Context: Levels of TSH respond to fluctuations in serum free T₄, but remain in a very narrow individual range. There exists current controversy regarding upper limit of normal serum TSH values above which treatment should be indicated.

Objective: We aimed to study whether the individually determined free T₄ - 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/L).

Design: Cross-sectional study.

Setting: A cohort of healthy men from the general population (n = 221).

Main Outcome Measures: Oral glucose tolerance, insulin sensitivity (S_I, minimal model), endothelium-dependent vasodilation (high resolution ultrasound) and plasma lipids were measured in relation to thyroid function tests.

Results: Both serum TSH and free T₄· TSH product (fT₄·TSH) were positively associated with fasting post-load insulin concentration, and negatively with S_I. After BMI stratification, these associations were especially significant among lean subjects.

Serum TSH and fT₄·TSH product also correlated positively with fasting triglycerides and negatively with HDL cholesterol. In a multiple linear regression analysis, age (P = 0.007) and S_I (P = 0.02), but not BMI, fasting triglycerides or serum HDL concentration contributed independently to 3.7% and 3.3%, respectively, of the variance in fT₄·TSH. Those subjects over the median of fT₄·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.