Year : 2020 | Volume
: 17 | Issue : 3 | Page : 104--109
Role of dietary factors in thyroid disorders: Current evidences and way forwards
MD Abu Bashar1, Nazia Begam2,
1 Department of Community Medicine, MM Institute of Medical Sciences and Research, Mullana, Haryana, India
2 Specialist Medical Officer (ENT), ECHS Hospital, Naraingarh, Haryana, India
Dr. MD Abu Bashar
Flat No. D/71, MMDU Campus, Mullana, Ambala - 133 207, Haryana
Thyroid disorders are one of the most common endocrine problems encountered at primary care. The role and importance of dietary factors in their prevention and management are largely unknown with inadequate scientific evidence. In this review, we examine the scientific evidence of the effect of various dietary elements in causation, prevention, and management of common thyroid disorders.
|How to cite this article:|
Bashar MA, Begam N. Role of dietary factors in thyroid disorders: Current evidences and way forwards.Thyroid Res Pract 2020;17:104-109
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Bashar MA, Begam N. Role of dietary factors in thyroid disorders: Current evidences and way forwards. Thyroid Res Pract [serial online] 2020 [cited 2021 Oct 28 ];17:104-109
Available from: https://www.thetrp.net/text.asp?2020/17/3/104/307563
Thyroid diseases, including hypothyroidism, hyperthyroidism, and thyroid nodules, are commonly seen in most primary care and endocrinology OPDs. In India, according to a projection from various studies on thyroid disease, it has been estimated that about 42 million people suffer from thyroid diseases.
In routine clinical practice, patients suffering from thyroid diseases often enquire regarding dietary modifications for treatment or for reversal of their disease from their health-care providers. Diet consists of nutrients that can be broadly divided into two categories: Macronutrients, and micronutrients. Macronutrients are nutrients that provide calories or energy and are required in large amounts to maintain body functions and carry out the activities of daily life. There are three broad classes of macronutrient: proteins, carbohydrates, and fats. However, the changes in food habits are not the same in all countries. In low-income countries, the daily caloric intake is insufficient (between 2000 kcal and 2300 kcal), and cereals contribute 60%–80% of total calorie intake, whereas in intermediate-income countries, the average per capita calorie supply is between 2700 kcal and 3000 kcal. Cereals contribute more than half of the calorie intake, whereas sugar consumption has risen considerably to reach an average level of 30–40 kg/per capita/annum. Similarly, fat consumption has also increased in several countries and contributes 20%–25% of the daily energy supply. In high-income countries, the traditional diet, which consisted of dates, milk, fresh vegetables and fruits, whole wheat bread and fish, has changed to a more diversified diet with an excess intake of energy-dense foods rich in fat and free sugars and deficient in complex carbohydrates.
Micronutrients enable the body to produce enzymes, hormones and other substances essential for proper growth and development. Although only required in very small amounts, even moderate levels of deficiency can have serious detrimental effects on human physiology. Micronutrient malnutrition has many adverse effects on human health, not all of which are clinically evident.
A third category of nutrient has also emerged which are known as 'functional food'. It is defined as modified food that claims to improve health or well-being by providing benefit beyond that of traditional nutrients it contains. Functional foods may include such items as cereals, breads, beverages that are fortified with vitamins, some herbs, and nutraceuticals.
The evidence is strongest for adequate but not excessive iodine intake to benefit thyroid health in general, as well as selenium supplementation for patients with Graves' disease. The other micronutrients apart from iodine and selenium, playing an important role in thyroid hormone synthesis are iron and zinc. Apart from these, there is sparse scientific data showing that dietary factors can significantly benefit hypo-or hyperthyroidism.
Previous observations indicate toward the presence of certain goitrogenic substances in the diet, identifying an important role of dietary constituents in thyroidology. The persistence of goitre even after the universal salt iodization led researchers to explore the relation of other dietary nutrients in the thyroid physiology.
