Humoral Hypercalcemia of Malignancy

Description

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.

Causes

  • 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)

Symptoms

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

Treatments

  • 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

http://www.uic.edu/classes/pmpr/pmpr652/Final/bressler/cancerhyper.html

Kumar, G. (n.d.). Tumor lysis syndrome and hypercalcemia of malignancy. Retrieved December 4, 2015, from http://www.slideshare.net/gk_crj/tumor-lysis-syndrome-and-hypercalcemia-of-malignancy

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

http://www.ncbi.nlm.nih.gov/pubmed/21897221

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

2015, from http://jasn.asnjournals.org/content/19/4/672.fullSherry 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: http://www.intechopen.com/books/t-cell- leukemia/mechanisms-of-humoral-hypercalcemia-of-malignancy-

in-leukemia-lymphoma