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

Abstract

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.

Ethanol injection under ultrasound guidance to palliate unresectable parathyroid carcinoma

“…Cinacalcet HCl proved to be an effective drug in parathyroid carcinoma hypercalcemia, but the remarkable result obtained after anti-PTH immunotherapy in one case with metastatic disease suggests that parathyroid immunology should deserve a deeper investigation. The result reported by Betea e col. in 2004 confirmed a previous report of the same group and it seems to open a promising window in the management of unresectable recurrent parathyroid carcinoma (11).…”

“…Parenteral bisphosphonates and cinacalcet are the most effective available drugs to lessen the catastrophic effect of excessive parathyroid hormone (PTH) (10). A very impressive result of anti-PTH immunization was reported, achieving not only metabolic control but also metastases regression (11). To our knowledge, palliative treatment of parathyroid carcinoma with ethanol injection has not previously reported in literature, and the experience observed in one case is here discussed.…”

A complex case of Multiple Endocrine Neoplasia type 1 with Metastatic Parathyroid Carcinoma

“…This method proved successful in reducing hypercalcaemia and concomitantly improved the patient's physical status, but there was no antitumour effect. In a recent study by Betea et al [17], they reported for the first time the long-term hormonal, biochemical, and antitumor effects of anti-PTH immunotherapy in a patient with refractory metastatic parathyroid cancer.…”

Current and Future Treatments for Parathyroid Carcinoma

“…Unfortunately, as with most medical therapies, treatment effect weakens over time and each of these options are unlikely to provide long-term relief. Limited efficacy of immunotherapy is reported [45,46]. In general, many adjuvant therapies are used anecdotally with no consensus on efficacy or response.…”