In this review, we discuss the common diet related factors influencing thyroid function and their role in causation, prevention and management of thyroid disorders based on the available scientific evidences.
Common Thyroid Disorders
Hypothyroidism affects up to 7% of the general population. Although endemic iodine deficiency is the leading cause of hypothyroidism globally, the most common aetiology of hypothyroidism in developed countries like United States is Hashimoto thyroiditis, an autoimmune condition characterized by positive serum thyroid autoantibody titres and lymphocytic infiltration of the thyroid, which may lead to destruction of thyroid follicular cells, thereby increasing the risk for hypothyroidism.
Levothyroxine as thyroid hormone replacement remains one of the most commonly prescribed medications. Many foods and substances such as, soy bean, papaya, grapefruit and coffee interfere with the intestinal absorption of oral levothyroxine and hence patients are advised to take the medication separately from meal times.
The majority of patients with hypothyroidism experience symptomatic improvement upon treatment with thyroid hormone replacement (THR). However, some may continue to experience and report hypothyroid symptoms despite the achievement of biochemical euthyroidism., Few others remain dissatisfied with the current available treatment options i.e., daily intake of levothyroxine tablets along with regular monitoring of serum thyroid hormone levels and seek alternative therapies., As such, these patients may seek dietary interventions to ameliorate symptoms or reverse their hypothyroidism.
Popular interventions include supplementation with various micronutrients such as iodine, selenium, certain vitamins, or minerals, or restricted intake of certain foods or food groups known to be goitrogenic such as cruciferous vegetables. Given the role of Hashimoto thyroiditis in the development of hypothyroidism, possible dietary intervention to specifically decrease serum thyroid autoantibody titers is also a common inquiry made by the patients. Supplemental iodine, however, may cause symptom flare-ups in people with Hashimoto's disease because it stimulates autoimmune antibodies.
Hyperthyroidism is present in up to 1.3% of the general population. Graves' disease is the leading cause of hyperthyroidism globally, but other aetiologies include toxic nodular goitre and the hyperthyroid phase of thyroiditis. Conventional therapies for the treatment of hyperthyroidism are anti-thyroid medications, radioactive iodine treatment, and thyroid surgery, each with their respective potential risks and benefits.
Serum thyroid-stimulating antibodies drive the onset and course of Graves' disease. Dietary iodine and selenium are the two micronutrients that can modify the thyroid antibody titers., In a study comparing plasma selenium concentrations in Graves' disease patients in remission or with persistent or recurrent disease following discontinuation of treatment with anti-thyroid drugs, although no significant differences were observed, selenium levels were the highest (>120 μg/l) in the remission group patients and a negative correlation was demonstrated between TSH antireceptor antibody and plasma selenium levels in this group.
Further, iodine status is an important consideration in individuals with thyroid nodules who are at risk for iodine-induced hyperthyroidism.
Thyroid nodules are detected incidentally on radiologic imaging. Criteria based on a combination of nodule size and sonographic characteristics inform the decision to pursue a thyroid nodule fine-needle aspiration biopsy, as there is an overall risk for malignancy of only 7%-15% in all nodules. Thyroid surgery is recommended if malignancy is highly suspected or confirmed, or if benign nodules are large enough to be associated with compressive symptoms to the anterior neck. Biopsy-benign or nonsuspicious nodules are monitored by ultrasound at regular intervals. Given the chronicity of monitoring needed for benign nodules, patients commonly seek dietary or other modalities to decrease the size of their thyroid nodules.
Specific Dietary Elements Affecting Thyroid Functioning
The production of thyroid hormone within the thyroid follicular cell requires adequate levels of circulating iodide taken in through the diet. The Recommended Dietary Allowance (RDA) for iodine is 150 μg/day in adults, and 220 μg/day and 290 μg/day in pregnant and lactating women, respectively. Common dietary sources of iodine include iodized salt, seafood (including seaweed and fish), and some breads and grains.
