Hypercalcaemia of malignancy

Question 1

What is hypercalcaemia of malignancy?

Answer 1

High levels of calcium causes by malignancy
- Hypercalcaemia occurs in 20-30% of patients with cancer

Question 2

What are the different causes of hypercalcaemia of malignancy?

Answer 2

1. Humoral Hypercalcaemia of Malignancy (80% of cases) → tumour secretion of PTHrP (PTH-related peptide). Occurs in SCC (lung, head and neck), renal cancer, bladder cancer, breast cancer, ovarian cancer.
2. Local Osteolytic Hypercalcaemia → local release of factors by bony metastases that promote osteoclast function. Occurs in multiple myeloma and breast cancer.
3. Calcitriol-Mediated Hypercalcaemia → autonomous production of calcitriol (1,25-dihydroxyvitamin D) due to 1α-hydroxylase activity in tumours cells. Occurs in hodgkin lymphoma and non-hodgkin lymphomas.

Question 3

What are the risk factors for hypercalcaemia of malignancy?

Answer 3

• non-metastatic malignancy (humoral hypercalcaemia)
• metastatic skeletal involvement (local osteolytic hypercalcaemia)
• lymphoma (calcitriol [(1,25-dihydroxyvitamin D)]-mediated hypercalcaemia)

Question 4

What are the presenting symptoms of hypercalcaemia of malignancy?

Answer 4

• Polyuria & Polydipsia
• Confusion & Fatigue
• Poor Skin Turgor or Dry Mucous Membranes
• Constipation
• Loss of Appetite
• Nausea
• Bone Pain
• Low Mood
• Hypercalcaemia → stones (renal), bones (bone pain), groans (abdo pain, N&V), thrones (polyuria), psychiatric overtones (confusion, depression, anxiety)

Question 5

What investigations are used to diagnose/ monitor hypercalaemia of malignancy?

Answer 5

1. Serum Calcium → elevated
2. Serum PTH → low, distinguish from PTH-mediated hypercalcaemia (eg. primary or tertiary hyperparathyroidism)
3. ALP ⇒ high if bone metastases, normal in multiple myeloma
4. ECG → shortened QT interval (hypercalcaemia)
5. Serum PTHrP → elevated in humoral hypercalcaemia of malignancy
6. Serum Calcitriol → elevated in calcitriol (1,25-dihydroxyvitamin D)-mediated hypercalcaemia

Question 6

How is hypercalcaemia of malignancy managed?

Answer 6

1. IV Saline (Fluids) → reverses dehydration. Initial management of hypercalcaemia.
2. IV Bisphosphonates (or Denosumab) → most effective agents for treating malignancy-associated hypercalcaemia. Block osteoclastic bone resorption.
3. Treatment of Underlying Malignancy