Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
Immunologic Research
Published in: Immunologic Research 2/2021

Open Access 01-04-2021 | Thyroid Disease | Review

Iodoprophylaxis and thyroid autoimmunity: an update

Authors: Claudia Teti, Marta Panciroli, Elena Nazzari, Giampaola Pesce, Stefano Mariotti, Antonella Olivieri, Marcello Bagnasco

Published in: Immunologic Research | Issue 2/2021

Login to get access

Abstract

Adequate iodine intake is necessary for normal thyroid function. Iodine deficiency is associated with serious complications, but also iodine excess can lead to thyroid dysfunction, and iodine supplementation aimed to prevent iodine deficiency disorders has been associated with development of thyroid autoimmunity. The epidemiology of thyroid diseases has undergone profound changes since the implementation of iodoprophylaxis, notably by means of iodine-enriched salt, specifically resulting in decreased prevalence of goiter and neonatal hypothyroidism, improved cognitive function development in infancy, and reduced incidence of more aggressive forms of thyroid cancer. The main question we address with this review is the clinical relevance of the possible effect on autoimmunity exerted by the use of iodine-enriched salt to correct iodine deficiency. In animal models, exogenous iodine is able to trigger or exacerbate thyroid autoimmunity, but it is still not clear whether the observed immunological changes are due to a direct effect of iodine on immune response, or whether they represent a secondary response to a toxic effect of iodine on thyroid tissue. Previous iodine status of a population seems to influence the functional thyroid response to increased iodine intake and possibly the development of thyroid autoimmunity. Moreover, the prevalence of thyroid antibodies, regarded as hallmark of autoimmune thyroid disease, varies between populations under the influence of genetic and environmental factors, and the presence of thyroid antibodies does not always coincide with the presence of thyroid disease or its future development. In addition, the incidence of autoimmune diseases shows a general increasing trend in the last decades. For all these reasons, available data are quite heterogeneous and difficult to analyze and compare. In conclusion, available data from long-term population surveys show that a higher than adequate population iodine intake due to a poorly controlled program of iodine prophylaxis could induce thyroid dysfunction, including thyroid autoimmunity mostly represented by euthyroid or subclinical hypothyroid autoimmune thyroiditis. Close monitoring iodine prophylaxis is therefore advised to ensure that effects of both iodine deficiency and iodine excess are avoided.
Literature
1.
Mcleod DSA, Cooper DS. The incidence and prevalence of thyroid autoimmunity. Endocrine. 2012;42:252–65.PubMedCrossRef
2.
Hayter SM, Cook MC. Autoimmunity reviews updated assessment of the prevalence, spectrum and case definition of autoimmune disease. Autoimmun Rev. 2012;11(10):754–65.PubMedCrossRef
3.
Giordano C, Richiusa P, Bagnasco M, Pizzolanti G, Di Blasi F, Sbriglia MS, et al. Differential regulation of Fas-mediated apoptosis in both thyrocyte and lymphocyte cellular compartments correlates with opposite phenotypic manifestations of autoimmune thyroid disease. Thyroid. 2001;11(3):233–44.PubMedCrossRef