Although eating a regular diet should meet nutritional iodine needs, some individuals may require supplementation to achieve RDA goals. Individuals with restricted diets, such as vegetarians and vegans, are at higher risk for inadequate iodine intake because vegetables are not a rich source of iodine.
Some “iodine for thyroid health” tablets, which are commonly available over the counter, may contain several hundred-fold the daily recommended amount of iodine, i.e., as high as 1.5–3 mg in just a single dose. Other products labeled “for thyroid support” include tablets or liquid supplements containing spirulina (a superfood derived from blue-green algae) or kelp. Some alternative medicine practitioners recommend these— which are high in iodine — for people with hypothyroidism.
Taking supplements with high iodine content is unlikely to help the thyroid health, and in fact may even pose harm. In some individuals, excess iodine exposure or ingestion i.e., above the RDA may induce hyperthyroidism or hypothyroidism, and chronic iodine excess may induce autoimmune thyroiditis, as highly iodinated thyroglobulin is immunogenic. The estimated tolerable upper level of iodine intake in most individuals is 1100 μg/day.
Iodine-induced thyroid dysfunction is found to be common in those who have a history of endemic iodine deficiency or pre-existing thyroid disease. For this reason, the American Thyroid Association recommends avoiding supplements containing >500 μg/day of iodine.
The term “goitrogen” refers to any substance that can produce goiter, the enlargement of the thyroid gland. This is usually accomplished through effects that decrease thyroidal iodine, but goitrogenic substances can also act by inhibiting any of the other components of normal thyroid hormone production. The most common examples of dietary goitrogens are cruciferous vegetables and soy products.
Cruciferous vegetables are defined as those in the Brassica genus and include broccoli, cabbage, Brussels sprouts, kale, turnips, cauliflower, collard greens, and bok choy. They are rich in glucosinolates, compounds that produce sulforaphane, and the phenethyl and indolylic isothiocyanates associated with anti-cancerous properties. However, glucosinolates also include the metabolite thiocyanate, which inhibits thyroid hormone synthesis. Thus, although eating cruciferous vegetables certainly has health benefits, frequent consumption of large quantities may induce or exacerbate hypothyroidism.
Data on the amount of cruciferous vegetable consumption needed to adversely affect thyroid function are limited., In a study of five euthyroid volunteers who ingested 15.2 ozs of a commercial kale juice twice per day for 7 days, the mean 6-h thyroid radioiodine uptake decreased by 2.52% compared with baseline values, but the serum thyroid function tests remained unchanged. It would be of much interest to see the results of a sufficiently powered large prospective study with longer-term ingestion of kale consumed.
In an extreme example, one case report described the development of myxoedema coma in an 88-year-old Chinese woman who consumed 1.0–1.5 kg of raw bok choy daily for several months in an attempt to improve her diabetes control. These data suggest that frequent intake of large amounts of cruciferous vegetables may decrease thyroid hormone production, however, no rigorous clinical studies exist to support the need to stop eating them at all for thyroid benefit or for preventing goiter.
Dietary soy products—including soy milk, tofu, soy sauce, tempeh, and miso—contain isoflavones. As isoflavones can inhibit the action of thyroid peroxidase, an important enzyme required for thyroid hormone synthesis, it has been proposed that dietary soy intake may increase the risk for hypothyroidism in euthyroid individuals or that a higher dose of thyroid hormone replacement may be required in patients being treated for hypothyroidism. A review concluded that although soya protein and isoflavones do not affect normal thyroid function in people with sufficient iodine intake but they may interfere with the absorption of synthetic thyroid hormone, causing increase in the dose of medication in hypothyroid patients. The available literature shows that in euthyroid individuals living in iodine-replete areas, consumption of soy probably has no adverse effects on serum thyroid function. However, there remains a theoretical concern, based on in vitro and animal data, that in individuals with compromised thyroid function and/or whose iodine intake is marginal, soy foods may increase risk of developing clinical hypothyroidism. Therefore, it is important for soy food consumers to make sure their intake of iodine is adequate. Another exception is when soy-based infant formula is used for neonates with congenital hypothyroidism; an increase in dose of levothyroxine may be required to adequately address thyroid hormone needs. A recent systematic review aimed to investigate the link between soy or soy product consumption and thyroid function found that soy supplementation has no effect on the thyroid hormones and only very modestly raises TSH levels, the clinical significance, of this rise being unclear.
