PATTERN OF ACTIVATION OF THE HYPOTHALAMIC-PITUITARY-ADRENAL AXIS IN ACUTE STROKE - RELATION TO ACUTE CONFUSIONAL STATE, EXTENT OF BRAIN-DAMAGE, AND CLINICAL OUTCOME

Background and Purpose The aim of this study was to characterize the r esponse of the hypothalamic-pituitary-adrenal system in the first hour s of ischemic stroke and to relate its extent to the occurrence of acu te confusional state, volume of brain damage, and clinical outcome. Me thods The secretion of corticotropin (adrenocorticotropic hormone [ACT H]) and cortisol was studied in 23 patients by determinations at hours 4, 6, 8, 10, and 14 and days 1, 3, 5, and 7 after onset of symptoms. Acute confusional state (DSM-III-R criteria), extent of lesion (volume try of computed tomographic scans), and neurological and functional ou tcome (Scandinavian Stroke Scale, Barthel Index scores) were assessed. Results The massive neuroendocrine response observed consisted of an initial phase with concomitantly increased levels of ACTH and cortisol and a second phase with decreased levels of ACTH while high concentra tions of cortisol persisted. Initial levels of ACTH but not cortisol w ere significantly increased in patients with acute confusional state a nd significantly correlated with volume of brain lesion and neurologic al and functional outcome. Conclusions An early and persisting activat ion of the hypothalamic-pituitary-adrenal axis was observed in relatio n to severity of disease. Its characteristic biphasic pattern suggests an initial central stimulation of release of ACTH followed by feedbac k suppression concomitant with an increased susceptibility of the adre nal gland. Because these hormones are known to exacerbate hypoxic inju ry to neurons, their massive release in hyperacute stroke may increase the extent of brain damage.