A 38-year-old woman with a 2 cm solitary thyroid nodule and a family history of medullary thyroid carcinoma (MTC) presents for preoperative evaluation. Physical examination reveals no palpable cervical lymph nodes. Which investigation is most appropriate to confirm the diagnosis before thyroid surgery?

Explanation

## Investigation of Choice for Suspected Medullary Thyroid Carcinoma **Key Point:** Serum calcitonin is the gold standard tumor marker for MTC. A calcitonin stimulation test (using calcium gluconate or pentagastrin) is the most sensitive confirmatory test when baseline calcitonin is borderline or normal. ### Why Calcitonin Testing? **High-Yield:** Medullary thyroid carcinoma arises from parafollicular C cells, which produce calcitonin. Elevated baseline calcitonin (>100 pg/mL) or an exaggerated response to stimulation is diagnostic of MTC and warrants total thyroidectomy with central neck dissection. ### Diagnostic Thresholds | Finding | Interpretation | |---------|----------------| | Baseline calcitonin > 100 pg/mL | Diagnostic of MTC | | Baseline 10–100 pg/mL + positive stimulation test | Highly suggestive of MTC | | Baseline < 10 pg/mL + negative stimulation test | MTC unlikely | **Clinical Pearl:** In a patient with family history of MTC (suggesting hereditary medullary thyroid carcinoma or MEN 2), calcitonin screening is mandatory before any thyroid intervention, as it guides the extent of surgery (total thyroidectomy + central compartment dissection vs. lobectomy). ### Why Not the Other Investigations? - **FNAC:** Cannot reliably diagnose MTC; cytology may show spindle cells but is not specific. FNAC is useful for papillary or follicular lesions, not MTC. - **Ultrasound/elastography:** Provides morphologic information but cannot confirm the cell type or hormone production. - **CT neck:** Useful for staging and assessing lymph node involvement *after* diagnosis is confirmed, not for initial diagnosis. **Mnemonic:** **C-CALCI** — C cells → Calcitonin → Calcitonin stimulation test for diagnosis.