2. Introduction
Normal range: 2.2-2.6 mmol/L
Free Ca2+ ≥ 3.0 mmol/L = EMERGENCY [1]
Ca2+ ≥ 4.0 mmol/L leads to death [2]
Hypercalcaemia develops in 10% of cancers [3]
Poor prognosis
o 80% die in first year even with treatment [2,4]
Most common in breast cancer, multiple myeloma and
lung cancer (also prostate cancer, lymphoma, and renal
cancer) [1-3]
50% of inpatient hypercalcaemia is caused by cancer [3]
3. Calcium Physiology
Adapted from Wallis DE, Penckofer S and Sizemore GW, 2008. [5]
PT
H
↑Ca2+
calcidiol calcitriol
Vitamin D3
from SKIN
calcitonin
-
+
+
+
+
+
-
-
4. Aetiology
Adapted from Wallis DE, Penckofer S and Sizemore GW, 2008. [5]
OSTEOLYSIS
Tumour cells activate
osteoclasts locally – bone
resorption
HUMOURAL
MEDIATORS
Parathyroid-related
protein (PTHrP)
expressed in
“normal” cells. Also
secreted by tumour
cells.
Acts like PTH:
• Bone
resorption
• Distal tubule
calcium
resorption DEHYDRATION
Calcium is a potent diuretic
– salt and water loss
6. Investigations
FBC
U&Es, corrected serum Ca2+, PO4-, Mg2+
LFTs
Plasma PTH ?and PTHrP [6]
Calcidiol and calcitriol levels [6]
ECG
o PR interval elongation,
o shortening of QT interval or
o a wide QRS complex
7. Management
Consider the aims of treatment!
1. Rehydration- IV 0.9% saline and monitor via catheter.
Ideally 3-6 L/24h.
2. Encourage mobility
3. Ca2+ restriction
4. Monitor U&Es- Ca2+ and albumin daily and monitor K+ and
Mg2+
5. Bisphosphonates- if 24 hours rehydration does not lower
corrected Ca2+ but risk metastatic calcium phosphate
deposition.[7]
IV Pamidronate infusion. Takes 48 hours to work. Ca2+
stabilises in 3-7 days. Works in 70% of patients but need to
repeat in 1-3 weeks as high recurrence rate. [4]
9. References
1. Cassidy J, Bissett D, Spence R, Payne M, editors. Oxford handbook of
oncology. 3rd ed. Oxford: Oxford University Press; 2010.
2. Watson M, Barrett A, Spence RAJ, Twelves C. Oncology (oxford core
texts). 2nd ed. Oxford: Oxford University Press; 2006.
3. Bower M, Waxman J. Oncology (lecture notes). 2nd ed. Chichester:
Wiley-Blackwell; 2010.
4. Legrand SB. Modern management of malignant hypercalcaemia. Am J
Hosp Palliat Care. 2011 Nov;28(7):515-7.
5. Wallis DE, Penckofer S, Sizemore GW. The “sunshine deficit” and
cardiovascular disease. Circulation. 2009 Sep 30;118(14):1476-85.
6. Clinical Key Elsevier: Hypercalcaemia associated with malignancy
[online]. 2012. [Accessed 2014 Feb 27]: [1 screen]. Available from:
https://www.clinicalkey.com/#!/ContentPlayerCtrl/doPlayContent/21-
s2.0-2001273/{"scope":"all"}
7. Donald A, Stein M, Scott Hill C. The hands-on guide for junior doctors.
4th ed. Chichester: Wiley-Blackwell; 2011
8. Hu MI, Glezerman I, Leboulleux S, et al; Denosumab for patients with
persistent or relapsed hypercalcemia of malignancy despite recent
bisphosphonate treatment. J Natl Cancer Inst. 2013 Sep
18;105(18):1417-20. doi: 10.1093/jnci/djt225. Epub 2013 Aug 29.
Editor's Notes
PTHrP is a normal gene product expressed in a wide variety of neuroendocrine, epithelial, and mesoderm-derived tissues.
Hypercalciuria: excessive calcium in the urine. Normal 100-250 mg/24h
Nephrocalcinosis: Calcium deposits in the renal parenchyma
FBC- Hb will decrease after fluids are given
U&Es (for general renal function), corrected serum Ca, PO (for PTH releaseing tumours), MG
LFTs ( ALK POS) and amylase
Plasma PTH- should not be present Plasma PTH should not increase in hypercalcaemia caused by malignacy but there may be another cause for the hypercalcaemia alongside the cancer. PTHrP assay should be ordered in patients with hypercalcemia and low PTH; levels are elevated in patients with malignancies that secrete this humoral factor
Levels of 25-hydroxyvitamin D 3 are elevated in vitamin D intoxication, a cause of hypercalcemia that must be differentiated from that due to malignancy
Levels of 1,25-dihydroxyvitamin D 3 are elevated in granulomatous diseases, myeloma, and lymphoma, particularly Hodgkin lymphoma presenting with hypercalcemia
ECG-
PR interval elongation,
shortening of QT interval or
a wide QRS complex
EXTRA
Serum protein electrophoresis will show monoclonal bands, which are diagnostic for myeloma; this test should be ordered when there is suspicion of myeloma or when no other cause of hypercalcemia with low or low-normal PTH is readily apparent
Urine 24-hour total protein electrophoresis will detect monoclonal light chains in patients with light chain disease and normal serum protein electrophoresis
Rehydration- 0.9% saline and reasess fluid status regularly. Put in a catheter and CVP to monitor fluid balance restore glomerular function, increase urinary ca excretion, aim for 3-6L/24 hours IV depedning on cardiac function and urine output.
Avoid mobility- lack of weight beating induces increased osteoclastic activity while reducing bone formation ( catheter hekps this
Ca restriction-
Monitor U&Es- K and Mg may fall with fluid intake so need IV replacement (k= 20-40mmol/L and `Mg= up to 2mmol/L of nomral saline. Check ca and albumin daily.
Bisphosphonates- if ca still above 3 even with fluids not below as risk metastatic ca/pi deposition. Stops osteoclast activity which lowers calcium. Pamidronate 60-90mg infused in a litre of normal salineover 2-24hrs, provided renal function ok after 24hr of hydration. Takes 48 hrs to work and calcium stabilises in 3-7 days, so fluid resus is essential in acute management. CANNOT REPEAT DOSE FOE 7 days and should be 3 weeks later when repeat. S/e= transient fever, hypocalcamiea. Zolendronic acid is bypassing pamidronate now as it only take 4mg IV over 15 mins to infuse and is more potent.
Albumin corrected calcium greater than 12.5mg/dL
Patients that have already had IV bisphosphonate treatment but still high calcium - subcutaneous denosumab on days 1, 8, 15, and 29, and then every 4 weeks
End point csc less than 11.5mg/dL within ten days of treatment initiation
By day 10, 80% patients had responded.
![Introduction
Normal range: 2.2-2.6 mmol/L
Free Ca2+ ≥ 3.0 mmol/L = EMERGENCY [1]
Ca2+ ≥ 4.0 mmol/L leads to death [2]
Hypercalcaemia develops in 10% of cancers [3]
Poor prognosis
o 80% die in first year even with treatment [2,4]
Most common in breast cancer, multiple myeloma and
lung cancer (also prostate cancer, lymphoma, and renal
cancer) [1-3]
50% of inpatient hypercalcaemia is caused by cancer [3]](data:image/gif;base64,R0lGODlhAQABAIAAAAAAAP///yH5BAEAAAAALAAAAAABAAEAAAIBRAA7)