Thus, soy products should be cautiously taken by hypothyroid individuals on hormone replacement therapy and by people having low or marginal iodine intake or living in iodine deplete areas.
Apart from iodine, data on other micronutrients and their effects on thyroid status remain inconsistent.
Selenium is a micronutrient important for thyroid hormone metabolism. The US RDA of selenium in men and nonpregnant, nonlactating women is 55 μg. The richest dietary sources of selenium are seafood and organ meats. Typical sources in the diet are breads, grains, meat, poultry, fish, and eggs.
The tolerable upper intake level for selenium is 400 μg/day. Although selenium toxicity is not commonly encountered in routine clinical practice, symptoms include nausea; nail discoloration, brittleness, and loss; hair loss; fatigue; irritability; and foul breath (often described as “garlic breath”).
Some studies have shown benefit from selenium supplementation in individuals with autoimmune thyroid disease, and low selenium levels have been associated with increased risk for goiter and thyroid nodules in European women. In areas of severe selenium deficiency, supplementation up to 100 μg/day may be beneficial. From the available evidence, however, routine selenium supplementation in individuals following unrestricted diets for the purpose of treating Graves' disease,, decreasing serum thyroid antibody titers, or maintaining normal thyroid function is mostly unsupported.
Selenium supplementation is, hence, not routinely recommended for the sole purpose of benefiting thyroid health. One exception is in patients with mild Grave's ophthalmopathy, in whom selenium supplementation may improve quality of life and the course of ocular disease. Supplementation in these patients is recommended by the European Thyroid Association/European Group on Graves' Orbitopathy as a 6-month course.
Other trace minerals
The roles of zinc, copper, and magnesium in thyroid hormone synthesis and metabolism are even less well defined. In the US National Health and Nutrition Examination Survey (2011–2012), levels of zinc, copper, and selenium were inconsistently associated with free or total serum thyroid hormone levels, whereas a meta-analysis of eight studies suggested a relationship between levels of selenium, copper, and magnesium with thyroid cancer. Given the available scientific evidence, supplementation of these trace minerals solely for the purpose of promoting thyroid function is not generally supported.
Other dietary considerations for thyroid
Finally, a number of many other dietary factors, less rigorous—and in some cases with absent—scientific data, are suggested to affect thyroid health. Coffee, tea, and alcohol appear to have no effect on thyroid cancer risk, although coffee decreases the absorption of oral levothyroxine in individuals being treated for hypothyroidism. The potential role of Vitamin D as a preventive or therapeutic agent for various thyroid diseases remains unclear.
Popular in the functional medicine community are interventions to treat leaky gut syndrome, the theory of increased intestinal permeability leading to various diseases. Gluten-free diets, sugar-free diets, and probiotics are advocated for promoting thyroid health. Although one small study demonstrated decreased serum thyroid antibody titers among 34 women who followed a gluten-free diet for 6 months, published data in the scientific literature on the effects of these interventions on thyroid health are lacking.
Apart from the definitive role of iodine and selenium deficiency in the causation of hypothyroidism, the role of other dietary factors in affecting thyroid health remains inconclusive based on available scientific evidence. Selenium supplementation has a definitive benefit in patients with grave's opthalmopathy, however, its routine supplementation for improving thyroid function is not recommended. Further, data on the role of cruciferous vegetables and soy as goitrogens are also limited. Based on available scientific evidence, it is evident that dietary factors do have an influence on thyroid health. However, much remains unknown about thyroid disease and their association with dietary factors and that there are areas of uncertainty in modern medicine for which continued research is required.
