Iodine-induced thyroid dysfunction
- Martin I Surks, MD
Martin I Surks, MD
- Professor of Medicine and Pathology
- Albert Einstein College of Medicine
The central role of iodide in thyroid physiology has been known for many years. The four iodine atoms of l-thyroxine (T4) constitute 65 percent of its weight; the three iodine atoms of triiodothyronine (T3) constitute 59 percent of its weight. Iodine is a trace element in the crust of the earth and its distribution is quite variable. Many areas, particularly inland and mountainous regions, have minimal iodine while others, often coastal regions, have sufficient or even excessive iodine.
Both iodine deficiency and excess can cause thyroid dysfunction. This topic will review the mechanisms by which normal subjects adapt to excess iodine and the mechanisms of iodine-induced thyroid disease. Iodine deficiency disorders and the therapeutic use of iodine in patients with hyperthyroidism are discussed separately. (See "Iodine deficiency disorders" and "Iodine in the treatment of hyperthyroidism".)
SOURCES OF IODINE
Iodide is essential for thyroid hormone synthesis. (See "Thyroid hormone synthesis and physiology".)
Iodine can be obtained by consumption of foods that contain it or to which it is added. Dietary iodine is absorbed as iodide and rapidly distributed in the extracellular fluid, which also contains iodide released from the thyroid and by extrathyroidal deiodination of the iodothyronines. Iodide leaves this pool by transport into the thyroid and excretion into the urine. The recommended minimum daily intake of iodine is 150 mcg for nonpregnant adults, 220 mcg for pregnant women, 290 mcg for lactating women, and 90 to 120 mcg/day for children aged 1 to 13 years . The average intake in the United States is about 150 to 200 mcg/day . In the United States, iodized salt contains 76 mcg of iodine/g. In many countries, however, it contains less, and in some countries iodized salt is not available. As a result, iodine deficiency is the most common cause of goiter, hypothyroidism, and mental deficiency worldwide. (See "Iodine deficiency disorders".)
Sources of excess iodine include over-the-counter and prescription medications that may be ingested or applied to the skin or vaginal mucosa, radiographic contrast agents, and dietary supplements (kelp, seaweed) (table 1). In the context of a person's usual dietary iodine intake, the amount of iodine in many of these substances is very large. As an example, a patient undergoing vascular imaging may receive several thousand mg of organic iodide. Those substances that contain organic iodide are partially deiodinated to form inorganic iodide, the form that has thyroidal actions. Some of these substances that are deiodinated to form inorganic iodine, such as amiodarone, are stored in fat and may provide excess iodide for months after the last dose is administered.
- Food and Nutrition Board Institute of Medicine. Dietary reference intake. Washington, DC: National Academy Press, 2001.
- Hollowell JG, Staehling NW, Hannon WH, et al. Iodine nutrition in the United States. Trends and public health implications: iodine excretion data from National Health and Nutrition Examination Surveys I and III (1971-1974 and 1988-1994). J Clin Endocrinol Metab 1998; 83:3401.
- WOLFF J, CHAIKOFF IL. Plasma inorganic iodide as a homeostatic regulator of thyroid function. J Biol Chem 1948; 174:555.
- WOLFF J, CHAIKOFF IL. The temporary nature of the inhibitory action of excess iodine on organic iodine synthesis in the normal thyroid. Endocrinology 1949; 45:504.
- BRAVERMAN LE, INGBAR SH. CHANGES IN THYROIDAL FUNCTION DURING ADAPTATION TO LARGE DOSES OF IODIDE. J Clin Invest 1963; 42:1216.
- GALTON VA, PITT-RIVERS R. The effect of excessive iodine on the thyroid of the rat. Endocrinology 1959; 64:835.
- NAGATAKI S, INGBAR SH. RELATION BETWEEN QUALITATIVE AND QUANTITATIVE ALTERATIONS IN THYROID HORMONE SYNTHESIS INDUCED BY VARYING DOSES OF IODIDE. Endocrinology 1964; 74:731.
- Dai G, Levy O, Carrasco N. Cloning and characterization of the thyroid iodide transporter. Nature 1996; 379:458.
