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CASE REPORT Iodine-Induced Hyperthyroidism (Jod-Basedow Phenomenon) in the Elderly Llanyee Liwanpo, MD, Raymond Tang, MD, and Michael Br yer-Ash, MD, FRCP(Lond), FRCP(C) I this phenomenon may be an increasing but underrecognized consequence of modern imaging procedures, which entail larger iodine loads, in the geriatric population. odine-induced hyperthyroidism, or Jod-Basedow phenomenon, a thyrotoxic condition caused by exposure to increased amounts of iodine, has historically been reported in regions deficient in iodine.1 However, with advances in contrast imaging, this hyperthyroidism has more recently been reported in patients following studies that require administration of iodine-containing contrast media,2-5 but has received little attention in the elderly,6,7 who frequently undergo such studies. The increasing application of these imaging techniques to evaluate and prognosticate diseases of advanced age, in combination with our growing life expectancy, make the geriatric population especially susceptible to the development of Jod-Basedow hyperthyroidism under this clinical setting. We report a case of Jod-Basedow hyperthyroidism in an elderly patient with no known prior thyroid disease who was exposed to iodinated contrast media for cardiac computed tomography (CT) imaging. Given that weight loss was the only clinical manifestation of hyperthyroidism in our patient, we contend that CASE PRESENTATION An 83-year-old Caucasian man was referred to the Endocrinology Clinic of the University of California, Los Angeles, Healthcare System, complaining of a 7pound weight loss over one week. On initial presentation to his primary care physician, the patient reported losing approximately one pound per day with only a modest reduction in his appetite. He denied insomnia, heat intolerance, or diaphoresis, nor did he complain of tremor, palpitations, or change in bowel habit. Approximately 10 days prior to the visit, the patient underwent elective coronary imaging, which involved a thin-section CT scan and administration of an iodinated contrast media. Two doses (20 mL, then 140 mL) of a contrast agent, iohexol, were given intravenously. The patient’s medications included dipyridamole/aspirin 200/25 mg 1 tablet daily, atorvastatin 10 mg nightly, tamsulosin 0.4 mg daily, and aspirin 81 mg daily. His past medical history was significant for hypertension, hyperlipidemia, and a right-sided cerebrovascular accident 3 years previously, from which he had recovered full Drs. Liwanpo and Tang are from the Department of Medicine, and Dr. Bryer-Ash is from the Department of Medicine and the Gonda (Goldschmied) Diabetes Center, Division of Endocrinology, Diabetes and Hypertension, David Geffen School of Medicine, University of California, Los Angeles. Clinical Geriatrics Volume 14, Number 3 33 March 2006 TA B L E I CASE REPORT Serial Thyroid Function Test Values Days after iohexol administration TSH (0.3-4.7 μIU/mL) Free T4 by dialysis (0.7-2.2 ng/dL) Free T3 (210-440 pg/dL) Total T3 (60-181 ng/dL) 5 0.02 … … … 16 <0.02 2.9 454 150 54* 19.2 0.5 172 80 77* 16.9 1.1 237 106 93 8.4 … … … 147 6.1 1.2 221 96 188 4.1 … … … TSH = thyroid-stimulating hormone; T4 = thyroxine; T3 = triiodothyronine. * Patient taking methimazole. Numbers in bold indicate abnormal values. … Indicates not performed. ng/dL (reference range, 1.0-4.4), and suppressed thyrotropin, or thyroid-stimulating hormone (TSH), of 0.02 μIU/mL (reference range, 0.34-5.6). Laboratory tests obtained at the initial visit to the endocrinology clinic showed a normal serum chemistry panel and complete blood cell count, while serum TSH was undetectable at < 0.02 μIU/mL (reference range, 0.34.7 μIU/mL). Serum free T4 by dialysis was elevated at 2.9 ng/dL (reference range, 0.7-2.2) and serum free triiodothyronine (T3) was high at 454 pg/dL (reference range, 210-440). Thyroid-stimulating immunoglobulin was normal at 92% of basal activity (reference range, 0-129), but antithyroperoxidase antibody was elevated at 32.7 IU/mL (reference range, < 2.0). Thyroid scintigraphy was not performed due to the recent iodine load. Approximately 3 weeks after the initial presentation, TSH determined at an outside laboratory remained