Background: A basal 17-hydroxyprogesterone (17-OHP) plasma level of 6.0 nmol/l was suggested as a threshold for the diagnosis of non-classical congenital adrenal hyperplasia (NCCAH), particularly in children presenting with precocious pubarche (PP).
Objective: The present study aimed to determine if this threshold could lead to underdiagnosis of NCCAH.
Method: In a retrospective study the cohort of pediatric patients (n=145, 22 males) diagnosed as NCCAH (defined by a post-ACTH 17-OHP plasma level >30 nmol/l), was stratified according to morning basal 17-OHP levels, using the value of 6.0 nmol/l as a cut-off. Clinical and laboratory characteristics of patients with basal 17-OHP <6.0 nmol/l and of those with higher basal levels were compared.
Results: Mean age at diagnosis was 8.35±4 years. Basal 17-OHP was <6.0 nmol/l (1.15.1) in 18/145 (12.4%) patients and in 6/40 (15%) referred for PP. No differences between the groups stratified by basal level were found for age, height-SDS, weight-SDS and extent of bone age advancement at diagnosis. This held true for gender distribution, age at glucocorticoid treatment initiation, dose, basal and stimulated plasma cortisol and testosterone levels. For the entire cohort, patients with basal 17-OHP <6.0 nmol/l had significantly lower androstendione (2.2±1.9 vs 4.6±4.3 nmol/l, P<0.03) and lower stimulated 17-OHP (68.5±46.4 vs 122.1±93.5 nmol/l, P<0.001). Similarly, children referred for PP with basal 17-OHP <6.0 nmol/l had lower plasma levels of androstendione (1.7±0.6 vs 5.0±4.5 nmol/l, P<0.02), testosterone (0.08±0.16 vs 0.75±0.77 nmol/l, P<0.02), and stimulated 17-OHP (60.5±48.4 vs 122.4±63.8 nmol/l, P<0.02).
Conclusion: A selective strategy based on a 6.0 nmol/l basal 17-OHP plasma level threshold carries the risk of overlooking the diagnosis of NCCAH. The lower levels of androstendione and stimulated 17-OHP may reflect a milder impairment in enzymatic activity in patients with lower basal 17-OHP at diagnosis.
20 - 22 Sep 2014
European Society for Paediatric Endocrinology