Endocrine Abstracts

Introduction: Parathyroid carcinoma (PC) is an extremely rare malignancy. A complete surgical excision is often difficult, and persistent/recurrent disease occurs in up to 65% of cases. Progression often leads to symptomatic hypercalcemia, the major contributor to poor quality of life and mortality. Treatment options beyond surgical resection are limited. Denosumab is an approved therapy for refractory hypercalcemia of malignancy, and its use in unresectable PC has been described, with favourable results. The use of radiotherapy (RT) in PC has few reported cases in the literature, but could also serve as a valid alternative for inoperable local relapse. We present a case in which both denosumab and RT were used as palliative treatment approaches.

Case description: A 72-year-old women with unresectable recurrence of PC was admitted with severe hypercalcemia (15.5mg/dl) and acute kidney injury. Additional investigation revealed PTH=1951pg/dl (9-72), obstructive nephrolithiasis and cervical lymph node metastases. Two weeks later, she underwent urgent palliative surgery due to refractory hypercalcemia, with marked improvement (calcium=10.8mg/dl, PTH=480pg/dl). 5 months later, she presented with symptomatic hypercalcemia (13.8mg/dl), despite therapy with zoledronic acid 4mg/month and cinacalcet 150mg/day. Cervical ultrasound confirmed tumour recurrence. Intravenous saline and bisphosphonate were, again, ineffective, with calcium nadir on the second day (11.6mg/dl) and subsequent increase (12.5mg/dl). Then, denosumab was started and calcium levels reduced on the third day (11.5mg/dl), with nadir on the seventh (10.8mg/dl). She was discharged under cinacalcet 180mg/day and denosumab 60mg/month. In the following months there were stable calcium levels (10.0-11.3mg/dl), despite ascending PTH levels (11993pg/ml). 6 months later she presented again with symptomatic hypercalcemia (13.8mg/dl). The multidisciplinary tumor board decided to opt for RT. It was delivered a radiation dose of 30 Gy in 10 fractions of 3 Gy, using an arc technique with 6 MV photons, at the cervical lesions. She tolerated well RT, and only developed grade I dermatitis. 3 months after RT, there was a progressive decrease in PTH (6453pg/ml) and calcium levels (9.7mg/dl). Currently, at 9-month RT-follow-up, calcium levels are within range (8.8-9.2mg/dl), and PTH levels are stable (4149-4858pg/ml), without further hospitalizations.

Conclusion: The approach to a relapse of PC remains a challenge. In inoperable cases, with severe hypercalcemia refractory to calcimimetic agents and bisphosphonates, treatment with denosumab may result in rapid reduction of calcium levels. As highlighted by this case, RT has also a role as a palliative treatment, with achievement of metabolic and symptomatic control of the disease.