Molecular Weight Forms of Immunoreactive Calcitonin in a Patient With Medullary Carcinoma of the Thyroid: Dynamic Studies With Calcium, Pentagastrin and Somatostatin

We have examined the characteristics of circulating immunoreactive human calcitonin (IR-hCT) by studying its different molecular weight (MW) forms under various secretory conditions in a patient with medullary carcinoma of the thyroid. Plasma IR-hCT (318 mg/l basal) increased 9 and 12 times, respectively, after calcium (0 . 3 mg/kg/min over 10 min i.v.) and pentagastrin (3 . 2 microgram i.v.) administration. Somatostatin infusion (500 microgram/h) caused a 41% decrease in plasma IR-hCT and markedly diminished the responses to both pentagastrin and calcium. Sephadex G50 chromatography separated different IR-hCT forms: hCT itself predominated after stimulation with either calcium or pentagastrin (52% and 62%, respectively), while it was reduced in the basal state (33%) and following somatostatin (11%); reciprocal changes were observed for the higher MW forms. Under denaturing conditions, with or without reducing agent, total plasma IR-hCT was resolved into one major peak co-eluting with 125I-hCT. Thus, the hCT monomer appears to be the major secretory product of the medullary carcinoma of the thyroid studied here. The predominance of higher MW forms in the basal state reflects their slower plasma disappearance rate. These high MW forms are mainly the result of aggregation or non-covalent protein binding of the hCT monomer.