Selenium and Iodine with Thyroid disease

Dr. Weeks Comment:   Low thyroid? High cholesterol?  If so, check your selenium level.   Selenium is an essential nutrient involved in healthy thyroid function.

Here are a review of interesting related articles:

Chem Biodivers. 2008 Mar;5(3):414-39.
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Selenium analogues of antithyroid drugs–recent developments.

Roy G, Mugesh G.

Department of Inorganic & Physical Chemistry, Indian Institute of Science, Bangalore 560012, India.

Thyroxine (T4), the main secretory hormone of the thyroid gland, is produced on thyroglobulin by thyroid peroxidase (TPO)/H(2)O(2)/iodide system and deiodinated to its active form (T3) by a selenocysteine-containing enzyme, iodothyronine deiodinase (ID). The activation of thyroid-stimulating hormone (TSH) receptor by auto-antibodies leads to ‘hyperthyroidism’, a life-threatening disease which is treated by antithyroid drugs such as 6-propyl-2-thiouracil (PTU) and methimazole (MMI). The present review describes the biological activities of a number of S/Se derivatives bearing the methimazole pharmacophore. It is shown that the isosteric substitutions in the existing drugs lead to compounds that can effectively and reversibly inhibit the heme-containing lactoperoxidase (LPO). In contrast to methimazole, the selenium analogue, MSeI, does not interfere with the enzyme directly, but it inhibits LPO by reducing the H(2)O(2) that is required for the oxidation of the Fe-center in LPO. These studies reveal that the degradation of the intracellular H(2)O(2) by the Se analogues of antithyroid drugs may be beneficial to the thyroid gland, as these compounds may act as antioxidants and protect thyroid cells from oxidative damage. Because the drugs with an action essentially on H(2)O(2) can reversibly inhibit the thyroid peroxidase, such drugs could be of great importance in the treatment of hyperthyroidism.

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PMID: 18357551 [PubMed – indexed for MEDLINE]

2: Med Chem. 2007 May;3(3):281-4.
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Serum selenium levels in patients with remission and relapse of graves’ disease.

Wertenbruch T, Willenberg HS, Sagert C, Nguyen TB, Bahlo M, Feldkamp J, Groeger C, Hermsen D, Scherbaum WA, Schott M.

Department of Endocrinology, Diabetes and Rheumatology, University Hospital Duesseldorf, Duesseldorf, Germany.

OBJECTIVE: Selenium (Se) in the form of selenocysteine is an essential component of the family of the detoxifying enzymes glutathione peroxidase (Gpx) and of the iodothyronine selenodeiodinases that catalyze the extrathyroidal production of tri-iodothyronine (T(3)). Thus, Se deficiency may seriously influence the generation of free radicals, the conversion of thyroxine (T(4)) to T(3) and a thyroidal autoimmune process. The aim of this study was to investigate whether serum Se levels may influence the outcome of Graves’ disease (GD). DESIGN AND METHODS: 83 patients (77 women, 6 men) with active GD were retrospectively analyzed (mean age 40,0 years). Twenty-four GD patients went into remission and were euthyroid during follow-up (median follow-up: 20.1 months), whereas 59 patients did not go into remission or developed relapse over the following 24 months. TSH receptor autoantibodies (TRAb) were measured using the second generation assay on the basis of human TSH receptor. Se levels were determined at the first visit in our outpatient clinic and were correlated with TRAb levels and clinical outcome of these patients. RESULTS: Median TRAb levels in the group of remission were significantly (p<0.0001) lower than TRAb values in the relapse group (2.1 as compared to 8.6 IU/l). By comparing mean serum Se levels in the remission and relapse group no significant differences were seen (73.0 vs. 71.7 microg/l). Detailed analyses of both groups of patients, however, revealed that highest serum Se levels (>120 microg/l) were seen in the remission group, indicating a positive effect of Se levels on the outcome of GD. In addition, we also compared these results with TRAb levels of these patients. We could show that TRAb levels and serum Se values were positively correlated in the relapse group, whereas a negative correlation of both parameters were seen in the remission group, supporting the idea of a positive effect of Se on thyroidal autoimmune process. CONCLUSION: Our data indicate that high serum Se levels (>120 microg/l) may influence the outcome of GD. This is important, as Se administration trials in GD, which are under discussion need to be performed with Se supplementation at higher dosages than used in autoimmune thyroiditis.

