Η εξέλιξη παιδιών με πρώιμη αδρεναρχή, με ή χωρίς διαταραχή, στο γονίδιο της 21-υδροξυλάσης

Abstract

Aim of the study: In the present study we investigated concurrent alterations in oxidative stress, hormonal, metabolic, inflammatory, coagulation and endothelial dysfunction markers in girls with a history of PA, and their modification by the presence of CYP21A2 gene mutations. Patients - Methods: The study group included 45 adolescent girls with history of PA. In all subjects studied, the levels of glucose, insulin, lipids, androgens, oestrogens, cortisol, adiponectin, inflammation markers [TNFα, CRP, Interleukin-6 (IL-6), Endothelin (ET1)], coagulation factors [PAI-1, vWF, t-PA], total oxidative stress (TOS) and total antioxidative status (TAS) were determined. An ovarian ultrasound was carried in 35 girls with PA and all normal girls. Furthermore, the girls with a history of PA were divided in two subgroups, according to the presence or absence of CYP21A2 mutations. Group Α consisted of 29 girls without CYP21A2 mutation, while group Β consisted of 16 heterozygotes for CYP21A2 mutation. In addition to the evaluation described above, in all girls with PA an oral glucose tolerance test and GnRH-analog stimulation of the ovaries were carried out. Results: A) Comparing the total group of PA girls with their normal peers we found no difference in chronologic age, pubertal status, ΒΜΙ and waist to hip ratio. Also the two groups did not differ in the levels of oestrogens, cortisol, adiponectin, vWF, ET1, IL-6 and TNFα. However, girls with PA had higher levels of androgens, insulin resistance, CRP and PAI-1, while they had lower t-PA concentrations compared to controls. Additionaly, significant ovarian morphology abnormalities were observed in PA group. Although the total oxidative stress (TOS) and total antioxidant status (TAS) were comparable in PA girls and controls, CRP and PAI-1 values were positively correlated with TOS and t-PA values were positively correlated with TAS. It should be mentioned that TOS and TAS were unrelated to hyperandrogenism and insulin resistance. Β) Comparing the PA girls, with and without CYP21A2 mutation, it was found that the two groups did not differ in their chronological age, the age of pubarche, pubertal status, ΒΜΙ, waist to hip ratio, adiponectin, androgen levels, indices of insulin resistance (HOMA-IR, insulin/glucose, insulinogenic index, area under the curve for insulin, Matsuda index) and of glycemia (area under the curve for glucose). In addition, the levels of oxidative stress, inflammation markers (CRP, ET1, IL-6, TNFa) and the coagulation factors (vWF, tPA) did not differ in the two groups. The results of ovarian androgen production post GnRH-analog stimulation were comparable among the two groups. However, PAI-1 values were significantly higher and t-PA lower in non carriers than in carriers of CYP21A2 mutation, whereas Endothelin values were significantly lower in carriers of CYP21A2 mutations.