4.
Caturegli P, De Remigis A, Rose NR. Hashimoto thyroiditis: clinical and diagnostic criteria. Autoimmun Rev. 2014;13(4–5):391–7.PubMedCrossRef
5.
6.
Andersen S, Iversen F, Terpling S, Pedersen KM, Gustenhoff P, Laurberg P. Maturitas Iodine deficiency influences thyroid autoimmunity in old age — a comparative population-based study. Maturitas. 2012;71(1):39–43.PubMedCrossRef
7.
Prummel MF, Strieder T, Wiersinga WM. The environment and autoimmune thyroid diseases. Eur J Endocrinol. 2004;150(5):605–18.PubMedCrossRef
8.
9.
Bagnasco M, Bossert I, Pesce G. Stress and autoimmune thyroid diseases. NeuroImmunoModulation. 2006;13(5–6):309–17.PubMedCrossRef
10.
Ferrari SM, Fallahi P, Antonelli A, Benvenga S. Environmental Issues in thyroid diseases. Front Endocrinol (Lausanne). 2017;8:50.CrossRef
11.
Pedersen IB, Knudsen N, Jørgensen T, Perrild H, Ovesen L, Laurberg P. Thyroid peroxidase and thyroglobulin autoantibodies in a large survey of populations with mild and moderate iodine deficiency. Clin Endocrinol (Oxf). 2003;58(1):36–42.CrossRef
12.
Vanderpump MP, Tunbridge WM, French JM, Appleton D, Bates D, Clark F, et al. The incidence of thyroid disorders in the community: a twenty-year follow-up of the Whickham Survey. Clin Endocrinol (Oxf). 1995;43(1):55–68.CrossRef
13.
Hollowell JG, Staehling NW, Flanders WD, Hannon WH, Gunter EW, Spencer CA, et al. Serum TSH, T(4), and thyroid antibodies in the United States population (1988 to 1994): National Health and Nutrition Examination Survey (NHANES III). J Clin Endocrinol Metab. 2002;87(2):489–99.PubMedCrossRef
14.
Tozzoli R, Bagnasco M, Giavarina D, Bizzaro N. TSH receptor autoantibody immunoassay in patients with Graves ’ disease: improvement of diagnostic accuracy over different generations of methods. Systematic review and meta-analysis. Autoimmun Rev. 2012;12(2):107–13.PubMedCrossRef
15.
Laurberg P. Iodine intake as a determinant of thyroid disorders in populations. Best Pract Res Clin Endocrinol Metab. 2010;24:13–27.PubMedCrossRef
16.
Dobson JE. The iodine factor in health and evolution. Geogr Rev. 2014;88(1):3–28.
17.
Gorstein JL, Bagriansky J, Pearce EN, Kupka R, Zimmermann MB. Estimating the health and economic benefits of universal salt iodization programs to correct iodine deficiency disorders. Thyroid. 2020;30(12):1802–9.PubMedPubMedCentralCrossRef
18.
Zimmermann MB, Boelaert K. Iodine deficiency and thyroid disorders. Lancet Diabetes Endocrinol. 2015;3(4):286–95.PubMedCrossRef
19.
Olivieri A, Trimarchi F, Vitti P. Global iodine nutrition 2020: Italy is an iodine sufficient country. J Endocrinol Invest. 2020;43(11):1671–2.PubMedCrossRef
20.
21.
Farebrother J, Zimmermann MB, Andersson M. Excess iodine intake: sources, assessment, and effects on thyroid function. Ann N Y Acad Sci. 2019;1446(1):44–65.PubMed
22.
23.
Sundick RS, Bagchi N, Brown TR. The role of iodine in thyroid autoimmunity: from chickens to humans: a review. Autoimmunity. 1992;13(1):61–8.PubMedCrossRef
24.
Li M, Boyages SC. Iodide induced lymphocytic thyroiditis in the BB/W rat: evidence of direct toxic effects of iodide on thyroid subcellular structure. Autoimmunity. 1994;18(1):31–40.PubMedCrossRef
25.
