Clinical review: Rare causes of hypercalcemia.
BACKGROUND
Although hypercalcemia is usually caused by primary hyperparathyroidism or malignancy, a number of other conditions can be important to consider. This review considers unusual causes of hypercalcemia that are generally not found in reviews on this subject.


METHODS
Articles describing rarely reported associations between hypercalcemia and unusual causes were identified through a computer search of the terms hypercalcemia/etiology and through the references listed in those articles. We grouped the 58 different reports into categories defined by a presumed etiology: increased levels of 1,25-dihydroxyvitamin D or PTHrP, occult milk-alkali syndrome, and undefined mechanisms. Reports in infants and children are listed separately, as are reports of pseudohypercalcemia, situations that are not truly hypercalcemic because the ionized calcium is normal.


RESULTS
In some situations, as this review points out, a number of unusual causes of hypercalcemia are important to consider. The search for an elusive cause of hypercalcemia is best accomplished by the most likely potential mechanism. An orderly search in this manner is likely to reveal the underlying cause.


CONCLUSIONS
That so many patients have been described with rare and usually poorly understood causes of hypercalcemia highlights our incomplete understanding of calcium metabolism in humans and suggests additional areas in which directed clinical investigation might improve our knowledge of the normal metabolism of calcium.
Jacobs
Thomas P
TP
Columbia University Medical Center, 161 Fort Washington Avenue, New York, New York 10032, USA. tpj1@columbia.edu
Bilezikian
John P
JP
D002117:Calcitriol / Q000097:blood; D002118:Calcium / Q000378:metabolism; D006801:Humans; D006934:Hypercalcemia / Q000209:etiology* / Q000628:therapy; D044162:Parathyroid Hormone-Related Protein / Q000378:metabolism
D044162:Parathyroid Hormone-Related Protein; D002117:Calcitriol; D002118:Calcium