ORF16-03 - Management of Refractory Hypercalcemia Due to Parathyromatosis

Introduction
Parathyromatosis is a rare phenomenon of recurrent hyperparathyroidism after parathyroidectomy due to inadvertent surgical seeding of parathyroid cells in the neck or chest, resulting in persistent hypercalcemia from inoperable residual disease. Case reports have described success with medical management, using antiresorptive therapy and calcimimetics. We present a case of parathyromatosis that failed surgical and typical medical therapies and discuss less conventional therapeutic options.

Case
A 65-year-old woman presented with severe hypercalcemia. She had been diagnosed with primary hyperparathyroidism at age 45 and underwent 6 parathyroid surgeries/neck dissections at 3 different institutions previously, including cervical thymectomy in 2023, for refractory hyperparathyroidism. Surgical pathology showed no evidence of malignancy. She was treated with 13 doses of zoledronic acid 5 mg from 2019 to 2023 and 2 more doses in 2025 prior to current admission. She previously failed denosumab due to hives and cinacalcet due to psychiatric symptoms. External beam radiation was not pursued due to proximity of lesions to the laryngeal nerve, esophagus, and trachea.

Upon admission she reported headaches, blurry vision, and progressive weight loss with a BMI of 16 kg/m2. Initial studies revealed a corrected calcium of 13.4 mg/dL, PTH 2,085 pg/mL (peak to 4,739), phosphorus 2.4 mg/dL, alkaline phosphatase of 647 U/L, 25-hydroxyvitamin D 30 ng/mL, and eGFR of 60 mL/min/1.73m2. CT neck showed sub-centimeter nodular lesions in the lower neck and tracheoesophageal groove similar to prior imaging. Parathyroid SPECT showed no focal areas of uptake corresponding with these lesions, however the lesions were technically below the resolution for accurate detection. She was treated with continuous IV fluids given at 250 cc/hr, one dose of zoledronic acid 4 mg followed three days later by denosumab under a desensitization protocol (total 60 mg SQ), and two doses of calcitonin dosed at 4 U/kg. Despite these interventions, calcium only reached a nadir or 11.1 mg/dL. Given partial improvement of symptoms she was eventually discharged with a stabilized calcium level of 12.4 mg/dL with plans for scheduled biweekly visits to the infusion center for IV fluids.

Conclusion/Teaching Points
Our case highlights the challenges of treating parathyromatosis and resultant refractory hypercalcemia. Cinacalcet, which is often a long-term agent of choice, could not be used in this case. Antiresorptive medications were only partially successful and long-term, frequent use is also tempered by the risk of atypical fractures. Calcitonin as a therapeutic option is limited by tachyphylaxis. Given these limitations, scheduled outpatient IV hydration with monitoring for surgically amenable lesions was the most optimal approach.