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Hormonal and Biochemical Normalization and Tumor Shrinkage Induced by Anti-Parathyroid Hormone Immunotherapy in a Patient with Metastatic Parathyroid Carcinoma

Departments of Endocrinology (D.B., A.F.D., A.B.) and Radiology (B.G.), University of Liège, Centre Hospitalier Universitaire Sart Tilman, 4000 Liège, Belgium; Department of Immunology (A.R.B., G.P.M.), University of Birmingham, The Medical School, Edgbaston, Birmingham B15 2TT, United Kingdom; Department of Medicine (T.C.H.), Walsall Manor Hospital, West Midlands WS2 9PS, United Kingdom; and Department of Immunology (H.S.-G.), University of Heidelberg, 69120 Heidelberg, Germany

Address all correspondence and requests for reprints to: Professor Albert Beckers, Service d’Endocrinologie, Centre Hospitalier Universitaire de Liège, Domaine Universitaire du Sart-Tilman, 4000 Liège, Belgium. E-mail: albert.beckers{at}chu.ulg.ac.be.

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.

Abbreviations: CT, Computed tomography; IRMA, immunoradiometric assay.

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