Endocrine Abstracts

Hydrocortisone therapy should be individualised in patients with adrenal insufficiency to avoid over and under replacement. We assessed hydrocortisone absorbtion at different times of day which may impact on treatment regimens. We assessed the oral absorption of hydrocortisone in 48 patients (21M) aged between 6.1 and 20.3 years with congenital adrenal hyperplasia due to P450c21 deficiency. Hydrocortisone dosing ranged between 11.5 and 22.6 mg/m² per day in three or four doses. Each patient underwent a 24 h plasma cortisol and 17-hydroxyprogesterone (17OHP) concentration profile with the morning dose used to calculate absorption parameters. Parameters derived were maximum plasma concentration (C_max), time of maximum plasma concentration (t_max), the cortisol concentration leading to 50% inhibition of 17OHP) (IC₅₀) and time to attaining plasma cortisol concentration less than 100 nmol/l (100 nmol/l was the IC₅₀ value). C_max, t_max and IC₅₀ were derived using conventional pharmacokinetic techniques from the absorption profiles. In a further 6 patients sampling was undertaken at 30, 60 and 120 minutes after the first (06.00–07.00 h) and last (23.00–00.30 h) dose of the day. The C_max for the 48 patients was 780.7±61.6 nmol/l and t_max 66.7 (range 20–118) min. The IC₅₀ for plasma cortisol suppression of plasma 17OHP was 100 nmol/l. Time taken to a plasma cortisol concentration less than 100 nmol/l was 289 (range 140–540) min. In the six patients who had studies morning and evening the evening dose C_max was significantly less than the morning dose (P=0.01) which reflected the lower dose overall given in the evening compared to the morning. Despite the reduction in C_max,t_max was prolonged with the evening dose compared to the morning peak (detected in most of the patients at 30 minutes). In the evening t_max occurred usually after 60 minutes and was associated with a longer time to a cortisol concentration less than 100 nmol/l than the morning peak (P=0.01). Absorption of hydrocortisone varies throughout the 24 hour period probably due to alterations in clearance. To determine the true peak and exposure to cortisol frequent sampling around a dose is required. Dosing regimens need to be incorporate these observations.