Does an altered leptin axis play a role in obesity among children and adolescents with classical congenital adrenal hyperplasia due to 21-hydroxylase deficiency?

Abstract

Objective: Congenital adrenal hyperplasia (CAH) patients are at a higher risk to develop obesity. The role of leptin in CAH is still controversial. Our study aimed to evaluate serum levels of leptin, the soluble leptin receptor (sOB-R), and the sOB-R: leptin molar ratios in a cohort of CAH children and adolescents, and their associations with clinical and metabolic parameters. Methods: We studied 51 CAH patients, aged 5.6-19.6 years (median 11.8, nZ30 females) crosssectionally. All patients had genetically proven CAH and received standard steroid substitution therapy. Blood specimens were taken after overnight fasting between 0800 and 1000 h. For the analyses of leptin and sOB-R, matched pairs were built with healthy Caucasian patients for sex, Tanner stage (TS), chronologic age (CA), and body mass index (BMI). Results: BMI and SDS were significantly elevated compared with the reference population. Leptin levels were not different between matched pairs, whereas sOB-R levels were significantly lower in CAH. Consequently, the sOB-R: leptin molar ratios were significantly decreased in CAH. Correlation analyses in CAH patients revealed significant relationship between leptin and CA, TS, BMI, and homeostasis model assessment of insulin resistance. Similar results were obtained for the matched control group. For sOB-R, we found no significant correlation for CA, TS, or BMI in CAH, but we did in the controls. There were significant correlations for androgens within the CAH group. Additional analyses revealed no correlation with steroid medication or metabolic control. Conclusions: Our data show that an altered leptin axis with normal serum leptin concentrations but decreased sOB-R serum levels may contribute to the increased risk of overweight and obesity in CAH.

Genetic, anthropometric and metabolic features of adult Norwegian patients with 21-hydroxylase deficiency

“…Glucocorticoid excess and elevated androgens in females, and decreased testosterone in males, may lead to insulin resistance (43,44), and many reports have demonstrated increased insulin resistance in 21OHD (45). We found normal fasting lipids, glucose, HbA1c and insulin levels and a rather favourable lipid profile in the women with elevated levels of HDL.…”

Health Problems in Congenital Adrenal Hyperplasia due to 21-Hydroxylase Deficiency

“…Increased total body fat has been described in adults with CAH using dual energy x-ray absorptiometry [21,25,27,28], but no change in body fat distribution has been found [39]. It has been speculated that an increased body weight and fat mass might be due to an altered leptin axis in CAH; however, current findings are not fully conclusive [40,41,42]. …”

Pioglitazone improves insulin resistance and decreases blood pressure in adult patients with congenital adrenal hyperplasia

“…Of the few studies that have explored insulin sensitivity in CAH, most have concluded that CAH patients are indeed characterized by insulin resistance (5)(6)(7)(8)(9)(10)(11). Many different methods have been used to assess insulin sensitivity, but studies using the euglycemic hyperinsulinemic clamp method, the gold standard to assess insulin sensitivity, are lacking.…”