Get 20M+ Full-Text Papers For Less Than $1.50/day. Start a 14-Day Trial for You and Your Team.

Learn More →

Iodine-Induced Thyroid Dysfunction: Comment on “Association Between Iodinated Contrast Media Exposure and Incident Hyperthyroidism and Hypothyroidism”

Iodine-Induced Thyroid Dysfunction: Comment on “Association Between Iodinated Contrast Media... In this issue of the Archives, Rhee et al1 report the findings of a nested case-control study examining associations between exposure to iodinated radiologic contrast media and development of incident thyroid dysfunction. They describe significant associations between contrast exposure and the development of hyperthyroidism. While no overall association exists between contrast exposure and all forms of hypothyroidism, an association was noted when cases were restricted to those with overt hypothyroidism. There was also an association between iodinated contrast media and incident hypothyroidism when the analysis was restricted to cases that occurred within 180 days of exposure, likely related to the transitory nature of iodine-induced hypothyroidism. These data represent an important contribution to our knowledge about a clinically relevant and understudied area. Strengths of the study include the large number of cases and controls, rigorous case definitions, and adjustment for multiple potential confounders. The study was limited by its retrospective design, by variability in intervals between thyroid function testing, and by the limited availability of peripheral thyroid hormone measurements. The study was conducted in Boston, Massachusetts, which is considered an iodine-sufficient area, and results may not be generalizable to parts of the world with insufficient dietary iodine intake. In the 1940s, Wolff and Chaikoff2 reported a transient inhibition of thyroid hormone synthesis lasting approximately 24 hours (the acute Wolff-Chaikoff effect) in rats treated with large amounts of intraperitoneal iodide. With continued administration of iodide, normal thyroid hormone synthesis resumed (the escape from the acute Wolff-Chaikoff effect). Stanley3 described similar findings in humans in 1949. Although it remains imperfectly understood, the mechanism responsible for the acute Wolff-Chaikoff effect may be the generation of intrathyroidal iodolactones or iodolipids that inhibit thyroid peroxidase activity.4 Escape from the acute Wolff-Chaikoff effect likely occurs due to an iodine-induced inhibition of synthesis of the sodium-iodide symporter that is responsible for the transport of iodine into thyroid follicular cells.5 The reduction in sodium-iodine symporter expression leads to a reduction in intrathyroidal iodine and a decrease in the iodine-induced inhibitors of hormone synthesis. Iodine-induced hyperthyroidism, or the jödbasedow phenomenon, was first described by Coindet6 in 1821. The most commonly reported risk factor for iodine-induced hyperthyroidism, although it could not be well ascertained in the study of Rhee et al,1 is a history of nontoxic diffuse or nodular goiter that occurs most frequently in areas of iodine deficiency. In fact, until 1972, when iodine-induced hyperthyroidism was reported in a group of patients with goiter in Boston, it was thought that iodine-induced hyperthyroidism could occur only in iodine-deficient regions.7 Iodine-induced hyperthyroidism has also been described in individuals with mild Graves disease. Although there had been scattered previous reports of the occurrence of iodine-induced hyperthyroidism in individuals without known underlying thyroid pathology, the study by Rhee et al1 suggests that this may occur more commonly than was previously recognized. Iodine-induced hypothyroidism is believed to result from a failure to escape from the acute Wolff-Chaikoff effect. Euthyroid individuals with some underlying compromise of thyroid function, such as a history of partial thyroidectomy, a history of treated Graves disease, or a history of postpartum or subacute thyroiditis, are thought to be at risk. Although it could not be definitively demonstrated by Rhee et al, the presence of Hashimoto thyroiditis, as indicated by the presence of detectable serum antibodies to thyroperoxidase, has previously been identified as an important risk factor.4 Many patients with the above risk factors for the development of iodine-induced hypothyroidism have underlying defects of thyroid hormone synthesis, as detected by a positive perchlorate discharge test.8 How should these data inform clinical practice? First, the ALARA (“as low as reasonably achievable”) principle should always be exercised in determining the need for radiation exposure, as potential risks of iodinated contrast studies extend beyond the thyroidal risk from iodine exposure. Second, particular care should be taken in patients at high risk to develop thyroid dysfunction after the administration of