Financial support and sponsorship
Conflicts of interest
There are no conflict of interest.
|1||Unnikrishnan AG, Menon UV. Thyroid disorders in India: An epidemiological perspective. Indian J Endocrinol Metab 2011;15:S78-81.|
|2||Nutrition Basics. Available from: https://mynutrition.wsu.edu/nutrition-basics. [Last accessed on 2020 May 02].|
|3||Macronutrients. Available from: http://www.emro.who.int/health-topics/macronutrients/index.html. [Last accessed on 2020 May 02].|
|4||Micronutrients. Available from: http://www.emro.who.int/health-topics/micronutrients/index.html. [Last accessed on 2020 May 02].|
|5||Medical Definition of Functional Food. Available from: https://www.medicinenet.com/script/main/art.asp?articlekey=9491. [Last accessed on 2020 May 02].|
|6||Chung HR. Iodine and thyroid function. Ann Pediatr Endocrinol Metab 2014;19:8-12.|
|7||Zheng H, Wei J, Wang L, Wang Q, Zhao J, Chen S, et al. Effects of selenium supplementation on graves' disease: A systematic review and meta-analysis. Evid Based Complement Alternat Med 2018;2018:3763565.|
|8||Hess SY. The impact of common micronutrient deficiencies on iodine and thyroid metabolism: The evidence from human studies. Best Pract Res Clin Endocrinol Metab 2010;24:117-32.|
|9||Cléro É, Doyon F, Chungue V, Rachédi F, Boissin JL, Sebbag J, et al. Dietary patterns, goitrogenic food, and thyroid cancer: A case-control study in French Polynesia. Nutr Cancer 2012;64:929-36.|
|10||Das S, Bhansali A, Dutta P, Aggarwal A, Bansal MP, Garg D, et al. Persistence of goitre in the post-iodization phase: Micronutrient deficiency or thyroid autoimmunity? Indian J Med Res 2011;133:103-9.|
|11||Taylor PN, Albrecht D, Scholz A, Gutierrez-Buey G, Lazarus JH, Dayan CM, et al. Global epidemiology of hyperthyroidism and hypothyroidism. Nat Rev Endocrinol 2018;14:301-16.|
|12||QVIA Institute for Human Data Science. Medicines Use and Spending in the U.S. A Review of 2016 and Outlook to 2021. May 4, 2017. Source. [Last accessed on 2019 Sep 24].|
|13||Liwanpo L, Hershman JM. Conditions and drugs interfering with thyroxine absorption. Best Pract Res Clin Endocrinol Metab 2009;23:781-92.|
|14||Jonklaas J, Bianco AC, Bauer AJ, Burman KD, Cappola AR, Celi FS, et al. Guidelines for the treatment of hypothyroidism: Prepared by the american thyroid association task force on thyroid hormone replacement. Thyroid 2014;24:1670-751.|
|15||Samuels MH, Kolobova I, Niederhausen M, Janowsky JS, Schuff KG. Effects of altering levothyroxine (L-T4) doses on quality of life, mood, and cognition in L-T4 treated subjects. J Clin Endocrinol Metab 2018;103:1997-2008.|
|16||Leung AM. Levothyroxine dose adjustment resulting in mild variations of serum TSH levels within or near the normal range has no effect on quality of life, mood, and cognition in hypothyroid individuals. Clin Thyroidol 2018;30:263-5.|
|17||Peterson SJ, Cappola AR, Castro MR, Dayan CM, Farwell AP, Hennessey JV, et al. An online survey of hypothyroid patients demonstrates prominent dissatisfaction. Thyroid 2018;28:707-21.|
|18||Stevens EW, Leung AM. A patient survey of hypothyroid individuals demonstrates dissatisfaction with treatment and with managing physicians. Clin Thyroidol 2018;30:175-8.|
