24-hour pulsatile and circadian patterns of cortisol secretion in alcoholic men.

Pulsatile and circadian patterns of cortisol secretion during acute (3 to 16 days) and chronic (29 to 39 days) abstinence were examined in alcoholic men with no clinical or laboratory evidence of hepatic dysfunction or nutritional deficiencies. Mean and integrated 24-hour serum concentrations of cortisol determined by sampling the blood every 20 minutes over a 24-hour period were increased in six out of 10 alcoholic subjects during acute abstinence when compared with normal controls. Sustained abstinence in seven subjects with follow-up studies caused significant decreases in the mean maximal cortisol peak amplitude (13 +/- 1.0 SEM acutely vs. 10.3 +/- 0.52 micrograms/dl follow-up; P = 0.01), mean 24-hour serum cortisol concentrations (10.9 micrograms/dl +/- 1.2 vs. 8.5 micrograms/dl +/- 0.26; P = 0.047), interpulse valley mean (9.3 micrograms/dl +/- 0.88 vs. 6.5 micrograms/dl +/- 0.34; P = 0.007), and valley nadir (7.9 micrograms/dl +/- 0.69 vs. 5.4 micrograms/dl +/- 0.30; P = 0.0036) concentrations. Cortisol pulse frequency was normal. Although circadian cortisol rhythmicity was maintained in alcoholics, the timing of the circadian acrophase was delayed significantly (P = 0.006) during acute abstinence (1022 [clocktime] +/- 34 min) as compared with normal controls (0743 [clocktime] +/- 34 min), and the amplitude of circadian cortisol rhythms exceeded normal in five of 10 alcoholics. Analysis of data in one alcoholic subject by a new multiparameter deconvolution method demonstrated increases in secretory burst amplitude (0.64 microgram/dl +/- 0.08 SD), mass of cortisol released per burst (9.8 micrograms/dl +/- 1.2 SD), and daily endogenous cortisol production rate (22 mg +/- 2.4 SD) during acute abstinence. These values were statistically different when compared with seven normal controls and the subjects' values during sustained abstinence (P less than 0.02). In conclusion, the results of the present study suggest increased daily production of cortisol as a possible mechanism underlying the elevated serum cortisol concentrations in chronic alcoholics during acute abstinence. This abnormality is shown to be reversible with sustained abstinence from alcohol.