C-Cell Hyperplasia Preceding Medullary Thyroid Carcinoma

Two sisters at risk for hereditary medullary carcinoma and having small but progressive increases of serum calcitonin in response to calcium infusion underwent thyroidectomy. The thyroid glands were studied for C-cell distribution. Middle and upper portions of the lateral thyroid lobes showed marked increases and clustering of calcitonin-containing cells in comparison with normal thyroid glands. Elevated calcitonin content (670 to 4100 Medical Research Council mU per gram), as compared to similar regions in normal thyroid tissue (<0.6 to 50.0 Medical Research Council mU per gram), correlated precisely with the cytologic localization. Histologic characteristics of the cells had the appearance of a preinvasive hyperplastic process. A third case from another kindred was studied with similar findings. C-cells thus appear to be distributed inhomogeneously in normal human thyroid tissue; an early change in persons destined to development of hereditary tumors of these cells is a multicentric, but anatomically restricted, increase in numbers of cells. (N Engl J Med 289:437–441, 1973)