Rare causes of calcitriol-mediated hypercalcemia: a case report and literature review.
BACKGROUND
Calcitriol-mediated hypercalcemia resulting from elevated extrarenal 25-hydroxyvitamin D-1alpha-hydroxylase (1alpha-hydroxylase) activity has not previously been described in giant cell polymyositis.


METHODS
We report an unusual case of hypercalcemia due to disseminated granulomatous disease in a 62-yr-old woman with profound proximal muscle weakness and weight loss. She was initially diagnosed with vitamin D deficiency myopathy with a low serum 25-hydroxyvitamin D; serum calcium at this time was low-normal. Vitamin D(3) 3000 IU daily was prescribed. One month later, blood work showed new hypercalcemia and hypercalciuria with normalized 25-hydroxyvitamin D. 1,25-dihydroxyvitamin D was high-normal, despite a suppressed PTH, undetectable PTHrP, and essentially normal renal function. Her hypercalcemia resolved, and her strength improved only after prednisone was added to bisphosphonate therapy. Two weeks later, she died from acute congestive heart failure.


RESULTS
Autopsy revealed a disseminated giant cell myositis affecting skeletal, cardiac, and gastrointestinal smooth muscle. Immunohistochemistry localized 1alpha-hydroxylase to the inflammatory infiltrates in skeletal and cardiac muscle.


METHODS
A review of English publications in Medline and Embase, including a reference search of retrieved articles, revealed that calcitriol-mediated hypercalcemia has been described in over 30 conditions, most of which are granulomatous in nature, ranging from inflammatory conditions and foreign body exposures to infections and neoplasms.


CONCLUSIONS
Hypercalcemia resulting from autonomous 1alpha-hydroxylase activity may be unmasked by low-dose vitamin D supplementation and should not be excluded from the differential diagnosis of nonparathyroid causes if the serum calcitriol is inappropriately normal, rather than frankly elevated.
Kallas
Melissa
M
Department of Medicine, University of Calgary, 1403 29 Street NW, Calgary, Alberta, Canada T2N 4J8.
Green
Francis
F
Hewison
Martin
M
White
Christopher
C
Kline
Gregory
G
D002117:Calcitriol / Q000097:blood*; D002762:Cholecalciferol / Q000627:therapeutic use; D017809:Fatal Outcome; D005260:Female; D006333:Heart Failure / Q000209:etiology; D006801:Humans; D006934:Hypercalcemia / Q000097:blood / Q000175:diagnosis* / Q000209:etiology; D008875:Middle Aged; D009460:Neurologic Examination; D017285:Polymyositis / Q000097:blood / Q000150:complications / Q000175:diagnosis*; D014808:Vitamin D Deficiency / Q000150:complications / Q000188:drug therapy
D002762:Cholecalciferol; D002117:Calcitriol