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The thyroid gland plays a major role in the regulation of many body processes, especially those related to metabolic function. Maintaining optimal function of the thyroid and balanced levels of its main hormones, triiodothyronine (T3) and thyroxine (T4), is vital for overall health. Dysfunction of thyroid hormone performance is quite common and may result from conditions such as thyroiditis and hypothyroidism. In the United States, hypothyroidism is estimated to affect approximately 10% of adults, with a potentially higher prevalence in older populations.1 The autoimmune condition known as Hashimoto’s thyroiditis is the most common type of hypothyroidism, affecting one to two percent of people in the US, most of them women.2 In this disorder, a dysregulated immune response impairs the production of thyroid hormones. On the flip side from a low-functioning thyroid is hyperthyroidism, which impacts about one percent of people in the US, with women and older adults more likely to develop the condition.3 Graves’ disease is the most common cause of hyperthyroidism in the US.4 In this autoimmune disorder, autoantibodies activate the thyroid-stimulating hormone receptor, inducing excessive thyroid hormone secretion.4
A low-functioning thyroid is conventionally treated by taking the thyroid hormone medicine levothyroxine,5 while hyperthyroid conditions such as Graves’ disease may be conventionally treated by antithyroid drugs, radioiodine, or potentially surgery.4 How can the functional medicine approach help restore thyroid hormone balance and promote thyroid health? Understanding the factors that may be at the root of an imbalance is an important place to start. In the following video, Patrick Hanaway, MD, IFM educator and senior advisor to IFM’s CEO, discusses functional medicine’s role in addressing low thyroid function and helping the thyroid to heal.
Endocrine Disruptors, Stress, and Inflammation
Among the different factors that may negatively affect thyroid health, endocrine disruptors can have a potentially major impact on the function of this gland.6,7 A 2023 systematic review of 237 observational studies investigated the association between endocrine-disrupting chemical (EDC) exposure and risk of endocrine-related malignancies.7 The review found that the most tumorigenic EDC groups were phthalates, heavy metals, particulate matter, and pesticides, and that the thyroid was the endocrine organ that presented the highest cancer risk after EDC exposure.
A 2021 investigation on EDCs, which are often found in foods, food packaging, water, and personal care products, indicated that EDCs such as bisphenol A (BPA), phthalates, and flame retardant compounds, including polychlorinated biphenyls (PCBs), can interfere with thyroid gland functioning and thyroid hormone transport through multiple mechanisms.8 Specific to BPAs, in vitro and in vivo studies report that antagonism with thyroid receptors, influencing gene expression at the thyroid and pituitary levels, and interruption of thyroid transport proteins are among the mechanisms leading to thyroid dysfunction.9 An additional study specific to phthalate exposure suggested that this toxicant may influence thyroid hormone levels through induced oxidative or nitrosative stress.10 Observational studies have also noted a higher prevalence of autoimmune thyroid diseases in people living in polluted areas, near petrochemical plants, and in areas contaminated with organochlorine pesticides or PCBs.11
Other factors that may impact thyroid hormone balance include stress as well as chronic inflammation. While the mechanisms have not been fully identified, impaired regulation of oxidative stress and inflammation, for example, characterizes the progression of subclinical hypothyroidism, which increases the risk for cardiovascular diseases, including hypertension.12,13 Specific to thyroid hormone changes due to psychological stress, a 2020 systematic review of 10 observational studies (n=674) examined the association between thyroid function and posttraumatic stress disorder (PTSD).14 The meta-analysis showed higher levels of free T3 in patients with combat-related PTSD compared with controls, with no differences in thyroid-stimulating hormone (TSH), free T4, or total T4 between groups, suggesting that PTSD may contribute to changes in thyroid function.14
Subclinical Hypothyroidism: The Controversy & Testing Challenges
Experts continue to make differing recommendations regarding the treatment of subclinical hypothyroidism15 and whether or not to give exogenous thyroid hormones. With this condition, TSH levels are elevated, while circulating thyroid hormone levels are normal. Some reports indicate that 90% of patients with subclinical hypothyroidism have TSH levels between 4 and 10 mIU/L15 while other reports define the thyroid condition based on a TSH screening level over 4.5 mIU/L.16 The upper limit of the TSH range for diagnosis and levothyroxine treatment is debated,17 as well as the effectiveness of conventional thyroid hormone therapy in mild hypothyroidism.18 Regardless of the mentioned controversy, some functional medicine strategies may help with low-functioning thyroid issues by using low-risk diet and lifestyle treatments that may improve thyroid function by addressing the root of the issue. In addition to a comprehensive thyroid evaluation, consideration of an individual patient’s specific disease, lifestyle, comorbidities, and other pertinent factors helps to create a valuable overview for potential treatment direction.
