Impaired Metabolism of Selenomethionine in Graves’ Disease: A Biokinetics Study of Soft Gel Capsule Formulation

Abstract

Patients with Graves' disease are known to have low selenium (Se) status, Se supplementation resulting in clinical and biochemical improvement. Selenomethionine (SeMet) in a new soft gel capsule formulation was used in a pilot study in 6 patients with acute Graves' disease and low selenium levels (61.3±12.9 μg/l) before and in 4/6 patients 3 months after combined treatment with methimazole and SeMet 200 μg/day (113.3±46.3 μg/l), as well as in 6 euthyroid controls (82±11.8 μg/l). The biokinetics were studied following ingestion of 200 μg SeMet (single dose) soft gel capsule, Se serum concentrations being measured at various time points within 24 h. Se levels rose variably in all patients and controls. While levels peaked in all subjects following 8 h of intake, the increase was somewhat slower in acute hyperthyroidism as compared to 3 months later when these patients had been rendered euthyroid, this possibly due to derangement of Se storage capacity by SEPP or increased requirements in the acute phase of the disease, leading to depletion of the trace element. The compound was shown to be bioavailable and safe and patients treated for 3 months exhibited higher Se levels at the different time points. These findings are of major importance for sufferers of GD since they indicate that early Se supplementation, with its beneficial antioxidant impact on inflammatory activity, could slow, or possibly even forestall, the clinical progression of the disease.

Selenium in the Treatment of Graves’ Hyperthyroidism and Eye Disease

“…ATD reduce the levels of oxidative stress markers, thereby improving the activity of the intra- and extracellular antioxidant defense systems, due to restoration of euthyroidism and possibly to their antioxidant properties ( 28 – 30 , 32 ). As discussed in another review on the same issue of this journal, oxidative stress also plays a role in GO, and the beneficial effect of antioxidant agents are supported by in vitro and human studies ( 1 – 6 , 11 , 37 – 46 ).…”

Mechanistic Pathways of Selenium in the Treatment of Graves’ Disease and Graves’ Orbitopathy

“…As mentioned above, several lines of evidence suggest that oxidative stress plays a role in hyperthyroidism [8][9][10][11][12]. The typical hypermetabolic state of thyrotoxicosis causes the release of large amounts of reactive oxygen species (ROS) in peripheral tissues [10], as observed both in hyperthyroid animals and humans [20,21].…”

“…A possible use of selenium has been proposed for the management of thyroid diseases, including chronic autoimmune thyroiditis, Graves' hyperthyroidism, and Graves' orbitopathy (GO) [1][2][3][4][5][6][7]. The use of selenium is based on its anti-oxidant properties, oxidative stress is believed to play an important role in Graves' hyperthyroidism [8][9][10][11], as well as in GO [12]. The latter eye condition affects ~30 % of patients with Graves' hyperthyroidism, and is rarely observed in patients with hypothyroid autoimmune thyroiditis or with subclinical evidence of thyroid autoimmunity, but in the absence of thyroid dysfunction [13,14].…”