Rare case of 3000 IU vitamin D being toxic – hypercalcemia April 2010

Rare Causes of Calcitriol-Mediated Hypercalcemia: A Case Report and Literature Review.
J Clin Endocrinol Metab. 2010 Apr 28. Epub ahead of print
Kallas M, Green F, Hewison M, White C, Kline G.
Department of Medicine (M.K., G.K.), University of Calgary, Calgary, Alberta, Canada T2N 4J8; Department of Pathology and Laboratory Medicine (F.G.), University of Calgary, Calgary, Alberta, Canada T2N 2N1; Department of Orthopaedic Surgery (M.H.), University of California, Los Angeles, California 90095-7358; and Department of Clinical Neurosciences (C.W.), University of Calgary, Calgary, Alberta, Canada T2N 2T9.
Context: Calcitriol-mediated hypercalcemia resulting from elevated extrarenal 25-hydroxyvitamin D-1alpha-hydroxylase (1alpha-hydroxylase) activity has not previously been described in giant cell polymyositis. Case: 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 D3 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.
Methods and 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.
Evidence: 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. PMID: 20427501