SUN-513 Parathyromatosis: A Case of Stubborn Hypercalcemia Treated with Denosumab

Abstract

Background: Parathyromatosis is a rare cause of recurrent or persistent hyperparathyroidism (HPT). Two proposed pathogenic mechanisms involve spillage and seeding of parathyroid tissue during parathyroid surgery and hyperplasia of embryologic rests of parathyroid tissue. Treatment of parathyromatosis remains a challenge as neither surgical nor pharmacological treatment has been successful in controlling the deleterious consequences of long-standing untreated HPT. We present a case of persistent parathyromatosis successfully treated with denosumab. Clinical Case: A 78 year old female with a history parathyromatosis was admitted to our teaching hospital with anorexia and acute renal failure after a cinacalcet dose increase. She had persistent hyperparathyroidism despite 7 operations including a right hemithyroidectomy and mediastinal split. Complications from her persistent hypercalcemia have included recurrent nephrolithiasis requiring 13 lithotripsies and osteoporosis treated with multiple doses of intravenous bisphosphonate over 26 years. She had known remnant parathyroid tissue within the neck and refused further surgeries, her most recent medical regimen included cinacalcet 180 mg/day and vitamin D analogues. Labs on admission included a serum calcium of 11.0 mg/dl (8.6 - 10.2 mg/dl), ionized calcium of 5.3 mg/dL (normal 4.8 - 5.2 mg/dL), PTH of 230.8 ng/l (normal 15.0 - 65.0 pg/mL), 250H-vitamin D of 39 ng/mL (normal 30 - 60 ng/mL), serum creatinine of 4.05 mg/dL (normal 0.51 - 0.95 mg/dL) and a 24-hour urine calcium of 242 mg (normal 100 - 240 mg/24hr). Imaging studies included a renal ultrasound (US) that showed bilateral nephrolithiasis without hydronephrosis, a parathyroid US and a technetium Tc 99m-sestamibi scan that showed known remnant parathyroid tissue within the thyroid bed. Because of her modest response to lower doses of cinacalcet and failure to tolerate higher doses; inability to use bisphosphonates due to ARF, denosumab at a dose of 60 mg was initiated. The use of denosumab in combination with a lower dose of cinacalcet resulted in successful control of hypercalcemia. Conclusion: Parathyromatosis remains a rare etiology of recurrent or persistent HPT. Successful treatment and control of parathyromatosis remains a challenge. Surgery remains the mainstay of therapy, but attempts at surgical cure are commonly unsuccessful, and medical therapy with calcimimetics and bisphosphonates appear to be of limited value. The addition of Denosumab, a monoclonal receptor activator of nuclear factor κB ligand (RANKL) antibody proved to be effective and appears to be a safe alternative for the management of refractory hypercalcemia.