Bone Age Maturation and Growth Outcomes in Young Children with CAH Treated with Hydrocortisone Suspension

Heba Al-Rayess; O Yaw Addo; Elise Palzer; Mu'taz Jaber; Kristin Fleissner; James Hodges; Richard Brundage; Bradley S Miller; Kyriakie Sarafoglou

doi:10.1210/jendso/bvab193

Bone Age Maturation and Growth Outcomes in Young Children with CAH Treated with Hydrocortisone Suspension

J Endocr Soc. 2021 Dec 25;6(2):bvab193. doi: 10.1210/jendso/bvab193. eCollection 2022 Feb 1.

Authors

Heba Al-Rayess¹, O Yaw Addo², Elise Palzer³, Mu'taz Jaber⁴, Kristin Fleissner¹, James Hodges³, Richard Brundage⁴, Bradley S Miller¹, Kyriakie Sarafoglou^{1

4}

Affiliations

¹ Division of Endocrinology, Department of Pediatrics, University of Minnesota Medical School, Minneapolis, MN 55454, USA.
² Department of Global Health, Rollins School of Emory University, Atlanta, GA 30322, USA.
³ Division of Biostatistics, University of Minnesota School of Public Health, Minneapolis, MN 55455, USA.
⁴ Department of Experimental and Clinical Pharmacology, University of Minnesota College of Pharmacy, Minneapolis, MN 55455, USA.

Abstract

Background: Young children with congenital adrenal hyperplasia (CAH) require small doses (0.1-1.25 mg) of hydrocortisone (HC) to control excess androgen production and avoid the negative effects of overtreatment. The smallest commercially available HC formulation, before the recent US Food and Drug Administration approval of HC granules, was a scored 5-mg tablet. The options to achieve small doses were limited to using a pharmacy-compounded suspension, which the CAH Clinical Practice Guidelines recommended against, or splitting tablets into quarters or eighths, or dissolving tablets into water.

Methods: Cross-sectional chart review of 130 children with classic CAH treated with tablets vs a pharmacy-compounded alcohol-free hydrocortisone suspension to compare growth, weight, skeletal maturation, total daily HC dose, and exposure over the first 4 years of life.

Results: No significant differences were found in height, weight, or body mass index z-scores at 4 years, and in predicted adult height, before or after adjusting for age at diagnosis and sex. Bone age z-scores averaged 2.8 SDs lower for patients on HC suspension compared with HC tablets (P < 0.001) after adjusting for age at diagnosis and sex. The suspension group received 30.4% lower (P > 0.001) average cumulative HC doses by their fourth birthday.

Conclusions: Our data indicate that treatment with alcohol-free HC suspension decreased androgen exposure as shown by lower bone age z-scores, allowed lower average and cumulative daily HC dose compared to HC tablets, and generated no significant differences in SDS in growth parameters in children with CAH at 4 years of age. Longitudinal studies of treating with smaller HC doses during childhood are needed.

Keywords: adrenal insufficiency; bone age; congenital adrenal hyperplasia; growth; hydrocortisone; suspension.