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An investigation was made of the increased serum calcitonin in patients with medullary thyroid cancer and bronchogenic carcinoma in order to determine whether these conditions can be differentiated immunochemically. Endogenous fractions of immunoreactive calcitonin were separated by gel filtration and radioimmunoassayed with calcitonin antibodies having different region specificities. The pattern of serum heterogeneity of patients with medullary thyroid cancer was characterized by the presence of at least seven different fractions of immunoreactive calcitonin, ranging from fraction I ([2267] 30 000 molecular weight (MW)) to fraction V ([ 223C] 2500 MW). In contrast, most patients with bronchogenic cancer had a predominance of high MW fractions (i. e. fractions I and II A). Following in vitro incubation of the serum, the typical large MW pattern of bronchogenic cancer serum could be converted to the more diffuse pattern seen in the serum of medullary thyroid cancer. We were able to differentiate, pre-operatively, the hypercalcitonaemia serum of medullary thyroid cancer patients from that of bronchogenic cancer patients by determination of the ratio of calcitonin as radioimmunoassayed with midportion versus carboxyl terminal antibody.When calcitonin (HCT), the hypocalcaemic hormone normally secreted by the thyroidal C-cells, was found to be greatly increased in the serum of patients with medullary thyroid cancer (Clark et al. 1969), it was assumed that hypercalcitonaemia would prove to be a marker exclusively for this tumour. Indeed.

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