iodinated contrast medium. Palpation of the neck for the detection of goiter is reasonable before ordering contrast studies, although nodular goiter may occasionally be missed even with a careful physical examination. Although not clearly demonstrated by Rhee et al, patients with detectable serum antibodies to thyroperoxidase are likely at increased risk for iodine-induced hypothyroidism and should have thyroid function monitored following exposure to iodinated media. Third, Rhee et al have demonstrated that a relatively large proportion of individuals who developed iodine-induced thyroid dysfunction were not known to have underlying risk factors. Therefore, patients who may be particularly unable to tolerate thyroid dysfunction, such as those with underlying unstable cardiovascular disease, are also good candidates for monitoring of thyroid function after iodine exposure. The short-term use of medications to prevent iodine-induced hyperthyroidism has been proposed in Europe for elderly patients with known thyroid autonomy. Either methimazole, which blocks thyroid hormone synthesis, or perchlorate, a competitive inhibitor of the sodium-iodide symporter, can be used.9 Either drug can be started 1 day prior to iodinated contrast exposure and continued for a total of 14 days. However, pharmaceutical-grade perchlorate is not marketed in the United States, and even short-term use of methimazole confers some risk. Until we are better able to define risk factors for iodine-induced hyperthyroidism, prophylactic antithyroid drug should not be routinely used. Although the acute Wolff-Chaikoff effect was first described more than 60 years ago, its mechanism still needs to be fully elucidated. Importantly, prospective studies are needed to better define risk factors for iodinated contrast-induced thyroid dysfunction in individual patients. Finally, based on studies of iodine-induced thyroid dysfunction associated with amiodarone use,10 hyperthyroidism following administration of iodinated contrast-medium hyperthyroidism is likely to be more prevalent in iodine-deficient regions, and hypothyroidism in iodine-sufficient areas. A better understanding of this geographic variation will also be important for developing region-specific clinical recommendations. Back to top Article Information Correspondence: Dr Pearce, Section of Endocrinology, Diabetes, and Nutrition, Boston University School of Medicine, 88 E Newton St, Evans 201, Boston, MA 02118 (elizabeth.pearce@bmc.org). Financial Disclosure: Dr Pearce reports receiving compensation from DuPont for testimony for the defense regarding the development of hypothyroidism after exposure to radioactive iodine released by the Hanford Nuclear Reservation, Hanford, Washington. References 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(2):153-159Google ScholarCrossref 2. Wolff J, Chaikoff IL. Plasma inorganic iodide as a homeostatic regulator of thyroid function. J Biol Chem. 1948;174(2):555-56418865621PubMedGoogle Scholar 3. Stanley MM. The direct estimation of the rate of thyroid hormone formation in man: the effect of the iodide ion on thyroid iodine utilization. J Clin Endocrinol Metab. 1949;9(10):941-95418142428PubMedGoogle ScholarCrossref 4. Markou K, Georgopoulos N, Kyriazopoulou V, Vagenakis AG. Iodine-Induced hypothyroidism. Thyroid. 2001;11(5):501-51011396709PubMedGoogle ScholarCrossref 5. Eng PHK, Cardona GR, Fang S-L, 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(8):3404-341010433193PubMedGoogle ScholarCrossref 6. Coindet JF. Nouvelles recherches sur les effets de l’iode et sur les précautions à suivre dans le traitement du goitre par ce nouveau remède. Bibl Univ Sci Belles Lettres Arts. 1821;16:140-152Google Scholar 7. Vagenakis AG, Wang CA, Burger A, Maloof F, Braverman LE, Ingbar SH. Iodide-induced thyrotoxicosis in Boston. N Engl J Med. 1972;287(11):523-5275050425PubMedGoogle ScholarCrossref 8. Braverman LE, Vagenakis AG, Wang CA, Maloof F, Ingbar SH. Studies on the pathogenesis of iodide myxedema. Trans Assoc Am Physicians. 1971;84:130-1384364605PubMedGoogle Scholar 9. Nolte MR, Muller R, Siggelkow H, Emrich D, Hufner M. Prophylactic application of thyrostatic drugs during excessive iodine exposure in euthyroid patients with thyroid autonomy: a randomized study. Eur J Endocrinol. 1996;134(3):337-3418616532PubMedGoogle ScholarCrossref 10. Martino E, Safran M, Aghini-Lombardi F, et al. Environmental iodine intake and thyroid dysfunction during chronic amiodarone therapy. Ann Intern Med. 1984;101(1):28-346428291PubMedGoogle Scholar http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Archives of Internal Medicine American Medical Association

Iodine-Induced Thyroid Dysfunction: Comment on “Association Between Iodinated Contrast Media Exposure and Incident Hyperthyroidism and Hypothyroidism”

Archives of Internal Medicine , Volume 172 (2) – Jan 23, 2012

Loading next page...
 
