University of Connecticut Farmington, Connecticut, United States
Disclosure(s):
Usheem Syed, MBBS: No financial relationships to disclose
Background: Radioactive iodine (RAI) therapy is a widely used definitive treatment for Graves’ disease and has historically been considered safe. However, large cohort studies and meta-analyses suggest a modest, dose-dependent association between RAI exposure and solid cancer mortality, including thyroid and breast cancers, raising renewed concern regarding long-term malignancy risk.
Case: A 73-year-old male was treated for Graves’ disease in 2009 with radioactive iodine ablation (I-131, 17.2 mCi). At the time of diagnosis and treatment, there were no known thyroid nodules and no evidence of thyroid malignancy. He subsequently developed permanent hypothyroidism and remained on long-term levothyroxine therapy. Sixteen years later, imaging revealed an enlarging right thyroid nodule. Ultrasound-guided fine-needle aspiration demonstrated malignant cytology (Bethesda VI), consistent with papillary thyroid carcinoma (PTC). Preoperative imaging showed a 2–2.9 cm right thyroid nodule without pathologic cervical lymphadenopathy.
The patient underwent total thyroidectomy with neck dissection. Pathology revealed multifocal classic-type PTC measuring 2.8 cm with lympho-vascular invasion, focal extrathyroidal extension, positive posterior margins, and metastatic involvement of two right lateral neck lymph nodes with extranodal extension. An incidental microscopic noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) was identified in the contralateral lobe. Final staging was pT2N1b (AJCC 8th edition). He subsequently received adjuvant radioactive iodine therapy (I-131, 144.6 mCi) following recombinant TSH stimulation, with post-therapy imaging showing uptake confined to the thyroid bed.
Conclusion: This case illustrates the development of differentiated thyroid carcinoma more than a decade after low-dose RAI therapy for Graves’ disease. While causality cannot be established, emerging epidemiologic evidence supports a dose-response relationship between RAI exposure and solid cancer mortality. This case underscores the importance of individualized risk–benefit discussions, patient counseling regarding long-term risks, and consideration of ongoing thyroid surveillance in selected patients treated with RAI for benign disease.
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