title: Treatment of sarcoidosis-associated hypercalcemia with ketoconazole.
abstract: A 47-year-old patient presented with hypercalcemia secondary to sarcoidosis and was successfully treated with 1 year of corticosteroids leading to improvement in his hypercalcemia, hypercalcuria, and elevated levels of 1,25-dihydroxyvitamin D. Angiotensin-converting enzyme levels (ACE) normalized and serum creatinine improved. When hypercalcemia recurred after a 3-year symptom-free interval, the patient refused repeat corticosteroid treatment and was placed on ketoconazole (initially 600 and eventually 800 mg/d). Ketoconazole controlled the patient's hypercalcemia (serum calcium, 3.2 to 2.6 mmol/L [12.8 to 10.4 mg/dL]), but only the larger dose suppressed serum 1,25-dihydroxyvitamin D levels into the normal range. Hypercalcuria was markedly improved with ketoconazole, decreasing from a peak of 23 mmol/d (940 mg/d) to less than 8.7 mmol/d (350 mg/d) on a dose of 800 mg. However, serum ACE levels remained elevated on ketoconazole. An attempt to taper the ketoconazole after 1 year resulted in rapid recurrence of hypercalcemia (serum calcium, 2.8 mmol/L [11.1 mg/dL]) and hypercalcuria (urinary calcium excretion, 11 mmol/d [451 mg/d]). After a total of 2 years of ketoconazole treatment, his defect in calcium metabolism remains well controlled despite persistent elevation in ACE levels. Serum cortisol levels and liver function tests remain normal on therapy, although there has been a slight decrease in serum testosterone levels accompanied by some decrease in libido. These data suggest that long-term use of ketoconazole may be a safe and effective alternative to corticosteroid treatment for sarcoid-associated hypercalcemia. Further study is needed to determine whether the long-term side effects of ketoconazole therapy or its failure to control disease activity in sarcoidosis outweigh its advantages in avoiding the known side effects of glucocorticoids.
authors.affiliation: Department of Internal Medicine, Yale University School of Medicine, New Haven, CT.
authors.forename: M J
authors.initials: MJ
authors.lastname: Bia
authors.forename: K
authors.initials: K
authors.lastname: Insogna
mesh_terms: D002117:Calcitriol / Q000378:metabolism; D002118:Calcium / Q000652:urine; D006801:Humans; D006934:Hypercalcemia / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D007654:Ketoconazole / Q000627:therapeutic use*; D007676:Kidney Failure, Chronic / Q000209:etiology; D008297:Male; D008875:Middle Aged; D011241:Prednisone / Q000627:therapeutic use; D012507:Sarcoidosis / Q000150:complications* / Q000188:drug therapy / Q000378:metabolism
chemical_list: D002117:Calcitriol; D007654:Ketoconazole; D002118:Calcium; D011241:Prednisone