Graves’ Orbitopathy in Thyroid Cancer: Beware Higher Doses of Radioactive Iodine
—A South Korean study followed patients with thyroid cancer to assess for risk of Graves’ orbitopathy, finding an association with radioactive iodine treatment.
Graves' orbitopathy (GO), an autoimmune condition affecting the eye sockets and surrounding tissues, is a well-recognized complication of Graves’ disease (GD) but its development is not well-characterized in other patient populations. Minjeong Kim and colleagues addressed this gap in a recent population-based, retrospective study focused on the National Health Insurance Service-National Sample Cohort (NHIS-NSC) in South Korea.1
The authors noted, “…few studies have explored the occurrence of GO after thyroidectomy in individuals without GD. There are limited reports of euthyroid GO’s association with thyroid cancer, and its pathogenesis remains unclear. Despite this, previous studies have noted both improvement and exacerbation of GO symptoms during thyroid cancer treatments, including surgery and RAI therapy.”
Low prevalence, potential RAI link to Graves' orbitopathy
The study revealed a low prevalence (0.14%) of GO in the nationwide cohort. The authors investigated development of GO in 8,499 patients with thyroid cancer without pre-existing hyperthyroidism or GO. Included patients were grouped based on having previous thyroidectomy. Notably, the 663 patients who had not undergone the surgery did not develop GO.
“Among the cancer patients who did not undergo a thyroidectomy, none were diagnosed with GO. Further studies are needed to ascertain whether the absence of GO among these patients was associated with the lack of surgery itself or with the low severity of their cancers (precluding the need for surgery),” stated Dr. Kim and coauthors.
Among the 7,836 patients who underwent thyroidectomy, 12 developed GO postoperatively, all of whom were women diagnosed with GO within 57 to 5473 days following thyroid cancer diagnosis. Among patients who did not develop GO, 81.3% were women.
Most patients in both the GO and non-GO groups underwent total thyroidectomy (83.3% and 78.6%, respectively). Prior to diagnosis with GO, the patients received thyroid hormone supplementation following thyroidectomy, at an average daily dose of 85 μg (range, 70 to 120). In addition, four of five patients who received RAI therapy before their GO diagnosis developed the condition within a year of treatment. The total RAI dose in these patients was 168.5 mCi (range, 139.8 to 203.8), significantly higher than the 104 mCi (range, 40 to 160) in non-GO patients.
Interestingly, the researchers observed that a higher total RAI dose was associated with development of GO. Patients in the GO group received a significantly higher average total RAI dose of 184 mCi (range, 153 to 200) compared with a dose of 104 mCi (range, 40 to 160) in the non-GO group (P = 0.036). The authors also noted that the follow-up period was shorter for the GO group because developing GO was considered the study end point.
Clinical implications and considerations
Healthcare providers managing patients with thyroid cancer, particularly those who opt for RAI treatment, should be aware of the potential for development of GO – albeit rare – even in the absence of pre-existing hyperthyroidism. This risk, along with other factors such as disease severity and overall health status, should be factored into treatment decisions and may influence RAI dosage or consideration of alternative treatment options.
Unanswered questions and areas for further research
While the study provides valuable insights, the authors acknowledged its limitations. First, their reliance on national insurance data means that patient-specific data are missing from the study. The authors also noted that they were unable to analyze pre-existing thyroid hormone levels or the impact of dosage on risk of developing GO. Although the limited number of GO cases prevented them from drawing strong conclusions, this was the first nationwide study on GO prevalence in patients with thyroid cancer.
The authors underscored the need for further investigation into the potential link between RAI and GO in thyroid cancer patients. Elucidating the underlying mechanisms behind this association could inform treatment protocols and improve patient management.
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