Chronopharmacology of hydrocortisone and 9 alpha-fluorhydrocortisone in the treatment for congenital adrenal hyperplasia.

The conventional treatment of CAH with hydrocortisone (16-19 mg/m2 per day) and 9 alpha-F-cortisol (just enough to normalise renin concentrations, started at 07:00 h) was ineffective in suppressing the early morning rise of 17-OH-progesterone and in turn androgens in about 20% of our patients. The present work explored the effect of a modified dosage regimen of the drug in five patients. The schedule was: 03:00 h F 33% + 9 alpha-F-F 33%; 07:00 h F 30%; 12:00 h F 22% + 9 alpha-F-F 33%; 17:30 h F 15% + 9 alpha-F-F 33%. Monitored levels of circulating 17-OH-progesterone, testosterone, and individual urinary 17-ketosteroids showed significant improvement, which was not achieved by giving higher or later evening doses. Menarche was induced in two girls (bone age 15 years). The modified dosage schedule offers on the one hand the possibility of better management of CAH, and on the other, cuts down the risk of enhanced Cushing-like effects, which in animal models have been related frequently to dosage schedules not corresponding to the circadian rhythm. The difficulty of administering the drugs at 03:00 h should be overcome by the development of a late-releasing preparation.