ESPE Abstracts

Context: Children with congenital adrenal hyperplasia (CAH) and adrenal insufficiency (AI) require hydrocortisone replacement from birth. Continuous monitoring of therapy during growth is necessary. Until now, children were dependent on off label use with divided hydrocortisone tablets or pharmacy compounded capsules. A licensed paediatric formulation that allows accurate dosing down to 0.5mg is now available.

Objective: A prospective safety and efficacy study of 0-8 year old children with CAH and AI treated with hydrocortisone granules and monitored through 17-OHP saliva profiles.

Methods: Seventeen children with CAH (9 male) and 1 with hypopituitarism (male) were evaluated in 3 cohorts according to age at study entry in the previous study: cohort 1 (2-<6 years, n = 9), cohort 2 (1 month-2 years, n = 6) and cohort 3 (<28 days, n = 3). Study visits were scheduled monthly for 3 visits and 3-monthly thereafter including physical examination, measurement of weight, length, blood pressure. Patients with CAH were asked to conduct a daily 17-OHP-saliva profile every three months.

Results: Study medication was given three times daily every eight hours; median duration of treatment (range) was 795 (1-872) days with 150 follow-up visits. Hydrocortisone dose was adjusted at 40/150 visits. In CAH patients this was based on 17-OHP monitoring (32 using salivary measurements, 8 based on blood sampling). Saliva sampling started at about 6 months of age. Mean daily hydrocortisone dose (mg/m²±SD) at study entry for cohorts 1, 2 and 3 was 11.06±3.01, 10.42±1.41 and 17.52±10.38 and at end of study was 10.47±2.67, 10.37±1.62 and 10.18±2.47. Hydrocortisone doses used at different time points varied from 0.5mg to 10mg and the dose distribution varied from the beginning to the end of the study within age groups. Youngest children (cohort 3) started with an equal dose distribution over the day (33-33-33%) while older children had a greater proportion in the morning and at night-time (40-20-40%). Height and weight showed no trends for accelerated or reduced growth. No adrenal crisis was observed despite 193 treatment-emergent adverse events, which were mainly common childhood illnesses. Nine severe adverse events were reported. None of the adverse events had a suspected causal relationship to study medication.

Interpretation: This first prospective study of glucocorticoid treatment in children with AI demonstrates that an individualized therapy with accurate dosing and monitoring from birth results in hydrocortisone doses at the lower end of the recommended dose range, normal growth, and no increase in adrenal crises.