Use of denosumab in parathyroid carcinoma with refractory hypercalcemia.

Parathyroid carcinoma is rare; accounting for 1% of all the causes of primary hyperparathyroidism. When the tumor is no longer amenable for surgery, medical therapy to control the hypercalcemia becomes the main focus of management. Unfortunately, parathyroid carcinoma mediated hypercalcemia is often severe and more resistant to medical therapy. We report a case of parathyroid carcinoma with refractory hypercalcemia treated with denosumab. A 26-year-old lady with recurrent parathyroid carcinoma initially presented in April 2012 with symptoms of hypercalcemia, a serum calcium of 4.0mmol/l with intact parathyroid hormone (iPTH) of 176 pmol/l. There was no family history of calcium or parathyroid disorders. She had no hoarseness of voice or palpable neck swelling. Neck ultrasound localized an enlarged right parathyroid nodule measuring 1.5 1.6 2.4 cm. She underwent right superior parathyroidectomy in May 2012 and the histopathology diagnosis was parathyroid neoplasm of uncertain malignant potential. She was lost to follow-up and resurfaced a year later with symptomatic hypercalcemia associated with neck pain and significant weight loss. Computed tomography (CT) scan of neck and thorax showed multiple cervical lymph nodes bilaterally. She underwent right hemithyroidectomy and right modified radical neck dissection following this but remained persistently hypercalcemic after surgery. Four months later a repeat CT scan showed evidence of an aggressive, recurrent disease with multiple matted cervical lymph nodes at the right thyroid bed and right supraclavicular lymphadenopathy. She underwent her third surgery (bilateral neck exploration, completion thyroidectomy, left parathyroidectomy, left neck dissection and resection of local recurrence). Despite this, her calcium levels remained elevated. Histopathology examinations from the last two surgeries were consistent with parathyroid carcinoma with lymph nodes metastases. As her disease progressed, she required multiple admissions for hypercalcemic crises and developed various complications from severe hyperparathyroidism such as nephrocalcinosis, renal tubular acidosis,