Glucocorticoid replacement regimens for treating congenital adrenal hyperplasia.
Level 1 - systematic review of randomized trials
Systematic review of randomized controlled trials
PubMed 32190901 · doi:10.1002/14651858.CD012517.pub2
What was done
Authors conducted a Cochrane systematic review searching electronic databases and trial registries through June 2019 for randomized controlled trials (RCTs) or quasi-RCTs comparing oral glucocorticoid replacement regimens in children and adults with congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency. Trial quality was assessed using standard Cochrane risk-of-bias tools and GRADE methodology.
What was found
Five RCTs were included (four crossover, one parallel; total 101 participants, sample sizes 6 to 44, ages 3.6 months to 21 years) with treatment durations from two weeks to six months per arm. Due to marked heterogeneity, no meta-analysis was possible. All outcomes had very low-quality evidence. Across trials, dosing schedules of hydrocortisone (HC), prednisolone (PD), and dexamethasone (DXA) showed mixed effects on hormonal control: one trial (n=15) found no difference between high morning versus evening HC dosing for 17-OHP, testosterone, or androstenedione; another (n=27) found HC and DXA suppressed 17-OHP and androstenedione more than PD at six weeks; and one trial (n=44) showed no differences between HC and PD in hormone levels or height velocity at one year. One trial (n=26) reported reduced height velocity at six months with HC 25 mg/m²/day compared to 15 mg/m²/day. No trials reported final adult height, adrenal crises, quality of life, osteopenia, adrenal rest tumors, or fertility.
Why it matters
Current clinical choices among glucocorticoid replacement regimens in CAH rely on surrogate biomarkers and low-certainty data, lacking evidence on key long-term clinical endpoints.
Limits
The total sample size across all included trials was only 101 participants, with individual trials ranging from 6 to 44 subjects. Risk of bias was moderate to high across studies due to unclear reporting. Follow-up was short (maximum 12 months), regimens were heterogeneous, and critical patient-important outcomes such as adrenal crisis prevention, fertility, and final adult height were not evaluated.