Phenotype ± screening

MEN = multiple endocrine neoplasia; MTC = medullary thyroid cancer.

MEN = multiple endocrine neoplasia; MTC = medullary thyroid cancer.

patient is determined to be a gene carrier. Genetic screening is preferable to biochemical screening because once a patient is found to have no germline mutation in a family with a known RET germline mutation, no further follow-up is required. In contrast, biochemical screening (1) requires yearly calcitonin measurements into adulthood before a patient can be assured of not being at risk of developing MTC, (2)

can be associated with uncomfortable side effects from provocative stimulation test with pentagastrin or calcium, and (3) is less accurate than genetic testing because of a false-positive or false-negative test result.

Taking a comprehensive history and physical examination is integral to making the diagnosis, as well as determining the familial nature of MTC. Patients should be questioned specifically about

Genetic testing for RET germline mutation in exons 10, 11, 13, 14

Genetic testing for RET germline mutation in exons 10, 11, 13, 14

Figure 3-9. Screening, diagnostic, and treatment algorithm for patients suspected of having hereditary medullary thyroid cancer (MTC).

local symptoms and symptoms that can occur from hypercalcitoninemia secondary to widely metastatic disease such as diarrhea and flushing. A thorough family history is important and should include questions regarding a family history of thyroid cancer, pheochromocytoma, hyperparathyroidism, or unexplained sudden death in family members (secondary to an undiagnosed pheochromocytoma). On examination, the extent of the thyroid mass should be carefully determined as well as the presence of lym-phadenopathy and any phenotypic features of MEN type IIB. We recommend germline RET mutation testing in patients with apparently sporadic MTC as up to 7% of these cases might represent the index case in a kindred with a de novo mutation.21 This would help determine if other family members would be at risk of developing MTC.

In all patients with hereditary MTC, preoperative urinary catecholamine and metabolite levels should be measured to rule out a pheochromocytoma. Operating on a patient with an undiagnosed pheochromocytoma can be catastrophic. We also recommend preoperative serum calcium levels to rule out hyperparathyroidism. Because the penetrance of hyperparathyroidism and pheochromocytoma in MEN type IIA is variable, some patients may have a pheochromocytoma even if no one in the kindred had a pheochromocytoma or hyperparathyroidism, thus mimicking familial MTC.

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