Hormonal criteria for the diagnosis of nonclassical 21-hydroxylase deficiency compared to the molecular study of the CYP21A2 gene

Fernanda de Azevedo Corrêa Tânia A.S. Sanchez Bachega About the authors

Diagnosis of the nonclassical form of 21-hydroxylase deficiency (NC-21OH) is based on clinical hyperandrogenism and basal 17-hydroxyprogesterone (17OHP) levels >5ng/mL or >10ng/mL after ACTH-stimulation. We present two children with precocious pubarche and a hormonal diagnosis of NC-21OH, whose molecular study of the CYP21A2 gene confirmed the diagnosis in just one case. After that, we re-evaluated the diagnosis of 58 patients with ACTH-stimulated 17OHP levels >10ng/mL with molecular studies of CYP21A2 gene. Only 37 (67%) of these patients had mutations detected in both alleles: basal 17OHP levels were >5ng/mL in 70%, normal in 11% and between 2 and 5ng/mL in the remaining patients. The lowest ACTH-stimulated 17OHP level in this group was 17ng/mL. We then analyzed 59 obligate carriers for 21-hydroxylase deficiency and found two asymptomatic subjects with ACTH-stimulated 17OHP levels of 11 and 15ng/mL, respectively. Based on these findings, we suggest that the current cut-off value for ACTH-stimulated 17OHP level overestimates the diagnosis of NC-21OH.

Precocious puberty; 21-Hydroxylase deficiency; Nonclassical form; 17-Hydroxyprogesterone; CYP21A2 gene


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