Hyperparathyroidism associated with malignant tumors of nonparathyroid origin

Abstract

Seventy‐three cases of hyperparathyroidism associated with malignant tumors of nonparathyroid origin, including 9 previously unpublished cases, are reviewed. Clinical correlation with tumor treatment and recurrence suggests that the tumors elaborate a substance with parathyroid hormone activity. Immunochemical and physicochemical data indicate a close similarity to, or identity with, parathyroid hormone. The hypothesis is advanced that the mechanism of production of a substance with parathyroid hormone activity by nonparathyroid neoplasms is a process of derepression of the coded genetic sequence that specifies synthesis of parathyroid hormone. This hypothesis leads to the predictions that such neoplastic cells are prepared with the protein synthetic machinery to produce the specified polypeptide structure and that the most probable polypeptide sequence for the substance is one identical with parathyroid hormone. An unexplained histologic association of chemical hyperparathyroidism with squamous cell and of hyperadrenocorticism with oat cell carcinoma of the lung is emphasized.

Hypercalcaemia in malignant lymphoma

“…In Case 1 the hypercalcaemia was responsible for the patient's stuporous condition and was therefore rapidly identified but in the other 2 cases the high serum calcium level might easily have been overlooked and it may be that the overall incidence of this complication of malignant lymphoma has been underestimated. Cases of hypercalcaemia with malignant disease, especially where there is an associated low or low normal serum phosphate and an absence of radiological evidence of bone involvement, have been regarded as examples of pseudohyperparathyroidism (Tashjian, Levine and Munson, 1964;Munson, Tashjian and Levine, 1965;Sherwood et al, 1967;Omenn, Roth and Baker, 1969) although adequate parathyroid hormone and radio-immunoassay data have rarely been obtained. It now seems likely that in the majority of cases parathyroid hormone-like activity produced ectopically by the tumour is not the underlying mechanism of the hypercalcaemia (Powell et al, 1972), and other mechanisms have been postulated.…”

Twenty-five years of PTHrP progress: From cancer hormone to multifunctional cytokine

“…Fuller Albright in 1941 (1), when discussing a patient with renal carcinoma, a solitary metastasis and hypercalcemia, suggested that some tumors might cause hypercalcemia by secreting PTH or something very like it. As with many of his predictions he was ultimately proved correct, but not before the passing of a few decades during which the concept of “ectopic PTH production” by cancers was promulgated as the cause of non-metastatic hypercalcemia (2;3). Doubts began to appear in the 1970’s, when improved radioimmunoassays for PTH indicated that the immunoreactivity in tumor or plasma of patients with cancer differed from authentic PTH (4–7), and with some assays PTH immunoreactivity could not be detected at all (8).…”

Osteoblast-Derived PTHRP and Breast Cancer Bone Metastasis

“…The rest of the PTHrP amino acid sequence is unique, however, and confers to the molecule many properties resulting from signal transduction cascades and nuclear translocation distinct from those ofPTH (6). PTHrP acts as an autocrine, paracrine, or intracrine factor in a wide range of developmental and physiological processes (7,8), it has growth-promoting and antiapoptotic propenies (6), and it plays a crucial role in the development of the mammary gland andskeleron (8)(9)(10). Of special imerest is the association ofPTHrP \.\-'ith oncologic pathologies such as breast cancer (11,12) and lung (13)(14)(15), prostate (16)(17)(18), renal (19), colorectal (20)(21)(22), skin (23,24), and gastric carcinomas (25,26).…”