Abstract Introduction Medullary thyroid carcinoma (MTC) is a rare neuroendocrine tumor that originates from parafollicular C-cells and typically presents with elevated serum calcitonin levels and thyroid nodules. The coexistence of MTC with thyrotoxicosis is uncommon, and MTC development during antithyroid treatment is even rarer. Clinical Case A 58-year-old female with no family history of thyroid cancer or prior radiation exposure presented in March 2022 with biochemical thyrotoxicosis. At that time, thyroid ultrasonography revealed no nodules, and basal serum calcitonin was within the normal range. Thyroid-stimulating immunoglobulin was positive, and thyroid scintigraphy demonstrated diffuse increased uptake consistent with Graves’ disease. The patient was subsequently diagnosed with Graves’ disease and initiated on methimazole at a dose of two tablets per day. The patient was lost to follow-up until October 2023, when she reappeared with persistent thyrotoxicosis. In May 2025, three years after the initiation of methimazole therapy, serum calcitonin was 53 ng/L, and repeat ultrasonography revealed multiple right thyroid lobe nodules, the most suspicious being a 4×5.5×5.5 mm hypoechoic nodule with indistinct borders and macrocalcifications in the superior medial segment. Fine-needle aspiration cytology of the nodule revealed malignant cells consistent with medullary thyroid carcinoma. Calcitonin washout from the nodule was 52,965 pg/mL. Two suspicious cervical lymph nodes were also sampled. Right level 6 and right level 3 cervical node cytology showed MTC infiltration with a calcitonin washout of 14,144 pg/mL and 80,114 pg/mL, respectively. The patient underwent total thyroidectomy with right central and lateral neck dissection. Final pathology confirmed multifocal MTC and metastatic lymph node involvement. Conclusion This case illustrates the potential for medullary thyroid carcinoma to arise or become clinically apparent during long-term antithyroid therapy, even in the absence of initial sonographic abnormalities or elevated calcitonin levels. It emphasizes the value of regular ultrasound surveillance and calcitonin monitoring in thyrotoxic patients under treatment, particularly when new nodules appear or clinical behavior changes. Early diagnosis is crucial, given the aggressive nature of MTC and its tendency for early lymphatic spread.Figure 1:Right superior medial thyroid nodule and metastatic cervical lymph nodesUltrasound image showing a suspicious hypoechoic nodule with macrocalcifications in the right thyroid lobe (superior medial segment), later confirmed as medullary thyroid carcinoma. Metastatic involvement of cervical lymph nodes was also detected (level 3 and 6). Table 1:Laboratory Findings
Baykal et al. (Thu,) studied this question.