Hypercalcaemia

High calcium levels in the blood serum

Aetiology

Excessive parathyroid (PTH) hormone secretion

  • Primary hyperparathyroidism - caused by a single adenoma (>80%) or diffuse hyperplasia of the parathyroid glands (15-20%)
  • Tertiary hyperparathyroidism

Malignant disease

  • Metastatic bone destruction
  • PTHrp from solid tumours
  • Osteoclast activating factors produced by tumours

Genetic syndromes

  • MEN1 and 2 - will almost always have developed a parathyroid adenoma with hypercalcaemia at a young age
  • Familial isolated hyperparathyroidism - adenoma as in primary hyperparathyroidism
  • Familial hypocalciuric hypercalcaemia - autosomal dominant deactivating mutation in the calcium sensing receptor which results in decreased sensitivity of the receptor to calcium
    • Usually benign/asymptomatic

Others

  • Drugs - Vit. D, thiazides
  • Granulomatous disease e.g. sarcoid, TB
  • High turnover - bedridden, thyrotoxic, Pagets

Clinical presentation

General

  • Gallstones (STONES)
  • Bone pain (BONES)
  • Abdominal pain (GROANS)
  • Psychiatric disturbances (PSYCHIC MOANS)

Acute

  • Thirst
  • Dehydration
  • Confusion
  • Polyuria

Chronic

  • Myopathy
  • Fractures
  • Osteopaenia
  • Depression
  • Hypertension
  • Pancreatitis
  • Duodenal ulcers
  • Renal calculi

Investigations

Biochemistry

  • Raised calcium
  • Serum PTH
    • Hallmark of primary hyperparathyroidism is hypercalcaemia and hypophosphataemia with detectable or elevated intact PTH levels during hypercalcaemia
    • Undetectable PTH with hypercalcaemia requires further investigation for malignancy
  • Serum alkaline phosphatase - raised in hypercalcaemia of malignancy

Imaging for malignancy

  • X-ray, CT, MRI, PET
  • Isotope bone scan

Familial hypocalciuric hypercalcaemia

  • Bloods - mild hypercalcaemia, reduced urine calcium excretion, PTH may be (marginally) elevated
  • Genetic screening

Management

Management of acute severe hypercalcaemia

  • Fluids - rehydrate with 0.9% saline 4-6L in 24 hours
  • Consider loop diurectics once rehydrated (avoid thiazides)
  • Bisphosphonates - single dose will lower Ca2+ over 2-3 days, max. effect at 1 week
  • Steriods occasionally used e.g. prednisolone 40-60mg/day for sarcoidosis

Primary hyperparathyroidism

  • Surgery (not always required) - indications include end organ damage, calcium >2.85 mmol/l, under age 50 and reduced eGFR (< 60 mL/min)
  • Cinacalcet - calcium mimetic, reduces PTH
    • Can be useful if need treatment but unfit for surgery
    • Licenced but not SMC approved
    • Approved for tertiary hyperparathyroidism and parathyroid carcinoma

Malignancy

  • Treat underlying malignancy
  • Chemotherapy may reduce calcium in malignant disease e.g. myeloma