Which of the following statements regarding medullary carcinoma of the thyroid are true?

a. Bilateral medullary carcinoma of the thyroid occurs in every patient with multiple endocrine neoplasia 1, 2a or 2b

c. 20% of medullary carcinoma of the thyroid cases are familial

d. Provocative testing with pentagastrin and calcium infusion for family members at risk for medullary carcinoma of the thyroid is diminished in importance by the recent development of specific genetic testing

Medullary thyroid carcinoma accounts for about 10% of all thyroid malignancies, and 20% of cases occur in the familial setting of MEN 2a, MEN 2B, or familial non-MEN medullary thyroid carcinoma. It is usually the first tumor that develops in these patients and typically occurs in the second or third decade of life. Tumors are virtually always bilateral and develop in multiple areas of the middle and upper portions of the thyroid lobe. Detection has historically been based on elaboration of calcitonin, particularly in response to provocative testing by the potent secretagogues calcium and pentagastrin. Patients with medullary carcinoma of the thyroid have striking increases in plasma calcitonin levels after provocative testing, which allows them to be readily identified. By employing provocative testing in kindred members at risk for disease, medullary carcinoma of the thyroid was diagnosed at a preclinical stage, and a greater percentage of these patients were cured by surgical therapy. With genetic testing now available, early treatment of medullary thyroid cancer should be possible for all affected people, to hopefully enhance the number of people cured of this cancer. The MEN 1, 2a and 2b syndromes are inherited in an autosomal dominant fashion with complete penetrance but variable phenotype. Bilateral medullary carcinoma of the thyroid occurs in every affected patient.