Balancing Thyroid Hormone: Nutrition, Gut Health, and Liver Function
Functional medicine recognizes that illness does not occur in isolation, and the IFM Matrix helps practitioners examine the body systems, symptoms, and risk factors associated with a specific condition. The matrix, located within the IFM Toolkit, provides an outline for the practitioner to organize the patient’s clinical imbalances in the following biological systems, called nodes: defense and repair, energy, biotransformation and elimination, transport, communication, structural integrity, and assimilation. Addressing toxicant exposures, systemic inflammation, and chronic stress are all approaches to enhancing thyroid health.
Another resource in the IFM Toolkit, called “Factors That Affect Thyroid Function,” can help the clinician identify the following:
- Factors that inhibit proper production of thyroid hormones.
- Factors that increase conversion of T4 to RT3.
- Factors that contribute to the proper production of thyroid hormones.
- Factors that increase conversion of T4 to T3.
- Factors that improve cellular sensitivity to thyroid hormones.
Personalized interventions that focus on biotransformation, anti-inflammatory diets, specific nutrients, and optimizing gut and liver health are important considerations for restoring thyroid hormone balance. Adequate intake and availability of micronutrients such as iodine and iron are crucial for thyroid hormone synthesis, while selenium and zinc are needed for the conversion of T4 to T3,19,20 which takes place primarily in the liver but also in other organs such as the intestines as well as intracellularly.21 In addition, supplements used as complementary treatments may positively impact thyroid functioning.11 For example, ashwagandha has been used to help address thyroid dysfunctions. Recently, a 2018 pilot study (n=50) compared the efficacy and safety of ashwagandha root extract in subclinical hypothyroid patients to a placebo.22 The treatment group received 600 mg of the root extract per day for eight weeks. Results showed an improved serum TSH and T4 at the end of treatment compared to placebo, with few mild and temporary adverse effects.22
Gut health and a balanced microbial landscape benefit many system processes in the body, including thyroid homeostasis.20,23 Dysbiosis and intestinal autoimmune diseases have been reported concurrently with autoimmune thyroid diseases.20,24,25 To further explore the relationship between gut and thyroid health, a 2020 clinical trial (n=60) investigated the effect of synbiotic supplementation (which combines pre and probiotic ingredients) on thyroid function.23 Patients with hypothyroidism on levothyroxine either received 500 mg/day of the synbiotic or a placebo for eight weeks. After treatment, results indicated a beneficial effect, with TSH concentration, levothyroxine dose, and fatigue severity scale scores significantly decreased in the synbiotic group compared to placebo.23
The thyroid-liver axis is another illustration of the system-wide impact of thyroid health. In this complex relationship, the liver plays an important role in thyroid hormone activation, transport, and metabolism, and thyroid hormones impact hepatocyte activity and liver metabolism.26 Therefore, an imbalance in thyroid hormones may consequently influence liver structure and function.27
Research continues to reveal the complexity of the thyroid’s hormonal interplay with other biological processes. At IFM’s Hormone Advanced Practice Module (APM), learn more about how lifestyle interventions can positively impact the intricate web of the endocrine system, gather tools such as IFM’s comprehensive Thyroid Support Decision Tree, and hear functional medicine experts discuss the latest thyroid-related research.
- Wyne KL, Nair L, Schneiderman CP, et al. Hypothyroidism prevalence in the United States: a retrospective study combining National Health and Nutrition Examination Survey and claims data, 2009-2019. J Endocr Soc. 2022;7(1):bvac172. doi:10.1210/jendso/bvac172
- US National Library of Medicine. Hashimoto thyroiditis. Medline Plus. Updated August 1, 2020. Accessed March 8, 2023. https://medlineplus.gov/genetics/condition/hashimoto-thyroiditis/#frequency
- National Institute of Diabetes and Digestive and Kidney Diseases. Hyperthyroidism (overactive thyroid). Reviewed August 2021. Accessed March 8, 2023. https://www.niddk.nih.gov/health-information/endocrine-diseases/hyperthyroidism
- Davies TF, Andersen S, Latif R, et al. Graves’ disease. Nat Rev Dis Primers. 2020;6(1):52. doi:1038/s41572-020-0184-y
- National Institute of Diabetes and Digestive and Kidney Diseases. Hypothyroidism (underactive thyroid). Reviewed March 2021. Accessed March 8, 2023. https://www.niddk.nih.gov/health-information/endocrine-diseases/hypothyroidism
