Homocysteine levels in subclinical hypothyroidism

Elevated levels of plasma total homocysteine (tHCy) have been recently reported in overt hypothyroidism. Homocysteine, a methionine metabolite, is now considered to be an independent risk factor for cardiovascular diseases. The aim of the present study was to assess the utility of tHCy as a peripheral index of thyroid hormone deficiency in subclinical hypothyroidism. In fact, for this disease, controversy over the need of treatment and the dose of L-T4 to be used still exists. 25 patients were enrolled, 20 women and 5 men, mean age 35.7 ± 4.3 years old, with TSH ranging from 4.2 to 8 mlU/L, normal free thyroid hormones and positivity of TgAb and TPOAb. 20 healthy euthyroid subjects were enrolled as control group, mean age 33.4 ± 2.8 years. Smokers, hypertensive, diabetic, hyperuricemic, dyslipidemic patients or subjects with systemic or hemocoagulative diseases regarding C and S proteins, antithrombin III, antiphospholipid antibodies were excluded. All the patients started treatment with a low dose of L-T4, 25 μg/day and then increased by 25 μg/day after 4 weeks until reaching an optimal dose (1.3-1.5 μg/kg/day). tHCy levels have been measured by immunoenzymatic assay in EDTA plasma before beginning treatment and on reaching euthyroidism. tHCy levels superior to 15 mmol/L were considered pathological. In all the patients the final dose of L-T4 was able to normalize TSH concentration (range 0.73-2.89 mU/L). Plasma basal tHCy levels were higher in the patients with subclinical hypothyroidism (18.3 ± 4.1 mmol/L) than in healthy euthyroid controls (9.2 ± 2.8 mmol/L) (p < 0.05). On reaching normal values of TSH with the optimal doses of L-T4, tHCy levels significantly decreased (8.4 ± 0.8 mmol/L) (p < 0.001). All the other parameters evaluated, arterial blood pressure, heart rate and lipid profile were into a normal range for age and sex at the end of the study. In conclusion these data show that tHCy levels increase even during mild forms of subclinical hypothyroidism and significantly decrease after thyroid hormone replacement. These data reinforce the suggestion of treating the patients with subclinical hypothyroidism with optimal L-T4 replacement doses.