Hypercalcaemia

Question 1

Causes of hypercalcaemia

Answer 1

Mnemonic: Thinking CHIMPANZEES

Thinking - Thiazides, thyroid
C - Calcium supplementation
H - Hyperparathyroidism
I - Immobilisation/inherited (FHH)
M - Milk-alkali syndrome, medications (lithium)
P - Paraneoplastic PTHrP
A - Adrenal insufficiency
N - Neoplasm (multiple myeloma, breast, lung)
Z - Zollinger-Ellison syndrome
E - Excessive vitamin D
E - Excessive vitamin A
S - Sarcoidosis and granulomatous diseases

Question 2

Acute management of severe hypercalcaemia (>3.5mg/dL)

Answer 2

• IV fluids with 0.9% NaCl (monitor carefully and consider loop diuretics in renal insufficiency/CHF)
• Bisphosponates
• Calcitonin
• Corticosteroids
• RANKL inhibitors

Question 3

Acute management of mild hypercalcaemia (2.5-3mg/dL)

Answer 3

No active or immediate management required. Identify and treat underlying cause.

Question 4

Acute management of moderate hypercalcaemia (3-3.5mg/dL)

Answer 4

If asymptomatic or mild symptoms, treat as for mild (2.5-3mg/dL)
If severe or rapid progression of symptoms, treat as for severe (>3.5mg/dL)

Question 5

Acute management of hypercalcaemic crisis or renal failure (>4.5mg/dL)

Answer 5

Haemodialysis; reserved for refractory life-threatening hypercalcaemia or if other therapies are contraindicated.

Question 6

PTH-mediated causes of hypercalcaemia

Answer 6

• Primary hyperparathyroidism
• Tertiary hyperparathyroidism
• Familial hypocalciuric hypercalcaemia

Question 7

Non-PTH mediated causes of hypercalcaemia

Answer 7

• Hypercalcaemia of malignancy
• Granulomatous disorders (e.g. sarcoidosis)
• Thyrotoxicosis
• Immobilisation
• Milk-alkali syndrome
• Adrenal insufficiency
• Thiazide diuretics
• Excess vitamin D intake
• Calcium supplementation
• Lithium medications

Question 8

Primary hyperparathyroidism is most commonly caused by:

Answer 8

Parathyroid adenoma or hyperplasia.

Question 9

Primary hyperparathyroidism causes hypercalcaemia through which mechanism?

Answer 9

Excess PTH → increased production of 1,25-dihydroxyvitamin D via stimulation of 1-alpha-hydroxylase synthesis in the kidneys → hypercalcaemia

Question 10

Tertiary hyperparathyroidism is caused by:

Answer 10

Renal failure

Question 11

Tertiary hyperparathyroidism causes hypercalcaemia via which mechanism?

Answer 11

CKD → decreased conversion of calcidiol to calcitriol in kidney → decreased serum calcitriol concentrations → decreased Ca2+ absorption from small intestine → hypocalcaemia → triggers increased PTH release → persistent PTH elevation → reactive hypercalcaemia

Question 12

Familial hypocalciuric hypercalcaemia mechanism

Answer 12

Autosomal dominant inactivating mutation in the CaSR gene → decreased sensitivity of Ca2+ sensing receptors in the parathyroid glands and kidneys; increased reabsorption of Ca2+ in the kidney → hypercalcaemia

Question 13

What investigation results are consistent with a diagnosis of FHH?

Answer 13

Hypocalciuria, mild hypercalcaemia and normal or increased PTH levels.

Question 14

Granulomatous disorders (e.g. sarcoidosis) cause hypercalcaemia through what mechanism?

Answer 14

Activation of mononuclear cells → increased hydroxylase activity → 1,25-dihydroxyvitamin D production outside the kidneys → increased intestinal absorption of calcium → hypercalcaemia

Question 15

Thiazide diuretics cause hypercalcaemia by:

Answer 15

reducing renal calcium excretion.

Question 16

Lithium medications cause hypercalcaemia by:

Answer 16

reducing renal calcium excretion and altering the PTH secretion set-point.

Question 17

Thyrotoxicosis causes hypercalcaemia by:

Answer 17

Increased thyroid hormone levels → increased osteoclastic activity → increased bone resorption

Question 18

Immobilisation results in hypercalcaemia by:

Answer 18

Lack of weight-bearing activities → osteoclast activation → bone demineralisation → hypercalcaemia

Question 19

Milk-alkali syndrome is caused by:

Answer 19

consumption of large amounts of calcium carbonate (antacids)

Question 20

What three features does milk-alkali syndrome present with?

Answer 20

Hypercalcaemia, metabolic alkalosis and AKI

Question 21

The most common mechanism of hypercalcaemia of malignancy is:

Answer 21

paraneoplastic production of PTHrP

Question 21

The most common mechanism of hypercalcaemia of malignancy is:

Answer 21

paraneoplastic production of PTHrP

Question 22

Multiple myeloma causes hypercalcaemia via:

Answer 22

osteolytic metastases which increase serum calcium levels due to local bone resorption

Question 23

What are the five common presenting signs of hypercalcaemia?

