Natural History of Familial Medullary Thyroid Carcinoma

Abstract

To detect familial medullary thyroid carcinoma in a premetastatic stage, we administered tests provocative of calcitonin secretion (infusion of calcium or pentagastrin or both) each year for seven years to members of a pedigree now numbering 107. Since 1970, 21 patients converted from normal to abnormal secretory responses (two separate tests in which calcitonin levels exceeded 0.58 ng per milliliter). Twenty of 21 glands removed showed C-cell hyperplasia, and eight of the 20 also showed foci of carcinoma. As compared to the 12 patients with tumors detected during the first year of screening, all of whom had bilateral carcinoma (seven of 12 with local metastases), later carcinomas were smaller (mean diameter of 0.2 vs. 0.8 cm), were unilateral (in all but two cases) and occurred in younger patients (mean age of 14.9 vs. 36.4 years), and none had detectable metastases.

Advances in risk-oriented surgery for multiple endocrine neoplasia type 2

“…The advent of sensitive calcitonin, catecholamine and parathyroid hormone assays and DNA-based screening programs changed the landscape for MEN2 (Graze et al 1978, Machens et al 2013a. Biochemical (i.e., calcitonin) screening was shown to be more sensitive than anatomical screening (i.e., neck ultrasonography) for microscopic disease (i.e., MTC) in asymptomatic children at risk of MEN2A (Morris et al 2013).…”

Screening for Familial Medullary Thyroid Carcinoma: A Review

“…Although a rising trend of calcitonin values may be sought as evidence of progressive tumour development, it should not necessarily be expected. Many investigators have reported fluctuation in levels between successive tests, even a normal result between two clearly abnormal ones (Graze et al 1978), presumably because of day-to-day variation in the calcitonin stores in the C-cells.…”

“…On the face of it, therefore, the earlier the diagnosis is made, the better. (3) In centres where screening programmes were initiated several years ago, whereas the first round of screening yielded many family members with advanced disease, regular follow-up screening revealed individuals at the stage of C-cell hyperplasia or microscopic tumour (Graze et al 1978). Only prolonged follow up will prove that these screened individuals are in fact at very low risk of metastatic disease: it could be argued that there is a minority of individuals who have aggressive disease in whom the disease spreads early, and that screening, even at the earliest stage, may not be of benefit.…”

Medullary Thyroid Carcinoma Associated with RET Mutations Located in Exon 8

“…(Roman 2006, Wells 1994, Graze 1978. During the last decade, a great progress in the diagnostic identification of MTC has been made.…”