Association of serum paraoxonase activity with insulin sensitivity and oxidative stress in hyperthyroid and TSH-suppressed nodular goitre patients.

OBJECTIVE: Low serum paraoxonase (PON) activity is thought to be a risk factor for the development of atherosclerosis. The present study was designed to evaluate PON1 activity and its relationship with preatherosclerotic markers such as lipid peroxidation and insulin resistance in hyperthyroid patients before and after propylthiouracil (PTU) treatment and in subjects with iatrogenic subclinical hyperthyroidism.

PATIENTS AND DESIGN: Twenty patients with hyperthyroidism, 20 patients with euthyroid multinodular goiter (MNG) and 20 age- and sex-matched healthy controls were enrolled in the study. Insulin sensitivity index, PON activity and lipid peroxidation were measured at baseline and 2 months after achieving euthyroidism or subclinical hyperthyroidism. Levothyroxine was given as a part of TSH suppression therapy in multinodular goitre patients.

MEASUREMENTS: Insulin sensitivity was determined by an oral glucose tolerance test (OGTT) based on the insulin sensitivity index (ISI) formula, serum paraoxonase activity was determined with a spectrophotometric method. Lipid peroxidation was measured by the formation of thiobarbituric acid reactive substances (TBARs).

RESULTS: ISI was significantly lower in the hyperthyroid group than baseline levels in MNG patients and controls (P < 0.001). While ISI increased after treatment in the hyperthyroid group (P < 0.01), it significantly decreased with L-T4 treatment in the MNG group (P < 0.01). Serum paraoxonase activity was significantly lower in the hyperthyroid group before treatment than baseline and final measurements of other groups (P < 0.05). While PON activity increased after restoration of the euthyroid state in the hyperthyroid group (P < 0.05), it decreased with L-T4 treatment in the MNG group (P < 0.05). Lipid peroxidation was significantly higher in hyperthyroid group compared to baseline levels of other groups (P < 0.05). It decreased after treatment in the hyperthyroid group (P < 0.05) but a significant increase was observed following L-T4 treatment in the MNG group (P < 0.05). Serum paraoxonase activity was found to be negatively correlated with serum TT4 (r = -0.32, P = 0.003), TT3 levels (r = -0.31, P = 0.004), TBARs levels (r = 0.32, P = 0.003) and positively correlated with ISI (r = 0.35, P = 0.001) and high-density lipoprotein (HDL) cholesterol levels (r = 0.35, P = 0.0011) in the hyperthyroid and MNG groups.

CONCLUSIONS: Iatrogenic thyroid hormone excess seems to mimic the effects of endogenous thyroid hormone excess on paraoxonase activity, insulin sensitivity and oxidative stress. These findings suggest that TSH suppression with levothyroxine may increase oxidative stress and LDL oxidation and thereby promote atherogenesis.