Malignant hypercalcemia is caused by excess calcium mobilization from bone that exceeds renal excretion thresholds. It is often seen in patients with bone metastases from breast, lung, kidney and multiple myeloma cancers. Treatment involves aggressive hydration, decreasing bone resorption with bisphosphonates, calcitonin, or corticosteroids, and in some cases antitumor therapy.

1. Malignant Hypercalcemia
• What is it?
• What causes it?
• Why to treat it?
• How to treat it?

2. What Is It?
Ca+ +
level
>10.3mg/dl
>2.57mmol/l
Total
Ionised
>5.1mg/dl
>1.27mmol/l
A symptomatic pt with normal total Ca level

3. • 1% of all ca pts suffer from HiCa
• Ca mobilisation exceeds renal threshold
• Causes in ambulatory vs. Hospitalised pts
• Tumour assoc HiCa caused by osteolysis
• 80% with malignant HiCa have bone mets
– 80% osteolytic
• PTHrP may be produced without bone
mets
What Causes It?

4. • Breast ca
• Bronchogenic ca
• Renal cell ca
• Multiple Myeloma
• Thyroid ca
• Sq cell ca H & N, oesophageal and ovarian
ca without osseous mets~
What Causes It?

5. • Is hypercalcemia always symptomatic?
• Early symptoms include nausea anorexia &
vomiting
• Permanent renal tubular damage may occur
• Myocardial instability may cause
arrhythmias/sudden death
• Neurological symptoms may predominate
Hypercalcemia
Therapy

6. Severe Hypercalcemia
Serum
total ca
(mmol/L)
4
3
2
16
12
8
(mg/dl)
Normal range for Serum calcium
Moderate Hypercalcemia
Mild Hypercalcemia
Normocalcemia
Mild hypocalcaemia
Serum
total ca

7. • Decrease oral intake of ca??
• Promote urinary excretion
• Decrease bone resorption
• Antitumor therapy
Hypercalcemia
Therapy

8. • Fluid deficit
• Which fluid---normal saline
• 300-500 ml/hr initially
• May need 3-4 litres in 24 hrs
• Saline diuresis 100-200 ml/hr
• Add frusemide once hydrated
Hypercalcemia
Therapy
Hydration

9. • Improves renal handling of ca only
• Aggressive fluid therapy assoc with high
morbidity
• May need ICU monitoring
• Hi ca may not be corrected
Hypercalcemia
Therapy
Hydration

10. • Corticosteroids
• Bisphosphonates
• Cacitonin
• Gallium nitrate
• Mithramycin
Hypercalcemia
Therapy
Decreasing bone
resorption

11. • Blocks bone resorption due to Cyk & Lyk
• High doses
– Increase ca excretion
– Inhibit Vit D metabolism
– Decrease ca absorption
– Neg ca balance in bone
• May inhibit growth of neoplastic tissue
Hypercalcemia Therapy
Corticosteroid
s

12. • Effective in hi ca due to Lymp/ MM/
Leuk/ ?Breast ca
• 200-300 mg hydrocortisone may be needed
dailyx3-5 days
• 100 mg Pred orally for several days
• Use in non haematological tumours??
• Use with calcitonin??
Hypercalcemia Therapy
Corticosteroid
s

13. • Decreases bone resorption
• Decrease tubular reabsorption
• Ca reduction within hours
• Tachyphylaxis may develop
• Down regulation of receptors on osteoclast
surface
Hypercalcemia Therapy
Calcitonin

14. • 4-8 MRC units/kg-12 hrly I/M, S/C
• Nausea/ flushing/ abdominal cramps/allergy
• If tachyphylaxis discontinue and reinstitute
• Add glucocorticoides
Hypercalcemia Therapy
Calcitonin

15. • Bind to hydroxyapatite crystals in bone
matrix
• Inhibits dissolution
• Blocks maturation of osteoclast
• Osteoclast apoptosis
• Affect the signalling pathway between
osteoblasts & osteoclasts
HypercalcemiaTherapy
Bisphosphonates

16. • Oral route unreliable 1-2% Bioavailibility
• I/V route preferred
• 3-5mg/kg/d, 3-5hrs/ 3-5 days
• Single infusion 4 hrs 1.5 g
• May be followed by oral Clodronate
Hypercalcemia Therapy
Clodronate

17. • Ca decreases in 2-3 days
• Duration of effect 10-12 days
• Humoral-hypercalcemia responds poorly
• 30% retained in bone 1/2 life >1yr
Hypercalcemia Therapy
Clodronate

18. • Gallium nitrate
• Mithramycin
• Phosphate
• Antitumour therapy
Hypercalcemia Therapy

19. • Hydration-fluid/electrolyte balance
• Bisphosphonates+/-Calcitonin
• Corticosteroids
• Early mobilization
• Care of constipation
• Avoid drugs causing hi ca
Hypercalcemia Therapy
Conclusion