Refractory hypercalcaemia secondary to parathyroid carcinoma: response to high-dose denosumab

Abstract

Objective: Hypercalcaemia is an important cause of increased morbidity and mortality in patients with parathyroid carcinoma. Surgical resection is the mainstay of treatment but, equally, managing hypercalcaemia is of paramount importance. At present, few therapies have been shown to be effective in the most severe cases. This report describes the efficacy of denosumab in a patient with parathyroid carcinoma when conventional therapies had been shown to be relatively ineffective. Subject, methods and results: A 50-year-old man presented with symptomatic hypercalcaemia 1 year after the surgery for his parathyroid carcinoma. Investigations revealed raised serum calcium and parathyroid hormone concentrations consistent with the recurrence of the disease. Imaging failed to localise any surgically remediable foci. Medical management with loop diuretics, calcimimetics and bisphosphonates failed to provide a sustained response. Denosumab, as a monthly injection, led to a gradual decrement in his peak calcium concentrations with the values now persistently below 3 mmol/l. Conclusions: Denosumab, a fully human MAB that binds to the 'receptor activator of nuclear factor kB ligand (RANKL)', was shown to have a profound effect in modulating malignant hypercalcaemia. This medication should be considered as an effective option in patients with refractory hypercalcaemia secondary to parathyroid carcinoma.

Primary hyperparathyroidism: the clinical picture, diagnostics, differential diagnostics, and methods of treatment

“…Деносумаб -эффективный препарат при тяже-лой гиперкальциемии [86,127]. Кроме того, прием препарата не ограничен при сниженной скорости клубочковой фильтрации и его эффект может длить-ся около полугода.…”

Current and Future Treatments for Parathyroid Carcinoma

“…Management of refractory hypercalcemia due to metastatic PC has included bisphosphonates and calcimimetic agents, however denosumab, a human monoclonal antibody against RANKL which inhibits osteoclast survival, has also been suggested as a safe alternative [41][42][43][44]. Unfortunately, as with most medical therapies, treatment effect weakens over time and each of these options are unlikely to provide long-term relief.…”

Molecular targeted therapies in adrenal, pituitary and parathyroid malignancies

“…Locoregional treatments including ethanol ablation, radiofrequency ablation and trans-arterial embolisation present palliative treatment methods (Wei & Harari 2012). There are also recent reports on the use of frequent denosumab for intractable hypercalcaemia (Karuppiah 2014). Chemotherapy with dacarbazine and several other regimens are mostly ineffective (Wei & Harari 2012), although radiofrequency ablation of metastatic parathyroid carcinoma may control disease with a survival benefits of up to 15 months (Iguchi et al 2008, Lourenco et al 2012.…”