College Answer

a)

• Clinical features:
  • CNS and PNS
  • Confusion
  • Coma
  • Hypotonia
  • Hyporeflexia
  • Paresis

• Renal findings
  • Renal stones
  • Volume depletion
  • Renal failure

• GI findings
  • Constipation and fecal impaction
  • Pancreatitis
  • Gastric ulcer

• Cardiac findings
  • Arrhythmias
  • Hypotension
  • Shortened QT interval

Signs related to underlying malignancy:

Treatment:

Treatment includes reduction of hypercalcaemia and treatment of underlying cause.

Measures for reduction of hypercalcaemia- (listing of agents adequate, doses & mechanism not expected)

Saline/frusemide diuresis- correction of dehydration with about 2L of fluid and 80mg Frusemide 2-4 hourly (only when volume has been adequately replaced) with replacement of urine losses with fluid & monitoring of potassium, calcium, phosphate and magnesium. Caution in cardiac or renal failure.

NB: Although use of frusemide is controversial/may not be beneficial, most current textbooks still include it.

• Bisphosphonates- Disodium etidronate or pamidronate
• Corticosteroids- especially if due to sarcoidosis or vit D toxicity
• Calcitonin

• Dialysis- Peritoneal or haemodialysis against calcium-free or low calcium concentration dialysate (citrate anticoagulation with CVVHDF)
• (Gallium nitrate)- nephrotoxic
• (Mithramycin)- contraindicated in renal or hepatic failure
• (Octreotide)

b)

Causes of ionised hypocalcaemia – any 4 individual causes:

• Decreased PTH activity:
  • Hypoparathyroidism
  • Pseudohypoparathyroidism
  • Hypomagnesaemia

• Vitamin D deficiency:
  • Malabsorption of vitamin D/calcium- steatorrhoea
  • Vitamin D deficient rickets, osteomalacia in adults

• Excess calcium losses/binding:
  • Rhabdomyolysis
  • Pancreatitis
  • Critical illness (burns, sepsis, toxic shock, etc.)
  • Frusemide and saline diuresis
  • Hyperphosphataemia
  • Citrate toxicity (CVVHDF)
  • Alkalosis / Hyperventilation
  • Fluoride toxicity
  • Oxalate poisoning
  • Tumour Lysis
  • Drugs – biphosphonates, calcitonin, phenytoin

• Unknown mechanism:
  • Hypermagnesaemia

Discussion

Features of hypercalcemia are discussed elsewhere.

The table below is a satisfactory short summary:

Management of hypercalcemia has indeed moved on since the frusemide diuresis days. All the positive evidence for this practice was published before bisphosphonates became available.

The college graciously allows the candidates to get by without mentioning drug doses.The modern medical approach to hypercalcemia is summarised as the following list, ordered by escalating invasiveness of therapy.

• Volume restoration
• Bisphosphonates
• Calcitonin
• Renal replacement therapy

Causes of hypocalcemia are discussed elsewhere. They are numerous. Though the college asks specifically about ionised hypocalcemia, they then give a list of all possible causes for this condition. In order to simplify revision, a table of causes is reproduced below:

Ionised hypocalcemia in isolation is rare. It is seen in only one scenario: citrate toxicity. When citrate is used to chelate calcium, the total calcium is normal, but the ionised fraction is low. This is because measurement instruments which detect calcium will also measure citrate-calcium complexes in the serum, but the electrode which measures ionised calcium will only measure the free fraction, which decreases with citrate chelation.