undetectable, and methimazole 10 mg daily was prescribed. Serial thyroid function tests (TFTs) are shown in Table I. On a follow-up visit 7 weeks later, the patient had returned to his previous weight. At that time, TSH was elevated at 19.2 μIU/mL, with both free T4 and T3 levels low, at 0.5 ng/dL and 172 pg/dL, respectively. Therefore, the dosage of methimazole was reduced to 5 mg daily, and later discontinued entirely on day 93. His thyroid function then gradually returned to the normal range (Table I). motor function. He denied any family history of thyroid or other endocrine disease. He had grown up in Hungary and immigrated to the United States as a young man. On physical exam, the patient was a healthyappearing gentleman who was alert and in no apparent distress. His weight was 160 pounds, and height was 5 feet 4 inches. He was afebrile, with a temperature of 96.7 degrees Fahrenheit. Pulse rate was 80 beats per minute, and blood pressure was 140/60 mm Hg. There was no eyelid lag, stare, exophthalmos, or scleral icterus. Oropharynx was clear. There was no palpable thyroid goiter, and the gland was nontender without bruits. Cardiovascular exam was significant for a grade II over VI systolic murmur radiating to the axilla and a soft mid-systolic murmur at the upper-left and -right sternal borders. Respiratory and abdominal examinations were unremarkable. Assessment of extremities showed a trace of pitting edema at both ankles, with no cyanosis or clubbing. His hands were warm, without tremor or diaphoresis. Neuromuscular exam revealed symmetrical and normal power and tone, with grossly normal coordination and reflexes. Laboratory data obtained at an outside laboratory five days after the cardiac imaging study showed an elevated total thyroxine (T4) level of 12.8 μg/dL (reference range, 4.5-12.5), elevated free T4 index of 4.9 Clinical Geriatrics Volume 14, Number 3 34 March 2006 CASE REPORT DISCUSSION iodine-deficient regions, as well as in individuals with underlying thyroid pathology, such as autonomous hyperfunctioning nodules. Therefore, excess iodine does not directly cause thyroid dysfunction; rather, in the setting of abnormalities, which prevent the gland’s normal adaptation to excess iodine, it conditions the development of disease.17 Clinical symptoms of iodine-induced hyperthyroidism occur days or weeks after exposure. Upon removal of the source of excess iodine, the condition usually resolves spontaneously. Anti-thyroid medication may be indicated in patients severely affected or subjected to a large iodine load. Although patients with Jod-Basedow phenomenon are likely to manifest in a clinically similar manner to those with Graves’ disease, our patient, who was 83 years of age at the time of diagnosis, complained only of a 7-pound weight loss during his initial hyperthyroid phase. Indeed, the lack of typical symptoms and signs of hyperthyroidism, also known as apathetic hyperthyroidism, occurs in about 15% of the elderly population with hyperthyroidism.18 In 1986, Tibaldi et al19 investigated the condition of thyrotoxicosis in 25 elderly patients with a mean age of 81.5 years. They reported the average number of thyrotoxic symptoms to be only two per patient, with the most common presenting symptom being weight loss, which occurred in 44%. Martin and Deam18 TA B L E I I Iodine-induced hyperthyroidism was first described in 1821 by Jean-François Coindet, at a time when iodine prophylaxis became widely used for prevention of goiter.8 The term Jod-Basedow was later coined by Emil Theodor Kocher in 1910.9 Prevalence of this phenomenon has often reflected developments in industry and diet. In 1976, Stewart and Vidor10 reported an increased incidence of thyrotoxicosis in Tasmania when the dairy industry began use of iodine-containing disinfectants, thus increasing the iodine content in milk. From 1965 to 1985, iodine supplementation in the United States resulted in increased prevalence of iodine-induced thyroid dysfunction.11-13 While Jod-Basedow hyperthyroidism still occurs upon ingestion of large quantities of iodine by persons in iodine-deficient regions, including Eastern Europe,14 new concerns have arisen in patients undergoing radiographic imaging with iodine-containing contrast