Liu J, Mao C, Dong L, Kang P, Ding C. Excessive iodine promotes pyroptosis of thyroid follicular epithelial cells in Hashimoto’s thyroiditis through the ROS-NF- κ B-NLRP3 pathway. Front Endocrinol. 2019;10:1–10.CrossRef
26.
Di Dalmazi G, Hirshberg J, Lyle D, Freij JB, Caturegli P. Reactive oxygen species in organ-specific autoimmunity. Auto Immun Highlights. 2016;7(1):11–22.PubMedPubMedCentralCrossRef
27.
Ruggeri RM, CampennÌ A, Giuffrida G, Casciaro M, Barbalace MC, Hrelia S, et al. Oxidative stress as a key feature of autoimmune thyroiditis: an update. Minerva Endocrinol. 2020;45(4):326–44.PubMed
28.
Ruggeri RM, Cristani MCBMT, Giovinazzo AAS, Trimarchi F. Serum levels of advanced glycation end products (AGEs) are increased and their soluble receptor (sRAGE) reduced in Hashimoto’s thyroiditis. J Endocrinol Invest. 2020;43(9):1337–42.
29.
Saboori AM, Rose NR, Burek CL. Iodination of human thyroglobulin (Tg) alters its immunoreactivity. II. Fine specificity of a monoclonal antibody that recognizes iodinated Tg. Clin Exp Immunol. 1998;113(2):303–8.
30.
Dai YD, Rao VP, Carayanniotis G. Enhanced iodination of thyroglobulin facilitates processing and presentation of a cryptic pathogenic peptide. J Immunol. 2002;168(11):5907–11.PubMedCrossRef
31.
32.
Saboori AM, Rose NR, Bresler HS, Vladut-Talor M, Burek CL. Iodination of human thyroglobulin (Tg) alters its immunoreactivity. I. Iodination alters multiple epitopes of human Tg. Clin Exp Immunol. 1998;113(2):297–302.
33.
Rasooly L, Rose NR, Saboori AM, Ladenson PW, Burek CL. Iodine is essential for human T cell recognition of human thyroglobulin. Autoimmunity. 1998;27(4):213–9.PubMedCrossRef
34.
Weetman AP, McGregor AM. Autoimmune thyroid disease: further developments in our understanding. Endocr Rev. 1994;15(6):788–830.PubMed
35.
Sercarz EE, Lehmann PV, Ametani A, Benichou G, Miller A, Moudgil K. Dominance and crypticity of T cell antigenic determinants. Annu Rev Immunol. 1993;11:729–66.PubMedCrossRef
36.
Carayanniotis G. The cryptic self in thyroid autoimmunity: The paradigm of thyroglobulin. Autoimmunity. 2003;36(6–7):423–8.PubMedCrossRef
37.
Latrofa F, Fiore E, Rago T, Antonangeli L, Montanelli L, Ricci D, et al. Iodine contributes to thyroid autoimmunity in humans by unmasking a cryptic epitope on thyroglobulin. J Clin Endocrinol Metab. 2013;98(11):E1768–74.PubMedCrossRef
38.
Laurberg P, Pedersen KM, Hreidarsson A, Sigfusson N, Iversen E, Knudsen PR. Iodine intake and the pattern of thyroid disorders: a comparative epidemiological study of thyroid abnormalities in the elderly in Iceland and in Jutland. Denmark J Clin Endocrinol Metab. 1998;83(3):765–9.PubMedCrossRef
39.
Suzuki H, Higuchi T, Sawa K, Ohtaki S, Horiuchi Y. “Endemic coast goitre” in Hokkaido. Japan Acta Endocrinol (Copenh). 1965;50(2):161–76.
40.
41.
Markou K, Georgopoulos N, Kyriazopoulou V, Vagenakis AG. Iodine-induced hypothyroidism. Thyroid. 2001;11(5):501–10.PubMedCrossRef
42.
Laurberg P, Bülow Pedersen I, Knudsen N, Ovesen L, Andersen S. Environmental iodine intake affects the type of nonmalignant thyroid disease. Thyroid. 2001;11(5):457–69.PubMedCrossRef
43.
Stanbury JB, Ermans AE, Bourdoux P, Todd C, Oken E, Tonglet R, Vidor G, Braverman LE, Medeiros-Neto G. Iodine-induced hyperthyroidism: occurrence and epidemiology. Thyroid. 1998;8(1):83–100.PubMedCrossRef
44.
