ENDOCRINE AND HEMODYNAMIC-EFFECTS OF STRESS VERSUS SYSTEMIC CRF IN ALCOHOLICS DURING EARLY AND MEDIUM-TERM ABSTINENCE

In alcoholics, disturbances of the autonomic nervous system as well as of the hypothalamic-pituitary-adrenal axis (HPA) are known. However, these two systems have never been analyzed, under stimulated condition s, in parallel in the same patients. Moreover, studies using intraveno us (iv) corticotropin releasing factor (CRF) to assess neuroendocrine function bypass the hypothalamic component of the HPA axis. Therefore, iv human (h) CRF (pituitary stimulation/exogenous CRF) and a multifac eted stress test (hypothalamic activation/endogenous CRF) were compare d with respect to their effects on hemodynamics as well as plasma nore pinephrine (NE), epinephrine (E), ACTH, and cortisol in abstinent alco holics (n = 11)versus healthy men (n = 10). Each stimulus was tested t wice, 12 weeks apart, in two separate experimental blocks (I and II). Alcoholics entered block I 8 days after the last ethanol ingestion and were controlled for abstinence up to block II. hCRF caused a fall in mean arterial pressure (MAP), most pronounced in alcoholics, particula rly in block II. In contrast, stress testing raised MAP in both groups and blocks. A sustained increase in ACTH, cortisol, and NE occurred a fter hCRF, although the ACTH response in alcoholics was blunted in bot h blocks. Stress testing elevated NE in both groups and blocks, while raising plasma ACTH and cortisol during block I only in controls. Howe ver, unlike the persistently blunted ACTH response to iv CRF, a normal ization of the stress-induced ACTH output occurred in alcoholics after 12 weeks of abstinence. During block I, basal E levels were elevated in alcoholics whereas NE levels tended to be lower than in controls, r esulting in a significantly decreased NE/E ratio that returned to near control values in block II. Neither CRF nor stress had any effect on circulating E in either group or block To conclude: (1) Normalization of the ACTH response to stress, but not to iv CRF, after 12 weeks of a bstinence, suggests that other ACTH secretagogues may be compensating for CRF dysfunction in alcoholics. (2) Despite the dramatically lowere d plasma NE/E ratio in alcoholics, the NE response to stimuli was unaf fected. (3) The exaggerated hypotensive reaction and blunted ACTH resp onse to iv CRF may reveal a longterm dissociative dysregulation of CRF actions in alcoholics.