Testicular adrenal rest tumours in boys, adolescents and adult men with congenital adrenal hyperplasia may be associated with the CYP21A2 mutation.

Congenital adrenal hyperplasia (CAH) is an autosomal recessive disorder with impaired function of the adrenal cortex caused by mutations in the CYP21A2 gene. Deficiency of steroid 21-hydroxylase accounts for 80-95% of CAH cases. Testicular adrenal rest tumours (TART) may be prevalent in up to 95% of CAH adults and may already appear during childhood. Whether genotype sub-types can account for the development of TART has not been investigated previously. We therefore investigated this by coupling clinical information of CAH patients with information of their genetic mutation. In 49 male patients (age 2.6-40.3 years) with 21-hydroxylase deficiency, testicular ultrasound examinations were performed and CYP21A2 genotypes determined. These were grouped according to the residual 21-hydroxylase activity: group Null (complete enzyme impairment), group A (almost complete enzyme impairment), group B (severe enzyme impairment) and group C (partial impairment). TART were observed in 27 of 49 patients (55%). For the 23 patients younger than 18 years, TART were present in 11 (48%), the youngest patient being 7.5 years old. The presence of TART was dependent on the CYP21A2 genotype: 27 of 37 patients (73%) with the most severe mutations (groups Null and A) had TART, whereas none of 12 patients with the milder mutations (groups B and C) had TART. We conclude that TART were most frequently detected in patients with severe CYP21A2 mutations, and may occur already in early childhood in such patients.