Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020437 (hypercalcemia)
 10,293 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:Treatment of sarcoidosis-associated hypercalcemia with ketoconazole. 196 57

The endocrine abnormalities associated with acquired immunodeficiency syndrome (AIDS) are reviewed. These include adrenal insufficiency, hyporeninemic hypoaldosteronism, panhypopituitarism, hypogonadism, and alterations in thyroid function tests. AIDS-related infections or neoplasms may lead to hypercalcemia, whereas malabsorption may cause hypocalcemia. The possibility that AIDS-associated cachexia and hypertriglyceridemia may be caused by cachectin (tumor necrosis factor) is discussed, along with possible therapy for cachexia with megestrol acetate. Ketoconazole, sulfonamides, and pentamidine have specific, potentially deleterious metabolic effects when used in AIDS patients. Because treatment of endocrinological abnormalities of AIDS is often effective, improved diagnosis and appropriate therapy of these abnormalities will result in improved quality of life and, possibly, longer survival of patients with AIDS.
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PMID:Endocrinologic and metabolic manifestations of the acquired immunodeficiency syndrome. 224 1

Administration of the antifungal drug ketoconazole reduces serum 1,25-dihydroxyvitamin D (1,25-D) levels in normal subjects. To determine whether a similar effect occurs in hypercalcemic patients, ketoconazole (200 mg every 8 h for 7 days) was given to nine patients with confirmed primary hyperparathyroidism, three patients with probable primary hyperparathyroidism who were awaiting surgery, and three patients with mild hypercalcemia of uncertain etiology who were being followed. Ketoconazole administration led to a significant reduction in mean serum 1,25-D levels in the hypercalcemic patients [basal, 64 +/- 7 (+/- SEM) pg/mL (154 +/- 17 pmol/L) vs. 36 +/- 5 pg/mL (86 +/- 12 pmol/L) after ketoconazole; P less than 0.001]. Serum total calcium fell slightly but significantly [basal, 11.05 +/- 0.17 mg/dL (2.76 +/- 0.04 mmol/L) vs. 10.77 +/- 0.16 (2.69 +/- 0.04 mmol/L) after ketoconazole; P less than 0.02], but the falls in total serum calcium and serum 1,25-D after ketoconazole treatment were not correlated with one another. Ketoconazole administration did not alter serum ionized calcium, 25-hydroxyvitamin D, phosphate, alkaline phosphatase, or PTH concentrations or urinary cAMP excretion. The responses to ketoconazole were similar in all three patient subgroups. We conclude that short term administration of ketoconazole to hypercalcemic patients causes a substantial fall in serum 1,25-D and a small fall in total serum calcium. These effects render ketoconazole a potentially useful agent for investigation of the importance of 1,25-D in patients with hypercalcemic disorders and for their treatment.
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PMID:Ketoconazole-induced reduction in serum 1,25-dihydroxyvitamin D and total serum calcium in hypercalcemic patients. 336 Sep 1

Hypercalcemia is a recognised complication of sarcoidosis due to excess 1,25-hydroxyvitamin D3 production by macrophages. Systemic corticosteroids inhibit 1,25-hydroxyvitamin D3 production, but long term therapy is often required to maintain normocalcemia. Ketoconazole is an imidazole antifungal that inhibits macrophage 1 alpha-hydroxylation of 25-hydroxyvitamin D3 and has been used in paraneoplastic hypercalcemia. We report a case series of four patients with relative contraindications to corticosteroids in whom treatment with ketoconazole allowed cessation or reduction in the maintenance dose of corticosteroids. We conclude that ketoconazole should be considered as an alternative therapy for hypercalcemic sarcoidosis when corticosteroids are relatively contraindicated.
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PMID:Ketoconazole for the treatment of refractory hypercalcemic sarcoidosis. 1103 44