Hyperinsulinemia during oral glucose tolerance test and high normal serum cortisol are associated with increased secretion of calcitonin in normal subjects

OBJECTIVE: Previous studies showed that insulin stimulated directly calcitonin (Ct) secretion in the pig thyroid, while dexamethasone stimulated the production of Ct and Ct mRNA in medullary thyroid carcinoma (MTC) cell lines. The objective of this study was to investigate if hyperinsulinemia during the oral glucose tolerance test (GTT) stimulates Ct secretion in normal subjects as well as to examine the relationship between serum cortisol and Ct. DESIGN: In 26 normal subjects (9 men and 17 women) with detectable basal serum Ct, aged 22-70 yr [51.5 +/- 14.6 (mean +/- SD), median 55.5], we measured serum or plasma Ct, cortisol, ACTH, insulin, and blood glucose before (0 min) and at 30, 60, 90, and 120 min after ingestion of 75 g glucose. RESULTS: During GTT mean serum cortisol increased slightly by 9.3% at 30 min, whereas mean serum insulin increased 9.4-fold, reaching a peak value at 60 min. Median serum Ct increased by 51% (p < 0.001) in normal subjects (by 27% in men, p = 0.004, and by 44% in women, p < 0.001) at 30 min and remained significantly higher thereafter (up to 120 min) when compared to median baseline level. Regression analysis showed that basal serum cortisol, but not basal serum insulin, was correlated with basal serum Ct (p = 0.01). Peak concentrations of Ct were also correlated with peak concentrations of cortisol at 30 min (p < 0.001) but not at later time points. Serum insulin was correlated with serum Ct at the serum insulin peak level (60 min), and at later time points (90 and 120 min) (p = 0.001). Multiple and simple regression analysis showed that calcitonin-AUC (Area Under Curve) values correlated with insulin-AUC (p = 0.003), and also with cortisol-AUC (p = 0.02) values, the standardized effect of insulin-AUC on Calcitonin-AUC being greater than that of cortisol-AUC. CONCLUSIONS: These findings suggest that acute hyperinsulinemia during GTT is very likely associated with increased Ct secretion in normal subjects. Serum cortisol within the physiological range was also correlated with serum Ct under basal conditions, as well as during GTT.