First Japanese Patient Treated with Parathyroid Hormone Peptide Immunization for Refractory Hypercalcemia Caused by Metastatic Parathyroid Carcinoma

Abstract

Parathyroid carcinoma is rare cause (less than 1%) of primary hyperparathyroidism [1]. Typically, higher serum levels of parathyroid hormone (PTH) are seen in parathyroid carcinoma (3 to 10 times, or even higher, the upper limit of the reference range) than in parathyroid adenoma and hyperplasia and are associated with extreme hypercalcemia (>14mg/dL) [1,2]. There may be associated severe bone pain and ossteitis fibrosa cystica [1]. Parathyroid carcinoma is an indolent tumor with low malignant potential and, in general, has a tendency to recur locally in the operative site or spread into contiguous tissues in the neck. Distant metastases are a late phenomenon with lymphatic or hematogenous spread to cervical lymph nodes and lungs and less commonly to the liv- , SHImeru kamIHara 2) anD kaTSumI egucHI er. The optimal treatment for parathyroid carcinoma is complete resection of the primary site, en bloc, including the surrounding tissues. When metastatic parathyroid tumors are found, surgical resection of the metastatic tumors is the optimal treatment. This is because parathyroid carcinoma is refractory to radiation and cytotoxic reagents [1]. medical management of hypercalcemia by infusing large amounts of fluid, along with bisphosphonates and perhaps calcitonin is briefly effective but, hypercalcemia eventually becomes uncontrolable. recently, cinacalcet, a calcimimetic agent [3], has been used effectively to reduce hypercalcemia in patients with primary hyperparathyroidism [4] and ~ two thirds of patients with parathyroid carcinoma also respond [5]. However, this treatment was not available in Japan for our patient in 2007, and, moreover, long-term efficacy has not been well established and calcimimetics do not inhibit proliferation of parathyroid cancer cells.It was recently shown that immunization with PTH peptides was effective in controlling hypercalcemia

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.…”

“…Long-term survival is possible, and routine surveillance can help identify early recurrence of disease [46,47]. Disease recurrence can be treated with surgical resection, if it is anatomically feasible.…”

“…In addition to medical treatment with calcimimetics and denosumab, experimental immunotherapy has reportedly caused tumor shrinkage in isolated cases of advanced PC [45,46]. Importantly, this treatment modality offers potential tumor shrinkage in addition to control of the refractory hypercalcemia.…”

Molecular targeted therapies in adrenal, pituitary and parathyroid malignancies

“…In vitro, the COX-2 inhibitor NS-398 suppressed parathyroid-related peptide (PTHrP) production in colorectal cancer (Saito et al 2007). Anti-PTH immunotherapy has been described in some case reports, demonstrating biochemical control and clinical improvement as well as reduction of the size of metastases (Betea et al 2004, Horie et al 2010. Despite these promising results, such therapy is not easily available.…”

Recent Advances in the Management of Endocrine Malignancies Associated with Hereditary Hyperparathyroidism Syndromes

“…Anti-PTH immunotherapy has shown promising results by reducing calcium levels and even imageable tumor burden in a few cases [11,33,34]. Its efficacy and safety still need to be further investigated.…”