Increased prevalence of heterozygous 21-OH germline mutations in patients with adrenal incidentalomas

As a result of the widespread use and the enhanced quality of high-resolution radiological techniques [computed tomography (CT), magnetic resonance imaging (MRI)] a high frequency (4-10%) of adrenal incidentalomas has been detected in the general population. It is still debated whether undiagnosed 21-hydroxylase (21-OH) deficiency, accounting for more than 90% of congenital adrenal hyperplasia (CAH) cases, predisposes for adrenal tumours. We therefore performed an analysis of the prevalence of 21-OH germline mutations in patients with non-functional adrenal incidentalomas.

Fifty Austrian patients with non-functional adrenal adenomas detected by CT for unrelated reasons were screened by PCR-based sequencing for the most common point mutations and by Southern blot analysis for large gene deletion/conversion events of the 21-OH gene.

Heterozygosity for large gene conversions was shown in 5 (10%), for Q318 point mutations in 2 (4%) and for the Intron2splice mutation in 1 (2%) of the 50 patients with adrenal adenomas. One (2%) patient (70 years of age), identified to have a chimeric CYP21AB gene with a junction site before Intron 2 on one and a large (30 kb) deletion on the other allele, was diagnosed to be affected by CAH.

21-OH mutation screening indicates a higher frequency of classic CAH carriers (16%) and of manifest CAH (2%) due to 21-OH-deficiency among patients with adrenal adenomas than in the general population (1-2% carrier frequency for classic CAH).