Hyperinsulinemia and Insulin Insensitivity in Women with Nonclassical Congenital Adrenal Hyperplasia due to 21-Hydroxylase Deficiency: The Relationship between Serum Leptin Levels and Chronic Hyperinsulinemia

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Abstract
Background/Aim: Nonclassical congenital adrenal hyperplasia due to 21-hydroxylase deficiency (NC-CAH) is associated with hyperandrogenemia, chronic anovulation, hirsutism, acne and adrenal hyperplasia. A few studies have shown hyperinsulinemia and insulin insensitivity in NC-CAH. Hyperinsulinemia can stimulate leptin secretion, and androgens can inhibit leptin secretion. Thus, we designed a study to investigate the insulin levels and insulin sensitivity and the effect of chronic endogenous hyperinsulinemia and androgens on leptin in patients with NC-CAH. Methods: Eighteen women with untreated NC-CAH and 26 normally cycling control women with a similar body mass index (BMI) were studied. Basal hormones, fasted and fed insulin levels, leptin and stimulated 17-hydroxyprogesterone (17-OHP) concentrations were studied. Homeostasis model assessment was used to assess insulin sensitivity. Results: The basal 17-OHP, the free testosterone (fT) and dehydroepiandrosterone sulfate (DHEA-S) were significantly different in the 2 groups (p < 0.05). Fasting and fed insulin levels of the NC-CAH group were higher than those of the control group (p < 0.05) and insulin sensitivity was lower in NC-CAH than in controls (p < 0.05). Insulin levels were correlated with fT and 17-OHP (p < 0.05). Serum leptin levels for NC-CAH (25.9 ± 12.5 µg/l) did not differ from the controls (25.4 ± 12.06 µg/l) and were positively correlated with BMI (r = 0.725) and percent body fat (r = 0.710) for both groups (both p < 0.001). Leptin levels were not correlated with estrogen or androgens, gonadotropins or insulin levels. Conclusion: Hyperinsulinemia and insulin insensitivity associated with hyperandrogenism were detected in untreated NC-CAH patients as in previous reports, whereas serum leptin levels did not differ from those of controls.