Loss of Adrenocortical Suppression after Acute Brain Injury: Role of Increased Intracranial Pressure and Brain Stem Function*

Abstract

The function of the pituitary-adrenal axis was studied in 23 acutely brain-injured, comatose patients (14 head trauma and 9 intracranial hemorrhage), who were treated with dexamethasone (16–64 mg/daily). Patients with normal intracranial pressure (ICP) and normal brain stem function (group 1) had decreased plasma cortisol levels (≤5 μg/dl) within 36 h (mean ± sem, 2.4 ± 0.3 μg/dl; t½, 18 h). In contrast, patients with elevated ICP (i.e. >20 mm Hg; midline shift, or compressed ventricles) and normal brain stem function (group 2) had persistently elevated cortisol concentrations (15.4 ± 2.6 μg/dl; P < 0.001). Superimposition of brain stem dysfunction resulted in generally low cortisol levels regardless of the presence (group 4; 3.9 ± 1.0 μg/dl; P < 0.001 compared to group 2) or absence (group 3; 2.1 ± 0.5 μg/dl) of elevated ICP. Plasma ACTH levels in 31 samples obtained before or during dexamethasone therapy in 14 patients irrespective of group were not elevated (45.6 ± 12.5 pg/ml); there was no correlation between plasma ACTH and cortisol levels. Despite elevated cortisol values in group 2, ACTH levels were low (22.4 ± 10.1 pg/ml). It is concluded that elevated ICP in the presence of normal brain stem function is a potent stimulus for adrenocortical activation which is not associated with elevated ACTH levels, and that the brain stem is involved in this response.