Hypercalcaemia

Background

  • Hypercalcaemia is mostly asymptomatic and is commonly an incidental finding after investigation for another reason.  It is relatively uncommon- so all cases should be investigated further
  • A note about calcium measurements:
    • About 50% of serum calcium is bound to plasma proteins (majority of which is albumin) and organic ions e.g. citrate/phosphate.  The rest is free and under hormonal control.
    • Labs routinely measure total serum calcium (free and bound).  However, they also routinely report a Corrected Calcium level which is the calcium level adjusted to the level of binding products e.g. albumin
      • E.g. if albumin is low, the corrected calcium levels increase (as more is free/unbound)
      • Both are relevant, but the corrected calcium levels show a more accurate representation of the physiological calcium levels (NB In practice, the two are often extremely close in the majority of patients.  Differ mainly in patients with underlying liver/kidney disease)

Presentation

  • Levels >2.21 (normal) but <2.8mmol/l
    • Patients may have polyuria/polydipsia; dyspepsia (calcium stimulates gastrin release); depression/low mood; mild cognitive impairment (may be acute or chronic)
  • Levels < 3.5mmol/l
    • + Muscle weakness; constipation; anorexia; nausea; fatigue (all general effects of calcium in muscle physiology)
  • Levels >3.5mmol/l
    • + Abdominal pain; vomiting; dehydration; lethargy; cardiac arrhythmias (shortened QT interval); pancreatitis; coma
  • Patients can also present with stone disease if the levels are chronically and insidiously raised.

Investigation

  • Repeat serum calcium (confirm hypercalcaemia)
    • Also look at albumin and urea levels (if raised, possible dehydration)
    • Other factors to inspect include Alk Phos; TFTs (thyrotoxicity)
  • Serum PTH
    • Raised/normal- diagnostic for primary hyperparathyroidism
      • Further tests may be considered by a specialist e.g. Urinary 24 hour calcium
        • Raised or normal suggest hyperparathyroidism
        • Low suggests familial hypocalciuric hypercalcaemia (found particularly in young people with a family history)
    • Low- consider another cause
      • Most commonly malignant hypercalcaemia
        • Radionucleotide bone scan is useful to look for malignant bone disease
  • Calcidiol testing can be done if no clear diagnosis is found from other tests (looking for Vit D toxicity
  • Other tests for complications which may be warranted include renal USS (for stone disease- may be an indication for removal of parathyroid glands); bone mineral density
  • Parathyroid imaging (USS, spect technetium scan)

Causes

  • Primary hyperparathyroidism is the most common cause (0.1-0.3% of the population)
  • Malignancy (myeloma or bony metastases)- suggested by rapidly progressive hypercalcaemia; second most common
  • Drugs e.g. lithium, thiazide diuretics
  • Rarer causes include
    • Tertiary hyperparathyroidism in end-stage renal disease
    • Granulomatous disease e.g. sarcoid, tuberculosis
    • Lymphoproliferative disorders
    • Vit D toxicity
    • Thyrotoxicosis
    • Addison’s disease
    • Familial Hypocalciuric Hypercalcaemia (1 in 78000) (see below)

Management (of hypercalcaemia)

  • If the patient is asymptomatic and hypercalcaemia is mild, identification of the underlying cause (+/- treatment) is all that is required
  • With acute/severe hypercalcaemia (>3mmol/l)
    • Rehydrate with saline (this can reduce the calcium by 0.5mmol/l
    • If severe, IV bisphosphonates e.g. disodium pamidronate or zoledronic acid may be helpful
      • Note that if this is due to hyperparathyroidism, bisphosphonates will only reduce calcium from bone resorption, not from renal reabsorption.

Familial Hypocalciuric Hypercalcaemia

  • Autosomal dominant disorder caused by inactivating mutation of the calcium sensing receptor gene, which reduces the ability of the parathyroid gland to sense calcium concentrations and an inability of renal receptors causing increased reabsorption of calcium.
    • Important to diagnose as these patients do NOT require parathyroid surgery
    • As well as calcium, PTH and urinary calcium tests, genetic tests may be available.
    • Patients only ever have mild hypercalcaemia (extremely rare to be symptomatic due to FHH) and no treatment is required.
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