Hypercalcaemia of malignancy

Question 1

Define hypercalcaemia of malignancy

Answer 1

This is when you get calcium levels higher than the normal of 2.5-2.8mmol/L

Question 2

Give a brief description of calcium regulation in the body as normal

Answer 2

• Calcium is made up of free ionised Ca2+ (active) and bound to plasma protein e.g. albumin (inactive)
• Normal corrected serum calcium is 2.5-2.8mmol/L
• In parathyroid gland, releases PTH
• Effects of PTH:
  1. ) Bone: increases absorption of Ca2+ into bone
  2. ) Kidney: increases re-uptake of Ca2+ in kidney
  3. ) Gut: increase calcitriol synthesis (active vit D) so increases gut absorption of calcium
• Parathyroid gland releases PTH
• In thyroid: specialised cells called parafollicular cells will release calcitonin. These aim to lower calcium levels and do the opposite of PTH

Question 3

Describe the epidemiology of hypercalcaemia of malignancy

Answer 3

• 20 to 30% of cancer patients will develop hypercalcemia and usually indicates a poor prognosis
• 1 in 1000 have mild asymptomatic hypercalcaemia
• Typically affects older women

Question 4

What are the causes/risk factors for developing hypercalcaemia?

Answer 4

1. ) PTHrP: parathyroid hormone regulating protein is released by the tumour and has similar effects on the body as PTH does. It increases calcium reabsorption in bone and and re-uptake in kidneys (but doesn’t increase amount of calcitriol)
2. ) Osteoclastic metastases: develop from certain cancers and form tumours in bone, which cause calcium release from bone
3. ) Tumour induced calcitriol release: more calcitriol released, increasing gut absorption of calcium

causes from sheff notes:
CHIMPANZEES
C: calcium supplementation
H: hyperparathyroidism
I: iatrogenic drugs - thiazides
M: milk alkali syndrome
O: paget's disease of the bone
A: acromegaly and addison's
N: 
Z: zolinger-ellison syndrome - MEN type 1
E: excess vit D
E: excess vit A
S: sarcoidosis

Question 5

What investigations and diagnosis would you give?

Answer 5

1. ) PTH test

- If high: most likely primary hyperparathyroidism (benign tumour on parathyroid gland)

Question 6

Describe the pathology of hypercalcaemia

Answer 6

Covered in causes

Question 7

Describe the signs and symptoms of hypercalcaemia

Answer 7

• Stones/Thrones/Groans/Bones/Psychiatric undertones + cardiac
• Stones: Kidney stones (more in chronic vs acute)/polyuria (develop nephrogenic diabetes insipidus)
• Thrones: constipation
• Groans: abdominal pain/peptic ulcers/pancreatitis
• Bones: muscle weakness and bone thinning
• Psychiatric undertones: depression/cognitive dysfunction/coma
• Cardiac: bradycardia/arrhythmia

Question 8

What investigations and diagnosis would you give?

Answer 8

1. ) PTH test
   - If high: most likely primary hyperparathyroidism (benign tumour on parathyroid gland)
   - If low: malignancy likely so you do additional tests
2. ) ECG: will show a tented T and a short QT interval
3. ) CXR: To rule out myeloma + non-Hodgkin’s lymphoma
4. ) 24-hour urinary calcium: measured in young patients + those w a family history to exclude hypocalciuric hypercalcaemia

Others:

• X-ray + protein electrophoresis for myeloma
• DEXA bone scan
• High resolution CT
• TSH to exclude hyperthyroidism
• Tetracosactide to exclude Addison’s

Question 9

Describe the treatment and management options

Answer 9

• If mild or moderate, no active treatment is recommended unless the hypercalcaemia is acute and has a very quick onset
• If severe: IV fluids/calcitonin /bisphosphonates: encourages osteoclasts to undergo apoptosis, so less brekadown
• If very severe: haemofiltration