Human calcitonin: Immunologic assay, cytologic localization and studies on medullary thyroid carcinoma

Abstract

Current assay methods do not define the absolute concentrations of calcitonin in plasma of normal man. In our experience, the concentration was <100 pg/ml in more than 75 per cent of 2,000 normal subjects and <250 pg/ml in the remainder. Low circulating calcitonin levels in man are in part due to the small number of calcitonin-producing cells (C cells) in the normal thyroid gland. The distribution of these cells has been mapped by using an immunoperoxidase bridge technic that identifies calcitonin-containing cells. Normal C cells are both parafollicular and intrafollicular in location and are concentrated, singly or as groups of 2 or 3 cells, in the middle third of the lateral lobes lying deep within the gland along a hypothetical central axis of each lobe. Distribution of calcitonin content within the gland correlates well with C cell distribution. Medullary carcinoma of the thyroid gland (MTC) is a calcitonin-producing tumor of C cells that responds to a simple calcium infusion test by increasing the rate of calcitonin secretion These findings form the basis for using measurements of calcitonin in serum as a means to identify, at an early stage of the disease, persons at risk for the familial form of the tumor. In studies of five kindreds, preoperative prediction of MTC was correct in 38 persons on the basis of serum calcitonin responses to calcium infusion; in fewer than 20 per cent of these cases was there any other clinical or laboratory evidence of disease. In four additional persons, annual testing revealed minimal progressive increases in serum calcitonin concentrations, and thyroid glands removed surgically showed focal hyperplasia of C cells in the middle and upper thirds of both lateral lobes. The prognosis after treatment early in the disease requires long-term follow-up; however, 40 to 50 per cent of such persons studied have had unmeasurable serum calcitonin values postoperatively (even after calcium infusion) for periods of up to 2 to 3 years. Preliminary findings suggest that the amyloid of MTC may be composed, in part, of calcitonin.