Humoral Hypercalcemia of Malignancy
Description
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