Eto S, Nakano Y, Okada Y
First Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan.
Gan To Kagaku Ryoho. 1993 Dec;20(15):2311-8.
Hypercalcemia is one of the life-threatening paraneoplastic syndromes and urgent medical treatments are needed since malignant hypercalcemia progresses very rapidly. The intravenous administration of sufficient quantities of isotonic saline sometimes with loop diuretic agents is the first and fundamental step in the management of malignant hypercalcemia. As hormonal therapeutic agents for malignant hypercalcemia, calcitonin and/or glucocorticoid are the usual candidates. Calcitonin exerts calcium-lowering effects both through its direct inhibitory effect on osteoclastic bone resorption and prevention of calcium reabsorption from renal tubulus. Among the anticalcemic agents available, calcitonin has the most rapid onset of action; the hypocalcemic effects appear within a few hours after administration. But continued usage diminishes its effect which is called the "escape phenomenon". The usual dosage of calcitonin is 80-160 unit/day. Glucocorticoid alone has sometimes calcium-lowering effects for malignant hypercalcemia, even in the case of solid cancer such as lung cancer, though the mechanism is not clear. In lymphocytic proliferative disorders, a direct inhibitory effect on the proliferation of malignant cells accounts for the calcium-lowering effects. Glucocorticoid is known to prolong the calcium-lowering effect of calcitonin. So, the combination of calcitonin and glucocorticoid is the most effective hormonal treatment for malignant hypercalcemia. Calcitonin is used for initial several days and glucocorticoid (30-40 mg/day) is continued along with calcitonin from the beginning of the treatment. Most effective and safe hypocalcemic agents for malignant hypercalcemia are the newly developed bisphosphonate compounds, which are not yet available in Japan. These agents interact chemically with hydroxyapatite on the bone surface and prevent osteoclastic function and activity. According to the data of our own investigation, pamidronate, one of the relatively new generation of bisphosphonates, showed clearly hypocalemic effects for malignant hypercalcemia due to various kinds of malignancy by one intravenous administration (30-60 mg) without any adverse effect. In near future, the combination of calcitonin and bisphosphonates will also be the most effective medical management for malignant hypercalcemia in Japan.
高钙血症是一种危及生命的副肿瘤综合征，由于恶性高钙血症进展非常迅速，因此需要紧急医学治疗。静脉输注足量的等渗盐水，有时联合襻利尿剂，是治疗恶性高钙血症的首要和基本步骤。作为治疗恶性高钙血症的激素治疗药物，降钙素和/或糖皮质激素是常用的选择。降钙素通过对破骨细胞骨吸收的直接抑制作用以及防止肾小管对钙的重吸收来发挥降低血钙的作用。在现有的降钙药物中，降钙素起效最快；给药后数小时内即可出现降钙作用。但持续使用会降低其效果，即所谓的“逃逸现象”。降钙素的常用剂量为80 - 160单位/天。单独使用糖皮质激素有时对恶性高钙血症也有降钙作用，即使在肺癌等实体癌的情况下也是如此，但其机制尚不清楚。在淋巴细胞增殖性疾病中，对恶性细胞增殖的直接抑制作用是其降钙作用的原因。已知糖皮质激素可延长降钙素的降钙作用。因此，降钙素和糖皮质激素联合使用是治疗恶性高钙血症最有效的激素治疗方法。降钙素使用最初几天，从治疗开始就与降钙素一起持续使用糖皮质激素（30 - 40毫克/天）。治疗恶性高钙血症最有效且安全的降钙药物是新开发的双膦酸盐化合物，在日本尚未上市。这些药物与骨表面的羟基磷灰石发生化学反应，阻止破骨细胞的功能和活性。根据我们自己研究的数据，新一代双膦酸盐之一的帕米膦酸，静脉注射一次（30 - 60毫克）对各种恶性肿瘤引起的恶性高钙血症均有明显的降钙作用，且无任何不良反应。在不久的将来，降钙素和双膦酸盐联合使用也将是日本治疗恶性高钙血症最有效的医学方法。
