Hypercalcemia

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Hypercalcemia
Calcium
ICD-10 E83.5
ICD-9 275.42
DiseasesDB 6196
MedlinePlus 000365
eMedicine med/1068  emerg/260 ped/1062
MeSH D006934

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Hypercalcaemia (in US English 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.

  • Calcium is the most abundant mineral in the the body
  • 99% of the calcium in the body is stored in the bone
  • Calcium in the plasma is either ionized or protein-bound and readily available for use
  • An increase in total plasma calcium concentration above 10.4 mg/dL signifies hypercalcemia
  • Serum concentration is regulated through parathyroid hormone (PTH), vitamin D and calcitonin

Causes

Main causes

hyperparathyroidism and malignancy account for ~90% of cases

Complete Differential Diagnosis of the Causes of Hypercalcemia

(In alphabetical order)

Complete Differential Diagnosis of the Causes of Hypercalcemia

(By organ system)

Cardiovascular No underlying causes
Chemical / poisoning Aluminum intoxication, Hypervitaminosis D (vitamin D intoxication), Vitamin A intoxication, Vitamin D intoxication
Dermatologic Leprosy
Drug Side Effect Lithium, Thiazide diuretics
Ear Nose Throat Oral candidiasis
Endocrine Abnormal parathyroid gland function, Acromegaly, Acute osteoporosis, Addison's Disease, Adrenal insufficiency, Autonomous hyperparathyroidism (post long-term renal failure), Bartter's Syndrome, Cushing's syndrome, Familial isolated hyperparathyroidism, Hyperparathyroidism (in the preceding oliguric-anuric phase), Hyperthyroidism, Isolated or multinodal adenoma, Multiple endocrine neoplasia (MEN), Parathyroid carcinoma, Parathyroid hyperplasia, Pheochromocytoma, Primary hyperparathyroidism, Primary Parathyroid hyperplasia, Secretion of prostaglandins, Severe secondary hyperparathyroidism, Solitary parathyroid adenoma, Vasoactive intestinal polypeptide-producing tumor (VIPoma)
Environmental No underlying causes
Gastroenterologic Hepatocellular carcinoma, Hypervitaminosis D (vitamin D intoxication), Oral candidiasis, Total parenteral nutrition
Genetic Familial hypocalcuric hypercalcemia, Familial isolated hyperparathyroidism, Gitelman syndrome, William's syndrome
Hematologic Hodgkin's lymphoma, Leukemia, Lymphoma, Multiple myeloma, Plasma cell granuloma, Polycythemia
Iatrogenic No underlying causes
Infectious Disease Coccidioidomycosis, Leprosy, Oral candidiasis
Musculoskeletal / Ortho Acute osteoporosis, Bone fracture, Paget's Disease, Rebound hypercalcemia after rhabdomyolysis
Neurologic No underlying causes
Nutritional / Metabolic Dehydration, Milk-alkali syndrome, Osteomalacia, Total parenteral nutrition, , Vitamin A intoxication, Vitamin D intoxication, Vitamin D metabolic disorders
Obstetric/Gynecologic Breast cancer, Ovarian cancer, Paget's Disease
Oncologic Breast cancer, Bronchial carcinoma, Carcinoma, Hematologic malignancy (multiple myeloma, lymphoma, leukemia), Hepatocellular carcinoma, Hodgkin's lymphoma, Isolated or multinodal adenoma, Kidney cancer, Leukemia, Lymphoma, Malignancy, Multiple endocrine neoplasia (MEN), Multiple Myeloma, Ovarian cancer, Paget's Disease, Parathyroid carcinoma, Pheochromocytoma, Plasma cell granuloma, Silicone-Induced granuloma, Solid tumor with humoral mediation of hypercalcemia (e.g. lung or kidney cancer, pheochromocytoma), Solid tumor with metastasis (e.g. breast cancer), Solitary parathyroid adenoma, Vasoactive intestinal polypeptide-producing tumor (VIPoma)
Opthalmologic No underlying causes
Overdose / Toxicity , Aluminum intoxication, Aspirin (in large amounts), Drugs, Hypervitaminosis D (vitamin D intoxication), Vitamin A intoxication, Vitamin D intoxication
Psychiatric No underlying causes
Pulmonary Berylliosis, Bronchial carcinoma, Granulomatous diseases with tuberculosis, Histoplasmosis, Sarcoidosis, Tuberculosis, Tuberculosis
Renal / Electrolyte Acute renal failure, After kidney transplant, Bartter's Syndrome, Chronic renal failure, Familial hypocalcuric hypercalcemia, Kidney cancer, Medullary sponge kidney, Milk-alkali syndrome, Rebound hypercalcemia after rhabdomyolysis, Renal failure
Rheum / Immune / Allergy Acute osteoporosis, Sarcoidosis, Sjogren's syndrome
Sexual No underlying causes
Trauma No underlying causes
Urologic Acute renal failure, Chronic renal failure, Milk-alkali syndrome, Renal failure
Miscellaneous Idiopathic hypercalcemia (in infants), Immobilization, Paraplegia

Diagnosis

Signs and symptoms

Hypercalcemia per se can result in fatigue, depression, confusion, anorexia, nausea, vomiting, constipation, pancreatitis or increased urination "Bones, stones, groans, and psychic moans" is a saying which will help you remember the signs and symptoms of hypercalcemia; if it is chronic it can result in urinary calculi (renal stones or bladder stones). Abnormal heart rhythms can result, and EKG findings of a short QT interval and a widened T wave suggest hypercalcemia.

Symptoms are more common at high calcium blood values (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.

Complete List of Possible Symptoms

Physical Examination

  • Evaluate for increased urination and/or renal stones
  • Mental status changes
  • Confusion
  • Tiredness
  • Hyporeflexia
  • Arrhythmias
  • Coma

Laboratory Findings

  • Complete blood count (CBC)
  • Serum and urinary calcium
  • Blood urea nitrogen (BUN)/creatinine
  • Parathyroid hormone (PTH)
  • PTH-related peptide
  • Albumin
  • Phosphate
  • Alkaline phosphatase
  • Vitamin D
  • Magnesium

Electrocardiographic Findings

  1. A shortening of the QTc interval
  2. The decrease is at the expense of the ST segment which becomes shortened or absent.
  3. This is true for Ca of up to 16 meq/li, after this QTc prolongation occurs
12 lead EKG:Hypercalcemia. Courtesy of Dr Jose Ganseman

Treatment

The goal of therapy is to treat the hypercalcemia 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 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 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) 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

Other therapies

See also

Template:Endocrine, nutritional and metabolic pathology

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