Impact of Prospective Screening for Multiple Endocrine Neoplasia Type 2

Prospective annual screening for hereditary medullary thyroid carcinoma (MTC) in the J-kindred, currently a 117-member family with multiple endocrine neoplasia type 2A, began in 1969. During the initial screening, 12 patients were found to have MTC. Subsequent screening has detected C-cell abnormalities (C-cell hyperplasia or microscopic MTC) in 22 of 23 addilional family members thyroidectomized for abnormal calcium- or pentagastrin-provocative calcitonin (CT) test results. Seven of the initial 12 patients thyroidectomized in 1970 to 1971 and 19 of 23 individuals thyroidectomized since 1971 remain disease-free by all criteria; three patients thyroidectomized since 1971 have had clearly abnormal serum CT measurements on one or more provocative tests. The significance of these abnormal test results is unclear because normal values were obtained when the samples were measured in another CT radioimmunoassay. Urine catecholamine abnormalities have been detected in 19 family members since 1969, resulting in ten bilateral and eight unilateral adrenalectomies. Four of the patients with initial unilateral adrenalectomy required reoperation for a pheochromocytoma in the contralateral gland nine to 13 years later. Hyperparathyroidism has not been observed in any of the family members with early C-cell disease. We conclude that prospective screening for hereditary MTC predicts histologic C-cell abnormalities in affected individuals, and follow-up of these patients provides support for the conclusion that early thyroidectomy is curative in most patients

High-Sensitivity Serum Calcitonin Assays Applied to Screening for Thyroid C-Cell Disease in Multiple Endocrine Neoplasia Type 2A

Two serum calcitonin assays with sensitivities ≤ 10 pg/mL were compared to our standard radioimmunoassay (sensitivity 100 pg/mL) in multiple endocrine neoplasia type 2A (MEN 2A) screening. Values from the Nichols displacement radioimmunoassay averaged 38% higher than values from the CIS immunoradiometric assay; values from both were highly correlated, r = 0.845. In three individuals, both of the newer assays revealed abnormalities in pentagastrin tests three to four years before abnormalities were detected by the standard assay. Pentagastrin tests after total thyroidectomy were assayed by the newer methods in patients with medullary thyroid carcinoma (MTC) diagnosed at initial testing (group I); in patients with early MTC diagnosed by prospective screening (group ll); and in patients with pure C-cell hyperplasia detected by prospective screening (group III). At least 64% of group I, at least 25% of group II, but none of group III had detectable postoperative C-cell function. Conclusions: 1) The previous estimate of 12 years as median age of onset of C-cell disease in MEN 2A is probably three to four years too old. 2) Patients diagnosed with early MTC by screening had not necessarily skipped a preneoplastic phase of C-cell hyperplasia. At least some early disease was not detected by the standard assay. Higher sensitivity assays should improve screening for C-cell disease by earlier disease detection. 3) Biochemical cure by thyroidectomy after the development of MTC is not as frequent as previously thought, but the apparent cure rate of pure C-cell hyperplasia remains 100%