- Yuan S, Du X, Liu H, et al. Association between bisphenol A exposure and thyroid dysfunction in adults: a systematic review and meta-analysis. Toxicol Ind Health. 2023;7482337231156284. doi:1177/07482337231156284
- Macedo S, Teixeira E, Gaspar TB, et al. Endocrine-disrupting chemicals and endocrine neoplasia: a forty-year systematic review. Environ Res. 2023;218:114869. doi:1016/j.envres.2022.114869
- Sokal A, Jarmakiewicz-Czaja S, Tabarkiewicz J, Filip R. Dietary intake of endocrine disrupting substances presents in environment and their impact on thyroid function. Nutrients. 2021;13(3):867. doi:3390/nu13030867
- Gorini F, Bustaffa E, Coi A, Iervasi G, Bianchi F. Bisphenols as environmental triggers of thyroid dysfunction: clues and evidence. Int J Environ Res Public Health. 2020;17(8):2654. doi:3390/ijerph17082654
- Huang PC, Waits A, Chen HC, Chang WT, Jaakkola JJK, Huang HB. Mediating role of oxidative/nitrosative stress biomarkers in the associations between phthalate exposure and thyroid function in Taiwanese adults. Environ Int. 2020;140:105751. doi:1016/j.envint.2020.105751
- Benvenga S, Elia G, Ragusa F, et al. Endocrine disruptors and thyroid autoimmunity. Best Pract Res Clin Endocrinol Metab. 2020;34(1):101377. doi:1016/j.beem.2020.101377
- Gluvic ZM, Obradovic MM, Sudar-Milovanovic EM, et al. Regulation of nitric oxide production in hypothyroidism. Biomed Pharmacother. 2020;124:109881. doi:1016/j.biopha.2020.109881
- Shimizu Y, Kawashiri SY, Noguchi Y, Nagata Y, Maeda T, Hayashida N. Anti-thyroid peroxidase antibody and subclinical hypothyroidism in relation to hypertension and thyroid cysts. PLoS One. 2020;15(10):e0240198. doi:1371/journal.pone.0240198
- Toloza FJK, Mao Y, Menon LP, et al. Association of thyroid function with posttraumatic stress disorder: a systematic review and meta-analysis. Endocr Pract. 2020;26(10):1173-1185. doi:4158/EP-2020-0104
- Peeters RP, Brito JP. Subclinical hypothyroidism: to treat or not to treat? Eur J Endocrinol. 2020;183(6):D15-D24. doi:1530/EJE-20-0621
- Kim D, Vazquez-Montesino LM, Escober JA, et al. Low thyroid function in nonalcoholic fatty liver disease is an independent predictor of all-cause and cardiovascular mortality. Am J Gastroenterol. 2020;115(9):1496-1504. doi:14309/ajg.0000000000000654
- Razvi S, Bhana S, Mrabeti S. Challenges in interpreting thyroid stimulating hormone results in the diagnosis of thyroid dysfunction. J Thyroid Res. 2019;2019:4106816. doi:1155/2019/4106816
- Stuber MJ, Moutzouri E, Feller M, et al. Effect of thyroid hormone therapy on fatigability in older adults with subclinical hypothyroidism: a nested study within a randomized placebo-controlled trial. J Gerontol A Biol Sci Med Sci. 2020;75(9):e89-e94. doi:1093/gerona/glaa123
- Rayman MP. Multiple nutritional factors and thyroid disease, with particular reference to autoimmune thyroid disease. Proc Nutr Soc. 2019;78(1):34-44. doi:1017/S0029665118001192
- Knezevic J, Starchl C, Tmava Berisha A, Amrein K. Thyroid-gut-axis: how does the microbiota influence thyroid function? Nutrients. 2020;12(6):1769. doi:3390/nu12061769
- Bianco AC, Dumitrescu A, Gereben B, et al. Paradigms of dynamic control of thyroid hormone signaling. Endocr Rev. 2019;40(4):1000-1047. doi:1210/er.2018-00275
- Sharma AK, Basu I, Singh S. Efficacy and safety of ashwagandha root extract in subclinical hypothyroid patients: a double-blind, randomized placebo-controlled trial. J Altern Complement Med. 2018;24(3):243-248. doi:1089/acm.2017.0183
- Talebi S, Karimifar M, Heidari Z, Mohammadi H, Askari G. The effects of synbiotic supplementation on thyroid function and inflammation in hypothyroid patients: a randomized, double-blind, placebo-controlled trial. Complement Ther Med. 2020;48:102234. doi:1016/j.ctim.2019.102234
- Gong B, Wang C, Meng F, et al. Association between gut microbiota and autoimmune thyroid disease: a systematic review and meta-analysis. Front Endocrinol (Lausanne). 2021;12:774362. doi:3389/fendo.2021.774362
- Cao J, Wang N, Luo Y, et al. A cause-effect relationship between Graves’ disease and the gut microbiome contributes to the thyroid-gut axis: a bidirectional two-sample Mendelian randomization study. Front Immunol. 2023;14:977587. doi:3389/fimmu.2023.977587
- Piantanida E, Ippolito S, Gallo D, et al. The interplay between thyroid and liver: implications for clinical practice. J Endocrinol Invest. 2020;43(7):885-899. doi:1007/s40618-020-01208-6
- Tanase DM, Gosav EM, Neculae E, et al. Hypothyroidism-induced nonalcoholic fatty liver disease (HIN): mechanisms and emerging therapeutic options. Int J Mol Sci. 2020;21(16):5927. doi:3390/ijms21165927