Betea D, Bradwell A R, Harvey T C, Mead G P, Schmidt-Gayk H, Ghaye B, Daly A F, Beckers A
Service d'Endocrinologie, Centre Hospitalier Universitaire de Liège, Domaine Universitaire du Sart-Tilman, 4000 Liège, Belgium.
J Clin Endocrinol Metab. 2004 Jul;89(7):3413-20. doi: 10.1210/jc.2003-031911.
Parathyroid carcinoma is a rare cause of primary hyperparathyroidism, and the efficacy of medical therapy and chemo- and radiotherapy is poor in recurrent or metastatic disease. We report the first case of PTH immunization in which tumor shrinkage accompanied hormonal, biochemical, and clinical improvements in a patient with metastatic parathyroid carcinoma.A 50-yr-old woman with refractory parathyroid carcinoma and pulmonary metastases was immunized eight times between February 2001 and December 2003 with bovine and modified human PTH fragments and intact human PTH, mixed with Freund's adjuvant. Total and ionized calcium and PTH levels were assayed weekly for 6 months and regularly thereafter. Thoracic computed tomography scans were performed regularly. Antibodies to all PTH fragments were detected after two immunizations. Baseline PTH and total calcium were 213.0 ng/liter and 13.96 mg/dl, respectively, and remained elevated during the first three immunizations. From the fourth immunization onward, PTH and calcium decreased, and the patient's clinical condition improved markedly. PTH and calcium levels have remained controlled for more than 24 months, and the sizes (surface area) of pulmonary metastases decreased from baseline by 39-71%. This is the first evidence that PTH immunization not only can improve clinical, hormonal, and biochemical measures in parathyroid carcinoma but also has an antitumor effect.
甲状旁腺癌是原发性甲状旁腺功能亢进症的一种罕见病因,对于复发性或转移性疾病,药物治疗、化疗和放疗的疗效均较差。我们报告首例甲状旁腺激素免疫治疗病例,一名转移性甲状旁腺癌患者在接受该治疗后肿瘤缩小,同时激素、生化指标及临床症状均有所改善。一名50岁患有难治性甲状旁腺癌并伴有肺转移的女性患者,于2001年2月至2003年12月期间,共接受了8次牛和改良人甲状旁腺激素片段以及完整人甲状旁腺激素与弗氏佐剂混合制剂的免疫治疗。在6个月内每周检测总钙、离子钙和甲状旁腺激素水平,此后定期检测。定期进行胸部计算机断层扫描。两次免疫后检测到针对所有甲状旁腺激素片段的抗体。基线甲状旁腺激素和总钙水平分别为213.0 ng/升和13.96 mg/分升,在前三次免疫期间一直保持升高。从第四次免疫开始,甲状旁腺激素和钙水平下降,患者临床状况明显改善。甲状旁腺激素和钙水平已持续控制超过24个月,肺转移灶的大小(表面积)较基线缩小了39%至71%。这是首个证据表明甲状旁腺激素免疫治疗不仅可改善甲状旁腺癌的临床、激素和生化指标,还具有抗肿瘤作用。