ESPE Abstracts

Introduction: Hydrocortisone (HC) has a short half-life and individualization of treatment is required for optimal treatment of CAH, balancing between under- and overtreatment. Twenty four hour profiling of HC concentrations has shown large interindividual variation in clearance of HC and therefore has been used to individualize treatment. We present a severely virialized girl with CAH, in whom high doses of steroids failed to suppress androgen production thought to be due to malabsorption. Investigations showed fast clearance of HC, and 24 hour profiling allowed for dose adjustment and improved disease control.

Clinical case: A 7.5year old girl with 21-hydroxylase deficiency and Prader Stage V virilization and enlarged adrenal glands was referred for assessment for continuous subcutaneous HC pump treatment. Poor control of CAH was thought due malabsorption due to complex bowel problems. Despite 8-hourly HC doses totaling 116mg/m²/d, her pre-dose saliva 17-hydroxyprogesterone (17-OHP) concentrations were very high. A HC clearance study using 15 mg HC IV, showed that HC was cleared quickly (5245 to 741 nmol/l in 150 min, t½ 57 minutes compared to usual 80 minutes) and that the 17-OHP could be suppressed. A 24-hour cortisol profile on her usual HC doses showed that HC was absorbed as she achieved cortisol concentrations up to 1439nmol/l. However 17OHP, androstenedione and ACTH concentrations were persistently high suggesting autonomous adrenal androgen production. In order to suppress that she was treated with oral dexamethasone and required 0.5 mg BD to suppress androgens and ACTH and normalize adrenal gland size. She was then switched back to her equivalent HC doses, and 24-hour cortisol profiles were used to allow gradual reduction of HC doses. Her 17OHP and androgens remained suppressed but once the dose was reduced to 32mg/m²/d in 3 divided doses, the 17-OHP increased whilst cortisol concentrations dropped quickly, in line with fast clearance. Under close follow up with 24-hour profiles, appropriate cortisol concentrations with appropriate suppression of androgen and 170HP production was achieved once increasing frequency of HC doses to 5 times daily with a total dose of 34 mg/m²/day. Fludrocortisone was required at a dose of 260mcg/m²/day.

Conclusion: This case of poorly controlled CAH, where in depth investigations revealed rapid clearance of hydrocortisone and autonomous adrenal androgen production, is an example of where 24-hour hydrocortisone profiling and frequent dosing of hydrocortisone can help to improve control of CAH.