Natural history of the familial medullary thyroid carcinoma pheochromocytoma syndrome and the identification of preneoplastic stages by screening studies: a five year report

In the fifth year of follow up, 8 of 12 patients thyroidectomized for medullary thyroid carcinoma (MTC) diagnosed solely by abnormal calcitonin values, were disease free by all criteria. Elevated calcitonin levels were the only manifestation of active disease in 3 patients with presumed metastases. Routine annual screening of susceptible individuals is a practical measure and has in 6 cases detected the premalignant condition of C cell hyperplasia and in 1 patient a premetastatic state of MTC. It is premature to conclude that yearly screening is sufficient to detect all cases of premetastatic disease and for this reason we are recommending a yearly screen with pentagastrin and calcium tests and the more convenient pentagastrin test at 6 month intervals for those in the high risk age group between 8 and 18. If screening at such intervals proves to be ineffective in preventing the disease in every case, consideration must be given to prophylactic thyroidectomy although we are not currently recommending this procedure. Pentagastrin injection is often a more effective secretagogue for calcitonin than is calcium infusion, but this is not uniformly true. We therefore recommend use of both tests as the most appropriate screening procedure. Epinephrine is a major secretory product of pheochromocytomas in the J kindred and sequential E/N ratios may be of use in the early detection of pheochromocytoma in other kindreds. Adrenal medullary hyperplasia has been found in 3 adrenal glands and is probably a preneoplastic condition analogous to C cell hyperplasia.