The 83,557insA variant of the gene coding 11β-hydroxysteroid dehydrogenase type 1 enzyme associates with serum osteocalcin in patients with endogenous Cushing's syndrome

Objective: The type 1 and type 2 isoenzymes of the 11β-hydroxysteroid dehydrogenase (HSD11B) play an important role in the prereceptor regulation of glucocorticoid bioavailability and action. The potential importance of gene variants coding HSD11B has not been previously evaluated in patients with endogenous hypercortisolism. The aim of the present study was to explore presumed associations between the 83,557insA variant of the HSD11B1 gene and circulating hormone concentrations, bone turnover and bone mineral density (BMD) in patients with endogenous Cushing's syndrome (CS).

Patients and methods: Forty one patients with ACTH-producing pituitary adenomas (Cushing's disease-CD), 32 patients with cortisol-producing adrenal tumors (ACS) and 129 healthy control subjects were genotyped for the 83,557insA variant of the HSD11B1 gene using restriction fragment length analysis. BMD was measured by dual-energy X-ray absorptiometry. Serum cortisol, ACTH, osteocalcin (OC) and C-terminal crosslinks (CTX) of human collagen type I (C-telopeptide) were measured by electrochemiluminescence immunoassay.

Results: No statistically significant differences were found in the allelic frequencies of the 83,557insA polymorphism among patients with CD, ACS and healthy controls. Among all patients with CS, heterozygous carriers of the 83,557insA had significantly higher serum OC as compared to non-carriers. Patients with ACS carrying the 83,557insA variant had higher plasma ACTH concentrations compared to non-carriers. The 83,557insA variant failed to associate with BMD in patients and controls.

Conclusions: Our present findings indicate that the 83,557insA variant of the HSD11B1 gene may influence serum markers of bone turnover, but not BMD in patients with endogenous Cushing's syndrome.