Publication Types:

PMID: 17504200 [PubMed – indexed for MEDLINE]

3: Curr Opin Rheumatol. 2007 Jan;19(1):44-8.
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Autoimmune thyroid diseases.

Caturegli P, Kimura H, Rocchi R, Rose NR.

Department of Pathology, The Johns Hopkins School of Medicine, Baltimore, Maryland 21205, USA.

PURPOSE OF REVIEW: Interesting clinical and basic studies have been published in the field of autoimmune thyroiditis (represented by Graves’ disease and Hashimoto’s thyroiditis) since January 2005. The review is organized into four main areas: genetics, environment, adaptive immune system, and innate immune system. RECENT FINDINGS: The quest continues for the identification of susceptibility genes for autoimmune thyroiditis. In addition to the classical major histocompatibility complex class II genes and cytotoxic T cell antigen-4, new studies have appeared on CD40 the protein tyrosine phosphatase-22. Too much iodine increases the incidence of Hashimoto’s thyroiditis, perhaps by augmenting the antigenicity of thyroglobulin. T regulatory cells, Toll-like receptors and presentation of lipid antigens by CD1 molecules are new areas of basic immunological investigation that have been applied to autoimmune thyroiditis. SUMMARY: Overall, the studies have greatly expanded our understanding of the pathogenesis of thyroiditis. They have opened new lines of investigations that will ultimately result in a better clinical practice.

Publication Types:

PMID: 17143095 [PubMed – indexed for MEDLINE]

4: Thyroid. 2006 May;16(5):455-60.
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Comment in:

The role of selenium in thyroid autoimmunity and cancer.

Duntas LH.

Endocrine Unit, Evgenidion Hospital, University of Athens, Medical School, Athens, Greece.

The essential micronutrient selenium (Se) occurs in the form of the amino acid selenocysteine in selenoproteins which exert various effects, while maintaining the cell reduction-oxidation balance. The discovery that all three deiodinases that convert thyroxine (T4) into triiodothyronine (T3) contain selenocysteine illustrates how the production of the active thyroid hormone is dependent on Se status. The selenoenzyme families of glutathione peroxidases (GPx) and thioredoxin reductases (TRx) possess powerful antioxidant properties and form a complex defense system that protects thyrocytes from oxidative damage. Se supplementation in patients with autoimmune thyroiditis seems to modify the immune response, probably by enhancing plasma GPx activity and decreasing excess levels of hydrogen peroxide. However, the enhancement of immunocompetence may also be the result of the synergistic action of various selenoproteins and not exclusively of GPx. There is evidence supporting considerable oxidative stress in Graves’ disease where Se supplementation, because of its free radical scavenging properties, may increase the enzymatic antioxidant activity. TRx has been found significantly elevated in GD revealing its involvement in the pathogenesis of this condition and representing a potential future target for therapeutical intervention. Low Se serum levels have also been associated with increased risk of thyroid cancer and may play a role in carcinogenesis. It is noteworthy, that the Food and Drug Administration has recently determined that there is sufficient evidence to warrant a qualified health claim for Se and cancer. Furthermore, the recent discovery that defects in the SECIS-binding protein 2 (SBP2), which is an indispensable protein for the incorporation of Se into the selenoproteins, result in thyroid dysfunction, together with the recognition of the many roles of selenoprotein P in Se distribution and storage in the human body, reveal not only the indispensability of Se and the selenoproteins as essential factors in thyroid metabolism and pathogenesis, but open up new prospects for enhanced treatment.

PMID: 16756467 [PubMed – indexed for MEDLINE]

5: Biol Trace Elem Res. 2006 Summer;111(1-3):229-38.
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Selenium supplement alleviated the toxic effects of excessive iodine in mice.

