What Lies Beneath? - Medullary Thyroid Cancer in Nodular Graves’ Disease

Abstract Background: Medullary thyroid carcinoma (MTC) accounts for 1%-2% of thyroid cancers in the United States (US). MTC originates from thyroid parafollicular C-cells, occurring either sporadically or hereditarily as part of type 2 multiple endocrine neoplasia (MEN) or familial MTC (FMTC). Hyperthyroidism is prevalent in approximately 1.2%, and Graves’ Disease (GD) is the most common cause of hyperthyroidism in the US. GD is an autoimmune disorder that results in increased thyroid hormone production due to the stimulation of TSH receptor by thyrotropin receptor antibodies (TRAb). Thyroid carcinoma in general is uncommon in GD patients, while MTC is extraordinarily rare. We report a case of sporadic MTC in GD, which is extremely rare. A recent publication stated that there were only 15 reported cases of MTC coexisting in GD until 2019. Clinical Case: A 62-year-old male with hypertension, diabetes and obesity presented to the endocrine surgery clinic with symptoms of diaphoresis, chest pain and fullness, shortness of breath, and palpitations. The patient had a brother with a pancreatic mass of unknown pathology and multiple family members with thyroid disease. On physical exam, there was a palpable non-tender left-sided nodule with no lymphadenopathy. His FT4 was 8.5 (0.76-1.46 ng/dL), TSH was <0.006 (0.36-3.74 μIU/dL) and thyroid-stimulating antibody was 1.25 (<0.10 IU/L). Ultrasound showed a multinodular goitre with a dominant nodule in the left lower pole measuring 2.3x1.9x1.5 cm. He was diagnosed with GD, treated with methimazole, and his symptoms improved. Subsequent nuclear medicine uptake scan showed diffusely increased uptake and a cold nodule in the left thyroid lobe. Repeat labs showed low TSH (<0.01μIU/dL) and elevated FT4, CEA, calcitonin, PTH, metanephrine, and normetanephrine (1.04 ng/dl, 5.2 (3-5 ng/ml), 796 (<18 pg/ml), 58.10 (18.40-88.00 pg/mL), 90 (< OR = 57 pg/ml) and 222 (< OR = 148 pg/ml), respectively). A thyroid fine-needle aspiration (FNA) was suggestive of MTC (Bethesda Category VI). Total thyroidectomy with left central lymph node dissection revealed a 2.5cm MTC confined in the left lobe with focal lymphovascular invasion. His postoperative course was uneventful, and CEA and calcitonin levels trended down (1.1 ng/ml and <2 pg/mL, respectively). Conclusion: The coexistence of medullary thyroid carcinoma and Graves’ Disease is rare, incidental, with five-year survival rates lower than other thyroid cancers. A delayed diagnosis of MTC would be detrimental. Patients with thyroid nodules and GD are five times more likely to be diagnosed with thyroid carcinoma. Radiation, chemotherapy and thyroidectomy are standard treatment options for MTC, with total thyroidectomy being the preferred option. It is necessary to evaluate patients with GD for possible thyroid cancers, especially in the presence of nodules.