Dose Distribution in Hydrocortisone Replacement Therapy Has a Significant Influence on Urine Free Cortisol Excretion

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Abstract
We investigated the influence of dose distribution in hydrocortisone replacement therapy on urine free cortisol excretion. To this end, we measured 24-hour urine free cortisol (24-h UFC) in 13 patients with hypocortisolism. The patients took 25 mg hydrocortisone/day according to the following schedules: either a single 25 mg hydrocortisone dose at 8:00 a.m., or 15 mg hydrocortisone at 8:00 a.m. and 10 mg hydrocortisone at 2:00 p.m., or 5 mg hydrocortisone at 8:00 a.m., 10:00 a.m., 2:00 p.m., 6:00 p.m. and 10:00 p.m. 24-h UFC decreased significantly with increasing division of the daily 25 mg hydrocortisone dose. When taking 25 mg hydrocortisone in a single morning dose, the mean 24-h UFC was 649 ± 52 nmol/day (mean ± SEM). When the daily dose was divided into doses of 15 mg and 10 mg hydrocortisone, 24-h UFC was reduced by 28 % to 466 ± 39 nmol/day (p < 0.002). After division into five doses of 5 mg, 24-h UFC was reduced by 42.8 % to 371 ± 36 nmol/day (p < 0.001) compared to the single 25 mg dose. These data demonstrate that consideration of the dose distribution in hydrocortisone replacement therapy when analysing 24-h UFC is of clinical importance. 1 In part presented at the 46th Symposium of the “Deutsche Gesellschaft für Endokrinologie”, Göttingen, Germany, February 27 - March 2, 2002.

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