Petersen M, Knudsen N, Carlé A, Andersen S, Jørgensen T, Perrild H, et al. Thyrotoxicosis after iodine fortification. a 21-year Danish population-based study. Clin Endocrinol. 2018;89(3):360–6.
45.
46.
Bürgi H, Kohler M, Morselli B. Thyrotoxicosis incidence in Switzerland and benefit of improved iodine supply. Lancet. 1998;352(9133):1034.PubMedCrossRef
47.
Bülow Pedersen I, Laurberg P, Knudsen N, Jørgensen T, Perrild H, Ovesen L, et al. Increase in incidence of hyperthyroidism predominantly occurs in young people after iodine fortification of salt in Denmark. J Clin Endocrinol Metab. 2006;91(10):3830–4.PubMedCrossRef
48.
Vejbjerg P, Knudsen N, Perrild H, Carlé A, Laurberg P, Pedersen IB, et al. Effect of a mandatory iodization program on thyroid gland volume based on individuals’ age, gender, and preceding severity of dietary iodine deficiency: a prospective, population-based study. J Clin Endocrinol Metab. 2007;92(4):1397–401.PubMedCrossRef
49.
Krohn K, Führer D, Bayer Y, Eszlinger M, Brauer V, Neumann S, et al. Molecular pathogenesis of euthyroid and toxic multinodular goiter. Endocr Rev. 2005;26(4):504–24.PubMedCrossRef
50.
Kasagi K, Iwata M, Misaki T, Konishi J. Effect of iodine restriction on thyroid function in patients with primary hypothyroidism. Thyroid. 2003;13(6):561–7.PubMedCrossRef
51.
Yoon SJ, Choi SRKD, et al. The effect of iodine restriction on thyroid function in patients with hypothyroidism due to Hashimoto’s thyroiditis. Yonsei Med J. 2003;44(2):227–35.PubMedCrossRef
52.
Yoshida H, Amino N, Yagawa K, Uemura K, Satoh M, Miyai K, et al. Association of serum antithyroid antibodies with lymphocytic infiltration of the thyroid gland: studies of seventy autopsied cases. J Clin Endocrinol Metab. 1978;46(6):859–62.PubMedCrossRef
53.
Arai T, Kurashima C, Utsuyama M, Sawabe M, Ito H. Measurement of anti-thyroglobulin and anti-thyroid peroxidase antibodies using highly sensitive radioimmunoassay: an effective method for detecting asymptomatic focal lymphocytic thyroiditis in the elderly. Endocr J. 2000;47(5):575–82.PubMedCrossRef
54.
Benvenga S, Trimarchi F. Changed presentation of Hashimoto’s thyroiditis in North-Eastern Sicily and Calabria (Southern Italy) based on a 31-year experience. Thyroid. 2008;18(4):429–41.PubMedCrossRef
55.
Pedersen IB, Laurberg P. Chapter 60 - Antibodies to thyroid peroxidase and thyroglobulin in iodine deficiencies. In Preedy VR, Burrow GN, Watson RR eds. Comprehensive Handbook of Iodine, Academic Press, 2009, Pages 575–85.
56.
Fenzi GF, Giani C, Ceccarelli P, Bartalena L, Macchia E, Aghini-Lombardi F, et al. Role of autoimmune and familial factors in goiter prevalence. Studies performed in a moderately endemic area. J Endocrinol Invest. 1986;9(2):161–4.PubMedCrossRef
57.
Loviselli A, Velluzzi F, Mossa P, Cambosu MA, Secci G, Atzeni F, et al. Sardinian Schoolchildren Study Group. The Sardinian Autoimmunity Study: 3. Studies on circulating antithyroid antibodies in Sardinian schoolchildren: relationship to goiter prevalence and thyroid function. Thyroid. 2001;11(9):849–57.
58.
Sun J, Teng D, Li C, Peng S, Mao J, Wang W, et al. Association between iodine intake and thyroid autoantibodies: a cross-sectional study of 7073 early pregnant women in an iodine-adequate region. J Endocrinol Invest. 2020;43(1):43–51.PubMedCrossRef
59.
