Hyperinsulinemic-euglycaemic clamp strengthens the insulin resistance in nonclassical congenital adrenal hyperplasia.

OBJECTIVE Insulin sensitivity evaluation by hyperinsulinemic-euglycaemic clamp in non-classical congenital adrenal hyperplasia (NC-CAH) due to 21-hydroxilase deficiency. DESIGN AND SETTING Cross-sectional study at University Hospital outpatient clinics. PATIENTS AND METHODS NC-CAH patients (25F/5M; 24 ± 10 years) subdivided into C/NC (compound heterozygous for one classical and one non-classical allele) and NC/NC (two non-classical alleles) genotypes were compared to controls. RESULTS At diagnosis, C/NC patients presented higher basal and ACTH-stimulated 17OHP and androstenedione levels than NC/NC genotype. Patients and controls presented similar weight, BMI, abdominal circumference, and total fat body mass. NC-CAH patients showed higher waist-to-hip ratio, lower adiponectin and HDL cholesterol levels with no changes in fasting plasma glucose, HbA1c, HOMA-IR, adiponectin, leptin, IL-6, TNF-alfa, CRP, and carotid-IMT. All patients had used glucocorticoid (mean time of 73 months). Among the twenty-two patients with successful clamp, thirteen were still receiving glucocorticoid - three patients using cortisone acetate, nine dexamethasone, and one prednisone (hydrocortisone equivalent dose of 5.5 mg/m²/day), while nine patients were off glucocorticoid but had previously used (hydrocortisone equivalent dose of 5.9 mg/m 2/day). The NC-CAH patients presented lower Mffm than controls (31±20 vs 55±23 µmol.min -1.kg -1, p=0.002). The Mffm values were inversely correlated with the duration of glucocorticoid treatment (r=-0.44, p=0.04). There was association of insulin resistance and glucocorticoid type but not with androgen levels. CONCLUSION Using the gold standard method, the hyperinsulinemic-euglycemic clamp, insulin resistance was present in NC-CAH patients and related to prolonged use and long-acting glucocorticoid treatment. Glucocorticoid replacement and cardiometabolic risks should be monitored regularly in NC-CAH.