Hypercalcaemia

Serum calcium concentration is tightly regulated between 2.1-2.6mmol/L. Severe hypercalcaemia is a life-threatening electrolyte emergency requiring prompt recognition and urgent treatment.  Do check out our video tutorial on this.

Classification

  • Mild (2.65 – 3.00 mmol/L): Patient usually asymptomatic
  • Moderate (3.01-3.40 mmol/L): Can be asymptomatic or symptomatic
  • Severe (>3.40 mmol/L): Risk of dysrhythmia and coma

Serum calcium is found in 2 forms = either bound to albumin or free. A ‘corrected’ calcium takes into account the serum albumin level and so reflects a more accurate calcium level. Patients with suspected hypercalcaemia may have a ‘normal’ calcium level reported if their albumin is low.

Causes

Hyperparathyroidism & Malignancy account for 90% of cases of hypercalcemia. Thus measuring the PTH is incredibly helpful: in hyperparathyroidism, PTH is inappropriately normal or high whereas in malignancy, PTH is appropriately low.
  • Hyperparathyroidism: commonest cause in non-hospitalised patients. This is a condition in which the parathyroid gland is overactive. This is often due to an adenoma or hyperplasia.
  • Malignancy: commonest cause in hospitalised patients. This may be due to a number of processes (in order of prevalence)
    • PTHrP = a polypeptide which has a similar structure and effects as PTH
    • Bone metastases
    • Overproduction of 1,25 Vitamin D (e.g. in lymphoma)
    • PTH-driven (e.g. in ectopic production or parathyroid carcinoma)
Suppressed/Low PTHHigh or Normal PTH
MalignancyPrimary hyperparathyroidism (adenoma)
Granulomatous diseaseTertiary hyperparathyroidism (chronic renal failure)
Drugs: Calcium and/or vitamin D supplements, Antacids, Thiazide diuretics, Lithium, Theophylline toxicityFamilial hypocalciuric hypercalcaemia (rare)
Rhabdomyolysis
Rarely: Adrenal insufficiency, Thyrotoxicosis, Phaeochromocytoma

Do note that secondary hyperparathyroidism is not a cause of hypercalcaemia. In this condition, there is increased PTH secretion secondary to hypocalcaemia as a result of CKD.

Signs & Symptoms

‘Bones, stones, groans and psychic moans’

Other: weight loss, fatigue, pyrexia, night sweats

Chronic symptoms are more consistent with hyperparathyroidism, whereas a more recent onset of symptoms suggests malignancy.

*Renal stones explained: high levels of serum calcium quickly exceed the kidneys capacity for re-absorption. Therefore the calcium spills into the urine and can bind with phosphate leading to the formation of kidney stones.

Examination

  • Assess for cognitive impairment/GCS
  • Fluid balance status
  • Any specific examination if appropriate for an underlying cause e.g. lymph nodes, abdomen etc

Investigations

  • Bloods: corrected calcium, phosphate, PTH, vitamin D, ALP, Mg, Albumin, U&Es
  • ECG: Shortened QT interval → Bradycardia → 1st degree heart block
  • CXR
  • (Serum ACE if sarcoidosis suspected)
CausePTHALPPhosphate
Primary or Tertiary hyperparathyroidismNormal/raisedNormal/raisedLow
Bone metastasesLowRaisedRaised
Myeloma, Vitamin D overdose or Granulomatous diseaseLowNormalRaised

Further Investigations

These are driven by specialist teams as they’re not always necessary and are usually performed by the endocrinology team as an outpatient.

  • 24 hour urinary calcium excretion
  • DEXA scan: osteoporosis
  • Parathyroid MIBI scan & US parathyroid (if the patient is a surgical candidate)

Management

You should always discuss patients with hypercalcaemia with a senior

First Line: Rehydration = IV 0.9% sodium chloride 4-6L in 24 hours. Hypercalcaemia can cause significant dehydration. Monitor the fluid balance for pulmonary oedema.

Second Line: IV bisphosphonates (zoledronate or pamidronate as per local guidelines). The patient must be well-hydrated before use. It takes around 48-72 hours before a response is seen which lasts around 7 days. Adverse effects include oesophagitis & osteonecrosis of the jaw.

Third Line: (under specialist advice) calcitonin, denosumab, calcimimetics or parathyroidectomy. Prednisolone may be used in lymphoma, granulomatous disease or Vitamin D poisoning.

Loop diuretics may be used in those that cannot tolerate aggressive fluid hydration. They must be used with caution, as they can worsen electrolyte disturbance & volume depletion.

Another option is dialysis in patients with anuria (AKI or CKD) or where fluid overload is a likely issue.

References / Further Reading

By Dr Angela Yan (FY2), Dr Ruth Allen (FY1) & Dr Akash Doshi (ST3 Endocrinology)

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