Answer 23

Nephrolithiasis (stones), arthralgias (bones), increased urinary frequency (thrones), abdominal pain/nausea/vomiting (groans), anxiety/depression/fatigue (psychiatric overtones)

Question 24

Hypercalcaemia causes acute pancreatitis via:

Answer 24

Ca2+ deposition in bile ducts blocking outflow of pancreatic secretions → increased intrapancreatic pressure → compression of pancreatic blood vessels--tissue ischaemia; activation of proteases--autodigestion of pancreatic tissue

Question 25

PTH effects bone by:

Answer 25

increasing bone resorption (induces RANKL expression in osteoblasts → binding of RANKL to RANK on osteoclasts → osteoclastic activation)

Question 26

PTH is produced by:

Answer 26

The chief cells of the parathyroid glands.

Question 27

Effect of PTH on the kidneys:

Answer 27

Increased urinary excretion of phosphate.

Question 28

The following blood picture fits which condition? Hypercalcaemia Hypophosphataemia High ALP High PTH

Answer 28

Primary hyperparathyroidism.

Question 29

The following blood picture fits which condition? Hypercalcaemia Hyperphosphataemia High ALP Very high PTH

Answer 29

Tertiary hyperparathyroidism

Question 30

PTH levels in hypercalcaemia of malignancy are usually:

Answer 30

suppressed unless concurrent primary hyperparathyroidism is present.

Question 30

PTH levels in hypercalcaemia of malignancy are usually:

Answer 30

suppressed unless concurrent primary hyperparathyroidism is present.

Question 31

An elevated serum PTHrP in combination with a suppressed serum PTH is suggestive of:

Answer 31

Hypercalcaemia of malignancy

Question 32

Phosphate levels in hypercalcaemia of malignancy are:

Answer 32

Low with hyperphosphaturia - PTHrP acts at the level of the kidney to reduce the renal phosphorus threshold.

Question 33

The following blood picture is consistent with which diagnosis? Hypercalcaemia Inappropriately normal or increased PTH Hypocalciuria

Answer 33

Familial hypocalciuric hypercalcaemia (FHH)

Question 34

Which two causes of hypercalcaemia are associated with hypophosphataemia?

Answer 34

Primary hyperparathyroidism PTHrP-mediated hypercalcaemia

Question 35

Increased levels of 1,25-dihydroxyvitamin can be caused by:

Answer 35

Lymphoma, granulomatous disease or calcitriol ingestion.

Question 36

Elevated 25-hydroxyvitamin D levels are due to:

Answer 36

vitamin D intoxication

Question 37

Patient's who opt for non-surgical treatment of parathyroid adenoma should:

Answer 37

- Avoid a high calcium intake - Limit vitamin D supplementation - Maintain a high water intake unless contraindicated

Question 38

Hypercalcaemia causes constipation by:

Answer 38

altering the charge balance across the cell membrane, decreasing contractility of GIT smooth muscle.

Question 39

Hypercalcaemia causes nephrolithiasis by:

Answer 39

the precipitation of Ca2+ with PO43- in the renal filtrate.

Question 40

Hypercalcaemia causes polyuria by:

Answer 40

Ca2+ directly inhibits the insertion of aquaporin channels in the collecting duct membrane → less water reabsorbed into renal vasculature → increased filtrate volume → polyuria

Question 41

Risk factors for primary hyperparathyroidism include:

Answer 41

Female sex, age > 60yo, positive FHx, current or historical lithium treatment, MEN1/2A/4 (autosomal dominant traits)

Question 42

MOA of bisphosphonates

Answer 42

Decrease bone resorption by inhibiting osteoclastic activity.

Question 43

Contraindications for bisphosphonates

Answer 43

Hypocalcaemia

Question 43

Contraindications for bisphosphonates

Answer 43

Hypocalcaemia

Question 44

Bisphosphonates adverse effects

Answer 44

Nausea, vomiting, hypocalcaemia, musculoskeletal pain

Question 45

MOA of calcitonin

Answer 45

Inhibits bone resorption and increases urinary excretion of calcium and phosphate

Question 46

Averse effects of calcitonin

Answer 46

Flushing, nausea, vomiting, dizziness, taste disturbance

Question 47

MOA of corticosteroids in the context of hypercalcaemia

Answer 47

Used for calcitriol-mediated hypercalcaemia. Inhibits 1-a-hydroxylase conversion of calcidiol into calcitrol, therefore lessening intestinal calcium absorption.

Question 48

Corticosteroid adverse effects

Answer 48

Short-term: fluid retention, hypertension, mood disturbances, weight gain. Long-term: glaucoma, cataracts, hyperglycaemia, increased susceptibility to infections, osteoporosis, adrenal suppression, delayed wound healing, Cushingoid features.

Question 49

MOA of denosumab

Answer 49

Human monoclonal antibody that binds receptor activator of RANKL, preventing activation of RANK → decreased osteoclastic activity → reduced bone resorption

Question 50

Adverse effects of denosumab

Answer 50

Eczema, hypercholesterolaemia, musculoskeletal pain

Question 51

MOA of cinacalcet

Answer 51

Increases the sensitivity of calcium-sensing receptors on the parathyroid glands to extracellular calcium, thus reducing excretion of PTH and reducing serum calcium concentration.