MON-327 A Case of Parathyroid Carcinoma in a Patient with Late Stage Chronic Kidney Disease

Abstract

Introduction: Parathyroid carcinoma (PC) is rare, representing 0.3-5% of primary hyperparathyroidism cases. Its pathophysiology is incompletely understood. Established predisposing factors are lacking, with the exception of known genetic mutation and possibly radiotherapy. The rarity of PC and the fact that its clinical and biochemical features overlap benign parathyroid disease make pre-operative diagnosis challenging. Often the diagnosis is made post-operatively through histopathology. It has been hypothesized that chronic kidney disease may predispose to PC, given chronic parathyroid stimulus related to hypocalcemia and hyperphosphatemia. Here we describe an unusual case of parathyroid cancer in a man with long-standing secondary hyperparathyroidism related to stage IV chronic kidney disease. Case report: A 70-year-old man with hypertension and stage IV chronic kidney disease (CKD) presented for treatment ofsuspected tertiary hyperparathyroidism. His intact parathyroid hormone (iPTH) was 384 (8-54 pg/ml) and serum calcium 11.3 (8.6-10.2 mg/dl). He initially opted not to pursue surgery. Five months later, he presented to theemergency department with shortness of breath and new onset of hoarseness. He was diagnosedwith left vocal cord paralysis. Neck ultrasound showed a 1.1 X 1.4 x 1.4 cm hypoechoic nodule posterior and inferior to the lower left thyroid gland with internal color flow, and he was referred to surgery. Pre-operative serumcalcium was 10.1 with iPTH 774. Intra operatively, the mass was adherent to the surrounding musculature, thyroid and esophagus. Biopsy suggested parathyroid cancer. He underwent an en bloc resection of the left lower parathyroid mass, left superior parathyroidectomy, and ipsilateral hemithyroidectomy. Intra-operative iPTH dropped from 747 to 245. Pathology was consistent witha 3 cm parathyroid carcinoma. The posterior margin was focally positive for tumor. PTH remained elevated post-operativelyat 249 with a corrected serum calcium of 8.6. PET CT was without evidence of metabolically active disease,and neck ultrasound was unremarkable.The patientdeclined HRPT2 mutation testing. Conclusion: The vast majority of PC cases present with primary hyperparathyroidism. The first case of PC diagnosed in secondary hyperparathyroidism was published in 1982. Most patients with long-standing CKD develop polyclonal hyperplasia. In some cases, a monoclonal form of nodular growth has been reported. This monoclonal transformation may involve somatic mutations, such as in the tumor suppressor gene WT1. Whether such cases could progress to malignancy is conceivable, although as yet unproven. Biochemical monitoring for PC recurrence in patients with underlying secondary hyperparathyroidism is challenging. PTH levels do not normalize after surgery, and PTH resistance may delay the development of recurrence-associated hypercalcemia.