Challenges and Pitfalls in the Management of Parathyroid Carcinoma: 17-Year Follow-Up of a Case and Review of the Literature

Abstract

A 29-year-old man presented to his primary care physician with nausea, severe weight loss and muscle weakness. He had a hard, fixed neck swelling. He was severely hypercalcaemic with 10-fold increased parathyroid hormone (PTH) concentrations. A diagnosis of primary hyperparathyroidism was established and the patient was referred for parathyroidectomy. At neck exploration, an enlarged parathyroid gland with invasive growth into the thyroid gland was found and removed, lymph nodes were cleared and hemithyroidectomy was performed. A suspected diagnosis of parathyroid carcinoma was confirmed histologically. Serum calcium and PTH levels normalised post-operatively, but hyperparathyroidism recurred within 3 years of surgery. Over the following 17 years, control of hypercalcaemia represented the most difficult challenge despite variable success achieved with repeated surgical interventions, embolisations, radiofrequency ablation of metastases and treatment with calcimimetics, bisphosphonates and haemodialysis using low-dialysate calcium. In this paper, we report the challenges and pitfalls we encountered in the management of our patient over nearly two decades of follow-up and review recent literature on the topic.

Severe Hypercalcemia Secondary to Primary Hyperparathyroidism

“…Because of their efficiency in normalizing serum calcium, they should be considered for use early in the course of treatment of severe hypercalcemia. Intravenous bisphosphonates have been successfully used in the treatment of severe hypercalcemia related to parathyroid adenoma or carcinoma as in our patients (Witteveen et al, 2010). The effect of a parenteral bisphosphonate to lower serum calcium is apparent within 2-4 days, with maximal effect within 7-10 days after commencing treatment.…”

Parathyroid carcinoma presenting as normocalcemic hyperparathyroidism

“…Nevertheless, it still remains a challenge to differentiate between cancer-associated hyperparathyroidism and the much more common adenoma-associated hyperparathyroidism. Severe hypercalcemia (up to 24 mg/dL) and very high levels of PTH, which are considered the main indicators of malignancy because they are unusual in parathyroid adenomas [1,3], are associated with kidney, bone, gastrointestinal and psychiatric symptoms more frequently than parathyroid adenomas [1][2][3]5]. To date, the few cases of normocalcemic PC reported in the literature were non-functioning PCs [8,9].…”

“…Parathyroid carcinoma (PC) is an uncommon endocrine malignancy, with about 800 cases reported worldwide [1][2][3][4][5]. It accounts for 0.005% of all cancers [4] and about 1% of cases of primary hyperparathyroidism [1][2][3].…”

“…This rare tumor is often difficult to diagnose preoperatively, thus limiting the efficacy of surgical cure [5]. The typical features of PC are represented by signs and symptoms of severe hypercalcemia, with renal and bone involvement in up to 80-90% of patients [1][2][3].…”

Current and Future Treatments for Parathyroid Carcinoma

“…No benefit for overall survival or local recurrence has been clearly identified, and use of radiotherapy is often restricted to palliative treatment of advanced disease or in the presence of distant disease [4,7,[36][37]. Cytotoxic chemotherapy is used even less frequently than external beam radiation therapy, and only isolated reports with very small numbers of patients exist [37,38]. Reports of successful radiofrequency embolization or transarterial catheter embolization of distant metastatic disease exist, but the number of cases in which it has been used is limited [39,40].…”