Hypercalcemia in Emergency Medicine Clinical Presentation
- Author: Thomas E Green, DO, MPH, FACOEP, FACEP; Chief Editor: Romesh Khardori, MD, PhD, FACP more...
Symptoms of hypercalcemia depend on the underlying cause of the disease, the time over which it develops (rapid increases in calcium cause more severe symptoms), and the overall physical health of the patient.
Mild elevations in calcium levels are usually asymptomatic and typically discovered on routine laboratory diagnostic testing (usually up to 11.5 mg/dL).
As calcium levels increase, the following symptoms may occur:
Alterations of mental status
Abdominal or flank pain (The workup of patients with a new kidney stone occasionally reveals an elevated calcium level.)
Weakness and vague muscle/joint aches
Polyuria, polydipsia, nocturia
Severe elevations in calcium levels may cause coma.
Elderly patients are more likely to be symptomatic from only moderate elevations of calcium levels.
Hypercalcemia of malignancy may lack many of the features commonly associated with hypercalcemia caused by hyperparathyroidism. In addition, the symptoms of elevated calcium level may overlap with the symptoms of the patient's malignancy.
Hypercalcemia associated with renal calculi, joint complaints, and ulcer disease is more likely to be caused by hyperparathyroidism.
Hypercalcemia has few physical examination findings specific to its diagnosis. Often it is the symptoms or signs of underlying malignancy that bring the patient with hypercalcemia to seek medical attention. The primary malignancy may be suggested by lung findings, skin changes, lymphadenopathy, or liver or spleen enlargement.
Hypercalcemia can produce a number of nonspecific findings, as follows:
Hypertension and bradycardia may be noted in patients with hypercalcemia, but this is nonspecific.
Abdominal examination may suggest pancreatitis or the possibility of an ulcer.
Patients with long-standing elevation of serum calcium may have proximal muscle weakness that is more prominent in the lower extremities; they also may have bony tenderness to palpation.
Hyperreflexia and tongue fasciculations may be present.
Anorexia or nausea may occur.
Polyuria and dehydration are common.
Lethargy, stupor, or even coma may be observed.
Long-standing hypercalcemia may cause band keratopathy, but this is rarely recognized in the ED.
If hypercalcemia is caused by sarcoidosis, vitamin D intoxication, or hyperthyroidism, patients may have physical examination findings suggestive of those diseases.
Hypercalcemia is divided into PTH-mediated hypercalcemia (primary hyperparathyroidism) and non–PTH-mediated hypercalcemia.[10, 11, 12]
PTH-mediated hypercalcemia is related to increased calcium absorption from the intestine.
Non–PTH-mediated hypercalcemia includes the following:
Hypercalcemia associated with malignancy: Unlike PTH-mediated hypercalcemia, the elevation of calcium that results from malignancy generally worsens until therapy is provided. Hypercalcemia caused by malignancy is the result of increased osteoclastic activity within the bone. This results from one or both of the mechanisms that follow:
- Extensive localized bone destruction may result from osteolytic metastasis of solid tumors. Evidence indicates that many malignant cells may release local osteoclastic activating factors.
- Increased calcium levels resulting from malignancy caused by a PTH-related protein (PTH-rp) is a second mechanism. This protein is a humeral factor that acts on the skeleton to increase bone reabsorption; it acts on the kidney to decrease excretion of calcium. The gene that produces this protein is present in many malignant tissues.
Granulomatous disorders: High levels of calcitriol may be found in patients with sarcoidosis and other granulomatous diseases. In these disorders, the increased level of calcitriol results from production within the macrophages, which constitute a large portion of some granulomas.
Iatrogenic: In some cases, elevation of calcium is a known adverse effect of appropriate dosage. In other cases, large ingestions must be taken to induce the increase in calcium levels. Obtain a complete review of current medications for patients presenting with hypercalcemia. Record any vitamin use.
Other causes of hypercalcemia
See the list below:
Neoplasms (nonparathyroid) - Metastasis to the bone from breast, multiple myeloma, and hematologic malignancies ( Breast cancer is one of the most common malignancies responsible for hypercalcemia.)
