Autoimmune Thyroid Disease Michael Friedman, ND Executive Director Association for the Advancement of Restorative Medicine Financial Disclosure:Owner and Science officer of Restorative Formulations 1 Thyroid Prevalence Diseases of the thyroid are not common in medical practice - 1967 13 million nationally may have undiagnosed abnormal thyroid function in 1995 11.7% abnormal TSH* 20 million 2017 *Canaris GJ, Manowitz, NR, Mayor G, Ridgway EC. The Colorado Thyroid Disease Prevalence Study. Arch Intern Med.2000;160:526-534 2 Autoimmunity Steady increase in the incidence and prevalence of autoimmunity worldwide. Rate of increase (% increase every year) globally – 19.1± 43.1.* *Lerner, A. , Jeremias, P. , & Matthias, T. (2015). The World Incidence and Prevalence of Autoimmune Diseases is Increasing.International Journal of Celiac Disease, 3(4), 151-155 4 5 6 Examples of Thyroid Diseases 1° Hypothyroidism Hyperthyroidism 7 www.hsc.missouri.edu/~daveg/thyroid/thy_dis.html 8 9 Autoimmunity – Genetics Vs Environment Autoimmune thyroid disease Genetics ~ Environmental triggers ~ Brent GA. Environmental Exposures and Autoimmune Thyroid Disease.Thyroid. 2010;20(7):755-761. 10doi:10.1089/thy.2010.1636. ❖Life stress Environmental triggers ❖Infections ❖Nutritional deficiencies (iodine, selenium) ❖Smoking ❖Medications such as Amiodarone and interferon ❖Radiation ❖Heavy metals & Pesticides ❖Environmental toxicants 11 ❖Intestinal dysbiosis Environmental Factors Coal combustion: 400 metric tons a year of mercury Rocket Fuel Combustion- 20 million pounds perchlorates in US per year (Lausanne). 2017 Mar 20;8:50. doi: 10.3389/fendo.2017.00050. eCollection 2017. Mercury emissions from the eight highest emitting industry sectors. Data for 2010 from the 2013 UNEP Global Mercury Assessment. Total estimated global anthropog Ferrari SM, Fallahi P, Antonelli A, Benvenga S. Environmental Issues 12 in Thyroid Diseases. Front Endocrinol enic mercury emissions are 1960 metric tons. Antibodies and Toxins: The Five Crucial Players That Affect Thyroid Function Sodium Iodide Symporter (NIS) Thyroglobulin Thyroid Peroxidase Iodothyronine Deiodinase (Conversion) Thyroid Receptors 13 Radiation affects NIS Release of Iodine 131 from nuclear power plants and nuclear weapon facilities. US atomic weapons tests in Nevada, Millstone nuclear power plant in Connecticut. Völzke H1J Clin Endocrinol Metab. 2005 Aug;90(8):4587-92. Epub 2005 May 10. 14 Occupational exposure to ionizing radiation is associated with autoimmune thyroid disease. Halogens affect NIS Chlorine, fluorine, and bromine - chemically related to iodine and compete with it, blocking iodine receptors in the thyroid gland. Chlorine /Fluoride - once and still used as a treatment option for hyperactive thyroid gland. 15 Perchlorate affects NIS Perchlorate - Environmental contaminant that blocks iodine/iodide uptake into the thyroid gland by affecting the iodine transport mechanism (the sodium/iodine symporter).* *Wolff J. Perchlorate and the thyroid gland. Pharmacol Rev. 1998 Mar;50(1):89-105. 16 Polybrominated diphenyl ethers (PBDEs) Found in 97% of U.S. residents serum. TSH declined 16% for every tenfold increase in PBDE’s. Lin SM, Chen FA, Huang YF, Hsing LL, Chen LL, Wu LS, Liu TS, Chang-Chien GP, Chen KC, Chao HR. Negative associations between PBDE levels and thyroid hormones in cord blood. Int J Hyg Environ Health. 2011;214(2):115-20. Chevrier J, Harley KG, Bradman A, Gharbi M, Sjödin A, Eskenazi B. Polybrominated diphenyl ether (PBDE) flame retardants and thyroid hormone during pregnancy. Environ Health Perspect. 2010;118(10):1444-1449. http://www.environmentalhealthnews.org/ehs/news/flame-retardants-linked-to-altered-thyroid-hormones-in-pregnant-women 17 Organochlorine Pesticides affect NIS Can result in euthyroid goiter or hypothyroidism.* Pesticide Exposure Thyroid hormone concentration change was consistently a response due to mixtures, but NOT usually to individual chemicals. ** *Howdeshell KL. A model of the development of the brain as a construct of the thyroid system. Environ Health Perspect. 2002; 110 Suppl 3:337-348. **Porter WP, Jaeger JW and Carlson IH. EndoEndocrine, immune and behavioral effects of aldicarb (carbamate), atrazine (triazine) and nitrate (fertilizer) mixtures at groundwater concentrations Toxicology and Industrial Health. 1999; 15 (1-2): 133-150. 