Adrenocorticotropin and Calcitonin in Medullary Thyroid Carcinoma: Frequency of Occurrence and Localization in the Same Cell Type by Immunocytochemistry*

Abstract

The frequency and distribution of ACTH immunoreactivity was assessed immunocytochemically in nine cases of medullary thyroid carcinoma by employing both indirect immunofluorescent and indirect immunoperoxidase techniques. ACTH immunoreactivity was demonstrable to a variable extent in all nine cases. Generally, in less cellular amyloid-rich neoplasms only scattered individual cells contained ACTH and immunostaining of amyloid was not observed, whereas in more densely cellular neoplasms, sheets of cells stained positively and intracytoplasmic granular staining was readily evident by both immunocytochemical techniques. Scattered para- and intrafollicular cells were seen to contain ACTH immunoreactivity in thyroid follicles adjacent to the neoplasms, and clusters of hyperplastic C cells adjacent to the neoplasms were also seen to stain positively on occasion. By sequential immunoperoxidase staining, ACTH and calcitonin were localized within the tumor tissue to the same cell type. The concurrent localization of both ACTH and calcitonin emphasizes the close biosynthetic relationship between the two hormones which may now be further explored by biochemical characterization, employing the protein synthetic machinery of the C cell. The high incidence of ACTH localization demonstrated in these tumors, relative to the few reported cases of ectopic Cushing's syndrome with medullary thryoid carcinoma, suggests either that the ACTH identified, if biologically active, is released only infrequently or that a higher incidence of ectopic Cushing's syndrome exists in association with medullary thyroid carcinoma than has been previously suspected.