|19||Dean S. Medical nutrition therapy for thyroid and related disorders. In: Mahan KL, Escott-Stump S, editors. Krause's Food, Nutrition, & Diet Therapy. 13th ed. Philadelphia, PA: Saunders; 2008. p. 711-24.|
|20||Bahn RS, Burch HB, Cooper DS, Garber JR, Greenlee MC, Klein I, et al. Hyperthyroidism and other causes of thyrotoxicosis: Management guidelines of the American Thyroid Association and American Association of Clinical Endocrinologists. Endocr Pract 2011;17:456-520.|
|21||Ross DS, Burch HB, Cooper DS, Greenlee MC, Laurberg P, Maia AL, et al. 2016 American Thyroid Association Guidelines for Diagnosis and Management of hyperthyroidism and other causes of thyrotoxicosis. Thyroid 2016;26:1343-421.|
|22||Adams DD, Kennedy TH, Stewart JC, Utiger RD, Vidor GI. Hyperthyroidism in Tasmania following iodide supplementation: Measurements of thyroid-stimulating autoantibodies and thyrotropin. J Clin Endocrinol Metab 1975;41:221-8.|
|23||Wertenbruch T, Willenberg HS, Sagert C, Nguyen TB, Bahlo M, Feldkamp J, et al. Serum selenium levels in patients with remission and relapse of graves' disease. Med Chem 2007;3:281-4.|
|24||Haugen BR, Alexander EK, Bible KC, Doherty GM, Mandel SJ, Nikiforov YE, et al. 2015 American Thyroid Association management guidelines for adult patients with thyroid nodules and differentiated thyroid cancer: The American Thyroid Association Guidelines Task Force on Thyroid Nodules and Differentiated Thyroid Cancer. Thyroid 2016;26:1-33.|
|25||Institute of Medicine of the National Academies. Dietary Reference Intakes: The Essential Guide to Nutrient Requirements. Washington, DC: The National Academies Press; 2006. [Last accessed on 2019 Sep 24].|
|26||Leung AM, Lamar A, He X, Braverman LE, Pearce EN. Iodine status and thyroid function of Boston-area vegetarians and vegans. J Clin Endocrinol Metab 2011;96:E1303-7.|
|27||Hypothyroidism: Should I Take Iodine Supplements? Available from: https://www.mayoclinic.org/diseases-conditions/hypothyroidism/expert-answers/hypothyroidism-iodine/faq-20057929. [Last accessed on Sep 24 2019].|
|28||Pramyothin P, Leung AM, Pearce EN, Malabanan AO, Braverman LE. Clinical problem-solving. A hidden solution. N Engl J Med 2011;365:2123-7.|
|29||Bürgi H. Iodine excess. Best Pract Res Clin Endocrinol Metab 2010;24:107-15.|
|30||Institute of Medicine. Dietary Reference Intakes. Washington, DC: National Academies Press; 2006.|
|31||Leung AM, Braverman LE. Consequences of excess iodine. Nat Rev Endocrinol 2014;10:136-42.|
|32||Leung AM, Avram AM, Brenner AV, Duntas LH, Ehrenkranz J, Hennessey JV, et al. Potential risks of excess iodine ingestion and exposure: statement by the american thyroid association public health committee. Thyroid 2015;25:145-6.|
|33||Bender DA. Goitrogens. A Dictionary of Food and Nutrition. 3rd ed. Oxford: Oxford University Press; 2009.|
|34||Felker P, Bunch R, Leung AM. Concentrations of thiocyanate and goitrin in human plasma, their precursor concentrations in Brassica vegetables, and associated potential risk for hypothyroidism. Nutr Rev 2016;74:248-58.|
|35||Kim SS, He X, Braverman LE, Narla R, Gupta PK, Leung AM. Letter to the editor. Endocr Pract 2017;23:885-6.|
|36||Chu M, Seltzer TF. Myxedema coma induced by ingestion of raw bok choy. N Engl J Med 2010;362:1945-6.|
