Lori J. Wirth, MD: The epidemiology of medullary thyroid cancer [MTC] is notable for the fact that it is a rare cancer. MTC accounts for less than 5% of all thyroid cancers that are diagnosed in the United States and worldwide. For the diagnostic work-up for MTC, typically patients will present with a neck mass that’s found incidentally on another imaging study or a neck mass that they notice or that their primary care physician notices on physical exam.

The next step typically is an ultrasound-guided fine-needle aspiration, and many times a cytologic diagnosis of medullary thyroid cancer will be made at that time. Sometimes it’s difficult for cytopathologists to put the nickel down on the diagnosis. Other testing can be helpful as well, particularly if MTC is suspected on cytology, a serum calcitonin can easily be checked to confirm the diagnosis because, as you know, medullary thyroid cancers do secrete calcitonin. That will typically be elevated at the time of diagnosis.

Following that, many patients will be referred to a surgeon for surgery. The 1 important thing to be aware of is that patients can have hereditary medullary thyroid cancer syndromes. Those MEN2A [multiple endocrine neoplasia type 2A] and MEN2B [multiple endocrine neoplasia type 2A] syndromes are also associated with pheochromocytoma. Before patients go to surgery when they have a new diagnosis of MTC, they should have pheochromocytoma ruled out on typically blood studies before they’re on the operating room because of the potentially devastating consequences of an unknown pheochromocytoma intraoperatively.

Do patients need to have a distant metastatic disease work-up prior to surgery? Not necessarily, because thyroidectomy plus nodal dissection to remove the disease that’s in the neck would be indicated even if a patient did have metastatic disease in most cases. Often, patients will proceed to surgery and then have further work-up subsequently. Further work-up can be determined in part by the postoperative calcitonin and CEA [carcinoembryonic antigen] levels. If postoperatively calcitonin and CEA levels are elevated, then certainly further work-up needs to be done to rule out distant metastatic disease.

It’s important to note that the half-life of the serum calcitonin and CEA is rather long, so you don’t want to look 2 weeks after surgery. Give it some time—4 to 6 weeks after surgery—to account for the longer half-life before measuring. When distant metastases are suspected based on serum calcitonin and CEA, then neck and chest CT can be done to rule out any residual neck disease and rule out mediastinal hilar adenopathy and lung metastases. In looking for disease beyond the chest, 1 of the most frequent sites of disease is liver metastases that can be difficult to find on routine abdominal CT. Liver-directed imaging with either liver sequences on CT scan or, perhaps even better, MRI can be helpful. We can also see small bone metastases in patients, so careful attention for bone metastases may be indicated as well.

Lastly, I note that many medullary thyroid cancers aren’t particularly FDG-avid, so a standard FDG [fluorodeoxyglucose]–PET [positron emission tomography]–CT may not be all that helpful. When available, a gallium Ga 68-DOTATATE PET CT, however, may be helpful.

Transcript Edited for Clarity