Hypercalcemia of malignancy: An update on pathogenesis and management

Abstract

Hypercalcemia of malignancy is a common finding typically found in patients with advanced stage cancers. We aimed to provide an updated review on the etiology, pathogenesis, clinical presentation, and management of malignancy-related hypercalcemia. We searched PubMed/Medline, Scopus, Embase, and Web of Science for original articles, case reports, and case series articles focused on hypercalcemia of malignancy published from 1950 to December 2014. Hypercalcemia of malignancy usually presents with markedly elevated calcium levels and therefore, usually severely symptomatic. Several major mechanisms are responsible for the development of hypercalcemia of malignancy including parathyroid hormone-related peptide-mediated humoral hypercalcemia, osteolytic metastases-related hypercalcemia, 1,25 Vitamin D-mediated hypercalcemia, and parathyroid hormone-mediated hypercalcemia in patients with parathyroid carcinoma and extra parathyroid cancers. Diagnosis should include the history and physical examination as well as measurement of the above mediators of hypercalcemia. Management includes hydration, calcitonin, bisphosphonates, denosumab, and in certain patients, prednisone and cinacalcet. Patients with advanced underlying kidney disease and refractory severe hypercalcemia should be considered for hemodialysis. Hematology or oncology and palliative care specialists should be involved early to guide the options of cancer targeted therapies and help the patients and their closed ones with the discussion of comfort-oriented care.

Metastatic T-cell lymphoma of unknown primary origin in a dog (Canis lupus familiaris)

“…Hypocalcemia observed in the dog was not consistent with the literature (MIRRAKHIMOV, 2015), since the majority of individuals with lymphoma present an increase in the serum calcium concentration due to the release of osteoclast activating factors, leading to an increase in bone resorption. This alteration is believed to be secondary to the production of parathyroid hormone-related protein (PTH) by neoplastic cells (BERGMAN, 2012;MIRRAKHIMOV, 2015). Hypocalcaemia was related to the likely occurrence of hypomagnesemia, vitamin D deficiency, massive cell lysis, osteoblastic metastasis, or low levels of PTH (FAROLFI et al 2015;OKAZAKI et al, 2017).…”

Synthetic biology-based cellular biomedical tattoo for detection of hypercalcemia associated with cancer

“…On the other hand, increasing blood Ca 2+ concentrations activate the calciumsensing receptor (CaSR), which acutely inhibits the secretion of PTH (15). Cancer is among the causes of hypercalcemia (16), and humoral hypercalcemia of malignancy is associated with a variety of cancers, including breast (5,16), colon (16), prostate (7), lung (17), and kidney cancers (18). It arises because the primary tumor, its metastases, or immune cells targeting the tumor secrete humoral factors (16) that act on bone, kidney, and intestine, thereby disrupting calcium homeostasis and resulting in increased blood-calcium concentration (19).…”

The coexistence of hypercalcemia and hypoglycemia in a patient with a renal tumor and B cell lymphoma

“…Hypercalcemia associated with cancer can be classified into four types: 1) local osteolytic hypercalcemia, results from the marked increase of osteoclastic bone resorption in areas surrounding the malignant cells within the marrow space, 2) humoral hypercalcemia of malignancy (HHM) which is caused by systemic secretion of PTHrP, and causes increased bone resorption and enhances calcium renal retention 3) 1,25-dihydroxyvitamin D secretion by some lymphomas and 4) ectopic secretion of authentic PTH, a rare cause of hypercalcemia (6)(7)(8)(9). HHM is the most common cause associated with cancer (6-9,10).…”