ADRENOCORTICOTROPIC HORMONE/CORTISOL RESPONSE TO PHYSICAL EXERCISE IN ABSTINENT ALCOHOLIC PATIENTS

BACKGROUND: Alterations in the hypothalamic-pituitary-adrenal (HPA) axis in alcoholic patients have been reported in various experimental conditions. METHODS: To establish whether alcoholism affects the HPA axis activation during physical exercise, 10 recent abstinent alcoholic patients (age range: 33-45 years; duration of alcohol dependence: range 4-6 years) were tested by exercising on a bicycle ergometer. Ten age-matched healthy nonalcoholic men participated as controls. The workload was gradually increased at 3-minute intervals until exhaustion and lasted about 15 minutes for all subjects. Alcoholic patients were tested at 3 time points, at 4, 6, and 8 weeks after alcohol withdrawal, whereas controls were tested only once. Main outcome measurements were circulating levels of adrenocorticotropic hormone (ACTH) and cortisol and physiological variables during physical exercise [heart rate, blood pressure, ventilation, frequency of breathing, tidal volume, oxygen consumption (VO2), carbon oxide production (VCO2), and respiratory exchange ratio (R)]. RESULTS: Similar basal and exercise-induced changes in physiological variables were observed in controls and alcoholic patients in all tests. Basal levels of ACTH and cortisol were similar in all tests performed on alcoholic patients and on normal controls. In normal subjects, exercise induced a significant increase in plasma ACTH and serum cortisol levels, with peak levels at 20 minutes for ACTH (84% higher than baseline) and at 30 minutes for cortisol (70% higher than baseline). After 4 weeks of abstinence, slight but not significant ACTH/cortisol responses to physical exercise were observed in alcoholic patients (mean peaks were 10 and 18% higher than baseline, respectively, for ACTH and cortisol). By contrast, when the exercise test was repeated after 6 weeks abstinence, ACTH/cortisol levels rose significantly versus baseline (mean peak levels of ACTH and cortisol were 48 and 38% higher than baseline, respectively, for ACTH and cortisol). However, the hormonal responses were significantly lower than in the normal controls. At 8 weeks of abstinence, ACTH/cortisol responses were significantly higher than 2 weeks previously, and were not distinguishable from the increments observed in the normal controls (76 and 68% higher than baseline, respectively, for ACTH and cortisol). CONCLUSIONS: In concurrence with previous reports showing alterations of the HPA axis in the central nervous system in alcohol-dependent subjects, these data show a defect of the neuroendocrine mechanism(s) underlying the ACTH/cortisol response to physical exercise for at least a month after alcohol withdrawal, with reconstitution of a normal hormonal response at 8 weeks