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Hypercalcaemia (or Hypercalcemia) is an elevated calcium level in the blood. (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 symptomsEdit
Hypercalcemia per se can result in fatigue, depression, confusion, anorexia, nausea, vomiting, constipation, pancreatitis or increased urination; if it is chronic it can result in urinary calculi (renal stones or bladder stones). Abnormal heart rhythms can result, and an EKG finding of a short QT interval suggests hypercalcemia.
Symptoms are more common at high calcium levels (12.0 mg/dL or 3 mmol/l). Severe hypercalcemia (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.
- hyperparathyroidism and malignancy account for ~90% of cases
- abnormal parathyroid gland function
- primary hyperparathyroidism
- lithium use
- familial hypocalciuric hypercalcemia/familial benign hypercalcaemia (OMIM 145980, OMIM 145981, OMIM 600740)
- vitamin-D metabolic disorders
- disorders related to high bone-turnover rates
- renal failure
The goal of therapy is to treat the hypercalcemia first and subsequently effort is directed to treat the underlying cause.
Initial therapy: fluids and diureticsEdit
- 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 thence pulmonary edema. 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 calcitoninEdit
- 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) zolendronate
- all patients with cancer-associated hypercalcemia 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 hypercalcemia will recur in the patient with hypercalcemia of malignancy. Use of bisphoponates in such circumstances, then, becomes both therapeutic and preventative
- patients in renal failure and hypercalcemia 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 hypercalcemia along with rehydration, diuresis, and bisphosphonates
- Helps prevent recurrence of hypercalcemia
- Dose is 4 Units per kg via subcutaneous or intramuscular route every 12 hours, usually not continued indefinitely
- rarely used, or used in special circumstances
- plicamycin inhibits bone resorption (rarely used)
- gallium nitrate inhibits bone resprotion and changes structure of bone crystals (rarely used)
- glucocorticoids increase urinary calcium excretion and decrease intestinal calcium absorption
- dialysis usually used in severe hypercalcemia complicated by renal failure. Supplemental phosphate should be monitored and added if necessary
- phosphate therapy can correct the hypophosphatemia in the face of hypercalcemia and lower serum calcium
- Calcium metabolism
- Dent's Disease
- Electrolyte disturbance
- Disorders of calcium metabolism
- ATC code V03#V03AG Drugs for treatment of hypercalcemia
amino-acids Phenylketonuria - Alkaptonuria - Ochronosis - Tyrosinemia - Maple syrup urine disease - Propionic acidemia - Methylmalonic acidemia - Isovaleric acidemia - Primary carnitine deficiency - Cystinuria - Cystinosis - Hartnup disease - Homocystinuria - Citrullinemia - Hyperammonemia - Glutaric acidemia type 1
carbohydrates Lactose intolerance - Glycogen storage disease (type I, type II, type III, type IV, type V), Fructose intolerance, Galactosemia
Lipid storage disorders Gangliosidosis - GM2 gangliosidoses (Sandhoff disease, Tay-Sachs disease) - GM1 gangliosidoses - Mucolipidosis type IV - Gaucher's disease - Niemann-Pick disease - Farber disease - Fabry's disease - Metachromatic leukodystrophy - Krabbe disease - Neuronal ceroid lipofuscinosis - Batten disease - Cerebrotendineous xanthomatosis - Wolman disease - Cholesteryl ester storage disease
List of fatty acid metabolism disorders - Hyperlipidemia - Hypercholesterolemia - Familial hypercholesterolemia - Xanthoma - Combined hyperlipidemia - Lecithin cholesterol acyltransferase deficiency - Tangier disease - Abetalipoproteinemia
mineral metabolism Disorders of calcium metabolism - Hypophosphatemia - Hypophosphatasia - Wilson's disease - Menkes disease - Hypermagnesemia - Hypomagnesemia - Hypercalcaemia - Hypocalcaemia
fluid, electrolyte and acid-base balance Electrolyte disturbance - Hypernatremia - Hyponatremia - Respiratory acidosis - Metabolic acidosis - Lactic acidosis - Hypervolemia - Hypokalemia - Hyperkalemia - Mixed disorder of acid-base balance - Hyperchloremia - Hypochloremia - Dehydration
porphyrin and bilirubin Acatalasia - Gilbert's syndrome - Crigler-Najjar syndrome - Dubin-Johnson syndrome - Rotor syndrome - Porphyria (Acute intermittent porphyria, Gunther's disease, Porphyria cutanea tarda, Erythropoietic protoporphyria, Hepatoerythropoietic porphyria, Hereditary coproporphyria, Variegate porphyria)
glycosaminoglycan Mucopolysaccharidosis - Hurler syndrome - Hunter syndrome - Sanfilippo syndrome - Morquio syndrome
glycoprotein I-cell disease - Pseudo-Hurler polydystrophy - Aspartylglucosaminuria - Fucosidosis - Alpha-mannosidosis - Sialidosis
other Alpha 1-antitrypsin deficiency - Cystic fibrosis - Familial Mediterranean fever - Lesch-Nyhan syndrome
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