Endocrine Abstracts

Hydrocortisone therapy needs to be individualised in congenital adrenal hyperplasia (CAH) patients to avoid over and under replacement. Plasma cortisol concentration is determined by absorption and half-life of cortisol influence glucocorticoid exposure. Terminal plasma half-life is the time required to divide the plasma concentration by two and is important when absorption may vary.

To ascertain a role for this measure we have studied 48 patients (21M) aged between 6.1 and 20.3 years with CAH due to CYP21A2 deficiency. Each patient underwent a 24 h plasma cortisol profile with the morning dose used to calculate absorption parameters along with an intravenous (IV) hydrocortisone (15 mg/m² body surface area) bolus assessment of half-life. Parameters derived were maximum plasma concentration (C_max), time of maximum plasma concentration (t_max), time to attaining plasma cortisol concentration less than 100 nmol/l and half-life of cortisol.

Mean half-life was 76.5±5.2 (range 40–225.3) min, C_max 780.7±61.6 nmol/l and t_max 66.7 (range 20–118) min. Time taken to a plasma cortisol concentration <100 nmol/l was 289 (range 140–540) min. Those with a fast half-life and slow t_max took longest to reach a plasma cortisol concentration less than 100 nmol/l (380±34.6 min), compared to those with a slow half-life and fast t_max (298±34.8 min) and those with a fast half-life and fast t_max (249.5±14.4 min) (P=0.009).

Both rate of absorption and half-life of cortisol in the circulation play important roles in determining overall exposure to oral glucocorticoid. Dose regimens need to incorporate estimates of these parameters into determining the optimum dosing schedule for individuals.