MON-420 - A Storm Is Brewing: Complications of Functional Metastatic Thyroid Cancer

Introduction: Follicular thyroid cancer (FTC) causes 10 to 15 percent of thyroid cancers. Distant metastasis is seen in seven to 23 percent of FTCs. FTC is the most common cancer to arise in hyperfunctioning thyroid nodules. Hyperfunctioning metastatic thyroid cancers tend to have large tumor sizes and widespread metastases (1).

Case description: A 56 y/o woman with metastatic follicular thyroid cancer s/p total thyroidectomy and s/p pelvic radiation was treated for confusion, tachycardia, and hyperthermia. She was on her home levothyroxine (LT4) dose 100 mcg daily. The thyroid stimulating hormone (TSH) was under 0.01 (0.55 to 4.78 uIU/mL), the free T4 (fT4) was 2.95 (0.89 to 1.76 ng/dL), and the free T3 (fT3) was 4.0 (2.30 to 4.20 pg/mL). The differential included LT4 overreplacement and thyroid storm. LT4 was held. The patient received propylthiouracil (PTU) and hydrocortisone. Despite being on PTU, fT3 and fT4 levels did not improve, so this was held. A diagnostic I-123 whole-body scan showed iodine-avid lesions in the left thyroid bed, right hip, left ilium, lungs, and retroperitoneum. A CT scan of the chest, abdomen, and pelvis showed retroperitoneal lymphadenopathy, a left iliac lytic lesion, and a left iliac mass extending into the sacrum, abdomen, and right hip. Despite being off LT4 for a week, the patient had persistently high fT4 levels. It was suspected that she had ectopic fT4 made by her metastatic lesions. PTU was restarted. The patient was shortly readmitted for confusion and poor functional status. She elected for hospice care and passed away.

Discussion: This case demonstrates the importance of considering metastatic hyperfunctioning thyroid cancer in the differential for patients with metastatic thyroid cancer who have had total thyroidectomies. Gain-of-function mutations in the TSH receptor gene (TSHR) are found in 10 percent of follicular thyroid cancers and can promote hyperthyroidism. TSH binds to the TSH receptor (TSHR) on follicular thyroid cells, activating G proteins that lead to adenyl cyclase activation and cyclic adenosine monophosphate production, causing follicular thyroid cell growth and fT4 synthesis (2). Thyrotoxicosis can be wrongly attributed to the use of excessive LT4 and treated with LT4 washout. If left untreated, patients can develop complications such as atrial fibrillation and heart failure. Findings from this study can make it easier to recognize and manage metastatic hyperfunctioning thyroid cancer.

1 Liu J, et al. Hyperfunctioning thyroid carcinoma: A systematic review. Mol Clin Oncol. 2019;11(6):535-550. 2 Wu MH, et al. Risk factors and prognosis for metastatic follicular thyroid cancer. 2 Front Endocrinol (Lausanne). 2022;13:791826.

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