Add-On Effect of Selenium and Vitamin D Combined Supplementation in Early Control of Graves’ Disease Hyperthyroidism During Methimazole Treatment

Abstract

Prompt and stable control of hyperthyroidism is fundamental to avoid the detrimental effects of thyroid hormone excess, and antithyroid drugs, mainly methimazole (MMI), represent the first-line treatment for Graves’ disease (GD) hyperthyroidism. Decreased serum concentrations of selenium (Se) and calcifediol (25(OH)D, VitD) have been reported in newly diagnosed GD patients in observational studies. Low Se levels might exacerbate oxidative stress by compromising the antioxidant machinery’s response to reactive oxygen species, and low VitD levels might hamper the anti-inflammatory immune response. We performed a randomized controlled clinical trial (EudraCT 2017-00505011) to investigate whether Se and cholecalciferol (VitD) addition to MMI is associated with a prompter control of hyperthyroidism. Forty-two consecutive patients with newly-onset GD and marginal/insufficient Se and VitD levels were randomly assigned to treatment with either MMI monotherapy or MMI combined with Se and VitD. Se treatment was withdrawn after 180 days, while the other treatments were continued. Combination therapy resulted in a significantly greater reduction in serum FT4 concentration at 45 days (-37.9 pg/ml, CI 95%, -43.7 to -32.2 pg/ml) and 180 days (-36.5 pg/ml, CI 95%, -42 to -30.9 pg/ml) compared to MMI monotherapy (respectively: -25.7 pg/ml, CI 95%, -31.6 to -19.7 pg/ml and -22.9 pg/ml, CI 95%, -28 to -17.3 pg/ml, p 0.002). Data at 270 days confirmed this trend (-37.8 pg/ml, CI 95%, -43.6 to -32.1 pg/ml vs -24.4 pg/ml, CI 95%, -30.3 to -18.4 pg/ml). The quality of life (QoL) score was investigated by the validated “Thyroid-related Patient-Reported Outcome” questionnaire (ThyPRO). ThyPRO composite score showed a greater improvement in the intervention group at 45 days (-14.6, CI 95%, -18.8 to -10.4), 180 (-9, CI 95%, -13.9 to -4.2) and 270 days (-14.3, CI 95%, -19.5 to -9.1) compared to MMI group (respectively, -5.2, CI 95%, -9.5 to -1; -5.4, CI 95%, -10.6 to -0.2 and -3.5, CI 95%, -9 to -2.1, p 0-6 months and 6-9 months <0.05). Our results suggest that reaching optimal Se and VitD levels increases the early efficacy of MMI treatment when Se and VitD levels are suboptimal.

Selenium and thyroid diseases

“…It showed significant relief of symptoms associated with subclinical hyperthyroidism and improved the quality of life of the patients, but no significant effect was seen in terms of thyroid function (28). In contrast, the results of Gallo, D. showed that MMI + antioxidants (83 ug selenomethionine + 17 ug Se yeast + vitamin D) treatment for 6 months improved thyroid activity more effectively than MMI use that alone (20). We speculate that this difference in results might be related to the type of Se supplementation, dose, duration of treatment and the status of other nutrients in the subject's organism.…”

Immunomodulatory role of vitamin D and selenium supplementation in newly diagnosed Graves’ disease patients during methimazole treatment

“…This was a randomized, single-blinded, monocentric, controlled, intervention trial (registration number on Eudract Clinical Trial Register SeMMIviD 2017-005050-11) (11). Study protocol, inclusion and exclusion criteria are summarized in Figure 1.…”

“…We recently reported, in a randomized control trial, that in newly diagnosed GD patients the association of cholecalciferol (VitD) and selenium (Se) supplementation with methimazole (MMI), in patients with low VitD and selenium levels, significantly accelerated the control of hyperthyroidism, during the first 6 months of treatment, compared to MMI alone (11). We postulated that this might be, at least partly, due to the influence of micronutrients on the immune response, as suggested by animal and cell system-based studies (12)(13)(14)(15)(16)(17)(18)(19)(20).…”

“…To address this issue, we investigated the effect of the association of selenium and cholecalciferol supplementation with standard MMI treatment on circulating Treg frequency and circulating NK cells frequency, NK cells phenotype and functions in GD patients enrolled in our previous study (11).…”

Selenium in Bodily Homeostasis: Hypothalamus, Hormones, and Highways of Communication

“…While selenium supplementation was reported to induce no significant therapeutic effect on patients with subclinical hypothyroidism [ 215 ], co-treatment of selenium was found to enhance the efficacy of levothyroxine sodium (LT4) in treating chronic lymphocytic thyroiditis patients with hypothyroidism, yielding greater improvements to inflammatory factors, compared to treatment with LT4 alone [ 216 ]. Selenium supplementation was also found to increase the efficacy of antithyroid drugs in the treatment of Graves’ disease [ 217 ].…”