Context: Relations between thyroid function and lipids remain incompletely understood.

Objective: To determine whether lipoprotein subparticle concentrations are associated with thyroid status.

Design: Prospective clinical study and cross-sectional cohort analysis.

Setting: University endocrine clinic and Framingham Heart Study.

Patients: 28 thyroidectomized patients with short-term overt hypothyroidism and 2,944 Framingham Offspring cohort participants.

Main Outcome Measures: Fasting subclass concentrations of very low density (VLDL), intermediate density (IDL), low density (LDL-C), and high density (HDL-C) lipoprotein particles were measured by nuclear magnetic resonance spectroscopy. TSH values were also measured.

Results: Total cholesterol and LDL-C were increased during short-term overt hypothyroidism. Large LDL subparticle concentrations increased during hypothyroidism (917±294 vs. 491±183 nmol/L; p<0.001), but more atherogenic small LDL was unchanged. Triglycerides marginally increased during hypothyroidism, small VLDL particles significantly increased (p<0.001), whereas more atherogenic large VLDL was unchanged. Total HDL-C increased during hypothyroidism (76±13 mg/dL vs. 58±15 mg/dL; p<0.001). There was no change in large HDL-C particle concentrations, whereas small (p<0.001) and medium (p=0.002) HDL-C particle concentrations decreased. Among Framingham women, adjusted total cholesterol and LDL-C were positively related to TSH categories (p0.003). This was due to a positive correlation between adjusted large LDL subparticle concentrations and log-TSH (p<0.0001); log small LDL subparticle concentrations decreased slightly as log-TSH increased (p=0.045). Among Framingham men, the only significant association was a positive association between log-TSH and log large HDL subparticle concentrations (p=0.04).

Conclusions: There is a shift toward less atherogenic large LDL, small VLDL, and large HDL subparticle sizes in hypothyroid women.