Levie D, Derakhshan A, Shu H, Broeren MAC, De Poortere RA. The association of maternal iodine status in early pregnancy with thyroid function in the SELMA study. Thyroid. 2019;29(11):1660–68.
60.
Harach HR, Ceballos GA. Thyroid cancer, thyroiditis and dietary iodine: a review based on the Salta. Argentina model Endocr Pathol. 2008;19(4):209–20.PubMedCrossRef
61.
Kahaly GJ, Dienes HP, Beyer J, Hommel G. Iodide induces thyroid autoimmunity in patients with endemic goitre: a randomised, double-blind, placebo-controlled trial. Eur J Endocrinol. 1998;139(3):290–7.PubMedCrossRef
62.
Zimmermann MB, Moretti D, Chaouki N, Torresani T. Introduction of iodized salt to severely iodine-deficient children does not provoke thyroid autoimmunity: a one-year prospective trial in northern Morocco. Thyroid. 2003;13(2):199–203.PubMedCrossRef
63.
Mazziotti G, Premawardhana LD, Parkes AB, Adams H, Smyth PP, Smith DF, et al. Evolution of thyroid autoimmunity during iodine prophylaxis—the Sri Lankan experience. Eur J Endocrinol. 2003;149(2):103–10.PubMedCrossRef
64.
Giassa Τ, Mamali I, Gaki Ε, Kaltsas G, Kouraklis G, Markou ΚΒ, et al. Iodine intake and chronic autoimmune thyroiditis: a comparative study between coastal and mainland regions in Greece. Hormones (Athens). 2018;17(4):565–71.CrossRef
65.
Pedersen IB, Knudsen N, Carlé A, Vejbjerg P, Jørgensen T, Perrild H, et al. A cautious iodization programme bringing iodine intake to a low recommended level is associated with an increase in the prevalence of thyroid autoantibodies in the population. Clin Endocrinol (Oxf). 2011;75(1):120–6.CrossRef
66.
Aghini Lombardi F, Fiore E, Tonacchera M, Antonangeli L, Rago T, Frigeri M, et al. The effect of voluntary iodine prophylaxis in a small rural community : the pescopagano survey 15 years later. J Clin Endocrinol Metab. 2013;98:1031–9.PubMedCrossRef
67.
Hong A, Stokes B, Otahal P, Owens D, Burgess JR. Temporal trends in thyroid-stimulating hormone (TSH) and thyroid peroxidase antibody (ATPO) testing across two phases of iodine fortification in Tasmania (1995–2013). Clin Endocrinol (Oxf). 2017;87(4):386–93.CrossRef
68.
Khattak RM, Ittermann T, Nauck M, Below H, Völzke H. Monitoring the prevalence of thyroid disorders in the adult population of Northeast Germany. Popul Health Metr. 2016;14:39 e-collection.
69.
Wan S, Jin B, Ren B, Qu M, Wu H, Liu L, et al. The relationship between high iodine consumption and levels of autoimmune thyroiditis-related biomarkers in a Chinese population: a meta-analysis. Biol Trace Elem Res. 2020;196(2):410–8.PubMedCrossRef
70.
Bournaud C, Orgiazzi JJ. Iodine excess and thyroid autoimmunity. J Endocrinol Invest. 2003;26(2 Suppl):49–56.PubMed
71.
Wang B, He W, Li Q, et al. U-shaped relationship between iodine status and thyroid autoimmunity risk in adults. Eur J Endocrinol. 2019;181(3):255–266.
72.
Teng X, Shan Z, Chen Y, et al. More than adequate iodine intake may increase subclinical hypothyroidism and autoimmune thyroiditis: a cross-sectional study based on two Chinese communities with different iodine intake levels. Eur J Endocrinol. 2011;164(6):943–950.
73.
Miranda DM, Massom JN, Catarino RM, Santos RT, Toyoda SS, Marone MM, et al. Impact of nutritional iodine optimization on rates of thyroid hypoechogenicity and autoimmune thyroiditis: a cross-sectional, comparative study. Thyroid. 2015;25(1):118–24.PubMedCrossRef
74.
