Long-term outcomes in patients with congenital adrenal hyperplasia treated with hydrocortisone modified-release hard capsules
Wiebke Arlt, Aude Brac de la Perrière, Angelica L Hirschberg, Deborah P Merke, John D C Newell-Price, Alessandro Prete, D Aled Rees, Nicole Reisch, Philippe A Touraine, Hanna Bendfeldt, John Porter, Helen Coope, Richard J M RossAbstract
Background
Hydrocortisone modified-release hard capsules (MRHC, development name Chronocort) replace the physiological overnight cortisol rise and improve the biochemical control of congenital adrenal hyperplasia (CAH).
Aim
To evaluate long-term safety, tolerability and efficacy of MRHC.
Methods
Open label follow-on study.
Results
Ninety-one patients with classic CAH, mean age 37 years, 68% female, 32% male, entered the study and 22 discontinued. Median treatment duration was 4 years (range 0.2 to 5.8). Median hydrocortisone dose at study entry was 30mg/day and reduced to 20mg/day after 24 weeks and stayed stable thereafter until 48 months (p<0.0001). Disease control improved on MRHC for the steroid disease markers serum 17-hydroxyprogesterone (17OHP) (p<0.03) and androstenedione (A4) (p<0.002). After 4 years, the majority of patients had a 17OHP <4-fold Upper Limit of Normal (ULN) (71%) and an A4 <ULN (90%). Measurement of 17OHP and A4 at 09:00h and 13:00h gave similar results. Of the 37 women <50 years of age who were not on contraceptives over the whole study period, 5 became pregnant (13.5%). 13.8% (4/29) of men had a partner pregnancy. Seven patients had an adrenal crisis with one patient reporting 8 of these giving an incidence of 3.9 crises per 100 patient years.
Conclusions
MRHC treatment resulted in hydrocortisone dose reduction followed by a stable dose with improved biochemical control associated with fertility. Biochemical control could be reliably monitored by a single blood sample taken between 09:00h and 13:00h. The incidence of adrenal crises was below that reported previously in patients with CAH.