The effect of L-thyroxine substitution on lipid profile, glucose homeostasis, inflammation and coagulation in patients with subclinical hypothyroidism.

AIMS: Subclinical hypothyroidism (SH) is associated with increased risk for atherosclerosis, mainly attributable to dyslipidaemia and hypercoagulability. However, conflicting data exist regarding the effect of L-thyroxine substitution on these parameters. The purpose of this study was to assess the effect of L-thyroxine therapy on lipidaemic profile, coagulation markers, high-sensitivity C-reactive protein (hsCRP) and glucose homoeostasis in SH patients. METHODS: It was a prospective open-label study. The following parameters were measured before and 6 months after intervention: anthropometric data, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), apolipoproteins B (apoB) and A1 (apoA1), lipoprotein (a) [Lp(a)], fasting plasma glucose and insulin, homoeostasis model assessment-insulin resistance (HOMA-IR), hsCRP, antithrombin III (AT-III), protein C (PC), protein S (PS), fibrinogen and homocysteine. RESULTS: Thirty-two patients (30 women) aged 52.1 ± 13.9 years with SH completed the study. Baseline mean TSH levels were 6.79 ± 2.58 mIU/ml. Achievement of euthyroidism significantly reduced systolic blood pressure (BP) in patients with SH (from 135.2 ± 18.5 to 129.7 ± 15.8 mmHg, p = 0.03) and diastolic BP only in those with baseline TSH levels > 7 mIU/ml (from 79.5 ± 9.8 to 72.1 ± 7.3 mmHg, p = 0.03). No significant changes in body weight, TC, LDL-C, HDL-C, TG, apoB, glucose, insulin, HOMA-IR, hsCRP, AT-III, PC, PS, fibrinogen or homocysteine levels were noticed after restoration of euthyroidism, except for a decrease in apoA1 (p = 0.04) and an increase in Lp(a) levels (p = 0.02). CONCLUSIONS: Except for a reduction in systolic and diastolic BP, thyroid substitution therapy does not affect lipidaemic profile, systematic inflammation, glucose homoeostasis or coagulation in patients with SH.

Oxidative stress and reduced antioxidative status, along with endothelial dysfunction in acromegaly.

Acromegaly is characterized by high cardiovascular morbidity and mortality. Oxidative stress and endothelial dysfunction are underlying mechanisms of atherosclerosis.The aim of this study was to evaluate the blood redox status and endothelial function by means of nitric oxide (NO) levels in patients with acromegaly. Total antioxidant capacity (TAC), catalase activity and glutathione concentration (GSH), as measures of antioxidative capacity, total oxidized glutathione (GSSG) and thiobarbituric acid reactive substances (TBARS), as indices of oxidative stress, and NO levels were assessed in 15 patients with acromegaly (age 55.4±10.5 years; 6 males) and 15 age- and sex-matched controls (age 58.4±8.1 years; 7 males). Active disease was present in 12 patients: 11 on current pharmacotherapy and 1 newly diagnosed. Three acromegalics were in remission after successful treatment. Acromegalics as compared with controls had significantly lower levels of catalase activity (8.2±5.8 vs. 51.3±29.1 mmol/ml/min, p<0.001), GSH (0.97±0.54 vs. 1.41±0.35 mmol/l, p=0.006), GSSG (0.27±0.19 vs. 2.04±1.32 mmol/l, p=0.002) and NO levels (6.0±3.1 vs. 43.0±29.8 mmol/l, p<0.001), but higher TBARS (16.3±8.9 vs. 10.1±10.8, nmol/ml, p=0.019). After adjustment for confounders, differences in catalase activity, NO levels and TBARS remained significant (p=0.004, p<0.001 and p=0.025, respectively). No association between IGF-I/GH and oxidative stress markers was noticed, except for a positive correlation between nadir GH and GSSG (r²=0.563, p=0.036). Acromegaly is associated with increased levels of oxidative stress coupled by diminished antioxidant capacity and endothelial dysfunction indicated by the presence of decreased NO levels.