Abstract
Adrenal tumors, discovered incidentally in approximately 4.5% of imaging procedures,
are known as adrenal incidentalomas. Nonclassic congenital adrenal hyperplasia, mild
form of 21-hydroxylase deficiency, may lead to the development of adrenocortical tumors.
The aim of the study was to evaluate prevalence of the most common nonclassic mutations
of CYP21A2 gene in patients with adrenal incidentalomas and investigate possible relationship
with clinical outcome. One hundred adult patients with such lesions were enrolled.
Clinical, imaging and biochemical evaluation were performed to rule out hormonal overproduction
or potential malignancy. All subjects and a control group of 100 neonates were genotyped
for P30L, P453S, and V281L mutations of CYP21A2 gene using direct sequencing. Clinical and imaging features as well as hormone levels
were analyzed. Heterozygous CYP21A2 gene mutations were detected in 8 subjects but not in the neonates. Thus, the risk
of carrying mutant allele was significantly higher in subjects with adrenal tumors
(OR=8.7; 95% CI=2.23–389.56; p=0.003). Mean concentrations of renin, basal, and stimulated
17-hydroxyprogesterone were higher and ACTH was lower in the carriers than in the
remaining subjects. Furthermore, the carriers had higher incidence of hypertension
(100 vs. 52.1%, p=0.008) and diabetes (50 vs. 11.9%, p=0.003). ACTH-stimulated 17-hydroxyprogesterone
levels varied widely among the carriers. In summary, prevalence of P30L, P453S, and
V281L mutations of CYP21A2 gene is increased in patients with adrenocortical tumors. In these subjects, carrying
the analyzed mutant alleles may increase the risk of diabetes and hypertension. ACTH-stimulation
test does not satisfactorily predict presence of heterozygous CYP21A2 mutations in patients with adrenal tumors.
Key words
adrenogenital syndrome (AGS) - incidentaloma - adrenal tumor - adrenal adenoma - CYP21A2
