Thyroid function is intrinsically linked to insulin sensitivity and endothelium-dependent vasodilation in healthy euthyroid subjects

Context: Levels of TSH respond to fluctuations in serum free T-4 (fT4) but remain in a very narrow individual range. There exists current controversy regarding the upper limit of normal serum TSH values above which treatment should be indicated. Objective: We aimed to study whether the individually determined fT(4)-TSH relationship was associated with plasma lipids, insulin sensitivity, and endothelial dysfunction in healthy subjects with strictly normal thyroid function according to recent recommendations (0.3-3.0 mU/liter). Design: This was a cross-sectional study. Setting: The study consisted of a cohort of healthy men from the general population (n = 221). Main Outcome Measures: Oral glucose tolerance, insulin sensitivity (SI, minimal model), endothelium-dependent vasodilation (high-resolution ultrasound), and plasma lipids were measured in relation to thyroid function tests. Results: Both serum TSH and fT(4)center dot TSH product were positively associated with fasting and postload insulin concentration and negatively with SI. After body mass index stratification, these associations were especially significant among lean subjects. Serum TSH and fT(4)center dot TSH product also correlated positively with fasting triglycerides and negatively with high-density lipoprotein cholesterol. In a multiple linear regression analysis, age (P = 0.007) and SI (P = 0.02) but not body mass index, fasting triglycerides, or serum high-density lipoprotein concentration contributed independently to 3.7 and 3.3%, respectively, of the variance in fT(4)center dot TSH. Those subjects over the median of fT(4)center dot TSH showed reduced endothelium-dependent vasodilation. Conclusions: Thyroid function tests are intrinsically linked to variables of insulin resistance and endothelial function. It is possible that underlying factors lead simultaneously to increased serum TSH, insulin resistance, ensuing dyslipidemia, and altered endothelial function even within current normal TSH levels.