|37||Chandra AK, Mukhopadhyay S, Lahari D, Tripathi S. Goitrogenic content of Indian cyanogenic plant foods and their in vitro anti-thyroidal activity. Indian J Med Res 2004;119:180-85.|
|38||Messina M, Redmond G. Effects of soy protein and soybean isoflavones on thyroid function in healthy adults and hypothyroid patients: A review of the relevant literature. Thyroid 2006;16:249-58.|
|39||Jabbar MA, Larrea J, Shaw RA. Abnormal thyroid function tests in infants with congenital hypothyroidism: The influence of soy-based formula. J Am Coll Nutr 1997;16:280-2.|
|40||Otun J, Sahebkar A, Östlundh L, Atkin SL, Sathyapalan T. Systematic review and meta analysis on the effect of soy on thyroid function. Sci Rep 2019;9:3964.|
|41||O'Kane SM, Mulhern MS, Pourshahidi LK, Strain JJ, Yeates AJ. Micronutrients, iodine status and concentrations of thyroid hormones: A systematic review. Nutr Rev 2018;76:418-31.|
|42||National Institutes of Health. Selenium: Fact Sheet for Health Professionals. Source Updated; 2 March, 2018. [Last accessed on 2019 Aug 20].|
|43||Schomburg L. Selenium, selenoproteins and the thyroid gland: Interactions in health and disease. Nat Rev Endocrinol 2011;8:160-71.|
|44||Hu S, Rayman MP. Multiple nutritional factors and the risk of Hashimoto's thyroiditis. Thyroid 2017;27:597-610.|
|45||Duntas LH. The evolving role of selenium in the treatment of Graves' disease and ophthalmopathy. J Thyroid Res 2012;2012:736161.|
|46||Winther KH, Bonnema SJ, Cold F, Debrabant B, Nybo M, Cold S, et al. Does selenium supplementation affect thyroid function? Results from a randomized, controlled, double-blinded trial in a Danish population. Eur J Endocrinol 2015;172:657-67.|
|47||Marcocci C, Kahaly GJ, Krassas GE, Bartalena L, Prummel M, Stahl M, et al. European Group on Graves' Orbitopathy. Selenium and the course of mild Graves' orbitopathy. N Engl J Med 2011;364:1920-31.|
|48||Bartalena L, Baldeschi L, Boboridis K, Eckstein A, Kahaly GJ, Marcocci C, et al. European Group on Graves' Orbitopathy (EUGOGO). The 2016 European Thyroid Association/ European Group on Graves' Orbitopathy guidelines for the management of Graves' orbitopathy. Eur Thyroid J 2016;5:9-26.|
|49||Jain RB. Thyroid function and serum copper, selenium, and zinc in general U.S. population. Biol Trace Elem Res 2014;159:87-98.|
|50||Shen F, Cai WS, Li JL, Feng Z, Cao J, Xu B. The association between serum levels of selenium, copper, and magnesium with thyroid cancer: A meta-analysis. Biol Trace Elem Res 2015;167:225-35.|
|51||Mack WJ, Preston Martin S, Dal Maso L, Galanti R, Xiang M, Franceschi L, et al. A pooled analysis of case control studies of thyroid cancer: Cigarette smoking and consumption of alcohol, coffee, and tea. Cancer Causes Control 2003;14:773-85.|
|52||Benvenga S, Bartolone L, Pappalardo MA, Russo A, Lapa D, Giorgianni G, et al. Altered intestinal absorption of L thyroxine caused by coffee. Thyroid 2008;18:293-301.|
|53||Kim D. The role of vitamin D in thyroid diseases. Int J Mol Sci 2017;18:1949.|
|54||Krysiak R, Szkróbka W, Okopień B. The effect of gluten-free diet on thyroid autoimmunity in drug-naïve women with Hashimoto's thyroiditis: A pilot study. Exp Clin Endocrinol Diabetes 2019;127:417-22.|