Xu J, Yang XF, Guo HL, Hou XH, Liu LG, Sun XF.

Department of Nutrition and Food Hygiene, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, People’s Republic of China.

The relationship between the iodine intake level of a population and the occurrence of thyroid diseases is U-shaped. When excessive iodine is ingested, hypothyroidism or hyperthyroidism associated with goiter might develop. The aim of the study was to evaluate the effect of Se supplementation on the depression of type 1 deiodinase (D1) and glutathione peroxidase (GSHPx) activities caused by excessive iodine. D1 activity was assayed by the method with 125I-rT3 as a substrate. Compared to the effect of iodine alone, iodine in combination with selenium increased the activities of D1 and GSHPx. The addition of selenium alleviated the toxic effects of iodine excess on the activities of D1 and GSHPx.

Publication Types:

PMID: 16943608 [PubMed – indexed for MEDLINE]

6: J Am Coll Nutr. 2006 Feb;25(1):1-11.
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Hypothesis: dietary iodine intake in the etiology of cardiovascular disease.

Hoption Cann SA.

Department of Health Care and Epidemiology, University of British Columbia, 5804 Fairview Avenue, Vancouver, BC, V6T 1Z3, Canada.

This paper reviews evidence suggesting that iodine deficiency can have deleterious effects on the cardiovascular system, and correspondingly, that a higher iodine intake may benefit cardiovascular function. In recent years, public health bodies have aggressively promoted sodium restriction as a means of reducing hypertension and the risk of cardiovascular disease. These inducements have led to a general decline in iodine intake in many developed countries. For example, a United States national health survey conducted in the early 1970s observed that 1 in 40 individuals had urinary iodine levels suggestive of moderate or greater iodine deficiency; twenty years later, moderate to severe iodine deficiency was observed in 1 in 9 participants. Regional iodine intake has been shown to be associated with the prevalence of hypothyroidism and hyperthyroidism, where autoimmune hypothyroidism is the more common of the two in regions with moderate to high iodine intake. Both of these thyroid abnormalities have been shown to negatively affect cardiovascular function. Selenium, an important antioxidant in the thyroid and involved in the metabolism of iodine-containing thyroid hormones, may play an interactive role in the development of these thyroid irregularities, and in turn, cardiovascular disease. Iodine and iodine-rich foods have long been used as a treatment for hypertension and cardiovascular disease; yet, modern randomized studies examining the effects of iodine on cardiovascular disease have not been carried out. The time has come for investigations of sodium, hypertension, and cardiovascular disease to also consider the adverse effects that may result from mild or greater iodine deficiency.

Publication Types:

PMID: 16522926 [PubMed – indexed for MEDLINE]

7: Internist (Berl). 2005 Dec;46(12):1318-23.
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[Therapy and prevention of hyperthyroidism]

[Article in German]

Woenckhaus U, Girlich C.

Klinik und Poliklinik für Innere Medizin I, Klinikum der Universität, 93042 Regensburg.

A decreased serum TSH level can be observed in more than 10% of the German population. Although treatment is not mandatory in each of these cases patients with an unrecognized autonomous thyroid dysfunction have a substantial risk of developing thyrotoxicosis when exposed to large amounts of iodine. Thionamid drugs in combination with potassium perchlorate are given for preventive and therapeutic reasons until definitive thyroidectomy or radioiodine therapy is performed. In younger patients Graves’ disease is the main cause of hyperthyroidism. Medical treatment with antithyroid drugs is established to render patients euthyroid. Having decreased the dose as far as possible, drug therapy is continued for 12-18 months to achieve a maximum rate of permanent remission. Ongoing clinical research aims to characterize clinical or laboratory predictors associated with a high risk of relapse after medication is stopped. Selenium supplementation is proposed to be a new therapeutic approach for autoimmune thyroid disease. It is already used quite liberally although data of powerful randomized trials are not available.