Nonmetastatic (humoral-induced) - Ovary, kidney, lung, head and neck, esophagus, cervix, lymphoproliferative disease, multiple endocrine neoplasia, pheochromocytoma, and hepatoma
Pharmacologic agents - Thiazide, calcium carbonate (antacid), hypervitaminosis D, hypervitaminosis A, lithium, milk-alkali syndrome, and theophylline toxicity
Familial hypocalciuric hypercalcemia
Tertiary hyperparathyroidism - Postrenal transplant and initiation of chronic hemodialysis
Ariyan CE, Sosa JA. Assessment and management of patients with abnormal calcium. Crit Care Med. 2004 Apr. 32(4 Suppl):S146-54. [Medline].
Dent DM, Miller JL, Klaff L, Barron J. The incidence and causes of hypercalcaemia. Postgrad Med J. 1987 Sep. 63(743):745-50. [Medline].
Edelson GW, Kleerekoper M. Hypercalcemic crisis. Med Clin North Am. 1995 Jan. 79(1):79-92. [Medline].
Cho KC. Electrolyte & Acid-Base Disorders. Papadakis MA, McPhee SJ, Rabow MW, eds. CURRENT Medical Diagnosis & Treatment 2013. New York, NY: McGraw-Hill; 2013. Chapter 21.
Disorder of Calcium Metabolism. Alpern RJ, Moe OW, Caplan M, eds. Seldin and Giebisch's The Kidney. 5th ed. Elsevier; 2013. 2273-309.
Blomqvist CP. Malignant hypercalcemia--a hospital survey. Acta Med Scand. 1986. 220(5):455-63. [Medline].
Hypercalcemia. Niederhuber JE, Armitage JO, Doroshow JH, Kastan MB, Tepper, JE, eds. Abeloff's Clinical Oncology. 5th ed. Churchill Livingstone; 2014. 581-90.
Mundy GR, Guise TA. Hypercalcemia of malignancy. Am J Med. 1997 Aug. 103(2):134-45. [Medline].
Khosla S. Hypercalcemia and Hypocalcemia. Longo DL, Fauci AS, Kasper DL, Hauser SL, Jameson JL, Loscalzo J, eds. Harrison's Principles of Internal Medicine. 18th ed. New York, NY: McGraw-Hill; 2012. Chapter 46.
Lindner G, Felber R, Schwarz C, Marti G, Leichtle AB, Fiedler GM, et al. Hypercalcemia in the ED: prevalence, etiology, and outcome. Am J Emerg Med. 2013 Apr. 31(4):657-60. [Medline].
Tsao YT, Lee SW, Hsu JC, Ho FM, Wang WJ. Severe hypercalcemia in nonobstructive pyelonephritis with acute renal failure: hit or miss?. Am J Emerg Med. 2012 Oct. 30(8):1665.e5-7. [Medline].
AlZahrani A, Sinnert R, Gernsheimer J. Acute kidney injury, sodium disorders, and hypercalcemia in the aging kidney: diagnostic and therapeutic management strategies in emergency medicine. Clin Geriatr Med. 2013 Feb. 29(1):275-319. [Medline].
Grill V, Ho P, Body JJ, et al. Parathyroid hormone-related protein: elevated levels in both humoral hypercalcemia of malignancy and hypercalcemia complicating metastatic breast cancer. J Clin Endocrinol Metab. 1991 Dec. 73(6):1309-15. [Medline].
Diaz Guardiola P, Vega Pinero B, Alameda Hernando C, Pavon de Paz I, Iglesias Bolanos P, Guijarro de Armas G. [Primary hyperparathyroidism. An alternative to the surgery.]. Endocrinol Nutr. 2009 Mar. 56(3):132-5. [Medline].
Stewart AF. Clinical practice. Hypercalcemia associated with cancer. N Engl J Med. 2005 Jan 27. 352(4):373-9. [Medline].