Horm Metab Res 2015; 47(09): 662-667
DOI: 10.1055/s-0035-1549911
Endocrine Care
© Georg Thieme Verlag KG Stuttgart · New York

Prevalence and Clinical Outcome of CYP21A2 Gene Mutations in Patients with Nonfunctional Adrenal Incidentalomas

B. Kiedrowicz
1  Department of Endocrinology, Metabolic and Internal Diseases, Pomeranian Medical University, Szczecin, Poland
,
A. Binczak-Kuleta
2  Department of Clinical and Molecular Biochemistry, Pomeranian Medical University, Szczecin, Poland
,
J. Lubikowski
3  Department of Surgery, West Pomeranian Oncology Center, Szczecin, Poland
,
M. Koziolek
1  Department of Endocrinology, Metabolic and Internal Diseases, Pomeranian Medical University, Szczecin, Poland
,
E. Andrysiak-Mamos
1  Department of Endocrinology, Metabolic and Internal Diseases, Pomeranian Medical University, Szczecin, Poland
,
M. Ostanek-Panka
2  Department of Clinical and Molecular Biochemistry, Pomeranian Medical University, Szczecin, Poland
,
A. Ciechanowicz
2  Department of Clinical and Molecular Biochemistry, Pomeranian Medical University, Szczecin, Poland
,
A. Syrenicz
1  Department of Endocrinology, Metabolic and Internal Diseases, Pomeranian Medical University, Szczecin, Poland
› Author Affiliations
Further Information

Publication History

received 22 September 2014

accepted 08 April 2015

Publication Date:
13 May 2015 (eFirst)

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.