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.

Frequency assessment of BRAF mutation, KRas mutation, and RASSF1A methylation in nodular goitre based on fine-needle aspiration cytology specimens Ocena częstości występowania mutacji genów BRAF, KRas oraz metylacji genu RASSF1A w wolu guzkowym na podstawie badania materiału cytologicznego uzyskanego drogą biopsji aspiracyjnej cienkoigłowej AbstractIntroduction: Standard pre-operative diagnosis of nodular goitre is not always conclusive. The decision about nodular goitre surgery is increasingly based on molecular methods. The aim of the study was to determine BRAF T1799A mutation and KRas proto-oncogene mutation, and the analysis of RASSF1A promoter methylation level in cytological material obtained from FNAB specimens of thyroid nodules. Material and methods:The study population consisted of 85 women and 12 men. The study material was genomic DNA isolated from peripheral blood and thyroid bioptates. Pyrosequencing was used for the evaluation of RASSF1 methylation level. KRas mutation was investigated with Sanger sequencing. BRAF mutation was analysed by standard methods of real-time amplification detection (real-time PCR) with the use of specific starters surrounding the mutated site. Results: A significant positive correlation was demonstrated between mean methylation of four CpG islands of RASSF1A gene and thyroid tumour volume and its largest diameter (p < 0.05). KRas mutation was not detected in any of the 97 patients. In 7/85 subjects (8.2%) BRAF mutation was observed. In 6/7 patients with BRAF mutation, FNAB of thyroid nodules confirmed a benign nature of the lesions; the material was non-diagnostic in one patient, and papillary thyroid cancer was diagnosed on the basis of postoperative histopathology assessment. Conclusions:The results of genetic tests reported in our study indicate that the presence of BRAF mutation or higher RASSF1A methylation levels in FNAB cytology specimens of benign lesions may be useful in the assessment of oncological risk, while the evaluation of KRas proto-oncogene mutation is not a valuable test in pre-operative diagnosis of nodular goitre. (Endokrynol Pol 2015; 66 (5): 384-393)

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