- Eng PH, Cardona GR, Fang SL, et al. Escape from the acute Wolff-Chaikoff effect is associated with a decrease in thyroid sodium/iodide symporter messenger ribonucleic acid and protein. Endocrinology 1999; 140:3404.
- Saberi M, Utiger RD. Augmentation of thyrotropin responses to thyrotropin-releasing hormone following small decreases in serum thyroid hormone concentrations. J Clin Endocrinol Metab 1975; 40:435.
- Markou KB, Paraskevopoulou P, Karaiskos KS, et al. Hyperthyrotropinemia during iodide administration in normal children and in children born with neonatal transient hypothyroidism. J Clin Endocrinol Metab 2003; 88:617.
- Braverman LE. Iodine and the thyroid: 33 years of study. Thyroid 1994; 4:351.
- Gartner W, Weissel M. Do iodine-containing contrast media induce clinically relevant changes in thyroid function parameters of euthyroid patients within the first week? Thyroid 2004; 14:521.
- Ordene KW, Pan C, Barzel US, Surks MI. Variable thyrotropin response to thyrotropin-releasing hormone after small decreases in plasma thyroid hormone concentrations in patients of advanced age. Metabolism 1983; 32:881.
- Martins MC, Lima N, Knobel M, Medeiros-Neto G. Natural course of iodine-induced thyrotoxicosis (Jodbasedow) in endemic goiter area: a 5 year follow-up. J Endocrinol Invest 1989; 12:239.
- Roti E, Uberti ED. Iodine excess and hyperthyroidism. Thyroid 2001; 11:493.
- Stanbury JB, Ermans AE, Bourdoux P, et al. Iodine-induced hyperthyroidism: occurrence and epidemiology. Thyroid 1998; 8:83.
- Skare S, Frey HM. Iodine induced thyrotoxicosis in apparently normal thyroid glands. Acta Endocrinol (Copenh) 1980; 94:332.
- Hintze G, Blombach O, Fink H, et al. Risk of iodine-induced thyrotoxicosis after coronary angiography: an investigation in 788 unselected subjects. Eur J Endocrinol 1999; 140:264.
- Bürgi H. Iodine excess. Best Pract Res Clin Endocrinol Metab 2010; 24:107.
- Fradkin JE, Wolff J. Iodide-induced thyrotoxicosis. Medicine (Baltimore) 1983; 62:1.
- Rhee CM, Bhan I, Alexander EK, Brunelli SM. Association between iodinated contrast media exposure and incident hyperthyroidism and hypothyroidism. Arch Intern Med 2012; 172:153.
- Lee SY, Chang DL, He X, et al. Urinary iodine excretion and serum thyroid function in adults after iodinated contrast administration. Thyroid 2015; 25:471.
- Conn JJ, Sebastian MJ, Deam D, et al. A prospective study of the effect of nonionic contrast media on thyroid function. Thyroid 1996; 6:107.
- Fricke E, Fricke H, Esdorn E, et al. Scintigraphy for risk stratification of iodine-induced thyrotoxicosis in patients receiving contrast agent for coronary angiography: a prospective study of patients with low thyrotropin. J Clin Endocrinol Metab 2004; 89:6092.
- Burman KD, Wartofsky L. Iodine effects on the thyroid gland: biochemical and clinical aspects. Rev Endocr Metab Disord 2000; 1:19.
- Bahn Chair RS, Burch HB, Cooper DS, et al. Hyperthyroidism and other causes of thyrotoxicosis: management guidelines of the American Thyroid Association and American Association of Clinical Endocrinologists. Thyroid 2011; 21:593.
- Martin FI, Deam DR. Hyperthyroidism in elderly hospitalised patients. Clinical features and treatment outcomes. Med J Aust 1996; 164:200.
- Muller R, Siggelkow H, Emrich D, et al. Prophylactic application of thyrostatic drugs during excessive iodine exposure in euthyroid patients with thyroid autonomy: a randomized study. Eur J Endocrinol 1996; 134:337.
- Lawrence JE, Lamm SH, Braverman LE. The use of perchlorate for the prevention of thyrotoxicosis in patients given iodine rich contrast agents. J Endocrinol Invest 1999; 22:405.
