Hypercalcemia and cancer: Differential diagnosis and treatment

Abstract

Incidentally detected hypercalcemia usually presents in an indolent manner and is most likely caused by primary hyperparathyroidism. In contrast, hypercalcemia in the patient with a history of cancer presents in a wide range of clinical settings and may be severe enough to warrant hospitalization. This form of hypercalcemia is usually secondary to hypercalcemia of malignancy and can be fatal. Hypercalcemia of malignancy is most commonly mediated by tumoral production of parathyroid hormone–related protein or by cytokines activating osteoclast degradation of bone. The initial workup, differential diagnoses, confirmatory laboratory testing, imaging, and medical and surgical management of hypercalcemia are described in the patient with cancer.

Cinacalcet for the Treatment of Humoral Hypercalcemia of Malignancy: An Introductory Case Report with a Pathophysiologic and Therapeutic Review

“…Hypercalcemia of malignancy (HCM) is most commonly mediated by parathyroid hormonerelated protein (PTHrP), wherein it is referred to as humoral HCM (HHM). The development of HHM is an ominous sign in the course of malignancy, where the mean survival after development of hypercalcemia is between 2 and 3 months and is often related to progression of the underlying malignancy [1]. Acute symptoms of HHM are generally managed with intravenous (IV) fluids, IV bisphosphonates (BPs), and subcutaneous calcitonin [1,2].…”

“…The development of HHM is an ominous sign in the course of malignancy, where the mean survival after development of hypercalcemia is between 2 and 3 months and is often related to progression of the underlying malignancy [1]. Acute symptoms of HHM are generally managed with intravenous (IV) fluids, IV bisphosphonates (BPs), and subcutaneous calcitonin [1,2]. Chronically, intermittent administration of IV BPs and/or subcutaneous denosumab on an outpatient basis are often used to manage HHM [1,2].…”

“…A trial of oral cinacalcet was initiated and improved calcium levels for 2 months despite a progressive rise in PTHrP and prior to subsequent disease progression. Based on the current body of literature, we propose that this calcium-lowering effect of cinacalcet occurs due to a potential effect on renal calcium excretion.Abnormal Renal Calcium Handling Related to PTHrP HHM is the most common etiology of malignancy-related calcium dysregulation and accounts for ∼80% of HCM cases [1,2]. Most often, it occurs in solid tumors of the lung, head and neck, esophagus, skin, cervix, breast, kidneys, prostate, and bladder [1, 2].…”

“…Most often, it occurs in solid tumors of the lung, head and neck, esophagus, skin, cervix, breast, kidneys, prostate, and bladder [1, 2]. These patients do not have bone metastases, and hypercalcemia occurs via PTHrP actions in both the bones and kidneys [1,2]. PTHrP has some homology with PTH, especially at the amino-terminus, and binds to the PTH-1 receptor, resulting in increased skeletal efflux of calcium and increased renal reabsorption of calcium by the mechanisms described earlier for PTH ( Fig.…”

“…Abnormal Renal Calcium Handling Related to PTHrP HHM is the most common etiology of malignancy-related calcium dysregulation and accounts for ∼80% of HCM cases [1,2]. Most often, it occurs in solid tumors of the lung, head and neck, esophagus, skin, cervix, breast, kidneys, prostate, and bladder [1, 2].…”