title: Palliative treatment of uncontrollable hypercalcemia due to parathyrotoxicosis: denosumab as rescue therapy.
abstract: Parathyroid carcinoma is a rare disease leading to severe hypercalcemia due to hyperparathyroidism. Surgery is the primary treatment option. A more progressive form of the disease is characterized by parathyrotoxicosis, and subsequent hypercalcemia is the most common cause of death. We report a case presenting with severe hypercalcemia due to parathyrotoxicosis from parathyroid carcinoma treated for the first time using the monoclonal antibody denosumab as a rescue therapy and present long-term follow-up data. The 71-year-old patient presented with severe hypercalcemia due to metastatic parathyroid carcinoma. Despite undergoing treatment with bisphosphonates, cinacalcet hydrochloride, and forced diuresis, the patient`s condition deteriorated rapidly due to resistant hypercalcemia. Surgery performed because of spinal metastasis and forced diuresis lowered calcium levels, albeit they remained in the hypercalcemic range and significantly increased when forced diuresis was stopped. Considering a palliative situation to overcome hypercalcemia, we decided to administer denosumab, a monoclonal antibody that binds to the receptor activator of nuclear factor-kappa B ligand. After a single subcutaneous administration of 60 mg denosumab, calcium levels normalized within one day. Subsequent denosumab injections led to permanent control of serum calcium for more than 2 years despite rising parathyroid hormone levels and repeated surgeries. Together with recent cases in the literature supporting our observation, we believe that denosumab is relevant for future trials and represents an effective tool to control hypercalcemia in patients with advanced stages of parathyroid cancer.
  
  
  CONCLUSIONS
  Severe hypercalcemia is the most common cause of death in patients with parathyroid carcinoma.The monoclonal antibody denosumab rapidly lowered severely elevated serum calcium levels due to parathyrotoxicosis.Denosumab was effective in the long-term treatment of hypercalcemia despite progression of parathyroid carcinoma.
authors.affiliation: Department of Endocrinology and Metabolic Diseases, Charité - Universitätsmedizin , Charitéplatz 1, Berlin, 10117 , Germany.
authors.forename: Reiner
authors.initials: R
authors.lastname: Jumpertz von Schwartzenberg
authors.affiliation: Department of Endocrinology and Metabolic Diseases, Charité - Universitätsmedizin , Charitéplatz 1, Berlin, 10117 , Germany.
authors.forename: Ulf
authors.initials: U
authors.lastname: Elbelt
authors.affiliation: Department of Endocrinology and Metabolic Diseases, Charité - Universitätsmedizin , Charitéplatz 1, Berlin, 10117 , Germany.
authors.forename: Manfred
authors.initials: M
authors.lastname: Ventz
authors.affiliation: Department of Endocrinology and Metabolic Diseases, Charité - Universitätsmedizin , Charitéplatz 1, Berlin, 10117 , Germany.
authors.forename: Knut
authors.initials: K
authors.lastname: Mai
authors.affiliation: Department of Endocrinology and Metabolic Diseases, Charité - Universitätsmedizin , Charitéplatz 1, Berlin, 10117 , Germany.
authors.forename: Tina
authors.initials: T
authors.lastname: Kienitz
authors.affiliation: Department of Endocrinology and Metabolic Diseases, Charité - Universitätsmedizin , Charitéplatz 1, Berlin, 10117 , Germany.
authors.forename: Lukas
authors.initials: L
authors.lastname: Maurer
authors.affiliation: Division of Rheumatology and Clinical Immunology, Medical Department, Charité - Universitätsmedizin , Charitéplatz 1, Berlin, 10117 , Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Rose
authors.affiliation: Department of General Visceral Vascular and Thoracic Surgery, Charité - Universitätsmedizin , Charitéplatz 1, Berlin, 10117 , Germany.
authors.forename: Jens C
authors.initials: JC
authors.lastname: Rückert
authors.affiliation: Department of Endocrinology and Metabolic Diseases, Charité - Universitätsmedizin , Charitéplatz 1, Berlin, 10117 , Germany.
authors.forename: Christian J
authors.initials: CJ
authors.lastname: Strasburger
authors.affiliation: Department of Endocrinology and Metabolic Diseases, Charité - Universitätsmedizin , Charitéplatz 1, Berlin, 10117 , Germany.
authors.forename: Joachim
authors.initials: J
authors.lastname: Spranger