Iodine-Based Contrast Media Cause Hyperthyroidism - Another Important Adverse Reaction to Contrast Media?

Abstract

Recently, Rhee et al. (1) in Archives of Internal Medicine concluded, based on a retrospective study, that iodine-based contrast exposure is associated with subsequent development of incident hyperthyroidism and incident overt hypothyroidism. It is well-known that increased intake of iodine may cause hyperthyroidism particularly in iodine deficient areas (2, 3). New iodine supplementation programs with the addition of iodine to food (e.g. bread, salt) cause a transient increase in the incidence of hyperthyroidism during the first years (4). One might ask if we should screen for the development of hyperthyroidism as a late adverse reaction to the use of iodine-based contrast medium, or we should know in more detail thyroid status and morphology before performing an iodine-enhanced examination? Iodine-induced hyperthyroidism is not a single etiologic entity. It may occur in patients with a variety of underlying thyroid diseases where Graves’ disease and nodular goiters are the most frequent diseases. The incidence of iodineinduced hyperthyroidism in iodine deficient areas has been estimated to be up to 1.7% per year, while in iodinesufficient areas, the incidence seems very low (2). Iodine-based contrast media are not the only sources of iodine in the modern world. Other sources of iodine include disinfectants, secretolytic agents, the iodine containing antiarrhythmic drug amiodarone, eye drops and ointments, seaweed, multivitamin preparations, skin ointments, toothpaste, et cetera. An important difference between those sources and iodine-based contrast agents, e.g. amiodarone, is that they are used daily whereas contrast media is a single event which may be repeated a couple of times over a 12-month period in some patients. It is unclear how much extra iodine the body receives per day through chronic administration. Furthermore, it is not given intravenously, but enters the body through the skin (e.g. ointment) or bowelwall (via seaweed andmulti-vitamin preparations, for example). A single injection of 200 mL iodine-based contrast medium (3000 mg/mL) for CT provides 7000 mg free iodine equivalent to approximately 45 times the recommended daily intake (3). This amount can fill the iodine deposits in the thyroid gland for up to 2months. In an iodine deficient area, Rendl and Saller (5) found 38 cases of severe hyperthyroidism due to contrast media within 1 year, during which period approximately 5 million contrast-enhanced studies were performed (0.0008%). In another study, in an iodine deficient area, a new episode of hyperthyroidism could be related to iodinebased contrast media in 15% of the patients (6). Surprisingly, 95% of these cases developed more than 3 months after the exposure to the contrast medium or at a time where the iodine deposits were no longer filled. In a non-iodine deficient area, seven patients with nodular goiter needed hospitalization due to clinically severe iodine-induced hyperthyroidism among a cohort of 24,000 CT scans (7). There are no reports about increased risk of hyperthyroidism in patients with severely reduced renal function where it may take days before the agent has left the body (8). At our institution, Copenhagen University Hospital Herlev, 230 new cases of hyperthyroidism were diagnosed in 2010. During the same period 30,000–35,000 injections of iodine-based contrast medium were given just for CT. Fourteen patients (6%) had had an iodine-based contrast medium injection within 2 years before the hyperthyroid episode. This corresponds to approximately 0.0004– 0.0005% of all contrast injections performed. Patients developing hyperthyroidism were those with a toxic nodular goiter, since 11 of 72 patients (15%) with this disease had had contrast medium within the last 2 years. In contrast the relation between iodine-based contrast medium given within the last 2 years was only evident in one (1%) of 101 patients with Graves’ disease. The remaining two episodes were seen in patients with thyroiditis induced by epilimumab and interferon treatment, but could also be due to the iodine-based contrast medium given repeatedly in these particular patients. Seven of the 230 patients had amiodarone induced hyperthyroidism. Rhee et al. (1) used the Partners HealthCare Research Patient Data Registry which covers information about 4.5 million people or 10 times as many our hospital serves. Over 20 years, they found 178 patients in their registry where iodine-based contrast medium could be the factor initiating the development of hyperthyroidism. Their data fit very well with our findings. Fourteen cases of a treatable disease after more than 30,000 injections are infrequent. Both areas were iodine sufficient. Therefore, systematic evaluation of thyroid function prior to iodine-based contrast medium administration in all patients will be like looking for a needle in a haystack. It might however be appropriate to identify those patients with a known nodular goiter, and to recommend thyroid function testing as follow-up during up to 2 years after