Parathyroid hormone‐related protein in hypercalcaemia associated with haematological malignancy

Abstract

The incidence of hypercalcaemia and its association with humoral mechanisms involving parathyroid hormone-related protein (PTHrP), parathyroid hormone (PTH), or 1.25(OH)2 vitamin D were assessed in a prospective study of patients admitted to a clinical haematology unit. Hypercalcaemia was detected in 18/165 patients, and was due to primary hyperparathyroidism in 3/17 patients in whom results of humoral mediator assessments were obtained. In the other patients, hypercalcaemia was associated in nine instances with myeloma, in five with B-cell non-Hodgkin's lymphoma (NHL), and in one with myeloid neoplasia. No evidence was obtained of a humoral mechanism involving 1.25(OH)2 vitamin D, but elevated circulating levels of PTHrP, comparable with those in humoral hypercalcaemia of malignancy, were present in 2/4 patients with NHL, and in 3/9 with myeloma. The relationship between presence or absence of elevated circulating PTHrP, and presence or absence of hypercalcaemia during the course of treatment, indicated PTHrP was involved in the production of hypercalcaemia. Such an association raises the possibility that PTHrP released by neoplastic cells in these disorders acts in a paracrine manner to produce local bone resorption, and when produced in greater amounts causes elevated circulating levels which make an additional humorally-mediated contribution to the development of hypercalcaemia.

PTHrP drives breast tumor initiation, progression, and metastasis in mice and is a potential therapy target

“…Of special interest is the association of PTHrP with 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). Circulating levels of PTHrP generally correlate with the more advanced stages of cancer (20,(27)(28)(29)(30)(31)(32), and PTHrP regulates the expression of several tumor-relevant genes (33). Despite the frequent association of PTHrP dysregulation with many tumor types, a precise and direct role for PTHrP in cancer development and progression has been difficult to prove, and its involvement in tumor initiation in vivo and in critical steps of malignant conversion is not clear.…”

Hypercalcemia due to sun exposure in a patient with multiple myeloma and elevated parathyroid hormone-related protein

“…In our patient, the increased availability of substrate (25OHD) during the summer may not be the sole factor which caused the unregulated production of calcitriol. Recently, the production and secretion of PTHrP by the MM cells in vitro and in vivo have been reported to occur very often (3,4,8). Simultaneous production of both IL-6 and PTHrP by a myeloma cell line has also been reported (9).…”

“…Recently, the secretion of PTHrP by the MM cells has been identified in a large proportion of hypercalcemic patients with this malignancy (3,4). These hypercalcemic agents apparently act in a paracrine manner stimulating the osteoclasts surrounding the myeloma cells.…”

Accelerated Phase of Chronic Myeloid Leukemia Presenting with Hypercalcemia and a Mediastinal Mass

“…However, humoral hypercalcemia is now recognized as the dominant form of malignancy-associated hypercalcemia, accounting for as much as 80% of the cases [11]. Although increased production of calcitriol was described in hypercalcemia associated with Hodgkin’s disease and non-Hodgkin lymphoma [12], there is substantial evidence that hypercalcemia of malignancy is most frequently caused by PTHrP released from the malignant cells [13]. …”