Teng D, Yang W, Shi X, Li Y, Ba J, Chen B, et al. An inverse relationship between iodine intake and thyroid antibodies: a national cross-sectional survey in Mainland China. Thyroid. 2020;30(11):1656–65.CrossRef
75.
Duntas LH. The catalytic role of iodine excess in loss of homeostasis in autoimmune thyroiditis. Curr Opin Endocrinol Diabetes Obes. 2018;25(5):347–35.
76.
Li Y, Teng D, Shan Z, et al. Antithyroperoxidase and antithyroglobulin antibodies in a five-year follow-up survey of populations with different iodine intakes. J Clin Endocrinol Metab. 2008;93:1751–7.PubMedCrossRef
77.
Petersen M, Bülow Pedersen I, Knudsen N, Andersen S, Jørgensen T, Perrild H, et al. Changes in subtypes of overt thyrotoxicosis and hypothyroidism following iodine fortification. Clin Endocrinol (Oxf). 2019;91(5):652–9.CrossRef
78.
79.
Biondi B, Cooper DS. The clinical significance of subclinical thyroid dysfunction. Endocr Rev. 2008;29(1):76–131.PubMedCrossRef
80.
Rago T, Chiovato L, Grasso L, Pinchera A, Vitti P. Thyroid ultrasonography as a tool for detecting thyroid autoimmune diseases and predicting thyroid dysfunction in apparently healthy subjects. J Endocrinol Invest. 2001;24(10):763–769.
81.
Cantisani TRV, Chiovato FIL, Durante RGC, Spiezia AFS. Thyroid ultrasonography reporting : consensus of Italian Thyroid Association (AIT), Italian Society of Endocrinology (SIE), Italian Society of Ultrasonography in Medicine and Biology (SIUMB) and Ultrasound Chapter of Italian Society of Medical Radiology (SIRM). J Endocrinol Invest. 2018;41(12):1435–43.PubMedCrossRef
82.
83.
84.
Rose NR. Prediction and prevention of autoimmune disease in the 21st century: a review and preview. Am J Epidemiol. 2016;183(5):403–6.PubMedCrossRef
85.
Rook GAW. Hygiene hypothesis and autoimmune diseases. Clin Rev Allergy Immunol. 2012;42(1):5–15.
86.
Kondrashova A, Viskari H, Haapala A, et al. Serological Evidence of thyroid autoimmunity among schoolchildren in two different socioeconomic environments. J Clin Endocrinol Metab. 2008;93:729–34.PubMedCrossRef
Metadata
Title
Iodoprophylaxis and thyroid autoimmunity: an update
Authors
Claudia Teti
Marta Panciroli
Elena Nazzari
Giampaola Pesce
Stefano Mariotti
Antonella Olivieri
Marcello Bagnasco
Publication date
01-04-2021
Publisher
Springer US
Published in
Immunologic Research / Issue 2/2021
Print ISSN: 0257-277X
Electronic ISSN: 1559-0755
DOI
https://doi.org/10.1007/s12026-021-09192-6

Other articles of this Issue 2/2021

Immunologic Research 2/2021 Go to the issue

Brief Report

Postural orthostatic tachycardia syndrome (POTS) and other autonomic disorders after COVID-19 infection: a case series of 20 patients

Original Article

Exploring genetic defects in adults who were clinically diagnosed as severe combined immune deficiency during infancy

Interpretive Synthesis Review Article

MyD88 and beyond: a perspective on MyD88-targeted therapeutic approach for modulation of host immunity

Original Article

Association of interleukin-12B rs6887695 with susceptibility to allergic rhinitis

Original Article

Native and IgE-primed rat peritoneal mast cells exert pro-inflammatory activity and migrate in response to yeast zymosan upon Dectin-1 engagement

Original Article

Potential role of viral infection and B cells as a linker between innate and adaptive immune response in systemic lupus erythematosus