/lp/american-medical-association/iodine-induced-thyroid-dysfunction-comment-on-association-between-LG0D079dqq
Publisher
American Medical Association
Copyright
Copyright © 2012 American Medical Association. All Rights Reserved.
ISSN
0003-9926
eISSN
1538-3679
DOI
10.1001/archinternmed.2011.1396
Publisher site
See Article on Publisher Site

Abstract

In this issue of the Archives, Rhee et al1 report the findings of a nested case-control study examining associations between exposure to iodinated radiologic contrast media and development of incident thyroid dysfunction. They describe significant associations between contrast exposure and the development of hyperthyroidism. While no overall association exists between contrast exposure and all forms of hypothyroidism, an association was noted when cases were restricted to those with overt hypothyroidism. There was also an association between iodinated contrast media and incident hypothyroidism when the analysis was restricted to cases that occurred within 180 days of exposure, likely related to the transitory nature of iodine-induced hypothyroidism. These data represent an important contribution to our knowledge about a clinically relevant and understudied area. Strengths of the study include the large number of cases and controls, rigorous case definitions, and adjustment for multiple potential confounders. The study was limited by its retrospective design, by variability in intervals between thyroid function testing, and by the limited availability of peripheral thyroid hormone measurements. The study was conducted in Boston, Massachusetts, which is considered an iodine-sufficient area, and results may not be generalizable to parts of the world with insufficient dietary iodine intake. In the 1940s, Wolff and Chaikoff2 reported a transient inhibition of thyroid hormone synthesis lasting approximately 24 hours (the acute Wolff-Chaikoff effect) in rats treated with large amounts of intraperitoneal iodide. With continued administration of iodide, normal thyroid hormone synthesis resumed (the escape from the acute Wolff-Chaikoff effect). Stanley3 described similar findings in humans in 1949. Although it remains imperfectly understood, the mechanism responsible for the acute Wolff-Chaikoff effect may be the generation of intrathyroidal iodolactones or iodolipids that inhibit thyroid peroxidase activity.4 Escape from the acute Wolff-Chaikoff effect likely occurs due to an iodine-induced inhibition of synthesis of the sodium-iodide symporter that is responsible for the transport of iodine into thyroid follicular cells.5 The reduction in sodium-iodine symporter expression leads to a reduction in intrathyroidal iodine and a decrease in the iodine-induced inhibitors of hormone synthesis. Iodine-induced hyperthyroidism, or the jödbasedow phenomenon, was first described by Coindet6 in 1821. The most commonly reported risk factor for iodine-induced hyperthyroidism, although it could not be well ascertained in the study of Rhee et al,1 is a history of nontoxic diffuse or nodular goiter that occurs most frequently in areas of iodine deficiency. In fact, until 1972, when iodine-induced hyperthyroidism was reported in a group of patients with goiter in Boston, it was thought that iodine-induced hyperthyroidism could occur only in iodine-deficient regions.7 Iodine-induced hyperthyroidism has also been described in individuals with mild Graves disease. Although there had been scattered previous reports of the occurrence of iodine-induced hyperthyroidism in individuals without known underlying thyroid pathology, the study by Rhee et al1 suggests that this may occur more commonly than was previously recognized. Iodine-induced hypothyroidism is believed to result from a failure to escape from the acute Wolff-Chaikoff effect. Euthyroid individuals with some underlying compromise of thyroid function, such as a history of partial thyroidectomy, a history of treated Graves disease, or a history of postpartum or subacute thyroiditis, are thought to be at risk. Although it could not be definitively demonstrated by Rhee et al, the presence of Hashimoto thyroiditis, as indicated by the presence of detectable serum antibodies to thyroperoxidase, has previously been identified as an important risk factor.4 Many patients with the above risk factors for the development of iodine-induced hypothyroidism have underlying defects of thyroid hormone synthesis, as detected by a positive perchlorate discharge test.8 How should these data inform clinical practice? First, the ALARA (“as low as reasonably achievable”) principle should always be exercised in determining the need for radiation exposure, as potential risks of iodinated contrast studies extend beyond the thyroidal risk from iodine exposure. Second, particular care should be taken in patients