Oxidative stress following administration of levothyroxine in subjects suffering from primary hypothyroidism

Oxidative stress (OS) in subjects with primary hypothyroidism under therapy with L-T4 might be the cause of the side effects commonly found with this treatment.

Twenty-four subjects of both sexes (11 M and 15 F), aged between 41 and 61 years, with primary hypothyroidism were assessed. All the subjects were followed for 30 days during the administration of a fixed dose of 75 μg of L-T4. Levels of T4, T3, TSH, hydroperoxides (as measure of OS ), hs-CRP were determined in plasma before and after the treatment. Side effects (anxiety/agitation, sweating, palpitations and headache) and number of days of discomfort were measured for 15 days before and for two subsequent 15-day periods.

Administration of L-T4 satisfactorily balanced the hypothyroidism. A high level of hydroperoxides, 370 ± 27.7 U.CARR. (Carratelli Units: 1 U.CARR. = 0.08 mg of H2O2/L), was observed before treatment, and L-T4 administration further increased the level up to 435 ± 39.5 U.CARR (p<0.05). The treatment produces a significant increase in hs-CRP, from 3.2 ± 2.32 to 4.0 ± 1.27 mg/L (P<0.05). Side effects, almost absent at the baseline 15-day control, occurred with high frequencies during the treatment: between 9.6 ± 1.14 days/15 days for sweating and 14.1 ± 0.93 days/15 days for palpitations. Some side effects were found to be linearly correlated with hydroperoxides (r=0.641, P<0.01 and r=0.658, P<0.01 respectively) or with hs-CRP, as in the case of anxiety/agitation (r=0.629, P<0.01). Following L-T4 administration the days of discomfort turned out to be particularly prominent during the two subsequent 15-day controls (3.8 ± 0.75 and 4.8 ± 0.78 days respectively).

Primary hypothyroidism and therapy with L-T4 at a dose of 75 μg/day cause OS. Side effects following L-T4 therapy depend on OS and cause daily discomfort and loss of working activity in about 1/3 of the days considered.