Humoral Hypercalcemia of Malignancy


Paraneoplastic disease caused by tumors as a result of various forms of cancer. HHM causes bone osteolysis and an increase in calcium levels in the body.


  • mutated proteins are released from malignant cells
  • Parathyroid hormone (PTH) mutated by the tumors, produce PTH-related peptides (PTHrP)
  • same N-terminal end, allows binding to parathyroid hormone receptor 1 (PTH1R)

Correct vs. Incorrect Mechanism

  • normal PTHrP: regulates Ca levels
  • PTHrP associated with HHM: bone resorption and Ca reabsorption

Signal Transduction Pathway Involved

cyclic adenosine monophosphate/protein kinase A (cAMP/PKA) and protein lipase C/protein kinase C (PLC/PKC)


  • lethargy
  • depression
  • cognitive disfunction
  • anorexia
  • nausea
  • vomiting
  • polyuria
  • polydipsia
  • renal or biliary stones
  • bone pains


  • Hydration with saline- promotes calcium excretion, takes effect within two days but treatment can be reversed if discontinued

  • Bisphosphonates- inhibit osteoclasts, prevent bone formation, and reduce calcium levels, administered through IV, takes effect and lowers calcium levels to normal within two to three days

  • Plicamycin- lowers and maintains calcium levels, administered as an IV bolus or infusion after hydration

  • Calcitonin- used to lower serum calcium acutely and cure renal insufficiency, administered through IV or SQ and takes effect within hours

Direction of Research

  • importance of osteoclasts in the development of HHM
  • more testing on drugs such as bisphosphonates

Works Cited

Bressler, L. (1997, November 1). CANCER ASSOCIATED HYPERCALCEMIA. Retrieved December 4, 2015, from

Kumar, G. (n.d.). Tumor lysis syndrome and hypercalcemia of malignancy. Retrieved December 4, 2015, from

Mechanisms and treatment of hypercalcemia of malignancy. (2011, December 1). Retrieved December 4, 2015, from

Mundy, G., & Edwards, J. (2008, February 6). PTH-Related Peptide (PTHrP) in Hypercalcemia. Retrieved December 4,

2015, from T. Shu, Wessel P. Dirksen, Katherine N. Weibaecher and Thomas J. Rosol (2011). Mechanisms of Humoral Hypercalcemia

of Malignancy in Leukemia/Lymphoma, T-Cell Leukemia, Dr Olga Babusikova (Ed.), ISBN: 978-953-307-400-9, InTech,

Available from: leukemia/mechanisms-of-humoral-hypercalcemia-of-malignancy-