18 HYPOTHALAMUS-PITUITARY THYROID AXIS DEIODINASE-CONTAINING TISSUES TRH PITUITARY TSH Development Growth Metabolism Cognition WT D2KO © 2013 BLab Exercise Triples Deiodinase 2 after Exercise The BiancoLab at RUSH University Medical Center in Chicago 20 Heavy Metals, Sunscreen and Stress Affect Conversion- 5'-deiodination Inhibition Cadmium, Mercury, Lead toxicity** Stress, Poor nutrition, Illness, Selenium deficiency 4-MBC and Octylmehtoxycinnamate* (found in sunscreen) Bioaccumulation in fish and human milk Decreases 5’ deiodinase activity **Gupta P, Kar A. Cadmium induced thyroid dysfunction in chicken: hepatic type I iodothyronine 5'-monodeiodinase activity role of lipid peroxidation. Comp Biochem Physiol C Pharmacol Toxicol Endocrinol 1999;123:39-44. *Schmutzler C, Hamann I, Hofmann PJ, Kovacs G, Stemmler L, Mentrup B, Schomburg L, Ambrugger P, Grüters A, Seidlova-Wuttke D, Jarry H, Wuttke W, Köhrle J. Endocrine active compounds affect thyrotropin and thyroid hormone levels in serum as well as endpoints of thyroid hormone action in liver, heart and kidney. Toxicology. 2004;205(1-2):95-102. 21 BPA –Affects Conversion Phthalates/BPA - Alter the body's thyroid hormone levels and potentially aggravate or even lead to thyroid disease. Andra SS, Makris KC. Thyroid disrupting chemicals in plastic additives and thyroid health. J Environ Sci Health C Environ Carcinog Ecotoxicol Rev. 2012;30(2):107-51. doi: 10.1080/10590501.2012.681487. 22 Polychlorinated biphenyl (PCB) Affects Thyroid Receptors Structure of PCB’s similar to thyroid hormone Bind to and interact with TH receptor Agonists or antagonists to TH 23receptor Intestinal Dysbiosis/ Microbiome Intestinal microbiota - Crucial for immunologic, hormonal and metabolic homeostasis Functional thyroid disorders - Associated with bacterial overgrowth and a different microbial composition Virili C, Centanni M. "With a little help from my friends" - The role of microbiota in thyroid hormone metabolism and enterohepatic 24 recycling.Mol Cell Endocrinol. 2017 Feb 4. Impact of Infections on the Thyroid Human parvovirus B19 (EVB19) and hepatitis C virus. Interleukin-1, Interleukin-6 and TNF inhibit thyrotropin secretion.# Mucocutaneous candidosis - 50% increase in hypothyroidism.* #Larsen P.R. et al Williams Textbook of Endocrinology 10th ed 2003;p101 *Coleman R and Hay RJ. Chronic mucocutaneous candidosis associated with hypothyroidism: a distinct syndrome? British Journal of Dermatology . 1997;36 (1):24-29. 25 Medications ▪Lithium, ▪Radioactive Iodine ▪Amiodarone ▪Interferon ▪High dose Glucocorticoids ('steroids') ▪Sulfonamides ▪Oral cholecystographic agents for ▪Bexarotene visualization of the gall bladder ▪Ethionamide ▪Sunitinib and other tyrosine kinase inhibitors ▪Anticonvulsants ▪Angiogenesis inhibitors such as lenalidomide Drugs that interact with levothyroxine: an observational study from the Thyroid Epidemiology, Audit and Research Study (TEARS) Clin Endocrinol (Oxf). 2014 Jul 17. doi: 10.1111/cen.12559 26 Vitamin D3 and Hashimoto’s Disease 1,25-Vitamin D levels are lower in individuals with Hashimoto’s disease. Supplementation with vitamin D3 in animal models prevents the development of autoimmune thyroiditis and MS. 27 Selenium and Thyroid Antibodies During the supplementation trial 50-100 mcg: • Serum selenium (Se) increased by 45%. • Plasma glutathione peroxidase (GPX3) by 21%. • TPO-Ab decreased by 76%. • Graves Ophthalmopathy 28 In Thyroid, What Happens to Iodine After Absorption? NIS Oxidation (H202+TPO) - - I I I2 Organification TG TSH δ –Iodolactone and MIT, DIT, T3, T4 other iodinated lipids However, organification of lipids will only occur with iodine intake in excess of the RDA. •Prostaglandins Other Lipid Mediat. 2014 Aug;112:27-33. doi: 10.1016/j.prostaglandins.2014.07.001. Epub 2014 Jul 10. •6-iodolactone, key mediator of antitumoral properties of iodine. Environmental Toxins Diagnose it Decrease toxic load Heavy metal removal Eliminate halogens in diet and body Consider alternatives to certain medications Treat and bacterial or myco-overgrowth 30 General Thyroid Autoimmune Protocol Nutrition: Hypoallergenic diet, treat dysbiosis Decrease environmental toxins Vitamin D3 50,000 IU twice a week, or min 4000 IU daily Fish oils (Omega 3-6-9) Ensure healthy gut microbiome Antioxidant supplements (selenium, vit E) which are thyro- protective 31 Environmental Triggers for Hypothyroid Lifestyle: Remove Heavy Metals: ➢ Exercise ➢ DMSA 500 MG three ➢ Treat Dysbiosis times a week Remove Halogens: ➢ Liposomal Glutathione ➢ 25-50 mg Iodine a day for 500 mg Daily ➢ Fiber-10 grams several months to remove supplementation daily halogens 32 Specifics for Hypothyroid Botanicals ➢ 25 mcg T3 BID supplements: Nutrition Supplementation: ➢ Or 100 mcg T4 ✓Iris, Kelp, Myrrh ➢ 5 drops of Lugol’s iodine or iodine supplement solution 12 mg BID for a min of three months to help with halogen displacement and iodine supplementation ➢ Selenium 400 IU ➢ Vitamin D3 4000 IU ➢ Methylcobalamin 800 mcg 33 Hashimoto’s Disease Case Study TSH TPO AB Initial After 5 years Initial After 5 years 34 15 year old boy Hashimoto’s Thyroiditis Iodine Case Study TSH T3 Initial