Hypercalcaemia

Hypercalcaemia
Classification and external resources
Calcium
ICD-10	E83.5
ICD-9	275.42
DiseasesDB	6196
MedlinePlus	000365
eMedicine	med/1068 emerg/260 ped/1062
MeSH	D006934

Hypercalcaemia (in American English, hypercalcemia) is an elevated calcium level in the blood.^[1] (Normal range: 9-10.5 mg/dL or 2.2-2.6 mmol/L). It can be an asymptomatic laboratory finding, but because an elevated calcium level is often indicative of other diseases, a diagnosis should be undertaken if it persists. It can be due to excessive skeletal calcium release, increased intestinal calcium absorption, or decreased renal calcium excretion.

Signs and symptoms

There is a general mnemonic for remembering the effects of hypercalcaemia: "groans (constipation), moans (psychotic noise), bones (bone pain, especially if PTH is elevated), stones (kidney stones), and psychiatric overtones (including depression and confusion)."

Other symptoms can include fatigue, anorexia, nausea, vomiting, pancreatitis and increased urination.

Abnormal heart rhythms can result, and ECG findings of a short QT interval^[2] and a widened T wave suggest hypercalcaemia. Finally, peptic ulcers may also occur.

Symptoms are more common at high calcium blood values (12.0 mg/dL or 3 mmol/l). Severe hypercalcaemia (above 15–16 mg/dL or 3.75-4 mmol/l) is considered a medical emergency: at these levels, coma and cardiac arrest can result.

Causes

Primary hyperparathyroidism and malignancy account for about 90% of cases of hypercalcaemia. ^[3][4]

Abnormal parathyroid gland function

• primary hyperparathyroidism
  • solitary parathyroid adenoma
  • primary parathyroid hyperplasia
  • parathyroid carcinoma
  • multiple endocrine neoplasia (MEN)
  • familial isolated hyperparathyroidism^[5]
• lithium use
• familial hypocalciuric hypercalcaemia/familial benign hypercalcaemia^[6][7][8]

Malignancy

• solid tumour with metastasis (e.g. breast cancer or classically squamous cell carcinoma, which can be PTHrP-mediated)
• solid tumour with humoral mediation of hypercalcaemia (e.g. lung or kidney cancer, pheochromocytoma)
• haematologic malignancy (multiple myeloma, lymphoma, leukaemia)

Vitamin-D metabolic disorders

• hypervitaminosis D (vitamin D intoxication)
• elevated 1,25(OH)₂D (see calcitriol under Vitamin D) levels (e.g. sarcoidosis and other granulomatous diseases)
• idiopathic hypercalcaemia of infancy^[9]
• rebound hypercalcaemia after rhabdomyolysis

Disorders related to high bone-turnover rates

• hyperthyroidism
• prolonged immobilization
• thiazide use
• vitamin A intoxication
• Paget's disease of the bone
• multiple myeloma

Renal failure

• severe secondary hyperparathyroidism
• aluminium intoxication
• milk-alkali syndrome

Treatments

The goal of therapy is to treat the hypercalcaemia first and subsequently effort is directed to treat the underlying cause.

Initial therapy: fluids and diuretics

• hydration, increasing salt intake, and forced diuresis.
  • hydration is needed because many patients are dehydrated due to vomiting or renal defects in concentrating urine.
  • increased salt intake also can increase body fluid volume as well as increasing urine sodium excretion, which further increases urinary calcium excretion (In other words, calcium and sodium (salt) are handled in a similar way by the kidney. Anything that causes increased sodium (salt) excretion by the kidney will, en passant, cause increased calcium excretion by the kidney)
  • after rehydration, a loop diuretic such as furosemide can be given to permit continued large volume intravenous salt and water replacement while minimizing the risk of blood volume overload and pulmonary oedema. In addition, loop diuretics tend to depress renal calcium reabsorption thereby helping to lower blood calcium levels
  • can usually decrease serum calcium by 1–3 mg/dL within 24 h
  • caution must be taken to prevent potassium or magnesium depletion

Additional therapy: bisphosphonates and calcitonin

• bisphosphonates are pyrophosphate analogues with high affinity for bone, especially areas of high bone-turnover.
  • they are taken up by osteoclasts and inhibit osteoclastic bone resorption
  • current available drugs include (in order of potency): (1st gen) etidronate, (2nd gen) tiludronate, IV pamidronate, alendronate, risedronate, and (3rd gen) zoledronate
  • all patients with cancer-associated hypercalcaemia should receive treatment with bisphosphonates since the 'first line' therapy (above) cannot be continued indefinitely nor is it without risk. Further, even if the 'first line' therapy has been effective, it is a virtual certainty that the hypercalcaemia will recur in the patient with hypercalcaemia of malignancy. Use of bisphoponates in such circumstances, then, becomes both therapeutic and preventative
  • patients in renal failure and hypercalcaemia should have a risk-benefit analysis before being given bisphosphonates, since they are relatively contraindicated in renal failure.

• Calcitonin blocks bone resorption and also increases urinary calcium excretion by inhibiting renal calcium reabsorption
  • Usually used in life-threatening hypercalcaemia along with rehydration, diuresis, and bisphosphonates
  • Helps prevent recurrence of hypercalcaemia
  • Dose is 4 Units per kg via subcutaneous or intramuscular route every 12 hours, usually not continued indefinitely

Other therapies

• rarely used, or used in special circumstances
  • plicamycin inhibits bone resorption (rarely used)
  • gallium nitrate inhibits bone resorption and changes structure of bone crystals (rarely used)
  • glucocorticoids increase urinary calcium excretion and decrease intestinal calcium absorption
    • no effect in calcium level in normal or primary hyperparathyroidism
    • effective in hypercalcaemia due to osteolytic malignancies (multiple myeloma, leukaemia, Hodgkin's lymphoma, carcinoma of the breast) due to antitumor properties
    • also effective in hypervitaminosis D and sarcoidosis
  • dialysis usually used in severe hypercalcaemia complicated by renal failure. Supplemental phosphate should be monitored and added if necessary
  • phosphate therapy can correct the hypophosphataemia in the face of hypercalcaemia and lower serum calcium

See also

• Calcium metabolism
• Dent's Disease
• Hypocalcaemia
• Electrolyte disturbance
• Disorders of calcium metabolism
• ATC code V03#V03AG Drugs for treatment of hypercalcemia

References