The Effect of Iatrogenic Hypothyroidism on Lipoprotein Subfractions and Markers of HDL Function in Patients with Differentiated Thyroid Carcinoma

Background/Objectives: We aimed to conduct a comprehensive assessment of how transient iatrogenic hypothyroidism, induced for diagnostic purposes during the follow up of patients with differentiated thyroid cancer, impacts both quantitative and qualitative lipid parameters. Methods: Blood samples were collected during continuous levothyroxine (LT4) supplementation and after four weeks of LT4 withdrawal. In addition to thyroid hormone levels and routine lipid parameters, LDL and HDL subfractions were analyzed using polyacrylamide gel electrophoresis (Lipoprint). Furthermore, the activities of HDL-associated human paraoxonase-1 (PON1) paraoxonase and arylesterase were measured spectrophotometrically, while the levels of myeloperoxidase and apolipoprotein M (ApoM) were determined using ELISA. The activity of key regulators in HDL remodeling was measured using activity assay kits. Results: In this prospective, single-center study, a total of 52 patients were enrolled (mean age 48 ± 15 years; 13 males and 39 females). Compared to values measured during continuous LT4 supplementation, total cholesterol, HDL-C, LDL-C, ApoA1, and ApoB100 levels were significantly elevated during iatrogenic hypothyroidism (p < 0.0001 for all parameters). Differences in lipoprotein subfraction patterns were also observed: in hypothyroidism, the mean LDL particle size decreased (p = 0.0007) and the proportion of HDL subfractions shifted to the larger HDL subfractions (p < 0.0001). The paraoxonase activity and ApoM level tended to be increased (p = 0.030 and p = 0.011, respectively). Conclusions: In short-term overt hypothyroidism, opposing changes were observed: the shift toward smaller, denser LDL subfractions is considered atherogenic, whereas the increased proportion of larger HDL subfractions, the trend for higher paraoxonase activity and apoM levels can be potentially anti-atherogenic. Our findings further characterize the functional alterations of lipoproteins in hypothyroidism.