Pitfalls of using denosumab preoperatively to treat refractory severe hypercalcaemia.

A 40-year-old man, with a history of metastatic parathyroid carcinoma, status post primary tumour resection and lung metastasectomy, was hospitalised for persistent severe hypercalcaemia and elevated parathyroid hormone levels despite conventional management and escalating doses of cinacalcet. A single dose (120 mg) of denosumab was given and his calcium level plummeted from 14.8 mg/dL to 5.5 mg/dL. After second lung metastasectomy, he developed prolonged hypocalcaemia that required calcium and vitamin D supplements for more than 3 years. In patients with severe hypercalcaemia refractory to conventional therapies, denosumab has been used off-label with some success. A known side effect of denosumab is hypocalcaemia, which is often short-lived. The risk of prolonged hypocalcaemia should be fully evaluated before using denosumab preoperatively, especially in patients with renal insufficiency, prolonged hyperparathyroidism or anticipated tumour debulking surgery.

Parathyroid cancer.

Parathyroid cancer is an uncommon malignancy and rare cause of primary hyperparathyroidism (HPT) with a high morbidity and patient death in advanced cases usually resulting from intractable hypercalcemia. Inactivation of the HRPT2/CDC73 gene, encoding the putative tumor-suppressor protein parafibromin and discovered in the context of the hyperparathyroidism-jaw tumor (HPT-JT) syndrome, is a common, somatic event in most parathyroid cancers. Approximately 25% of patients with apparently sporadic parathyroid cancer carry germline HRPT2/CDC73 mutation. Germline DNA analysis for HRPT2/CDC73 mutation is recommended in all patients with parathyroid cancer because of the potential benefit for first-degree relatives, who should nevertheless undergo serum calcium screening. The histopathologic diagnosis of parathyroid cancer is nonspecific unless vascular, lymphatic, capsular, or soft tissue invasion is seen, or metastases are clinically evident. Immunohistochemical analysis of parathyroid tumors for loss of parafibromin expression offers promise as a diagnostic tool. En bloc tumor resection offers the highest chance of cure in patients with suspected parathyroid carcinoma. No adjuvant chemotherapy regimen has yet proven effective, and the role of local adjuvant radiotherapy is being evaluated. Metastatic disease can be palliated with surgical debulking. Medical therapy with the calcimimetic cinacalcet and bisphosphonates can ameliorate hypercalcemia in patients with inoperable disease.

Utility of rapid intraoperative parathyroid hormone assay to predict severe postoperative hypocalcemia after reoperation for hyperparathyroidism.

BACKGROUND: Patients undergoing reoperative parathyroidectomy may develop severe transient or permanent hypoparathyroidism. This study's purpose was to determine the utility of intraoperative parathyroid hormone (IO-PTH) values in predicting the development of severe hypocalcemia for patients undergoing reoperation for primary hyperparathyroidism. METHODS: Between March 1999 and October 2001, 68 patients with persistent or recurrent hyperparathyroidism underwent reoperation using IO-PTH measurements. The maximum percent decrease and lowest actual PTH value obtained at surgery were compared to determine any correlation with the development of postoperative hypocalcemia requiring supplementation. RESULTS: Of 68 patients, 25 required calcium and calcitriol postoperatively and 43 did not. There was a significant difference between the 2 groups with respect to lowest IO-PTH value (18.4 +/- 2.6 vs 28.0 +/- 3.9 pg/mL; P =.02), percent decrease in IO-PTH (89% +/- 1% vs 80% +/- 3%; P =.03), and lowest postoperative ionized calcium (1.06 +/- 0.01 vs 1.19 +/- 0.01 mmol/L; P <.001). A percent decrease in IO-PTH of 84% or greater was found to be predictive of patients experiencing hypocalcemia requiring supplementation with a positive predictive value of 46% and a negative predictive value of 82%. CONCLUSIONS: Although a maximum percent decrease in IO-PTH of 84% or greater was associated with an increased incidence of postoperative hypocalcemia requiring supplementation in the 68-patient cohort, on further analysis the association was significant only for patients with multiglandular disease and not those with single adenomas. This value may be useful for identifying patients who will need closer postoperative monitoring or prophylactic supplementation.