Publication Types:

PMID: 16231171 [PubMed – indexed for MEDLINE]

8: Annu Rev Nutr. 2006;26:293-322.
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Nutritional epidemiology and thyroid hormone metabolism.

Vanderpas J.

Ecole de Santé Publique, Université Libre de Bruxelles, Bruxelles 1020, Belgium.

Severe iodine deficiency was the main cause of endemic goiter and cretinism. Most of the previously iodine-deficient areas are now supplemented, mainly with iodized salt. The geographical distribution of severe endemic areas has been progressively reduced, and at present, approximately 200 million people living in remote places are still at risk of severe iodine deficiency. International public health programs should be focused first on reaching these populations, and second on auditing and monitoring the operational work of supplementation programs. This second point is essential to prevent iodine-induced hyperthyroidism or interruptions of iodine supplement distribution, which could be catastrophic for the fetus and the young infant. Echography brings a complementary tool to clinical assessment of goiter by palpation. Inductively coupled plasma-mass spectrometry brings at least a definitive gold standard for iodine measurement and thyroid hormone measurement. Thiocyanate overload has been clearly documented as a goitrogen in Central Africa, and when associated with selenium deficiency, it may be included as risk factor for endemic myxedematous cretinism. Variable exposure to different environmental risk factors is likely the explanation of the variable distribution of two types of endemic cretinism (neurological and myxedematous), and the clinical overlap of the pathogeny of both syndromes is more important than previously described. It is possible that Kashin-Beck osteoarthropathy is another evanescent endemic disease that will disappear with the correction of iodine deficiency.

Publication Types:

PMID: 16704348 [PubMed – indexed for MEDLINE]

9: Clin Chem Lab Med. 2005;43(4):383-8.
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The effect of antioxidant supplementation on superoxide dismutase activity, Cu and Zn levels, and total antioxidant status in erythrocytes of patients with Graves’ disease.

Bacic-Vrca V, Skreb F, Cepelak I, Mayer L, Kusic Z, Petres B.

Department of Clinical Pharmacy, School of Pharmacy and Biochemistry, University of Zagreb, Croatia.

The effects of supplementation with a fixed combination of antioxidants (vitamins C and E, beta-carotene and selenium) on superoxide dismutase activity, copper and zinc concentrations, and total antioxidant status were monitored in erythrocytes derived from a group of patients with Graves’ disease treated with methimazole, with respect to the rate of achieving euthyroidism. Thyroid-stimulating hormone (TSH), thyroid hormones and the above-mentioned parameters were measured before therapy, and on days 30 and 60 after therapy initiation. The patients receiving antioxidant supplementation along with methimazole therapy (group A, n = 27) achieved euthyroidism at a faster rate than those treated with methimazole alone (group B, n = 28). The activity of superoxide dismutase decreased significantly in both patient groups during the treatment; however, there was no significant difference between the groups. There was no significant change in the erythrocyte concentration of copper, whereas the zinc concentration and total antioxidant status showed significant between-group differences. The study results clearly show that antioxidant supplementation in the treatment of Graves’ disease is justified, while zinc and total antioxidant status in erythrocytes seem to be sensitive indicators of the efficacy of supplemental therapy.

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PMID: 15899653 [PubMed – indexed for MEDLINE]

10: Acta Pharm. 2004 Jun;54(2):79-89.
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Supplementation with antioxidants in the treatment of Graves’ disease: the effect on the extracellular antioxidative parameters.

Bacić Vrca V, Skreb F, Cepelak I, Mayer L.

Department of Clinical Pharmacy, Dubrava University Hospital, Zagreb, Croatia.

In this study, the effect of supplementation with a fixed combination of antioxidants (vitamins C and E, beta-carotene and selenium) on concentrations of antioxidative parameters in serum was monitored. Measurements were performed prior to the commencement of therapy and after 30 and 60 days in patients with Graves’ disease treated with methimazole. Patients who received extra supplementation with antioxidants (group A, n = 29) attained euthyroidism faster than the patients treated only with methimazole (group B, n = 28). Statistically significant differences were achieved after supplementation with antioxidants for all investigated parameters (uric acid, transferrin, ferritin), except TAS and glucose. Nevertheless, due to the fact that all measured parameters remained within the range of referent values, they may not be proposed as reliable indicators of the level of oxidative stress in Graves’ disease.

