EFFECT OF THEOPHYLLINE ON CORTISOL SECRETION

[摘要] Theophylline may improve asthma by increasing intracellular cAMP levels. In experimental animals elevation of intracellular cAMP in the adrenal cortex increased secretion of cortisol. Whether therapeutic doses of theophylline given i.v. and orally to human subjects over 3 days would increase cortisol secretion was studied. A single-blind, 6 day protocol was employed in 5 normal and 5 asthmatic volunteers. Adrenal function was monitored by 800 h and 1600 h serum cortisol and ACTH levels; daily 24 h urine for urinary-free cortisol (UFF), 17-hydroxysteroids (17-OH) and 17-ketosteroids (17-KS); and alternate-day cortisol secretory rates (FSR) measured by isotope dilution after i.v. 14C-cortisol. Serum theophylline concentration was monitored. Results in normal and asthmatic subjects were similar. Theophylline caused a significant but transient increase in UFF and 17-OH excretion. Urine volumes increased significantly, suggesting that the renal effect of theophylline accounted for the increased UFF and 17-OH excretion. FSR increased during the first 24 h after theophylline in 8 of 9 cases (P < 0.05 by sign test), mean values increasing from 14.2-19.3 mg, but this effect had dissipated by day 3 of theophylline administration. Theophylline had no effect on serum cortisol or ACTH or urinary 17-KS. Serum cortisol and ACTH may remain unchanged as the increase in cortisol secretion was offset by a concomitant increase in cortisol clearance. Theophylline produces a small, transient increase in cortisol secretion and clearance and this effect is similar in asthmatic and normal subjects.