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Hypercalcemia in granulomatous diseases

Zalman S Agus, MD
Section Editor
Clifford J Rosen, MD
Deputy Editor
Jean E Mulder, MD


Hypercalcemia is a relatively common clinical problem. It results when the entry of calcium into the circulation exceeds the excretion of calcium into the urine or deposition in bone. This occurs when there is accelerated bone resorption, excessive gastrointestinal absorption, or decreased renal excretion of calcium. In some disorders, however, more than one mechanism may be involved.

Hypercalcemia has been described in patients with most granulomatous disorders. This topic card will review hypercalcemia associated with granulomatous diseases. Other disorders that lead to hypercalcemia are reviewed separately. (See "Etiology of hypercalcemia" and "Diagnostic approach to hypercalcemia".)


The signs and symptoms of hypercalcemia are similar regardless of the etiology (see "Clinical manifestations of hypercalcemia"). Symptoms and signs of chronic hypercalcemia (nephrolithiasis, nephrocalcinosis, renal insufficiency, and polyuria due to reduced responsiveness to antidiuretic hormone) can occur (see "Renal disease in sarcoidosis"). However, many patients with hypercalcemia and granulomatous disease are asymptomatic.


Hypercalcemia has been described in patients with most granulomatous disorders [1,2]. Among them, sarcoidosis [3-9] and tuberculosis [10-14] are probably most common. Other causes include berylliosis [15], coccidioidomycosis [16], histoplasmosis [17,18], candidiasis [19], Crohn's disease [20,21], Langerhans-cell histiocytosis (also called histiocytosis X, and including eosinophilic granuloma) [22], silicone-induced granulomas [23,24], methacrylate injection [25], cat-scratch disease [26], Wegener's granulomatosis [27], and Pneumocystis carinii pneumonia [28].

Sarcoidosis — The mechanism responsible for the abnormal calcium metabolism in granulomatous disease has been most completely evaluated in sarcoidosis. Approximately 30 to 50 percent of patients with this disorder have hypercalciuria, and 10 to 20 percent have hypercalcemia, which is aggravated by exposure to sunlight [1,3,4]. Increased intestinal calcium absorption induced by high serum calcitriol concentrations (1,25-dihydroxyvitamin D, the most active metabolite of vitamin D) is the primary abnormality, although a calcitriol-induced increase in bone resorption may also contribute [5-8].


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Literature review current through: Sep 2016. | This topic last updated: Oct 29, 2015.
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