33: Circadian variation: 30 diurnal patterns of plasma progesterones determined every 60min. in children with CAH

Abstract

In untreated congenital adrenal hyperplasia (CAH) the plasma levels of glucocorticoid precursors progesterone (P) and 17-Hydroxy-Progesterone (17-OHP) are elevated. Few investigations suggest circadian variations of these. But two factors remain uncertain: first the time of maximal peaks which may be important for timing of replacement therapy and second to what extent therapy has to suppress circadian variations. To elucidate this we estimated plasma progesterones in 60 min. intervalls over a period of 24 hours. The method as reported previously, does not differentiate between P and 17-OHP. 13 untreated patients showed circadian variations as known for cortisol: the lowest values were noticed at 7 p.m. (51±14 ng/ml, range:6-156), the highest at 4 a.m. (202±26 ng/ml, range:78-379). In 7 untreated patients dexamethasone (2 mg/d) caused a marked decrease of plasma levels within a few hours. Circadian variations were abolished and plasma levels at 7 p.m. (8±1 ng/ml, range: 4-13) and 4 a.m. (10±2 ng/ml, range:6-21) were low. 10 patients treated with 25 mg/m²/d hydrocortisone revealed suppressed but still visible diurnal patterns with a maximal increment at 7 a.m. (88±20 ng/ml, range:26-226). Trials of different dosage and timing of replacement therapy failed to have a convincing effect on flattening the circadian curves. Current replacement therapy obviously does not cause complete suppression. This possibly is brought about by overdosage only. Growth under usual therapy might be related to the average hight of the circadian curves.

Supported by Deutsche Forschungsgemeinschaft, SFB 34

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