Hypercalcemia
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More Specific Terms
Introduction
- Elevation of serum/ plasma Ca+2, clinically significant when ionized Ca+2 is increased. Albumin binds 45% of serum Ca+2, thus a normal calcium in the face of hypoalbuminemia may result in clinically significant hypercalcemia.
Etiology
- common causes of hypercalcemia:
-
- most cases of hypercalcemia in ambulatory patients [2]
- 85% are due to adenoma of a single gland
- 15% due to hyperplasia of all 4 glands
- 1% due to parathyroid carcinoma
- responsible for most hypercalcemia found in hospitalized patients
- see pathology
- uncommon causes of hypercalcemia
- pharmacologic causes:
- antacids with absorbable alkali ( milk-alkali syndrome)
- thiazides
- vitamin D
- lithium
- estrogens & antiestrogens
- androgens
Epidemiology
-
- common, especially in elderly women
- annual incidence of 2/1000
Pathology
- hypercalcemia of malignancy occurs largely via 2 mechanisms:
- local osteolytic hypercalcemia
- cytokines produced by tumor cells act locally to stimulate bone resorption
- extensive bone involvement of tumor, especially in breast carcinoma, myeloma & lymphoma
- PTH-related peptide or other related peptides secreted by tumor cells act systemically to stimulate bone resorption &/or inhibit Ca+2 excretion
- squamous cell carcinoma of the lung, head & neck, or esophagus, or carcinoma of the kidneys, bladder, or ovary are most frequently implicated
- in the setting of renal failure, macrophage 1-alpha hydroxylase activity can cause increased calcitriol
Clinical-manifestations
- most patients with primary hyperparathyroidism have asymptomatic hypercalcemia found incidentally
- GU: polyuria, polydypsia, dehydration, nephrolithiasis
- GI: nausea/vomiting, anorexia, constipation
- neurologic: weakness, fatigue, confusion, stupor, coma
- cardiac: hypertension, increased susceptibility to digitalis toxicity
- clinical manifestations of hypercalcemia tend to occur when serum Ca+2 rises above 12 mg/dL
- ectopic soft tissue calcification occurs when the Ca+2 rises above 13 mg/dL
Laboratory
- 24 hour urine Ca+2 excretion generally > 4 mg/kg
- serum ionized Ca+2
- serum Ca+2: high
Diagnostic-procedures
- electrocardiogram:
- shortened QT interval
- AV block (rare)
Management
-
- 1st line therapy for acute hypercalcemia
- avoid thiazide diuretics which impair Ca+2 excretion
- reserved for volume-repleted patients who have failed pamidronate & calcitonin
- glucocorticoids (1,25 (OH)2 vit D-mediated hypercalcemia
- oral phosphate
- gallium nitrate
More General Terms
Additional Terms
- calcium (Ca+2) in serum
- etidronate (Didronel)
- familial hypocalciuric hypercalcemia
- hyperparathyroidism
- milk-alkali syndrome (Burnett syndrome)
- pamidronate (Aredia)
References
- Harrison's Principles of Internal Medicine, 13th ed. Companion Handbook, Isselbacher et al (eds), McGraw-Hill Inc. NY, 1995, pg 830
- Manual of Medical Therapeutics, 28th ed, Ewald & McKenzie (eds), Little, Brown & Co, Boston, 1995, pg 490
- Medical Knowledge Self Assessment Program (MKSAP) 11, American College of Physicians, Philadelphia 1998
- Mayo Internal Medicine Board Review, 1998-99, Prakash UBS (ed) Lippincott-Raven, Philadelphia, 1998, pg 680-681
- Hypercalcemia (PDQ) [1]
