Table 2.

Selenium in Graves’ Orbitopathy (GO).

Reference	Journal and years	Type of study	Methods	Dosage of compounds used	Results
Rotondo Dottore G. et al. (65)	Thyroid 2016	In vitro study	Primary cultures of orbital fibroblasts from 6 GO patients and 6 control subjects were obtained. To induce oxidative stress, cells were incubated for 24 h with medium containing H2O2 at various concentrations. The primary objective was to assess the effects of selenium in GO fibroblasts.	Cells were pre-incubated for 2 days with medium without compounds or containing Se-methyl-selenocysteine hydrochloride (SeMCys) or, as control, methyl-cysteine at various concentrations. Cell proliferation, hyaluronic acid (HA) and pro-inflammatory cytokines production were measured	Selenium reduced proliferation and release of HA and cytokines in GO fibroblasts. H2O2 promoted an increased release of glutathione disulfide (GSSG), a marker of oxidative stress, and of fibroblast proliferation, which were reduced by selenium. H2O2 promoted the production of cytokines involved in GO pathogenesis, namely TNF-α, IL1-β and IFN-γ. The increase in TNF-α and IFN-γ was rescued by selenium. Whereas the effects of selenium were similar in GO and control fibroblasts concerning oxidative stress and cytokines, they were exclusive to GO fibroblasts concerning proliferation and HA production.
Rotondo Dottore G. et al. (66)	Endocrine. 2017		Primary cultures of orbital fibroblasts from 6 patients with long lasting inactive GO and 6 control subjects were obtained. To induce oxidative stress, cells were incubated for 90 min at 37°C with medium containing H2O2 50 μM. The aim of the study was to evaluate the effects of selenium in GO fibroblasts.	Cells were preincubated for 2 days at 37°C with medium without compounds containing SeMCys or, as control, methyl-cysteine (MCys) at a 10 μM concentration. Cell vitality, lactate dehydrogenase production (as a measure of cell necrosis) and apoptosis were measured	Selenium reduced cell damage in GO fibroblasts SeMCys rescued from H2O2-dependent cytotoxicity, by reducing necrosis and apoptosis, with no difference between GO and control fibroblasts. MCys had no effect. To determine whether the findings reflected the antioxidant actions of selenium, the assessment of GSSG was performed. H2O2 promoted the increased production of GSSG, which was counteracted by SeMCys, but not by MCys, with no differences between GO and control fibroblasts.
Marcocci C. et al. (4)	N Engl J Med 2011	Prospective, multicenter, placebo-controlled clinical trial	One hundred fifty-nine patients with mild GO were randomized to receive sodium selenite or compared with placebo for 6 months	Sodium selenite (100 μg twice daily orally), or pentoxifylline (600 mg twice daily orally)	Beneficial effect of selenium in mild GO. Compared with placebo, Selenium, but not pentoxifylline, leads to the improvement of quality of life (P < 0.001), eye overall outcome (P = 0.01) and slowed the progression of GO (P = 0.01), at the 6 months evaluation.