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PMID: 15274752 [PubMed – indexed for MEDLINE]

11: Clin Chim Acta. 2004 Mar;341(1-2):55-63.
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Supplementation with antioxidants in the treatment of Graves’ disease; the effect on glutathione peroxidase activity and concentration of selenium.

Vrca VB, Skreb F, Cepelak I, Romic Z, Mayer L.

Department of Clinical Pharmacy, Faculty of Pharmacy and Biochemistry, University of Zagreb, Croatia.

BACKGROUND: The effect of supplementation with a fixed combination of antioxidants (vitamins C and E, beta-carotene and selenium) was monitored on the speed of attaining euthyroidism in a group of patients with Graves’ disease, treated with methimazole. METHODS: The activity of glutathione peroxidase in whole blood and the concentrations of selenium, pituitary and thyroid hormones in serum were measured, prior to commencement of therapy and after 30 and 60 days. RESULTS Patients who received supplementation with antioxidants in addition to therapy with methimazole (Group A, n=29) attained euthyroidism faster than the patients treated with only methimazole (Group B, n=28). The concentration of selenium in the serum of patients in Group A increased significantly during treatment (p<0.001), while there was no statistically significant change in the patients in Group B. The concentration of selenium in the serum between the groups differed statistically significantly 30 days (p<0.05) and 60 days (p<0.01) after the commencement of therapy. Activity of glutathione peroxidase in whole blood increased during treatment in both groups of patients. However, a statistically more significant increase occurred in Group A compared to Group B, 30 days after the commencement of therapy (p<0.01). CONCLUSION: The results of the study clearly indicate that supplementation with antioxidants in the treatment of Graves’ disease is justified, particularly those containing selenium.

Publication Types:

PMID: 14967159 [PubMed – indexed for MEDLINE]

12: Zhonghua Yi Xue Za Zhi. 2003 Dec 10;83(23):2036-9.
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[An epidemiological study on the relationship between selenium and thyroid function in areas with different iodine intake]

[Article in Chinese]

Tong YJ, Teng WP, Jin Y, Li YS, Guan HX, Wang WB, Gao TS, Teng XC, Yang F, Shi XG, Chen W, Man N, Li Z, Guo XJ.

Department of Endocrinology, First Affiliated Hospital of China Medical University, Shenyang 110001, China.

OBJECTIVE: To investigate the relationship between selenium status and thyroid dysfunction in 3 areas with different iodine intake. METHODS: An epidemiological research was performed in the rural communities of Panshan County (iodine-deficient area) and Zhangwu County (iodine-sufficient area), Liaoning Province, and Huanghua County, Hebei Province (iodine-excessive area). Serum selenium, TSH, FT3 and FT4 levels were examined in 329 patients with thyroid dysfunction (including clinical hypothyroidism, subclinical hypothyroidism, clinical hyperthyroidism and subclinical hyperthyroidism) and 183 normal inhabitants. RESULTS: The median serum selenium concentrations in Panshan, Zhangwu and Huanghua were 91.4, 89.1, and 83.2 microg/L respectively. There was no difference in serum selenium levels between the patients with subclinical hypothyroidism, clinical hypothyroidism, and clinical hyperthyroidism and their normal controls. The median serum selenium concentration of the subclinical hyperthyroidism patients was 82.6 microg/L, significantly lower than that of the normal controls (87.3 microg/L). The FT3/FT4 ratio was decreased, the FT4 level was increased in the subclinical hyperthyroidism patients in comparison with the normal controls, and no significant difference in FT3 level was found between them. No significant effect of sex and age was found on serum selenium level of normal inhabitants. In normal controls serum selenium was inversely correlated with serum TSH level, and the subjects with serum selenium < or = 80 microg/L had the median TSH level of 2.10 mU/L, markedly higher than that of the subjects with the serum selenium of 80-100 microg/L (1.29 mU/L) and that of the subjects with the serum selenium of 100 approximately 120 micro g/L (1.28 mU/L). For the thyroid dysfunction patients with positive thyroid auto-antibody (TPOAb) in Zhangwu County, the serum selenium was negatively associated with TPOAb level. The serum selenium level of the TPOAb highly positive group (TPOAb > 600 IU/ml) was 83.6 IU/ml, significantly lower than those of the TPOAb lowly positive group and TPOAb moderately positive group (83.6, 92.9 and 95.6 microg/L respectively). CONCLUSION: No obvious effect of selenium status is found on the development of thyroid dysfunction in these three areas. But selenium deficiency can impair thyroid function by means of disturbing thyroid hormone metabolism and decreasing antioxidant ability of the thyroid.

