Parathyromatosis Recurrent Hyperparathyroidism and Refractory Hypercalcemia Successfully Managed With Addition of Denosumab: A Case Report

Abstract Introduction: Parathyromatosis is a rare cause of recurrent hyperparathyroidism in which multiple nodules of hyperplastic parathyroid tissue are scattered throughout the neck and superior mediastinum. It is proposed to be a result of spillage and seeding of parathyroid tissue during parathyroid surgery. It presents as recurrent or persistent PTH mediated hypercalcemia. Management of Parathyromatosis is challenging and frequently refractory to surgical intervention; hence there is a need for an effective medical treatment. Case: 34 year old female was diagnosed with hyperparathyroidism in 2003 at the age of 16 years. She presented with fatigue, muscle weakness, bone pain and markedly elevated calcium and PTH levels. Sestamibi scan showed parathyroid adenoma with a cystic lesion. She underwent surgical removal, which was complicated by parathyroid cyst rupture. However, the patient remained asymptomatic for 4 years of follow-up. Then in 2007, she had a recurrence of the same initial presentation with laboratory values confirming relapse of hyperparathyroidism. A nuclear parathyroid scan showed remnant parathyroid tissue inferior and posterior to the right thyroid lobe along with multiple subcutaneous nodules. Neck exploration was performed, and histopathological examination showed multiple nodules of hyperplastic parathyroid tissue and cystic changes consistent with the diagnosis of Parathyromatosis. Attempts at satisfactory surgical resection failed, and the patient had recurrent replaces with multiple hospitalizations for nephrolithiasis and had undergone 4 more surgical interventions for remnant parathyroid tissue in a span of 10 years (2008–2018). We started the patient on cinacalcet in August 2018 with an initial dose of 60 mg/day that was gradually increased to 180 mg/day, besides vitamin D analog. This helped in achieving a partial but not full control of calcium levels, so we decided to add Denosumab in April 2019 at the dose of 60 mg SC every 6 months. Dexa scan was done before starting treatment and showed a normal Z score. This regimen has successfully maintained a stable calcium level with normal corrected calcium, and our patient has been in remission with no recurrence of renal stones or other symptoms for the past 18 months, with the last follow-up showing a calcium level of 2.64 mmol/l (2.2–2.65), PTH of 23 pmol/l (1.1–8.43), vitamin D of 24 ng/ml (20–32), albumin of 38 g/L (35–52) and creatinine of 58 umol/l (49 - 90), compared to calcium level of 2.93 mmol/l, PTH of 50 pmol/l and Vitamin D 13 ng/ml before starting treatment. Conclusion: Although it is a rare condition, Parathyromatosis should be kept as a differential diagnosis in the event of recurrent hyperparathyroidism. The Addition of Denosumab to Cinacalcet can make a big difference in achieving a successful medical treatment of the condition, therefore avoiding the detrimental effects of long-standing hypercalcemia.