Selenium and the Course of Mild Graves' Orbitopathy

Marcocci, Claudio; Kahaly, George J.; Krassas, Gerasimos E; Bartalena, Luigi; Prummel, Mark F.; Stahl, Matthias; Altea, Maria Antonietta; Nardi, Marco; Pitz, Susanne; Boboridis, Kostas; Sivelli, Paolo; Arx, George von; Mourits, Maarten P.; Baldeschi, Lelio; Bencivelli, W.; Wiersinga, Wilmar M.

doi:10.1056/nejmoa1012985

Cited by 502 publications

(354 citation statements)

References 31 publications

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“…Although the pathogenesis of GO is not yet clarified, immunological cross-reactivity of thyroid and orbital antigens in muscular, connective, and adipose tissues is thought to play a key role (2). Different longitudinal studies confirm that spontaneous improvement or stabilization of eye symptoms and signs may occur when GO is mild (3,4,5,6,7,8,9). It is well known that GO has a self-limiting natural course, characterized by a phase of active inflammation of the orbital tissues, in which disease severity generally progresses, followed by a phase of stabilization and improvement of inflammation, as described by the 'Rundle curve' (10,11) (Fig.…”

Section: Introductionmentioning

confidence: 99%

THERAPY OF ENDOCRINE DISEASE: Endocrine dilemma: management of Graves’ orbitopathy

Campi

Vannucchi

Salvi

2016

European Journal of Endocrinology

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Management of Graves' orbitopathy (GO) must be based on the correct assessment of activity and severity of the disease. Activity is usually assessed with the Clinical Activity Score, whereas severity is classified according to a European Group On Graves' Orbitopathy (EUGOGO) consensus statement as mild, moderate-to-severe, and sight-threatening. Myopathic and chronic congestive forms are uncommon clinical presentations of GO. Restoration and maintenance of stable euthyroidism are recommended in the presence of GO. In moderate-to-severe disease, steroids have been widely employed and have shown to possess an anti-inflammatory activity, but about 20 -30% of patients are not responsive and present recurrence. Some novel immunosuppressors have already been employed in clinical studies and have shown interesting results, although the lack of randomized and controlled trials suggests caution for their use in clinical practice. Potential targets for therapy in GO are the thyroid-stimulating hormone and the insulin-like growth factor 1 receptor on the fibroblasts, inflammatory cytokines, B and T cells, and the PIK3/mTORC1 signaling cascades for adipogenesis. A recent open study has shown that tocilizumab, an anti-sIL-6R antibody, inactivates GO. Consistent reports on the efficacy of rituximab have recently been challenged by randomized controlled trials. As the main goal of treatment is the well-being of the patient, the therapeutic strategy should be addressed to better suit the patient needs, more than improving one or more biological parameters. The increasing availability of new therapies will expand the therapeutic options for GO patients and allow the clinician to really personalize the treatment to better suit the patients' personal needs.

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Section: Introductionmentioning

confidence: 99%

THERAPY OF ENDOCRINE DISEASE: Endocrine dilemma: management of Graves’ orbitopathy

Campi

Vannucchi

Salvi

2016

European Journal of Endocrinology

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“…A number of trials in Hashimoto's thyroiditis have thus far not clarified the role of selenium supplementation (39). A single trial reported promising results for a subset of Graves' orbitopathy patients (45), and two Danish randomized trials are currently investigating clinical effects of selenium supplementation in Graves' disease (46) and chronic autoimmune thyroiditis (47).…”

Section: Discussionmentioning

confidence: 99%

Does selenium supplementation affect thyroid function? Results from a randomized, controlled, double-blinded trial in a Danish population

Winther¹,

Bonnema²,

Cold³

et al. 2015

European Journal of Endocrinology

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Objective: Selenium is present in the active site of proteins important for thyroid hormone synthesis and metabolism. The objective of this study is to investigate the effect of selenium supplementation in different doses on thyroid function, under conditions of suboptimal dietary selenium intake. Design: The Danish PREvention of Cancer by Intervention with SElenium pilot study (DK-PRECISE) is a randomized, doubleblinded, placebo-controlled trial. A total of 491 males and females aged 60-74 years were randomized to 100 mg (nZ124), 200 mg (nZ122), or 300 mg (nZ119) selenium-enriched yeast or matching yeast-based placebo tablets (nZ126). A total of 361 participants, equally distributed across treatment groups, completed the 5-year intervention period. Methods: Plasma samples were analyzed for selenium and serum samples for TSH, free triiodothyronine (FT 3 ), and free thyroxine (FT 4 ) at baseline, and after 6 months, and 5 years of supplementation. Results: Plasma selenium concentrations increased significantly and dose-dependently in treatment groups receiving selenium (P!0.001). Serum TSH and FT 4 concentrations decreased significantly and dose-dependently by 0.066 mIU/l (PZ0.010) and 0.11 pmol/l (PZ0.015), respectively, per 100 mg/day increase, with insignificant differences between 6 months and 5 years. No significant effects were found for FT 3 and FT 3 :FT 4 ratio. Conclusions: In euthyroid subjects, selenium supplementation minutely and dose-dependently affects thyroid function, when compared with placebo, by decreasing serum TSH and FT 4 concentrations. Based on these findings, selenium supplementation is not warranted under conditions of marginal selenium deficiency. However, a role for selenium supplementation in the treatment of autoimmune thyroid diseases is still unresolved.

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“…13 Furthermore, clinical studies indicate that oral Selenium, an essential component of antioxidant enzymes, 14 can slow progression of the disease in patients with mild Graves' orbitopathy. 15,16 In a randomised placebo-controlled trial in patients with mild active TED, Marcocci et al 15 compared the effect of a six month treatment regimen with oral sodium selenite (100 mg twice daily), or oral pentoxifylline (600 mg twice daily), against a placebo. 15 Compared with placebo, at the end of 6 months treatment, and 6 months after cessation of treatment, oral selenite (but not pentoxifylline) was associated with a significant improvement in the quality of life, reduced ocular disease, and less risk of disease progression.…”

Section: Mild Tedmentioning

confidence: 99%