agents, particularly in those with pre-existing thyroid pathology.2-5 Some iodide-containing agents that may cause Jod-Basedow hyperthyroidism are shown in Table II.15 Normally, when the thyroid gland is subjected to a sudden large iodine load, biosynthesis of T4 and T3 decreases due to the inhibitory effect of iodine on organification and thyroid hormone formation. This self-regulatory mechanism, known as the Wolff-Chaikoff effect, temporarily protects against the production of excess thyroid hormone.16 Over time, the thyroid gland either adapts to the Commonly Used Iodide-Containing Contrast Media increased iodine concentration Radiographic Contrast Agents Iodide Content or escapes from the self-regulatIohexol 140 mg/mL to 350 mg/mL ing mechanism, resulting in a Diatrizoate meglumine and sodium 370 mg/mL Iodized oil 380 mg/mL rise in thyroid hormone producIopanoic acid 333 mg/tablet tion. The latter phenomenon Ipodate 308 mg/capsule most commonly occurs in Iothalamate 480 mg/mL Metrizamide Clinical Geriatrics Volume 14, Number 3 35 483 mg/mL before dilution March 2006 CASE REPORT CONCLUSION examined 60 Australian patients with a mean age of 80.2 years for clinical features of hyperthyroidism. They also found that weight loss, present in 83% of patients, was the most common clinical manifestation. All patients in both of these reports had underlying thyroid disorders, such as Graves’ disease, multinodular goiter, or toxic adenoma. Indeed, increased susceptibility to iodine-induced hyperthyroidism has been reported in patients from iodine-sufficient areas who have autonomous thyroid nodules.2-5,20 Nevertheless, there is also evidence that iodine-induced hyperthyroidism may occur in patients with no apparent thyroid dysfunction residing in an iodine-sufficient area.21 The course of Jod-Basedow hyperthyroidism often depends on the underlying thyroid disorder.22 Duration of the hyperthyroid state is usually, though not always, self-limited and generally resolves within 12 weeks of iodine withdrawal in patients with or without underlying thyroid pathology.20,21 Management is directed both at reduction of symptoms and inhibition of hormone synthesis. Beta-blocking agents, such as propranolol, are indicated when patients exhibit overt clinical manifestations. Anti-thyroid medications, such as methimazole, may shorten recovery time if the load of iodine is large, or if symptomatic hyperthyroidism does not resolve in a short space of time. Approaches such as 131iodine ablative therapy and surgery should be reserved for patients with large multinodular goiters or recurrent Graves’ disease after the iodine-induced component of the hyperthyroid state has subsided,22 as such treatment will then be more effective. Prophylactic use of thionamide drugs may be useful in patients with evidence of thyroid autonomy prior to contrast administration,23,24 but their use is not yet routinely recommended. In this case of iodine-induced hyperthyroidism in the setting of exposure to iodinated contrast media, the only symptom of hyperthyroidism exhibited by this elderly patient was weight loss. Considering the current trend towards more elective contrast imaging, this condition may become increasingly common. If left undetected, especially in the geriatric population, iodine-induced hyperthyroidism can lead to serious cardiac arrhythmias or complications such as congestive heart failure or embolic stroke. In these patients, thyroid function evaluation both prior to and after imaging is recommended. Patients found to have subclinical autonomy may benefit from short-term prophylactic therapy. In general, after administration of a large dose of iodinated contrast media, elderly patients should be monitored for hyperthyroidism. Treatment is warranted for overt symptoms and signs of hyperthyroidism or markedly elevated thyroid hormone levels. Given that the course of this disease depends on the underlying thyroid pathology, management with anti-thyroid medications is necessary in certain individuals. Acknowledgments This case report was supported by funds from the Leslie and Susan Gonda (Goldschmied) Family Endowment. Dr. Inder J. Chopra kindly reviewed and commented on this manuscript. 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