Surgery for primary hyperparathyroidism (PHPT) improves health-related quality of life (HRQoL), but it is unclear whether the effects are sustained after medium-term (>2 years) follow-up, and whether the results on some or all dimensions of HRQoL will reach that of the general population. We performed a follow-up of HRQoL on average 3.3 years after surgery for PHPT using the 15D in our patient cohort (n=124) and compared the results to those of an age- and gender-standardized general population (n=1099). We studied self-reported blood pressure and current medications; new comorbidities were retrieved from electronic patient records. A total of 104 (83%) patients [eight with serum calcium (1.34-1.46 mmol/l)] returned the questionnaires. After a follow-up of 3.3 years (range 23 to 55 months), systolic and diastolic blood pressure had decreased significantly compared to baseline (the situation before surgery, p<0.001). Thirty-four (33%) had acquired a new diagnosis (range 1-7), the most common being cardiovascular disease and cancer. Mean 15D score was significantly better compared to baseline (p<0.001), the dimensions of sleeping, mental function, discomfort and symptoms, and depression had further improved (p<0.01), and no longer differed from that of the general population. In PHPT, after >2 years follow-up, surgery improves blood pressure and restores neurocognitive function and sleep to the level of the general population. The improvements observed in overall HRQoL at one year after surgery are sustained, but overall HRQoL does not reach that of the general population.

Parathyroid carcinoma is a rare cause of primary hyperparathyroidism with rather poor prognosis. Apart from surgery, no evidence‐based treatments exist. A 48‐year‐old woman presented with weight loss, nausea, constipation, hypercalcemic crisis, and a recurrent neck tumor 5 years after primary surgery of a parathyroid tumor that primarily was classified as an adenoma. Histopathological reevaluation of the original tumor revealed the correct diagnosis to be parathyroid carcinoma (PC). The patient underwent surgery of the recurrent tumor, which was locally invasive with metastatic spread to the mediastinum and neck lymph nodes. Computed tomography demonstrated large lytic bone lesions in both iliac bones including, on the right, a soft tissue mass compatible with bone metastasis. The patient was treated with cinacalcet, repeated zoledronic acid infusions, and temozolomide cycles for 1 year. She underwent two additional neck surgeries for PC and sternotomy for resection of mediastinal metastases. Massive osteolytic lesions in both femoral necks caused imminent fracture risk and therefore both femurs were prophylactically stabilized by intramedullary nail. Serum calcium normalized after the third neck surgery, cinacalcet was discontinued, and parathyroid hormone gradually normalized during continued treatments with temozolomide, adjuvant radiotherapy, and zoledronic acid, with no signs of active disease on imaging and normal biochemistry. The patient remains in remission 17 years after successful combined treatments for recurrent, metastasized PC. The parathyroid tumor tissue demonstrated high O 6 ‐methylguanine DNA methyltransferase (MGMT) promoter methylation status, a known predictor of positive temozolomide treatment response in other tumors. In addition, synergistic effects of multiple treatments may have accounted for the favorable response. © 2018 The Authors. JBMR Plus is published by Wiley Periodicals, Inc. on behalf of the American Society for Bone and Mineral Research.

Objective: Parathyroid carcinoma (PC), atypical parathyroid tumors (APT) and parathyroid adenoma (PA) present with hypercalcemia. Diminished calcium-sensing receptor (CaSR) expression is reported in PC but is rare in benign tumours. Filamin A (FLNA) binds to the CaSR and activates the mitogen-activated protein kinase (MAPK) signalling pathway. FLNA is related to tumour aggressiveness in several cancers, but its role in parathyroid neoplasia is unknown. Design: We examined FLNA, CaSR and parafibromin expression in PCs (n = 32), APTs (n = 44) and PAs (n = 77) and investigated their potential as diagnostic and/or prognostic markers. Methods: Tissue microarray slides were immunohistochemically stained with FLNA, CaSR and parafibromin. Staining results were correlated with detailed clinical data. Results: All tumours stained positively for CaSR, with two tumours (one PC and one APT) showing diminished expression. Carcinomas were characterized by increased cytoplasmic FLNA expression compared to APTs and PAs (p = 0.004). FLNA expression was not correlated with Ki-67 proliferation index or loss of parafibromin expression. Cytoplasmic FLNA expression was also associated with higher serum calcium, PTH concentrations and male sex (p = 0.014, p = 0.017 and p = 0.049, respectively). Using a combined marker score, we found that parathyroid tumours with low FLNA expression and positive parafibromin staining were extremely likely to be benign (p < 0.001). Conclusion: Cytoplasmic and membranous FLNA expression is increased in parathyroid carcinomas compared to benign tumours. A combined FLNA and parafibromin expression score shows potential as a prognostic predictor of indolent behaviour in parathyroid neoplasms.