Growth pattern and pubertal development in patients with classic 21-hydroxylase deficiency

Background: The goal of treatment in children with congenital adrenal hyperplasia (CAH) is to normalize growth and pubertal development. There are limited studies reporting on growth and pubertal outcome in CAH patients from low-resource settings as in Thailand, where CAH newborn screening is lacking, and standard medications are not widely available.

Objective: We analyzed the longitudinal growth data, and pubertal characteristics in children and adolescents with CAH, compared with population-based references.

Methods: Fifty-eight patients with classic 21-hydroxylase deficiency (21OHD) [49 had salt-wasting (SW)-CAH and 9 patients had simple virilizing (SV)-CAH] were retrospectively assessed for growth and pubertal development until they reached their final height (FH). Details of treatment, and hormonal profiles were recorded.

Results: Mean FH SD scores (SDS) of patients were in the lower range of normal population (SW boys -1.88±0.6, SW girls -1.88±1.1 and SV boys -1.06, SV girls -1.56±1.4). Nine of the 19 male, and 6 of the 39 female patients had BMI SDS >2.0. Mean ages of pubertal onset in SW, and SV boys were 8.2±2.4 years, and 7.1±1.9 years, respectively, while in SW girls were 9.7±2.2 years, and SV 7.0±1.7 years. Twelve of the 38 patients had central precocious puberty and required GnRH analog treatment. Total pubertal growth was significantly decreased in the SW group, but not in the SV group; SW boys 15.5±10.6 cm (reference 22.1±3.6 cm), and SW-females 10.6±5.5 cm (reference 18.3±4.0 cm). Glucocorticoid dose was not associated with FH-SDS (n = 19, r = -0.132, p = 0.589). Markedly elevated 17-hydroxyprogesterone and testosterone levels were observed during the pubertal period.

Conclusion: Our results demonstrate poor final height outcome in Thai children with classic 21OHD. Obesity, secondary central precocious puberty, and poor hormonal control are common. These findings necessitate early diagnosis and treatment by establishing newborn screening system in Thailand as well as new treatment regimen and monitoring methods.