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

Abstract

Objective. 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.

Patients. 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.

Results. 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.

Conclusion. 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.

Key words:

• Subarachnoid haemorrhage
• cortisol
• ACTH
• diurnal variation
• cerebral oedema.

Acknowledgements

The authors are grateful to the always enthusiastic staff in the neurointensive care and neurointermediate care in Uppsala University Hospital. Especially, we are thankful to Inger Ståhl-Myllyaho, MD, for organising and handling all the blood and urine samples as well as our research database. We also thank Timothy P. Howells, MD, PhD, for correcting the language in the manuscript.

Financial support: Swedish Research Council, Uppsala University Hospital, Selander Foundation, Åhlén Foundation.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.

Ethics: The Uppsala University Regional Ethical Review Board for clinical research granted ethical permission for the study. Written consent was obtained from the patients or their relatives.

Author contributions: MZ: The main author, conducted the study in cooperation with ERE, analysed the data and wrote the manuscript. LeH: Neuroradiologist, evaluated the CT scans. BEE: A major contributor to the concept of the study, the evaluation of the data and the writing of the manuscript. LaH: Critical reviewing and intellectual contribution to the discussion in the manuscript and knowledge of analysis methods. PE and TK: Critical reviewing and intellectual contribution to the process of evaluating data and writing the manuscript. ERE: The last author is the supervisor of the main author and has contributed substantially to the conduct of the study and the production of the manuscript.