Department of Medicine, University of Calgary, 1403 29 Street NW, Calgary, Alberta, Canada T2N 4J8.
J Clin Endocrinol Metab. 2010 Jul;95(7):3111-7. doi: 10.1210/jc.2009-2673. Epub 2010 Apr 28.
Calcitriol-mediated hypercalcemia resulting from elevated extrarenal 25-hydroxyvitamin D-1alpha-hydroxylase (1alpha-hydroxylase) activity has not previously been described in giant cell polymyositis.
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.
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.
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.
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.
甲状旁腺素之外的肾脏 25- 羟维生素 D-1α-羟化酶（1α-羟化酶）活性升高导致的降钙素介导的高钙血症以前并未在巨细胞性多肌炎中描述过。
我们报告了一例罕见的因播散性肉芽肿性疾病导致的高钙血症病例，患者为 62 岁女性，有严重的近端肌无力和体重减轻。她最初被诊断为维生素 D 缺乏性肌病，血清 25-羟维生素 D 低；此时血清钙处于低正常水平。给予维生素 D3 3000IU 每日。一个月后，血液检查显示新的高钙血症和高钙尿症，同时 25-羟维生素 D 正常化。1,25-二羟维生素 D 处于高正常水平，尽管甲状旁腺激素抑制，无甲状旁腺激素相关蛋白（PTHrP），且肾功能基本正常。她的高钙血症得到缓解，只有在双膦酸盐治疗中加入泼尼松后，她的肌力才得到改善。两周后，她死于急性充血性心力衰竭。
尸检显示散发性巨细胞性肌炎影响骨骼、心脏和胃肠道平滑肌。免疫组化将 1α-羟化酶定位在骨骼和心肌的炎症浸润中。
在 Medline 和 Embase 中检索英文文献并进行参考文献检索，回顾性分析了 30 多种情况，包括炎症性疾病、异物暴露、感染和肿瘤等。发现降钙素介导的高钙血症已在其中大多数情况下被描述。
如果血清 1,25-二羟维生素 D 水平不适当正常而不是明显升高，则低剂量维生素 D 补充可能会揭示自主 1α-羟化酶活性引起的高钙血症，并且在非甲状旁腺原因的鉴别诊断中不应排除这种情况。
