Modulation of pituitary-adrenocortical function: decreased secretory episodes and blunted circadian rhythmicity in patients with alcoholic liver disease.

Twenty-four-hour episodic secretion of cortisol was studied in patients with chronic alcoholic liver disease in order to define how and if feedback inhibition of the hypothalamic-pituitary-adrenocortical axis had occurred. The patients had prolonged disappearance rates of endogenous cortisol and corticosteroid-binding globulin-binding capacity was low. Multiple sampling (every 20 min) for levels of free and total plasma cortisol was carried out. Mean 24-h total and free plasma cortisol levels were not significantly different from normal, although the mean percentage of free cortisol was high. Cortisol secretion was decreased, as judged by urinary free cortisol values and the percentage of time that secretory activity occurred. Circadian rhythmicity of plasma cortisol levels appeared to be normal, but the amplitude of rhythmicity was decreased. Modulation of cortisol secretion in liver disease patients was shown by fewer secretory peaks and decreased secretory time during 24-hr studies. In the subjects studied, the numbers of secretory episodes and the duration of secretory time correlated positively with levels of corticosteroid-binding globulin and negatively with the half-time of cortisol in plasma. These studies suggest that feed-back inhibition modifies bot the frequency and the amplitude of cortisol secretion in patients with liver disease while the underlying circadian rhythm is preserved.