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Thyroid Function and Lipid Subparticle Sizes in Patients with Short-Term Hypothyroidism and a Population-Based Cohort

Section of Endocrinology, Diabetes, and Nutrition (E.N.P., L.E.B.), Boston University Medical Center, and Department of Biostatistics (Q.Y.), Boston University School of Public Health, Boston, Massachusetts 02118; Department of Medicine (P.W.F.W.), Cardiology Division, Emory University School of Medicine, Atlanta, Georgia 30306; and National Heart, Lung, and Blood Institute’s Framingham Heart Study (R.S.V.), Framingham, Massachusetts 01702

Address all correspondence and requests for reprints to: Elizabeth N. Pearce, M.D., M.Sc., Boston University Medical Center, 88 East Newton Street, Evans 201, Boston, Massachusetts 02118. E-mail: elizabeth.pearce{at}bmc.org.

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

Objective: Our objective was to determine whether lipoprotein subparticle concentrations are associated with thyroid status.

Design and Setting: We conducted a prospective clinical study and cross-sectional cohort analysis at a university endocrine clinic and the Framingham Heart Study.

Subjects: Subjects included 28 thyroidectomized patients with short-term overt hypothyroidism and 2944 Framingham Offspring cohort participants.

Main Outcome Measures: Fasting subclass concentrations of very-low-density lipoprotein (VLDL), intermediate-density lipoprotein, low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) 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/liter; 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 (P 0.003). 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.