Growth Analysis in Patients with 21-Hydroxylase Deficiency Influence of Glucocorticoid Dosage, Age at Diagnosis, Phenotype and Genotype on Growth and Height Outcome

Abstract

Objective: To evaluate the impact of hydrocortisone dosage, age at diagnosis, compliance, genotype and phenotype on growth and height outcome in 21-hydroxylase-deficient patients. Methods: We analyzed 37 patients with 21-hydroxylase deficiency (17 had completed growth, 20 still growing). Final (FH)/predicted final height (pFH) and loss of height potential related to target height (TH) were calculated and the impact of 4 hydrocortisone (HC) dosage regimens on height outcome and growth velocities was evaluated. Mean FH SDS and pFH SDS were analyzed in accordance to age at diagnosis, compliance, genotype and phenotype. Results: Mean (FH SDS, pFH SDS) was –1.8 ± 1.06 SD, with 35.1% of all 37 patients exhibiting short stature. Doses >20 mg/m²/day during the first year and >15 mg/m²/day during age 1–5 and at puberty resulted in significantly lower FH SDS, pFH SDS and greater height losses. Age at diagnosis, compliance, genotype and phenotype played only a minor role in growth development. Conclusions: Hydrocortisone substitution in 21-hydroxylase-deficient patients should be kept at the lowest efficient level, if possible <20 during the first year and <15 mg/m²/day until age 5 and during puberty. Normal growth and not complete androgen suppression should be aimed for.

Clinical Characteristics of a Cohort of 244 Patients with Congenital Adrenal Hyperplasia

“…Although we did not find a statistical association between age at diagnosis and height outcome, the fact that our cohort was mostly diagnosed before the initiation of neonatal screening, with late diagnosis of SV males, could have contributed to this finding. Final adult height has been negatively correlated with childhood glucocorticoid dosing (22). We were unable to evaluate lifetime exposure to glucocorticoid dosing due to the cross-sectional nature of our study.…”

Adrenal Steroidogenesis and Congenital Adrenal Hyperplasia

“…A meta-analysis of data from 35 centers concluded that the near-final height of patients with classic 21OHD was -1.38 SD below the population mean and -1 SD below the predicted mid-parental height 50 . A multitude of factors influence adult height, including severity of disease 51 , age at diagnosis 49 , treatment regimen 52,53 and compliance. These known factors, however, failed to prove significant individually in pooled data, possibly because of heterogeneity and inconsistent reporting between studies.…”

“…A total of 10-17 mg/m 2 daily divided in 2-3 doses is typically recommnended 29 , although it remains unclear if a specific dose distribution throughout the day has a significant clinical impact 102 . The lowest possible dose should be used in order to avoid growth suppression 51,53,103,104 .…”

Growth in Patients with Classic Congenital Adrenal Hyperplasia due to 21-Hydroxylase Deficiency

“…It is also commonly believed that most treated CAH patients achieve a final adult height that is shorter than that predicted based on mean parental height [7]. There are numerous publications showing that final adult height of CAH patients is less than the general population and that of the midparental height [8,9,10,11,12,13,14,15,16,17,18,19,20,21]. Comparison of different studies is limited, since different reference standards were used in different studies.…”