was shown to be a predictor of S-cortisol at admittance. Patients in better WFNS grade displayed higher U-cortisol. All patients showed diurnal variations of S-cortisol and P-ACTH. A reversed diurnal variation of S-cortisol was more frequently found in mechanically ventilated patients. Periods of suppressed P-ACTH associated with S-cortisol peaks occurred especially in periods of secondary brain ischaemia.
There was an HPA response acutely after SAH with an increase in P-ACTH and S-cortisol. Higher U-cortisol in patients in a better clinical grade may indicate a more robust response of the HPA system. Global cerebral oedema was associated with higher S-cortisol at admission and was a predictor of S-cortisol concentrations. Global cerebral oedema may be the result of the stress response initiated by the brain injury. Periods of suppressed P-ACTH occurred particularly in periods of brain ischaemia, indicating a possible connection between brain ischaemia and ACTH suppression.

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    • "One consequence of aneurysmal SAH that has been reported is a stress response, including the release of ACTH, cortisol and catecholamines. [1], [2] The benefit of this hormonal response may be increased systemic blood pressure and a restored cerebral blood flow. On the other hand, systemic stress load is potentially harmful. "
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    ABSTRACT: BackgroundAneurysmal subarachnoid hemorrhage (SAH) may produce cerebral ischemia and systemic responses including stress. To study immediate cerebral and systemic changes in response to aneurysm rupture, animal models are needed.ObjectiveTo study early cerebral energy changes in an animal model.MethodsExperimental SAH was induced in 11 pigs by autologous blood injection to the anterior skull base, with simultaneous control of intracranial and cerebral perfusion pressures. Intracerebral microdialysis was used to monitor concentrations of glucose, pyruvate and lactate.ResultsIn nine of the pigs, a pattern of transient ischemia was produced, with a dramatic reduction of cerebral perfusion pressure soon after blood injection, associated with a quick glucose and pyruvate decrease. This was followed by a lactate increase and a delayed pyruvate increase, producing a marked but short elevation of the lactate/pyruvate ratio. Glucose, pyruvate, lactate and lactate/pyruvate ratio thereafter returned toward baseline. The two remaining pigs had a more severe metabolic reaction with glucose and pyruvate rapidly decreasing to undetectable levels while lactate increased and remained elevated, suggesting persisting ischemia.ConclusionThe animal model simulates the conditions of SAH not only by deposition of blood in the basal cisterns, but also creating the transient global ischemic impact of aneurysmal SAH. The metabolic cerebral changes suggest immediate transient substrate failure followed by hypermetabolism of glucose upon reperfusion. The model has features that resemble spontaneous bleeding, and is suitable for future research of the early cerebral and systemic responses to SAH that are difficult to study in humans.
    Full-text · Article · Jun 2014 · PLoS ONE
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    ABSTRACT: The purpose of this study was to assess cortisol dynamics in the acute phase after aneurysmal subarachnoid hemorrhage (SAH) and to set the parameters of cortisol release in relation to the severity of illness and outcome. In 22 consecutive patients with aneurysmal SAH, cortisol, corticosteroid binding globulin, interleukin-6, and adrenocorticotrophic hormone were measured immediately after hospital admission (t(0)), 7 days (t(1)) later, and at least 14 days later (t(2)). Additionally, diurnal profiles of cortisol secretion were assessed at t(1) and t(2), and area under the curve (AUC) was computed for calculated free serum cortisol (CFSC). In this study, normal diurnal CFSC profiles were associated with a significantly shorter ICU-stay, less complications, and a more favorable outcome than abnormal diurnal profiles. AUC and 8 a.m. cortisol were not related to clinical course or outcome. It is concluded that cortisol secretion patterns are associated with the severity and outcome of SAH. For an appraisal of the hypothalamo-pituitary-adrenal axis in SAH patients, single cortisol measurements are insufficient.
    No preview · Article · Sep 2009 · Journal of neurotrauma
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    ABSTRACT: Subarachnoid haemorrhage (SAH) is a life-threatening condition that may be aggravated by acute pituitary damage and cortisol insufficiency. Robust diagnostic criteria for critical illness-related corticosteroid insufficiency (CIRCI) are lacking. The aim of this study was to assess the frequency of CIRCI in the acute phase (0–240 h) after SAH and to evaluate associations between cortisol levels and clinical parameters (sedation, circulatory failure, gender, age, severity of disease, treatment). CIRCI was defined as a single morning serum cortisol (mSC) < 200 nmol/L. The lower limit for calculated free cortisol (cFC) was set at < 22 nmol/L, and for saliva cortisol at < 7.7 nmol/L. Fifty patients were included. Serum/saliva cortisol and corticosteroid-binding globulin were obtained every second morning. A logistic regression model was used for multivariate analysis comparing cortisol levels with clinical parameters. Of the patients, 21/50 (42%) had an mSC < 200 nmol/L and 30/50 (60%) had a cFC < 22 nmol/L. In patients with continuous intravenous sedation, the odds ratio for a mSC to be < 200 nmol/L was 18 times higher (95% confidence interval 4.2–85.0, P < 0.001), and the odds ratio for a cFC to be < 22 nmol/L was 2.4 times higher (95% confidence interval 1.2–4.7, P < 0.05) compared with patients with no continuous intravenous sedation. Continuous intravenous sedation was significantly associated with cortisol values under defined limits (mSC < 200, cFC < 22 nmol/L). The possibility that sedating drugs per se may influence cortisol levels should be taken into consideration before CIRCI is diagnosed.
    No preview · Article · Nov 2012 · Acta Anaesthesiologica Scandinavica
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