Publication Types:

PMID: 14703411 [PubMed – indexed for MEDLINE]

13: J Trace Elem Med Biol. 1998 Nov;12(3):177-82.
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The TSH-dependent variation of the essential elements iodine, selenium and zinc within human thyroid tissues.

Bellisola G, Brätter P, Cinque G, Francia G, Galassini S, Gawlik D, Negretti de Brätter VE, Azzolina L.

Istituto di Immunologia e Malattie Infettive, Università di Verona, Policlinico Borgo Roma, Italy.

Instrumental Neutron Activation Analysis was used in order to measure iodine, selenium and zinc concentration in thyroid samples. A pair of samples of normal and nodular tissue were collected from the thyroid gland from 72 patients selected on the basis of pathological criteria (44 cases of multinodular goiter, 12 of chronic lymphocytic thyroiditis (CLT), 6 of thyroid adenoma (TA) and 12 of thyroid cancer (TC)). The check for tissue homogeneity and sampling error was performed by means of the coefficient of variation (CV%) of the elements in replicate samples of normal and altered tissues. High CV% values (> 15%) for iodine reflected a functional variability in thyroid follicles, while low CV% values (< 10%) for selenium and zinc indicated that the composition of selected tissues was rather homogeneous. The variation of the element’s concentration was compared in normal and altered tissues. The mean element concentrations had values close to those already reported in the literature; furthermore, our patients had marginal iodine and selenium deficiency. Both normal and nodular tissues in CLT showed statistically significant lower zinc values as compared with the other thyroid diseases. To evaluate the thyroid function, thyroid stimulating hormone (TSH) and thyroxine (T4) levels were measured in the serum of patients. Two arbitrary serum-TSH threshold levels (TSH < 1.0 and > 4.0 mU/L) were introduced in order to classify, respectively, hyperthyroidism and hypothyroidism, as well as euthyroid conditions (1.0 < TSH < 4.0 mU/L), and each patient was assigned to one of these groups. The influence of TSH in the variation of the concentration of iodine, selenium and zinc in normal and altered human thyroid tissues was significant.

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PMID: 9857330 [PubMed – indexed for MEDLINE]

14: Ann Endocrinol (Paris). 1997;58(4):310-5.
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[Relationships between selenium deficiency and 3,5,3′-triiodothyronine (T3) synthesis]

[Article in French]

Bouvier N, Millart H.

Laboratoire de Pharmacologie, C.H.U., Reims.

Several enzymes, the main being type I 5′ deiodinase, ensure thyroxin (T4) into 3,5,3′-triiodothyronine (T3) deiodination, both in the thyroid and in peripheral tissues. One of the feature of this enzymatic reaction is its regulation. It depends in part on individual selenium and iodine status. It has been shown by an analysis of thyroid hormones concentrations variations, when one of these trace elements is missing. During thyroid hormone synthesis, selenium and iodine are also implied in oxidative process control. Then, how selenium and iodine status balance modifications contribute to thyroidal diseases outbreak, becomes easier to understand. Besides, providing, adapted to individual requirements, selenium and iodine supplies could be useful for hypothyroidism and hyperthyroidism

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