High serum calcium in malignancy its causes and management

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