The effect of iatrogenic hypothyroidism on lipoprotein subfractions and serum paraoxonase activity in patients with differentiated thyroid cancer

Background and Aims : The development of atherogenic lipid profile has a major role in hypothyroidism induced accelerated atherosclerosis. In a group of patients with differentiated thyroid cancer (DTC) subclinical hyperthyroidism is maintained after thyroidectomy, interrupted annually with short-term overt hypothyroidism for diagnostic purposes. The effects of short-term overt hypothyroidism on lipid parameters, lipoprotein subfractions and paraoxonase-1 (PON1) activity were studied in these patients.Methods: Twenty-one patients who underwent total thyroidectomy and ablative radioiodine therapy for DTC were enrolled in the study. Blood samples were collected during continuous TSH-suppressive levothyroxine (L-T4) therapy and after four weeks of L-T4 withdrawal. Thyroid hormones, lipid parameters and PON1 paraoxonase and arylesterase activity were measured, analysis of lipoprotein subfractions was performed by Lipoprint system.Results: Compared to values measured during continuous L-T4 therapy, total cholesterol, HDL-C, LDL-C, ApoA1, ApoB levels were significantly elevated during iatrogenic hypothyroidism. Differences in the subfraction pattern of lipoproteins were also observed: in hypothyroidism, the mean LDL size decreased (26.9±0.4 nm vs 27.1±0.4 nm, p<0.01) and the proportion of small and medium-sized HDL subfractions decreased (29.5±9.9% vs 33.8±8.6%, p<0.001, and 43.8±4.6% vs 46.1±5.1%, p=0.005, respectively), while the proportion of large HDL subfractions increased (26.8±9.8% vs 20.0±6.9%, p<0.0001). The PON1 paraoxonase and arylesterase activities were increased during L-T4 withdrawal (113±67 U/L vs 106±67 U/L, p=0.005; and 159±44 U/L vs 134±21 U/L, p<0.01; respectively).Conclusions: In short-term overt hypothyroidism both atherogenic and anti-atherogenic changes were found: the shift toward lower density LDL subfractions is atherogenic, while the increased proportion of larger HDL subfractions and increased paraoxonase activity are anti-atherogenic. Background and Aims : The development of atherogenic lipid profile has a major role in hypothyroidism induced accelerated atherosclerosis. In a group of patients with differentiated thyroid cancer (DTC) subclinical hyperthyroidism is maintained after thyroidectomy, interrupted annually with short-term overt hypothyroidism for diagnostic purposes. The effects of short-term overt hypothyroidism on lipid parameters, lipoprotein subfractions and paraoxonase-1 (PON1) activity were studied in these patients. Methods: Twenty-one patients who underwent total thyroidectomy and ablative radioiodine therapy for DTC were enrolled in the study. Blood samples were collected during continuous TSH-suppressive levothyroxine (L-T4) therapy and after four weeks of L-T4 withdrawal. Thyroid hormones, lipid parameters and PON1 paraoxonase and arylesterase activity were measured, analysis of lipoprotein subfractions was performed by Lipoprint system. Results: Compared to values measured during continuous L-T4 therapy, total cholesterol, HDL-C, LDL-C, ApoA1, ApoB levels were significantly elevated during iatrogenic hypothyroidism. Differences in the subfraction pattern of lipoproteins were also observed: in hypothyroidism, the mean LDL size decreased (26.9±0.4 nm vs 27.1±0.4 nm, p<0.01) and the proportion of small and medium-sized HDL subfractions decreased (29.5±9.9% vs 33.8±8.6%, p<0.001, and 43.8±4.6% vs 46.1±5.1%, p=0.005, respectively), while the proportion of large HDL subfractions increased (26.8±9.8% vs 20.0±6.9%, p<0.0001). The PON1 paraoxonase and arylesterase activities were increased during L-T4 withdrawal (113±67 U/L vs 106±67 U/L, p=0.005; and 159±44 U/L vs 134±21 U/L, p<0.01; respectively). Conclusions: In short-term overt hypothyroidism both atherogenic and anti-atherogenic changes were found: the shift toward lower density LDL subfractions is atherogenic, while the increased proportion of larger HDL subfractions and increased paraoxonase activity are anti-atherogenic.