Marked Hypercalcitoninemia without Medullary Thyroid Carcinoma: A Case Report

Hypercalcitoninemia without MTC

Abstract

This case report investigates the diagnostic difficulties associated with persistently elevated calcitonin levels in a patient with nodular thyroid disease, where biochemical evidence strongly indicated medullary thyroid carcinoma (MTC), yet histopathological analysis ultimately identified benign nodular hyperplasia with C cell activation.
We describe a 35-year-old male with hypothyroidism who exhibited persistently elevated serum calcitonin levels (35–47 ng/L). The diagnostic assessment comprised thyroid autoantibody panels, high-resolution ultrasound, serial fine-needle aspiration cytology (FNAC) with calcitonin washout measurements, a calcium stimulation test, and genetic testing for RET proto-oncogene mutations. The patient then had a total thyroidectomy and removal of the central lymph nodes.
The preoperative workup showed that the levels of anti-thyroglobulin and anti-thyroid peroxidase antibodies were very high, and the TSH level was also high (8.1 mIU/L). An ultrasound revealed two iso- to hypoechoic nodules and several cervical lymph nodes that appeared suspicious. FNAC results differed among samples: some were Bethesda II–III, while others were non-diagnostic. One nodule had a calcitonin washout level of 92 ng/L. The calcium stimulation test yielded a robust positive response, with peak calcitonin levels surpassing 500 ng/L (579 ng/L at 2 minutes). The genetic test for RET mutations came back negative. Following total thyroidectomy, histopathology confirmed nodular hyperplasia without evidence of MTC and all resected lymph nodes showed only reactive changes. After surgery, serum calcitonin levels returned to normal.
This case demonstrates that a combination of moderately elevated basal calcitonin levels, a positive calcitonin washout from FNAC, and a strong response to calcium stimulation—exceeding recently suggested sex-specific thresholds—does not conclusively indicate MTC. Nodular hyperplasia with functional C cell activation can closely resemble the biochemical profile of medullary carcinoma. Our results demonstrate the importance of integrating biochemical, cytological, and histopathological data to avoid overly aggressive surgery. Reporting these cases helps to improve diagnostic thresholds and shows that a careful, step-by-step approach is needed to evaluate hypercalcitoninemia, particularly in distinguishing between nodular hyperplasia and medullary carcinoma.