Bone Age and Growth Prediction in Congenital Adrenal Hyperplasia

Children with well-controlled congenital adrenal hyperplasia may not need additional growth treatment; bone age may not be an accurate predictor.

Children with well-controlled congenital adrenal hyperplasia (CAH) may not need additional growth-promoting therapies. These findings, from a retrospective, multi-center study, were published in The Journal of Clinical Endocrinology & Metabolism.

Medical records from 4 pediatric clinics in Switzerland between 1990 and 2012 of 41 patients were reviewed for this study. Bone age (BA) was calculated yearly on the basis of hand radiographs. BA retardation was calculated as BA minus chronological age (BA-CA), target height as mean parental height ± 6.5 cm, and final height as growth velocity <1 cm/year or aged ³18 years. “Before adrenarche” was defined as aged <6 years and “adrenarche” as aged  ³6 years to puberty onset.

Patients were 63% girls, 76% had a cytochrome P450 family 21 subfamily A member 2 (CYP21A2) genotype, and their average dose of hydrocortisone was 14.1-16.2 mg/m2/day. Among girls, pubarche (10.5 vs 11.3 years) and puberty (10.3 vs 10.9 years) was earlier than European reference, respectively.

Final height was reached by 20 girls and 7 boys.

Among all children in the study, mean BA-CA was delayed before adrenarche but not after (P =.014). BA accelerated during adrenarche among 49% of the children and progressed normally in 51%. These differences were not observed during puberty.

Boys had a higher estimated final height than girls during adrenarche and puberty using the Bayley and Pinneau method, but the estimates remained the same when calculated at either of these time points. Values increased from adrenarche to puberty for both boys and girls using the Bonfig and Schwarz method.

The children who had accelerating BA-CA during adrenarche were estimated to have a lower final height using either prediction method, but this discrepancy disappeared by puberty.

Factors associated with lower estimated final height during adrenarche included accelerating BA (coefficient, -1.12; 95% CI, -1.7 to 0.5), female gender (coefficient, -0.98; 95% CI, -1.6 to 0.3), and 17-hydroxyprogesterone (17-OHP) >30 nmol/l (coefficient, -0.37; 95% CI, -0.7 to 0.0). Higher estimated final height was associated with fludrocortisone doses >50 mg/day (coefficient, 0.34; 95% CI, 0.0 to -0.6).

During puberty, the factor most associated with lower estimated final height was female gender (coefficient, -1.00; 95% CI, -1.7 to -0.3).  Androstenedione >11 nmol/l (coefficient, 0.25; 95% CI, 0.1 to 0.4) was associated with higher estimated final height.

Among boys, the average final height was 176.4 cm and their parental target height was 179.2 cm.  For girls, the final height was 160.1 cm compared with a parental target of 163.7 cm. These values indicated that children with CAH reached their target final average height of both parents within 6.5 cm.  

This study may have been limited by defining bone age progression during adrenarche by age alone.

Researchers concluded children with CAH receiving near-physiologic glucocorticoid treatment “[achieved] a final height that is close to normal.”

“[Bone age] may not be the best marker of metabolic control in CAH patients during the period of adrenarche,” the researchers added, “and additional growth-promoting treatments in otherwise well-controlled CAH patients seem unnecessary.”

Disclosure: At least one author declared affiliations with pharmaceutical companies, and the research was supported in part by a grant from Novo Nordisk Switzerland. Please see the original reference for a full list of disclosures.


Troger T, Sommer G, Lang-Muritano M, et al. Characteristics of growth in children with classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency during adrenarche and beyond. J Clin Endocrinol Metab. dgab701, https://doi:10.1210/clinem/dgab701