Iodinated Contrast Agents Tied to Potential Thyroid Dysfunction

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Iodinated contrast media exposure is associated with development of hyperthyroidism as well as overt hypothyroidism, according to results from a study published online January 23, 2012, ahead of print in Archives of Internal Medicine.

For the nested, case-control study, Connie M. Rhee, MD, of Brigham and Women’s Hospital (Boston, MA), and colleagues looked at patients who did not have preexisting hyperthyroidism or hypothyroidism and were exposed to contrast between January 1990 and June 2010. Cases of incident hyperthyroidism (n = 178) and hypothyroidism (n = 213) were matched to 655 and 779 controls, respectively, who had normal thyroid function. Matching was based on age, sex, race/ethnicity, estimated glomerular filtration rate, follow-up thyrotropin measurement date, and interval between baseline and the follow-up date.

Contrast Exposure Increases Risk for Thyroid Disease 

Thyrotropin levels did not change between baseline and follow-up among controls, but as expected they fell among incident hyperthyroid cases and rose among incident hypothyroid cases. Iodinated contrast media was administered in 361 of 4,096 patient intervals (8.8%) for cardiac catheterization or CT exam.

Iodinated contrast media exposure was associated with incident hyperthyroidism (OR 1.98; 95% CI 1.08-3.60; P = 0.03). A similar relationship was found between contrast exposure and incident overt hyperthyroidism, defined as follow-up thyrotropin level of 0.1 mIU/L or less (OR 2.5; 95% CI 1.06-5.93; P = 0.04).

Compared with the other hyperthyroid cases, patients developing overt hyperthyroidism were more likely to be female (P = 0.03) but were similar in age, prevalence of renal dysfunction, and non-white race/ethnicity.

A relationship between exposure and hypothyroidism was seen but did not reach significance (OR 1.58; 95% CI 0.95-2.62; P = 0.08). But overt hypothyroidism, defined as follow-up thyrotropin level of greater than 10 mIU/L, was significantly increased by iodinated contrast (OR 3.05; 95% CI 1.07-8.72; P = 0.04).

Compared with the remaining hypothyroid cases, patients developing overt hypothyroidism were less likely to have renal dysfunction (P = 0.003) but were similar in age, female sex, and non-white race/ethnicity.

‘Important Contribution’ to Knowledge Base

In a telephone interview with TCTMD, Dr. Rhee said even though the literature had established “biologic plausibility” of a relationship between iodinated contrast use and thyroid disease, she was surprised by the “magnitude of the association” and the “potent effect” that exposure had on hyperthyroidism in particular.

The study specifically looked at the extreme outliers of thyroid disease, she said, because the categories are “clinically important designations. . . . [T]he cutoffs that we used to define the more overt disease have actually been associated with more severe cardiovascular outcomes.”

In addition, the study was performed in Boston, which Dr. Rhee referred to as an “iodine sufficient” area, or one that has high iodine exposure. Therefore, the findings stand out even more because prior studies have mainly been relegated to iodine-deficient regions, where contrast exposure may merely “unmask unrecognized thyroid dysfunction,” she explained.

In an accompanying editorial, Elizabeth N. Pearce, MD, MSc, of Boston University School of Medicine (Boston, MA), lauded the study, claiming its strengths include the large number of cases and controls, rigorous case definitions, and adjustment for multiple potential confounders.

“These data represent an important contribution to our knowledge about a clinically relevant and understudied area,” she writes.

Unclear Statistics

But Peter A. McCullough, MD, MPH, of Providence Park Heart Institute (Novi, MI), told TCTMD in a telephone interview that he is “very skeptical of this whole study.”

“It’s basically like a time series study where they take a snapshot of patients in time who had exposure to contrast then they take a different group in a different snapshot of time who didn’t have exposure to iodine,” he said. “The cases of thyroid disease that they are reporting occurred a median of 116 days after exposure. And that’s just too long. I don’t buy it.”

Out of nearly 4,000 patient intervals considered by the study, only 16 required medication for hyperthyroidism, Dr. McCullough pointed out. “The bottom line is that could just be the natural incidence of thyroid disease. For instance, in women in the United States over the course of life, about 11% of them have thyroid disease. Because [the study] looked at one snapshot in time and found 0.4% of individuals go on thyroid medicine, it doesn’t really implicate the contrast exposure in my view.”

Moreover, since contrast is used for numerous procedures, Dr. McCullough said he has “a hard time believing that this is a worrisome problem” for cardiology.

Awareness and Monitoring Needed

Dr. Rhee, however, stressed that thyroid disease can have important clinical consequences on cardiovascular disease. When physicians are considering giving contrast to a patient, they consider the risk for kidney failure as well as anaphylactic-related reactions, but not necessarily for thyroid disease, she said.

Although procedures involving contrast are crucial to patient management, “We have to really judiciously think about all of the risks and benefits for each of our patients before giving this test,” Dr. Rhee said, adding that further study is needed to confirm the findings in other populations and to understand the clinical significance of thyroid disease acquired from contrast exposure.

Dr. Pearce, meanwhile, argues in the editorial that increased observation might prevent potential thyroid issues in higher-risk patient groups.

The current study “demonstrated that a relatively large proportion of individuals who developed iodine-induced thyroid dysfunction were not known to have underlying risk factors,” she writes. “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.”

Dr. McCullough said that, going forward, it would be reasonable to pursue a prospective study measuring thyroid function before and after contrast exposure. Even so, he commented, “it’s probably going to be a nonissue.”

 

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Sources:
1. Rhee CM, Bhan I, Alexander EK, et al. Association between iodinated contrast media exposure and incident hyperthyroidism and hypothyroidism. Arch Intern Med. 2012;Epub ahead of print.

2. Pearce EN. Iodine-induced thyroid dysfunction: Evaluating the risks of iodinated contrast medium. Arch Intern Med. 2012;Epub ahead of print.

 

 

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