MON-394 - Metastatic Thyroid Carcinoma in Patient with Graves' Disease and Thyroid Ophthalmopathy : Challenges in Management

Introduction
The coexistence of thyroid cancer and Graves’ disease has been reported at varying frequencies; however, the concurrence of thyroid cancer, Graves’ disease, and Graves’ ophthalmopathy is rare. We describe a case of metastatic papillary thyroid cancer occurring with severe Graves’ ophthalmopathy, highlighting diagnostic and therapeutic challenges.

Case
A 71-year-old African American man presented with thyrotoxicosis, was diagnosed with Graves’ disease, and started on methimazole. Thyroid ultrasound showed a nodule with subsequent FNA biopsy demonstrating benign cytology (Bethesda II). In 2024, he developed severe Graves’ ophthalmopathy and was treated with Teprotumumab with symptomatic improvement. Later that year, he noted a rapidly enlarging neck mass; biopsy revealed papillary thyroid carcinoma. He underwent total thyroidectomy with extensive neck dissection. Pathology demonstrated multifocal papillary thyroid carcinoma (classic and follicular variants), largest focus 3.5 cm, no extrathyroidal extension, negative margins, and 14/41 positive lymph nodes. Final staging was Stage II (pT2m pN1b). He was started on levothyroxine with TSH suppression ( < 0.01 μIU/mL) and received Thyrogen-stimulated radioactive iodine (RAI) ablation with 132 mCi I-131, along with high-dose steroids pre- and post-treatment. Ophthalmopathy did not worsen. Post-ablation whole-body scan showed iodine-avid lesions in the neck, chest, and abdomen. Stimulated thyroglobulin was 79.3ng/mL, with persistently elevated unstimulated thyroglobulin (117 ng/mL) and negative thyroglobulin antibodies. Neck ultrasound showed no thyroid bed recurrence. Multidisciplinary discussions are ongoing regarding repeat RAI versus tyrosine kinase inhibitor (TKIs) therapy.

Discussion
While Graves’ disease was once considered protective against thyroid cancer, recent studies report an incidence of 0.4–9.8%, compared with ~2% in the general population. Data on prognosis are conflicting, with some studies suggesting increased aggressiveness. The association between thyroid ophthalmopathy and thyroid cancer remains poorly understood. The role cross talk between TSH receptor and IGF-1 receptor in thyroid ophthalmopathy and thyroid cancer is unclear. Blocking TSH receptor with k1-70 in a patient with thyroid cancer and Graves’ ophthalmopathy was found to be beneficial. Given the risks of RAI in ophthalmopathy and TKIs increasing risk of keratitis, further studies are needed to guide management. We will review the available literature and and discuss this complex interaction.

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