Modified-Release Hydrocortisone Lowers 17OHP in Pediatric CAH

Key Takeaways

• Among the 31 children and adolescents with available morning 17OHP data, switching to hydrocortisone modified-release capsules was associated with lower morning salivary 17OHP, from 337 ng/L before switch to 214 ng/L after switch, with an average reduction factor of 0.64 (p < 0.01).
• In pediatric classic congenital adrenal hyperplasia, hydrocortisone modified-release capsules were associated with a shift in growth velocity from 0.1 SDS/year (95% CI 0.0 to 0.2) before switch to -0.1 SDS/year (95% CI -0.2 to 0.1) after switch, alongside a median 0.50-year reduction in bone age minus chronological age in 13 children with paired data.
• Among children and adolescents with classic congenital adrenal hyperplasia receiving hydrocortisone modified-release capsules, mean hydrocortisone dose increased from 12.4 to 14.8 mg/m²/day and mean fludrocortisone dose increased by 11.7 µg/day, while BMI and blood pressure showed no observed treatment-change effect and no adrenal crisis was observed.

Morning salivary 17OHP fell from 337 ng/L to 214 ng/L after children and adolescents with classic congenital adrenal hyperplasia switched to an HMRC-based regimen (with HMRC used for the evening dose or for all hydrocortisone administrations), an average reduction factor of 0.64 (p < 0.01), in Lankes and colleagues’ pediatric HMRC registry analysis in classic congenital adrenal hyperplasia. The single-center retrospective pre-post registry analysis included 36 children and adolescents with classic CAH, median age 10 years, including 15 prepubertal and 21 pubertal or postpubertal participants. The switch was also associated with a different growth trajectory and higher replacement dosing over follow-up.

The within-patient comparison came from a single-center observational analysis of the I-CAH registry in which all participants had 21-hydroxylase deficiency and were receiving hydrocortisone plus fludrocortisone before and during HMRC exposure. Morning control was classified as predominantly good or overtreated in 24/31 children (77%) after the switch versus 14/31 (45%) beforehand, while evening 17OHP did not differ significantly. Some children younger than 12 years received HMRC off-label after informed discussion, as described by the investigators.

Growth and skeletal maturation formed the secondary signal in the paired outcomes. Growth velocity changed from 0.1 SDS/year, 95% CI 0.0 to 0.2, before the switch to -0.1 SDS/year, 95% CI -0.2 to 0.1, during HMRC treatment. Bone age minus chronological age changed by a median -0.50 years, IQR -1.17 to 0.27, in the 13 children with paired radiographic data. The authors also described an average narrowing in deviation from parental target height, while noting that growth deceleration was seen across pubertal strata and subgroup interpretation was limited.

When the investigators summarized morning 17OHP, growth, bone-age, and dosing outcomes after HMRC switch, mean hydrocortisone dose had increased by 2.4 mg/m²/day, from 12.4 to 14.8 mg/m²/day, and mean fludrocortisone dose had increased by 11.7 µg/day. BMI and blood pressure showed no observed treatment-change effect, and no adrenal crisis was observed during HMRC therapy. The authors noted that the analysis was single-center, retrospective, and pre-post without a concurrent control group, that p-values were exploratory and not adjusted for multiple testing, and that post-switch follow-up was limited for some children even though the longest observation reached 3.5 years.

Clinician Questions

How did morning salivary 17OHP change after switching children with classic congenital adrenal hyperplasia to modified-release hydrocortisone?

In 36 children and adolescents with classic congenital adrenal hyperplasia, switching to hydrocortisone modified-release capsules was associated with a fall in morning salivary 17OHP from 337 ng/L before switch to 214 ng/L after switch, with an average reduction factor of 0.64 and p < 0.01.

What growth and bone-age changes were reported after modified-release hydrocortisone in pediatric classic CAH?

In children and adolescents with classic congenital adrenal hyperplasia, growth velocity changed from 0.1 SDS/year before switch to -0.1 SDS/year after switching to hydrocortisone modified-release capsules, and bone age minus chronological age decreased by a median 0.50 years in the 13 children with paired bone-age data. The study also described an average reduction in deviations from parental target height.

Did hydrocortisone modified-release capsules affect dose requirements or safety outcomes in children with classic CAH?

In children and adolescents with classic congenital adrenal hyperplasia treated with hydrocortisone modified-release capsules, mean hydrocortisone dose increased by 2.4 mg/m²/day from 12.4 to 14.8 mg/m²/day, mean fludrocortisone dose increased by 11.7 µg/day, BMI and blood pressure showed no observed treatment-change effect, and no adrenal crisis was observed during treatment.