at high risk to develop thyroid dysfunction after the administration of iodinated contrast medium. Palpation of the neck for the detection of goiter is reasonable before ordering contrast studies, although nodular goiter may occasionally be missed even with a careful physical examination. Although not clearly demonstrated by Rhee et al, patients with detectable serum antibodies to thyroperoxidase are likely at increased risk for iodine-induced hypothyroidism and should have thyroid function monitored following exposure to iodinated media. Third, Rhee et al have demonstrated that a relatively large proportion of individuals who developed iodine-induced thyroid dysfunction were not known to have underlying risk factors. Therefore, patients who may be particularly unable to tolerate thyroid dysfunction, such as those with underlying unstable cardiovascular disease, are also good candidates for monitoring of thyroid function after iodine exposure. The short-term use of medications to prevent iodine-induced hyperthyroidism has been proposed in Europe for elderly patients with known thyroid autonomy. Either methimazole, which blocks thyroid hormone synthesis, or perchlorate, a competitive inhibitor of the sodium-iodide symporter, can be used.9 Either drug can be started 1 day prior to iodinated contrast exposure and continued for a total of 14 days. However, pharmaceutical-grade perchlorate is not marketed in the United States, and even short-term use of methimazole confers some risk. Until we are better able to define risk factors for iodine-induced hyperthyroidism, prophylactic antithyroid drug should not be routinely used. Although the acute Wolff-Chaikoff effect was first described more than 60 years ago, its mechanism still needs to be fully elucidated. Importantly, prospective studies are needed to better define risk factors for iodinated contrast-induced thyroid dysfunction in individual patients. Finally, based on studies of iodine-induced thyroid dysfunction associated with amiodarone use,10 hyperthyroidism following administration of iodinated contrast-medium hyperthyroidism is likely to be more prevalent in iodine-deficient regions, and hypothyroidism in iodine-sufficient areas. A better understanding of this geographic variation will also be important for developing region-specific clinical recommendations. Back to top Article Information Correspondence: Dr Pearce, Section of Endocrinology, Diabetes, and Nutrition, Boston University School of Medicine, 88 E Newton St, Evans 201, Boston, MA 02118 (elizabeth.pearce@bmc.org). Financial Disclosure: Dr Pearce reports receiving compensation from DuPont for testimony for the defense regarding the development of hypothyroidism after exposure to radioactive iodine released by the Hanford Nuclear Reservation, Hanford, Washington. References 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(2):153-159Google ScholarCrossref 2. Wolff J, Chaikoff IL. Plasma inorganic iodide as a homeostatic regulator of thyroid function. J Biol Chem. 1948;174(2):555-56418865621PubMedGoogle Scholar 3. Stanley MM. The direct estimation of the rate of thyroid hormone formation in man: the effect of the iodide ion on thyroid iodine utilization. J Clin Endocrinol Metab. 1949;9(10):941-95418142428PubMedGoogle ScholarCrossref 4. Markou K, Georgopoulos N, Kyriazopoulou V, Vagenakis AG. Iodine-Induced hypothyroidism. Thyroid. 2001;11(5):501-51011396709PubMedGoogle ScholarCrossref 5. Eng PHK, Cardona GR, Fang S-L, 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(8):3404-341010433193PubMedGoogle ScholarCrossref 6. Coindet JF. Nouvelles recherches sur les effets de l’iode et sur les précautions à suivre dans le traitement du goitre par ce nouveau remède. Bibl Univ Sci Belles Lettres Arts. 1821;16:140-152Google Scholar 7. Vagenakis AG, Wang CA, Burger A, Maloof F, Braverman LE, Ingbar SH. Iodide-induced thyrotoxicosis in Boston. N Engl J Med. 1972;287(11):523-5275050425PubMedGoogle ScholarCrossref 8. Braverman LE, Vagenakis AG, Wang CA, Maloof F, Ingbar SH. Studies on the pathogenesis of iodide myxedema. Trans Assoc Am Physicians. 1971;84:130-1384364605PubMedGoogle Scholar 9. Nolte MR, Muller R, Siggelkow H, Emrich D, Hufner M. Prophylactic application of thyrostatic drugs during excessive iodine exposure in euthyroid patients with thyroid autonomy: a randomized study. Eur J Endocrinol. 1996;134(3):337-3418616532PubMedGoogle ScholarCrossref 10. Martino E, Safran M, Aghini-Lombardi F, et al. Environmental iodine intake and thyroid dysfunction during chronic amiodarone therapy. Ann Intern Med. 1984;101(1):28-346428291PubMedGoogle Scholar

Journal

Archives of Internal MedicineAmerican Medical Association

Published: Jan 23, 2012

Keywords: hyperthyroidism,hypothyroidism,iodine,thyroid diseases,ionic iodinated contrast media

References