Natural history of familial medullary carcinoma of the thyroid gland (MCT) pheochromocytoma syndrome and the identification of preneoplastic stages by screening tests. A five year report

Two kindreds (109 patients, ages 4-68) have been followed prospectively for five years with annual provocative calcium infusion tests of calcitonin secretory reserve and urinary catecholamine and/or metabolite excretion. Pentagastrin bolus, 0.5 μg/kg i.v., has also been used and is equally valuable in detecting C cell disease. In the first year of screening, 12 occult cases of MCT were detected by provocative tests (peak calcitonin > 0.55 ng/ml). 8 of 12 were found to have local metastasis at the time of operation (thyroidectomy with central node dissection). In 5 of the 8, calcitonin reserve dropped to normal after surgery and remains normal. Over the next 4 years 8 previously normal patients have developed abnormal calcitonin reserve. Four have C cell hyperplasia of the thyroid, 1 has normal appearing C cells with increased gland content of calcitonin, 3 await surgery. The authors conclude that MCT is preceded by C cell hyperplasia. Annual provocative testing has in every case detected a preneoplastic stage. Eight patients initially were found to have pheochromocytoma, all without hypertension. Four non hypertensive patients have subsequently developed increased epinephrine excretion. In the 2 operated cases adrenal medullary hyperplasia has been detected suggesting that the pheochromocytoma may develop on a background of diffuse medullary hyperplasia analogous to the C cell hyperplasia which antedates MCT.