Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, University of Alabama at Birmingham, Veterans Affairs Medical Center, Birmingham, Alabama 35294-0012, USA.
Curr Opin Endocrinol Diabetes Obes. 2011 Dec;18(6):339-46. doi: 10.1097/MED.0b013e32834b4401.
Hypercalcemia of malignancy is a common paraneoplastic syndrome and a frequent complication of advanced breast and lung cancer, and multiple myeloma. The development of this malignancy complication often purports a poor prognosis. Thorough evaluation to establish the cause of hypercalcemia is essential because some patients may actually have undiagnosed primary hyperparathyroidism.
Production of humoral factors by the primary tumor, collectively known as humoral hypercalcemia of malignancy (HHM), is the mechanism responsible for 80% of cases. The vast majority of HHM is caused by tumor-produced parathyroid hormone-related protein followed by infrequent tumor production of 1,25-dihydroxyvitamin D and parathyroid hormone. The remaining 20% of cases are caused by bone metastasis with consequent bone osteolysis and release of skeletal calcium. Key therapies are saline hydration to promote calciuresis and bisphosphonates to reduce pathologic osteoclastic bone resorption. Calcitonin and glucocorticoids, especially in 1,25-dihydroxyvitamin D-mediated HHM, also have calcium-lowering effects.
Recent discoveries on mechanisms of malignancy-associated hypercalcemia highlight the critical role of the osteoclast. Bisphosphonates and other novel therapies being evaluated in clinical trial target this bone-resorbing cell type and provide effective and durable serum calcium reduction.
恶性肿瘤相关性高钙血症是一种常见的副肿瘤综合征，也是晚期乳腺癌、肺癌和多发性骨髓瘤的常见并发症。这种恶性肿瘤并发症的发生往往预示着预后不良。因此，建立高钙血症病因的全面评估至关重要，因为一些患者实际上可能患有未确诊的原发性甲状旁腺功能亢进症。
主要肿瘤产生的体液因子，统称为恶性肿瘤相关性体液性高钙血症（HHM），是导致 80%病例的原因。绝大多数 HHM 是由肿瘤产生的甲状旁腺激素相关蛋白引起的，其次是罕见的肿瘤产生 1,25-二羟维生素 D 和甲状旁腺激素。其余 20%的病例是由骨转移引起的，导致骨溶骨和释放骨骼钙。关键治疗方法是盐水水化以促进钙排泄和双膦酸盐以减少病理性破骨细胞骨吸收。降钙素和糖皮质激素，特别是在 1,25-二羟维生素 D 介导的 HHM 中，也具有降低血钙的作用。
最近关于恶性肿瘤相关性高钙血症发病机制的发现强调了破骨细胞的关键作用。正在临床试验中评估的双膦酸盐和其他新型疗法针对这种破骨细胞类型，提供了有效和持久的血清钙降低。
