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Clinically overt thyroid dysfunction is associated with alterations in triglyceride (TG) metabolism. The effect of subclinical thyroid disease on very-low-density lipoprotein (VLDL) kinetics is not known.Our objective was to investigate whether subclinical thyroid disease is associated with alterations in hepatic VLDL metabolism.We measured VLDL-TG and VLDL-apolipoprotein B-100 (apoB-100) kinetics by infusing stable isotopically labeled tracers, in conjunction with mathematical modeling.Ten women with subclinical hypothyroidism, 10 women with subclinical hyperthyroidism, and 25 euthyroid women, matched on age, body mass index, and percent body fat, were studied in the Clinical Research Unit at Washington University School of Medicine.Plasma VLDL-TG concentrations were 0.75 ± 0.13, 0.51 ± 0.06, and 0.37 ± 0.07 mmol/liter (P = 0.029), and hepatic VLDL-TG secretion rates were 6.5 ± 0.7, 5.0 ± 0.4, and 4.1 ± 0.6 μmol/liter·min (P = 0.026) in hypothyroid, euthyroid, and hyperthyroid women, respectively. The differences in VLDL-TG secretion rates were due to differences in the incorporation of systemic plasma free fatty acids into VLDL-TG (4.3 ± 0.3, 3.1 ± 0.3, and 2.5 ± 0.3 μmol/liter·min in hypothyroid, euthyroid, and hyperthyroid women, respectively; P = 0.005). Plasma VLDL-apoB-100 concentration and hepatic secretion rate did not differ among groups (P > 0.400), so the molar ratios of VLDL-TG to VLDL-apoB-100 secretion rates were 21,469 ± 3,477, 16,025 ± 1,273, and 11,889 ± 1,319 in hypothyroid, euthyroid, and hyperthyroid women, respectively (P = 0.019).Subclinical thyroid disease affects hepatic VLDL-TG but not VLDL-apoB-100 metabolism: subclinical hypothyroidism increases, whereas subclinical hyperthyroidism decreases, hepatic VLDL-TG secretion rate compared with the euthyroid state. Plasma VLDL-TG concentration is greater in subclinical hypothyroid than euthyroid and hyperthyroid subjects, due to greater secretion of large, TG-rich VLDL particles from the liver.