A 57-year-old man comes to the office for follow-up after recent thyroid surgery. A month ago, he was found to have a solitary thyroid nodule, and a fine-needle aspiration biopsy of the mass revealed a neoplasm arising from parafollicular cells. He underwent an uncomplicated total thyroidectomy and removal of surrounding lymph nodes. He feels well and is taking levothyroxine as prescribed. Medical history is otherwise significant for well-controlled hypertension. The patient has no family history of thyroid cancers, and germline RET mutation testing was negative. Vital signs are within normal limits. On examination, there is a well-healing incision on his lower anterior neck with no surrounding erythema or edema. There are no enlarged cervical lymph nodes. The remainder of the examination shows no abnormalities. Blood cell counts and serum chemistry studies are within normal limits. Periodic surveillance with which of the following is most appropriate in this patient?

Question

A 57-year-old man comes to the office for follow-up after recent thyroid surgery.  A month ago, he was found to have a solitary thyroid nodule, and a fine-needle aspiration biopsy of the mass revealed a neoplasm arising from parafollicular cells.  He underwent an uncomplicated total thyroidectomy and removal of surrounding lymph nodes.  He feels well and is taking levothyroxine as prescribed.  Medical history is otherwise significant for well-controlled hypertension.  The patient has no family history of thyroid cancers, and germline RET mutation testing was negative.  Vital signs are within normal limits.  On examination, there is a well-healing incision on his lower anterior neck with no surrounding erythema or edema.  There are no enlarged cervical lymph nodes.  The remainder of the examination shows no abnormalities.  Blood cell counts and serum chemistry studies are within normal limits.  Periodic surveillance with which of the following is most appropriate in this patient?

Quizplus · Accepted Answer

This patient has medullary thyroid cancer (MTC), a neuroendocrine malignancy arising from the calcitonin-secreting parafollicular C cells. Most cases of MTC are sporadic, although approximately 25% are due to germline mutations in the RET proto-oncogene (eg, multiple endocrine neoplasia type 2 [MEN2], characterized by: MTC; pheochromocytoma; and either parathyroid hyperplasia [type 2A] or marfanoid habitus and mucosal neuromas [type 2B]). MTC most commonly presents as an asymptomatic thyroid nodule. A minority of patients have diarrhea and flushing (due to hormone secretion by the tumor). Unless there is concomitant hyperparathyroidism (eg, MEN2A), serum calcium is usually normal, possibly due to downregulation of calcitonin receptors. The diagnosis of MTC is confirmed with fine-needle aspiration. Primary treatment is total thyroidectomy, and therefore postoperative thyroid replacement therapy (ie, levothyroxine) is necessary. MTC is often metastatic at the time of diagnosis, primarily to the cervical lymph nodes and upper aerodigestive tract. Serum calcitonin levels correlate with the risk of metastasis and are measured at the time of diagnosis; they also correlate with risk of recurrence and are therefore measured serially following surgery. Carcinoembryonic antigen also correlates with disease progression and is typically measured with calcitonin. (Choice A) Antithyroid peroxidase antibodies are associated with chronic lymphocytic (Hashimoto) thyroiditis and related disorders. They are most often assayed in patients with goiter and elevated TSH, and are not useful in following MTC. (Choice B) The dexamethasone suppression test is used in the evaluation of hypercortisolism (ie, Cushing syndrome); suggestive manifestations include proximal muscle weakness, facial plethora, and supraclavicular fat pads. Hypercortisolism is not associated with MEN2 or sporadic MTC. It is occasionally seen in MEN1 (which is not associated with MTC), generally due to ACTH-secreting pituitary tumors or adrenal tumors. (Choice D) Primary hyperparathyroidism is a major manifestation of MEN1 (characterized by parathyroid, pituitary, and enteropancreatic endocrine cell tumors but not associated with MTC) and MEN2A (unlikely in a patient with negative RET germline mutation testing). Transient hypoparathyroidism can develop after thyroidectomy; patients are often given calcium supplementation, with the dose tapered off based on calcium (not parathyroid hormone) measurements. (Choices E and G) Thyroglobulin is a glycoprotein that serves as a substrate for the production of thyroid hormone. Levels are elevated in differentiated papillary/follicular thyroid cancer, for which it is used as a cancer marker, but not in MTC (which does not produce thyroid hormone). Thyroglobulin levels are also elevated in goiter, Graves disease, and thyroiditis. Similarly, thyroid scintigraphy uses radiolabeled iodine to assess iodine uptake as a marker for thyroid metabolic activity; papillary and follicular thyroid cancers take up radiolabeled iodine, but MTC does not. (Choice F) Serum thyroxine is used in the initial diagnosis of hypo- and hyperthyroidism. Thereafter, levothyroxine dose adjustments are primarily based on serum TSH, and thyroxine measurement has little utility. Educational objective: Medullary thyroid cancer arises from the calcitonin-secreting parafollicular C cells. Serum calcitonin levels correlate with the risk of metastasis and recurrence, and are measured serially following surgery. References: Medullary thyroid carcinoma. (http://www.ncbi.nlm.nih.gov/pubmed/23512389)

A 57-Year-Old Man Comes to the Office for Follow-Up After