Non-classical 21-hydroxylase deficiency in boys with prepubertal or pubertal gynecomastia

Abstract

This report describes two boys who were evaluated for the first time at the ages of 9.8 (patient 1) and 13.4 years (patient 2), due to either prepubertal or pubertal gynecomastia. The diagnosis of non-classical (NC) 21-hydroxylase deficiency (21-OH-D) was substantiated by the finding of increased baseline and adrenocorticotropic hormone (ACTH)-stimulated 17-hydroxy-progesterone levels and was supported by molecular analyses of the CYP21A2 gene, which revealed V281L homozygosis in patient 1 and V281L/P30L compound heterozygosis in patient 2. In both boys, gynecomastia completely regressed 5–8 months after the institution of glucocorticoid substitutive treatment. We conclude that it is mandatory to suspect NC 21-OH-D in the clinical evaluation of either prepubertal or pubertal gynecomastia, since this association might be more frequent than reported so far, and that it is important that diagnosis is made by the first months after gynecomastia development, since a longstanding gynecomastia is unlikely to respond completely to medical therapy.