Diagnosis, Pathophysiology and Management of Hypercalcemia in Malignancy: A Review of the Literature

Abstract

Hypercalcemia of malignancy is the most common life-threatening metabolic disorder in patients with advanced stage cancers and is a sign of poor prognosis. It usually presents with markedly elevated calcium level and is severely symptomatic. It is associated with hematological malignancies, such as multiple myeloma, non-Hodgkin lymphoma, leukemias and solid cancers, particularly renal and breast carcinomas as well as squamous cell carcinomas of any organ. Several mechanisms have been implicated in the development of hypercalcemia of malignancy amongst them the osteolytic related hypercalcemia, parathyroid hormone-related peptide (PTHrP) mediated hypercalcemia, extrarenal 1,25 dixydroxyvitamin D (calcitriol) mediated hypercalcemia and parathyroid hormone (PTH) related hypercalcemia either ectopic in origin or in patients with parathyroid carcinoma. Clinical history and and physical examination could point towards the correct diagnosis confirmed by the above-mentioned biochemical mediators of hypercalcemia. Early diagnosis and treatment lowering calcium levels in the blood can improve symptoms and the quality of life of these patients and avoid delays for further antitumor therapy.

Actualización: Fisiopatología, Diagnóstico y Manejo de la Hipercalcemia Maligna

“…El PTHrP parece no aumentar la producción de 1.25 dihidroxivitamina D, por lo cual la absorción intestinal de calcio y fósforo no está aumentada a diferencia de la hipercalcemia por producción ectópica de calcitriol; la hipercalcemia hormonal no aumenta los niveles de fósforo (1, 4). El segundo mecanismo fisiopatológico más frecuente corresponde a las metástasis osteolíticas, las cuales son responsables del 20% de los casos de hipercalcemia maligna (10,11). Las causas comunes de tales metástasis son mieloma múltiple, cáncer de mama y pulmón, seguido de leucemia y linfoma (11,12).…”

Patients’ values and other decisional factors regarding treatment of hypercalcemia of malignancy: A Systematic Review Protocol

“…In fact, one third of cancer patients will eventually experience hypercalcemia with the most common causes being breast cancer, lung cancer and multiple myeloma (2,3). HCM arises due to four main mechanisms: humoral secretion of parathyroid hormone related peptide (PTHrP) accounts for over 80% of cases and occurs most commonly in breast cancer and squamous cell carcinoma of the lung, head and neck, and the kidney, local osteolytic release of calcium, known as local osteolytic hypercalcemia (LOH), such as seen with multiple myeloma and some breast cancers, high levels of calcitriol (1,25-dihydroxyvitamin D) such as noted in leukemias, HTLV1, and some lymphomas, or secretion of the native parathyroid hormone (PTH) from a carcinoma, or ectopic PTH secretion by some cancers including neuroendocrine tumors (Table 1) (4,5). These include tumors in the head and neck, thorax, gastrointestinal system, or genito-urinary system (6).…”

Patients’ values and other decisional factors regarding treatment of hypercalcemia of malignancy: A Systematic Review Protocol

“…humoral secretion of parathyroid hormone related peptide (PTHrP) accounts for over 80% of cases and occurs most commonly in breast cancer and squamous cell carcinoma of the lung, head and neck, and the kidney, local osteolytic release of calcium, known as local osteolytic hypercalcemia (LOH), such as seen with multiple myeloma and some breast cancers, high levels of calcitriol (1,25-dihydroxyvitamin D) such as noted in leukemias, HTLV1, and some lymphomas, or secretion of the native parathyroid hormone (PTH) from a carcinoma, or ectopic PTH secretion by some cancers including neuroendocrine tumors (Table 1) (4,5). These include tumors in the head and neck, thorax, gastrointestinal system, or genito-urinary system (6).…”

“…Treatment of hypercalcemia of malignancy constitutes of hydration, calciuresis and inhibition of bone resorption (4,8), regardless of the operating mechanism ( Table 2). The e cacy of different bisphosphonates was investigated in several clinical trials to determine their value in HCM treatments (9)(10)(11)(12).…”