calcitonin and Pituitary-Neoplasms

Rat pituitary tumors induced by synthetic salmon calcitonin (TZ-CT) were studied by the indirect peroxidase-labeled antibody method, together with ultrastructure and serum hormone measurement. Immunohistochemically, TZ-CT-induced pituitary tumors showed staining for only rLH alpha subunit, and were negative for other peptide hormones including GH, PRL, alpha MSH and ACTH, and the beta subunit of glycoprotein hormones. Electron microscopic examination showed that the majority of tumor cells possessed numerous small secretory granules, 100 to 200 nm in diameter. The serum PRL concentrations of rats with TZ-CT-induced pituitary tumors were markedly elevated, but not beyond 130 ng/ml. From our data, TZ-CT-induced pituitary tumors are considered to be endocrinologically inactive and to produce alpha subunit. Furthermore, these tumors are thought to be potentially useful models of alpha subunit-producing pituitary tumors in humans. This is the first report to document the tumorigenesis of alpha subunit-producing pituitary tumors in rats after long-term treatment with calcitonin.

Topics: Animals; Calcitonin; Immunoenzyme Techniques; Male; Pituitary Hormones, Anterior; Pituitary Neoplasms; Rats; Rats, Inbred Strains

Calcitonin is widely used in the treatment of post-menopausal osteoporosis. The present study was designed to investigate the effects of salmon calcitonin (SCT) on the incidence of the pituitary tumors in Sprague-Dawley (SD) rats. Subcutaneous injections of SCT at a dose of 160 IU/kg/day for 6 months reduced body weight and induced one pituitary hyperplasia and three pituitary adenomas in 4 of 5 animals, while 5 controls did not show any changes. Prolactin-positive cells were located at the periphery of the affected pituitaries adjacent to the prolactin-negative adenomas. In addition, serum concentrations of prolactin and TSH were lower than in the controls, although serum calcium or LH levels were not significantly different from the controls. Among 7 animals treated with SCT for 6 months followed by no medication for another 6 months, 5 adenomas were detected, one of which had invasive growth toward the adjacent tissue, whereas only one adenoma was found in 9 controls. These results suggest that SCT administration at a high dose may induce the formation of pituitary adenoma, or may accelerate the development of spontaneous pituitary adenomas, some of which show frequent mitotic figures and invasive growth into the surrounding tissue, possibly resulting in malignant transformation. This indicates the need for caution in considering whether calcitonin injections into patients with osteoporosis as well as Paget's disease may induce such pituitary tumors.

Topics: Adenoma; Animals; Calcitonin; Calcium; Dose-Response Relationship, Drug; Injections, Subcutaneous; Luteinizing Hormone; Male; Organ Size; Pituitary Gland; Pituitary Neoplasms; Prolactin; Radioimmunoassay; Rats; Rats, Inbred Strains; Thyrotropin