Hypercalcaemia

Question 1

What is hypercalcaemia?

Answer 1

• Normal serum / plasma total calcium should be 2.13-2.63 mmol/L (8.5-10.5 mg/deciliter)
• ionised calcium should be 1.15-1.27 mmol/L (4.6-5.1 mg/deciliter).

Question 2

What are the causes of hypercalcaemia?

Answer 2

in 90 of cases

• Endocrine: primary hyperparathyroidism
  
  • 85% of cases are due to a single adenoma of one of the parathyroid glands
  • most of the other 15% is four-gland disease
  • than 1% of cases are caused by parathyroid cancer
• Malignancy: cancer
  
  • 1) Bony involvement by the tumour may lead to massive osteoclastic activity (osteolytic lesions) when the calcium flux simply overwhelms homeostatic mechanisms.
  • 2) A variety of tumours release PTH-related peptide acting on PTH receptors (paraneoplastic syndrome)

less frequent aetiologies:

• Endocrine
  
  • Hyperthyroidism –> leads to hypercalcaemia and almost always hypercalciuria as a consequence of rapid bone turnover.
• Bone diseases
  
  • ​Excess bone metabolism of any aetiology e.g. immobilisation
  • Paget’s disease
• Granulomatous conditions
  
  • ​Sarcoidosis –> Vitamin D is elevated (mechanism is enhanced conversion of vitamin D by macrophages)
• Diet
  
  • ​excess vitamin A intake
    
    • associated with excess bone turnover with hypercalcaemia and suppressed PTH
  • excess vitamin D intake
• Iatrogenic
  
  • ​Drugs: Lithium (affects Ca perception) & thiazides (affect renal function & rapid bone turnoever)

Question 3

Which specific malignancies can cause hypercalcaemia?

Answer 3

• multiple myeloma
• leukaemia
• lung cancer
• breast cancer

usually advanced cancer

Question 4

What are the presenting symptoms of hypercalcaemia?

Answer 4

depends on cause:

primary hyperparathyroidism

• renal stones
• chronic symptoms

malignancy

• Hx of weight loss
• Bone pain (mets)
• new onset symptoms

Both

• lethargy
• easy fatigue
• confusion
• depression
• irritability
• constipation
• polyuria/ polydipsia
• classic GI symptoms: (nausea, vomiting, abdominal pain, peptic ulcer disease, pancreatitis)

Moans, stones, groans, bones and psychiatric overtones

Question 5

What are the signs of hypercalcaemia O/E?

Question 6

What are the primary investigations for ?hypercalcaemia?

Answer 6

bloods

• PTH
  
  • =elevated in primary hyperparathyroidism
  • = malignancy, the PTH might be very low
• repeat Ca (total serum + ionised)
  
  • = elevated in Ca

imaging

• Bone imaging
• CXR
• Abdo XR

Question 7

What are some secondary investigations for ?hypercalcaemia ?

Answer 7

• 24-hour urine calcium
  
  • for primary hyperparathyroidism
  • may help further differentiate between familial hypocalciuric hypercalcaemia and primary hyperparathyroidism
• serum vitamin D levels
  
  • for vitamin D intoxication
• serum creatinine
  
  • for chronic renal failure and secondary hyperparathyroidism
• kidney ultrasound
  
  • for chronic renal failure and secondary hyperparathyroidism

Question 8

What is the management plan for hypercalcaemia?

Answer 8

FOR MODERATE - SEVER HYPERCALCAEMIA, W/O KIDNEY DISEASE

• IV saline
  
  • ​forced rehydration (due to abnormal kidney function)
• loop diuretic e.g. furosemide
  
  • permit continued large volume intravenous salt and water replacement while minimizing the risk of blood volume overload and pulmonary oedema
  • In addition, loop diuretics tend to depress calcium reabsorption by the kidney thereby helping to lower blood calcium levels
• IV bisphosphonate or denusomab
  
  • Bisphosphonates effectively block osteoclastic bone resorption (i.e. breakdown)
• IM/SC Calcitonin (while awaiting effect of bisphosphonate)
  
  • Calcitonin interferes with osteoclastic bone resorption (i.e. breakdown)
  • & increases urinary calcium excretion by inhibiting calcium reabsorption by the kidney
• IV hydrocortison/ prednisolone
  
  • Glucocorticoid therapy may be efficacious
  • increase urinary calcium excretion and decrease intestinal calcium absorption
  • no effect on calcium level in normal or primary hyperparathyroidism
  • effective in hypercalcaemia due to osteolytic malignancies (multiple myeloma, leukaemia, Hodgkin’s lymphoma, carcinoma of the breast) due to antitumour properties
  • also effective in hypervitaminosis D and sarcoidosis

FOR MODERATE - SEVER HYPERCALCAEMIA, W KIDNEY DISEASE

• renal dialysis
  
  • ​for hypercalcaemia complicated by renal failure
• + denusomab

Question 9

What are the possible complications of hypercalcaemia?

Answer 9

• sequale of bone loss, including fractures, osteitis fibrosa cystica, osteoporosis
• AKI
  
  • ​Hypercalcaemia can lead to renal vasoconstriction, volume depletion, and a subsequent reversible decrease in glomerular filtration rate. Long-standing hypercalcaemia and hypercalciuria can lead to calcification, degeneration, and renal tubular atrophy/necrosis
• coma
  
  • Hypercalcaemia is associated with neuropsychiatric symptoms, of which coma is serious complication
• acute pancreatitis
  
  • due to calcium deposition in the pancreatic duct, and to activation of trypsinogen in the pancreatic parenchyma, leading to pancreatitis
• electrolyte abnormalities: K, Mg, Phosphate depletion