Hypercalcaemia of malignancy (E&M)

Question 1

What different types of hypercalcaemia of malignancy are there? (4)

Answer 1

• humoral hypercalcaemia of malignancy
• local osteolytic hypercalcaemia
• calcitriol-mediated hypercalcaemia
• ectopic hyperparathyroidism (very rare)

Question 2

What is humoral hypercalcaemia of malignancy?

Answer 2

Tumour secretion of PTH-related peptide (PTHrP)

Question 3

What cancers does humoral hypercalcaemia of malignancy occur in? (7)

Answer 3

SCC ROBBLE

• SCC (lung, head and neck)
• Renal
• Ovarian
• Bladder
• Breast
• human T-lymphotrophic virus-associated Lymphoma
• Endometrial

Question 4

What is local osteolytic hypercalcaemia?

Answer 4

Local release of factors, including PTHrP, by bony metastases that promote osteoclast differentiation and function

Question 5

What cancers does local osteolytic hypercalcaemia occur in? (2)

Answer 5

• multiple myeloma
• breast cancer

Question 6

What is calcitriol-mediated hypercalcaemia?

Answer 6

Autonomous production of calcitriol (1,25-dihydroxyvitamin D) by lymphoma cells, due to 1-alpha hydroxylase activity in tumour cells

Question 7

What cancers does calcitriol-mediated hypercalcaemia occur in? (2)

Answer 7

• Hodgkin lymphoma
• Non-Hodgkin lymphoma
• (associated with lymphomas of all types, but also with granulomatous disease e.g. active sarcoidosis or TB)

Question 8

What are some risk factors for hypercalcaemia of malignancy? (3)

Answer 8

• non-metastatic malignancy (humoral hypercalcaemia of malignancy)
• metastatic skeletal involvement (local osteolytic hypercalcaemia)
• lymphoma (calcitriol-mediated hypercalcaemia)

Question 9

What medication can cause hypercalcaemia?

Answer 9

Thiazides

Question 10

What are the clinical features of hypercalcaemia of malignancy?

Answer 10

Stones, Bones, Thrones, Abdominal Groans, Psychic Moans

• Stones (renal)
• Bones (bone pain)
• Thrones (polyuria, polydipsia, poor skin turgor and dry mucous membranes)
• Abdominal Groans (pain, constipation, anorexia, nausea)
• Psychic Moans (confusion, low mood, anxiety)

Question 11

What are the first-line investigations for hypercalcaemia of malignancy? (6)

Answer 11

• total serum calcium - elevated
• serum ionised calcium elevated
• serum intact PTH - low –> differentiate from PTH-mediated hypercalcaemia e.g. hyperparathyroidism
• PTHrP - elevated in humoral hypercalcaemia of malignancy
• ALP - high in bone metastases –> local osteolytic hypercalcaemia, normal in multiple myeloma
• calcitriol - high in calcitriol-mediated hypercalcaemia

Question 12

What imaging can we do for hypercalcaemia of malignancy?

Answer 12

• resting ECG - may show shortened QT interval and dysrhythmias
• skeletal survey - may show osteopenia, osteolytic lesions or pathological fractures
• CXR - may show typical findings of lung cancer, TB or sarcoidosis

Question 13

How can we differentiate between the three main types of hypercalcaemia of malignancy?

Answer 13

• humoral hypercalcaemia of malignancy - high PTHrP
• local osteolytic hypercalcaemia - high ALP (normal in multiple myeloma)
• calcitriol-mediated hypercalcaemia - high calcitriol

Question 14

What are some differential diagnoses for hypercalcaemia of malignancy? (7)

Answer 14

• primary hyperparathyroidism
• hyperthyroidism
• adrenal insufficiency
• phaeochromocytoma
• sarcoidosis
• medication-related hypercalcaemia (thiazide diuretics, lithium, OTC antacids, large doses vitamin D)
• TB

Question 15

What do we give as INITIAL management of hypercalcaemia of malignancy?

Answer 15

IV saline (fluids) to reverse dehydration

Question 16

How do we manage hypercalcaemia of malignancy - humoral and local osteolytic?

Answer 16

IV bisphosphonates (or denosumab) - most effective for treating hypercalcaemia of malignancy by blocking osteoclastic bone resorption

Question 17

How do we manage hypercalcaemia of malignancy - calcitriol-mediated?

Answer 17

Glucocorticoids

Question 18

How do we manage hypercalcaemia of malignancy if CKD?

Answer 18

Renal dialysis +/- denosumab

Question 19

What do we eventually need to manage to treat hypercalcaemia of malignancy?

Answer 19

Underlying malignancy

Question 20

What are some complications of hypercalcaemia of malignancy? (4)

Answer 20

• AKI
• coma
• acute pancreatitis
• bisphosphonate-induced flu-like syndrome

Question 21

Describe the prognosis of hypercalcaemia of malignancy.

Answer 21

• IV hydration and pharmacological therapy can provide transient restoration of normocalcaemia
• eradication of underlying malignancy is crucial for permanent reversal of hypercalcaemia