Clinical characteristics of a cohort of 244 patients with congenital adrenal hyperplasia

Abstract

Context: Patients with congenital adrenal hyperplasia (CAH) often suffer from long-term complications secondary to chronic glucocorticoid therapy and suboptimal treatment regimens.

Objective: The aim of the study was to describe clinical characteristics of a large cohort of pediatric and adult CAH patients.

Design and setting: We conducted a cross-sectional study of 244 CAH patients [183 classic, 61 nonclassic (NC)] included in a Natural History Study at the National Institutes of Health.

Main outcome measure(s): Outcome variables of interest were height sd score, obesity, hypertensive blood pressure (BP), insulin resistance, metabolic syndrome, bone mineral density, hirsutism (females), and testicular adrenal rest (TART).

Results: The majority had elevated or suppressed androgens, with varied treatment regimens. Mean adult height SD score was -1.0 ± 1.1 for classic vs. -0.4 ± 0.9 for NC patients (P = 0.015). Obesity was present in approximately one third of patients, across phenotypes. Elevated BP was more common in classic than NC patients (P ≤ 0.01); pediatric hypertensive BP was associated with suppressed plasma renin activity (P = 0.001). Insulin resistance was common in classic children (27%) and adults (38% classic, 20% NC); 18% of adults had metabolic syndrome. The majority (61%) had low vitamin D; 37% of adults had low bone mineral density. Hirsutism was common (32% classic; 59% NC women). TART was found in classic males (33% boys; 44% men).

Conclusions: Poor hormonal control and adverse outcomes are common in CAH, necessitating new treatments. Routine monitoring of classic children should include measuring BP and plasma renin activity. Osteoporosis prophylaxis and TART screening should begin during childhood. A longitudinal study is under way.

Trial registration: ClinicalTrials.gov NCT00250159.

Fig. 1.

Geographic distribution of the CAH patient population (n = 244).

Fig. 2.

Prevalence of treatment and hormonal characteristics according to phenotype in pediatric and adult patients with CAH due to 21-hydroxylase deficiency. A, Glucocorticoid therapy (HC, hydrocortisone; Pred, prednisone/prednisolone; Dex, dexamethasone). B, 17-OHP in nanograms per deciliter. To convert to SI units, multiply 17-OHP by 0.0302. C, Androstenedione. D, Testosterone. Suppressed, normal, and elevated levels are based on age- and sex-specific normal range.

Fig. 3.

A, Predicted height SDS by age according to phenotype in pediatric patients with CAH. B, Corrected predicted height SDS by age according to phenotype in pediatric patients with CAH. C, Adult height SDS by age according to phenotype in patients with CAH. D, Corrected adult height SDS by age according to phenotype in patients with CAH. Normal range is marked in gray.

Fig. 4.

Prevalence of clinical characteristics according to phenotype in pediatric and adult patients with CAH due to 21-hydroxylase deficiency. A, BMI. B, BP, SBP, and DBP. C, Insulin resistance based on HOMA-IR (13); pediatric includes adolescents (≥13 yr). D, BMD; pediatric includes those at least 8 yr old.