- Roti E, Minelli R, Gardini E, et al. Impaired intrathyroidal iodine organification and iodine-induced hypothyroidism in euthyroid women with a previous episode of postpartum thyroiditis. J Clin Endocrinol Metab 1991; 73:958.
- Kämpe O, Jansson R, Karlsson FA. Effects of L-thyroxine and iodide on the development of autoimmune postpartum thyroiditis. J Clin Endocrinol Metab 1990; 70:1014.
- Clark OH, Cavalieri RR, Moser C, Ingbar SH. Iodide-induced hypothyroidism in patients after thyroid resection. Eur J Clin Invest 1990; 20:573.
- Costigan DC, Holland FJ, Daneman D, et al. Amiodarone therapy effects on childhood thyroid function. Pediatrics 1986; 77:703.
- Alexandrides T, Georgopoulos N, Yarmenitis S, Vagenakis AG. Increased sensitivity to the inhibitory effect of excess iodide on thyroid function in patients with beta-thalassemia major and iron overload and the subsequent development of hypothyroidism. Eur J Endocrinol 2000; 143:319.
- Markou K, Georgopoulos N, Kyriazopoulou V, Vagenakis AG. Iodine-Induced hypothyroidism. Thyroid 2001; 11:501.
- Roti E, Gnudi A, Braverman LE. The placental transport, synthesis and metabolism of hormones and drugs which affect thyroid function. Endocr Rev 1983; 4:131.
- Novaes Júnior M, Biancalana MM, Garcia SA, et al. Elevation of cord blood TSH concentration in newborn infants of mothers exposed to acute povidone iodine during delivery. J Endocrinol Invest 1994; 17:805.
- Smerdely P, Lim A, Boyages SC, et al. Topical iodine-containing antiseptics and neonatal hypothyroidism in very-low-birthweight infants. Lancet 1989; 2:661.
- AvRuskin TW, Greenfield E, Prasad V, et al. Decreased T3 and T4 levels following topical application of povidone-iodine in premature neonates. J Pediatr Endocrinol 1994; 7:205.
- Koga Y, Sano H, Kikukawa Y, et al. Effect on neonatal thyroid function of povidone-iodine used on mothers during perinatal period. J Obstet Gynaecol (Tokyo 1995) 1995; 21:581.
- l'Allemand D, Grüters A, Beyer P, Weber B. Iodine in contrast agents and skin disinfectants is the major cause for hypothyroidism in premature infants during intensive care. Horm Res 1987; 28:42.
- Chanoine JP, Boulvain M, Bourdoux P, et al. Increased recall rate at screening for congenital hypothyroidism in breast fed infants born to iodine overloaded mothers. Arch Dis Child 1988; 63:1207.
- Teng W, Shan Z, Teng X, et al. Effect of iodine intake on thyroid diseases in China. N Engl J Med 2006; 354:2783.
- Pedersen IB, Laurberg P, Knudsen N, et al. An increased incidence of overt hypothyroidism after iodine fortification of salt in Denmark: a prospective population study. J Clin Endocrinol Metab 2007; 92:3122.
- Sato K, Okamura K, Hirata T, et al. Immunological and chemical types of reversible hypothyroidism; clinical characteristics and long-term prognosis. Clin Endocrinol (Oxf) 1996; 45:519.
- Sato K, Ohmori T, Shiratori K, et al. Povidone iodine-induced overt hypothyroidism in a patient with prolonged habitual gargling: urinary excretion of iodine after gargling in normal subjects. Intern Med 2007; 46:391.
- SOURCES OF IODINE
- NORMAL ADAPTATION TO IODIDE INTAKE
- Follicular cell autoregulation
- Iodide effects on thyroid hormone secretion
- IODINE-INDUCED THYROID DISEASE
- Iodine-induced hyperthyroidism
- - Diagnosis
- - Evaluation for underlying thyroid disease
- - Management
- - Prevention in older adults
- Iodide-induced hypothyroidism
- - Diagnosis and management
- SUMMARY AND RECOMMENDATIONS