Hypercalcaemia

Question 1

What is the normal reference range for serum calcium?

Answer 1

2.2–2.6 mmol/L

Question 2

Why must calcium be adjusted for albumin?

Answer 2

Because calcium binds to albumin, and low albumin can falsely lower total calcium.

Question 3

What is the formula for corrected calcium?

Answer 3

Corrected Ca (mmol/L) = (0.02 × (40 – Albumin)) + Measured Ca

Question 4

Which organs are involved in calcium homeostasis?

Answer 4

Kidneys, parathyroid glands, intestines, and bones.

Question 5

What are the two main mechanisms causing malignant hypercalcaemia?

Answer 5

1. PTH-related peptide (PTHrP) secretion → ↑ bone resorption & renal reabsorption
2. Direct bone destruction by tumour (e.g. multiple myeloma)

Question 6

How does PTHrP cause hypercalcaemia?

Answer 6

• Activates osteoclasts → ↑ bone resorption
• Increases renal tubular calcium reabsorption

Question 7

How does direct bone lysis cause hypercalcaemia?

Answer 7

Tumour cells (e.g. in myeloma or metastases) destroy bone, releasing calcium directly into the bloodstream.

Question 8

What are the most common cancers associated with hypercalcaemia?

Answer 8

• Squamous cell carcinoma (lung, head & neck, bladder, anal canal, vulva)
• Small cell lung cancer
• Renal cell carcinoma
• Breast cancer (advanced)
• Multiple myeloma

Question 9

What are non-malignant causes of hypercalcaemia?

Answer 9

• Primary hyperparathyroidism
• Sarcoidosis
• Vitamin D intoxication
• Thyrotoxicosis
• Medications (e.g. thiazides, lithium)

Question 10

How does malignant hypercalcaemia differ from non-malignant causes?

Answer 10

• Malignant - Rapid onset, severe, low PTH, often advanced cancer
• Non-malignant - Slower onset, raised PTH (if parathyroid driven), more chronic

Question 11

What are general symptoms of hypercalcaemia?

Answer 11

Lethargy and dehydration

Question 12

What are the neurological symptoms?

Answer 12

• Limb weakness
• Cognitive dysfunction, confusion, mood changes, coma

Question 13

What are gastrointestinal symptoms?

Answer 13

Anorexia, nausea, constipation, polydipsia

Question 14

What are genitourinary symptoms?

Answer 14

Polyuria and renal impairment

Question 15

What are cardiac manifestations of hypercalcaemia?

Answer 15

• Shortened QT interval
• Arrhythmias/dysrhythmias

Question 16

What should you assess on examination?

Answer 16

• Hydration status
• Abdomen
• Urine output
• Other cancer-related signs

Question 16

What are chronic complications of prolonged hypercalcaemia?

Answer 16

• Pancreatitis
• Peptic ulcers
• Kidney stones

Question 17

What investigations are required?

Answer 17

• U&Es, electrolytes, albumin, ALP
• Medication review
• ECG (if Ca > 3.5 mmol/L or arrhythmia)

Question 18

What ECG change is typical in hypercalcaemia?

Answer 18

Shortened QT interval.

Question 19

What conditions may mimic or coexist with hypercalcaemia in cancer patients?

Answer 19

• Infection
• Renal failure
• Brain metastases
• Spinal cord compression
• Depression
• Bowel obstruction
• Opioid side effects

Question 20

What is the first-line management of hypercalcaemia?

Answer 20

Rehydration with 2–4 L of 0.9% saline IV over 24 hours.

Question 21

What should you be cautious about when rehydrating?

Answer 21

Elderly patients, cardiac disease, renal failure, or obstructive uropathy.

Question 22

What are the next-line treatments after fluids?

Answer 22

• IV bisphosphonates (e.g. zoledronic acid or pamidronate)
• Glucocorticoids (reduce vitamin D activation)
• Denosumab or calcitonin (if resistant)

Question 23

Why are glucocorticoids used in hypercalcaemia?

Answer 23

They inhibit 1,25-OH vitamin D production, reducing calcium absorption.

Question 24

When may loop diuretics be used?

Answer 24

Only if the patient becomes fluid overloaded after rehydration.

Question 25

What is the mechanism of action of bisphosphonates?

Answer 25

They inhibit osteoclast activity, reducing bone resorption and calcium release.

Question 26

What are cautions/side effects of zoledronic acid (Zometa)?

Answer 26

- Renal impairment - Flu-like symptoms - Hypocalcaemia - Osteonecrosis of the jaw (with long-term use)

Question 27

How do you monitor response to treatment?

Answer 27

- Fluid balance (input/output) - Repeat calcium levels - Monitor renal function and electrolytes

Question 28

When do symptoms typically improve after treatment?

Answer 28

Within 2–4 days, once calcium normalises.

Question 29

What is the prognosis of malignant hypercalcaemia?

Answer 29

- Poor - except in multiple myeloma - median survival is usually months.

Question 30

Which anti-hypertensive medication should be withheld in hypercalcaemia?

Answer 30

Thiazide diuretics (they increase calcium reabsorption).

Question 31

What would you expect serum PTH levels to be in malignant hypercalcaemia?

Answer 31

Low or suppressed (due to PTHrP or bone destruction, not true PTH overproduction).

Question 32

When should you perform an ECG in hypercalcaemia?

Answer 32

- When calcium >3.5 mmol/L - If arrhythmia suspected - Expect shortened QT interval