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Home | Articles | Electrolyte Disturbances | Hypercalcaemia

Hypercalcaemia

Last updated 3rd December 2020

Last updated on 14th March 2016 by Fiona Green & Ranjit Thomas.  Update due 14th March 2017.

Introduction

  1. About 99% calcium is found in bone
  2. Serum calcium is adjusted for serum albumin to give an indirect measure of ionised calcium – reference range in Dumfries is 2.12-2.62mmol/l
  3. Calcium is regulated by PTH, Calcitonin and Vit D. PTH releases calcium from bone, Calcitonin does the opposite and 1,25OHD increases absorption of calcium from gut
  4. Numerous mechanisms exist for hypercalcaemia – see below

Causes

  1. 90% causes are due to:
    1. Malignancy esp Breast (parathyroid related protein), Lung (ectopic PTH) and Myeloma (release of osteoclastic activating factors)
    2. Primary hyperparathyroidism
  2. All other causes are much less common. They include:
    1. Drugs eg Vitamin D (increased absorption calcium from gut), Lithium (increased secretion PTH) and Thiazides (reduced tubular excretion calcium)
    2. Sarcoidosis (hydroxylation of vit D in granulomas)
    3. Thyrotoxicosis (increased osteoclastic activity)
    4. Milk alkali syndrome
    5. Tertiary hyperparathyroidism

Presentation

  1. Classically ‘bones, stones, abdominal groans, psychic moans, thrones and hypertones’ indicating osteoporosis, renal colic, peptic ulcer, depression, polyuria/constipation and hypertension
  2. In reality 50% patients are asymptomatic and many have non specific symptoms eg lethargy and malaise
  3. Acute severe hypercalcaemia may present with shock, coma and renal failure

Investigations

  1. The most useful investigation is PTH in 2.5ml EDTA tube, sent to lab asap even if out of hours
  2. If PTH detectable or ↑ then primary hyperparathyroidism is likely diagnosis
  3. If PTH is ↓ or undetectable and no other cause apparent then malignancy with or without bony metastases is likely
  4. Unless source of tumour obvious then screen for malignancy with CXR, Myeloma screen and CT chest abdo pelvis as appropriate

Serum Calcium <3mmol/l

  1. Usually asymptomatic and does not require urgent correction
  2. Advise to avoid factors that can aggravate hypercalcemia, including thiazide diuretic and lithium therapy, volume depletion, prolonged bed rest or inactivity, and a high calcium diet (>1000 mg/day)

Serum Calcium 3-3.5mmol/l

  1. May be well tolerated if has risen slowly but may be symptomatic and prompt treatment usually indicated
  2. Rehydrate then give IV biphosphonate

Serum Calcium >3.5mmol/l or Symptomatic

  1. Requires urgent treatment because risk of shock, coma, renal failure
  2. Rehydrate then give IV biphosphonate
  3. May need to consider dialysis if severe renal failure

Rehydration

  1. Rehydrate with IV N saline 3-4 litres in first 24 hours & 2-3 litres daily thereafter aiming for urine output urine output >2 litres/day
  2. IV fluid lowers serum Ca, but will not restore normocalcaemia
  3. Give Frusemide if required to avoid volume overload and heart failure and promote urinary calcium excretion
  4. Be more cautious in elderly with renal impairment and with LV dysfunction.

After Rehydration – IV Biphosphonates

  1. IV Biphosphonates are most beneficial for hypercalcaemia of malignancy but can still be used in other causes of hypercalcaemia.
  2. Do not use until patients are rehydrated
  3. If GFR >30ml/min and still hypercalcaemic after adequate hydration, give IV Zoledronate 4mg over 15 minutes in 100ml 0.9% sodium chloride
  4. If GFR <30ml/min after hydration give Pamidronate according to the corrected calcium as follows
    • Calcium <3.0: 30mg
    • Calcium 3-3.5: 60mg
    • Calcium >3.5: 90mg
  5. Add pamidronate disodium to sodium chloride 0.9% infusion as below and give over:
    • 30mg in 100ml – 250ml over 90min
    • 60mg in 250ml over 3 hours
    • 90mg in 250ml – 500ml over 4 hours
  6. Full effect of IV biphosphonate may take 3-7 days with duration of action 1-2 weeks.
  7. If Calcium remains high after 72 hours, a further dose of zolendronic acid may be given
  8. Patients with refractory hypercalcaemia may require corticosteroids and Calcitonin
  9. Myeloma patients with hypercalcaemia routinely receive dexamethasone 40mg for 4 days along with omeprazole & allopurinol (corrected for renal function).

Maintenance Therapy

  1. Discuss treatment options with relevant consultant
  2. Patients contemplating long term maintenance with bisphosphonates should receive appropriate counselling re osteonecrosis of the jaw and ideally a dental check before treatment
  3. IV Zolendronate is preferred maintenance for myeloma and SC Denosumab for breast cancer
  4. Oral Clodronate sometimes still used for myeloma if cannot tolerate IV Zolendronate otr if patient choice because reduced risk osteonecrosis.

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