{"doi":"10.1210/clinem/dgab524","title":"<i>Ex Vivo</i> Intact Tissue Analysis Reveals Alternative Calcium-sensing Behaviors in Parathyroid Adenomas","abstract":"CONTEXT: The biochemical basis for clinical variability in primary hyperparathyroidism (PHPT) is poorly understood. OBJECTIVE: This study aimed to define parathyroid tumor biochemical properties associated with calcium-sensing failure in PHPT patients, and to relate differences in these profiles to variations in clinical presentation. METHODS: Preoperative clinical data from a sequential series of 39 patients undergoing surgery for PHPT at an endocrine surgery referral center in a large, public university hospital were evaluated for correlation to parathyroid tumor biochemical behavior. An intact tissue, ex vivo interrogative assay was employed to evaluate the calcium-sensing capacity of parathyroid adenomas relative to normal donor glands. Tumors were functionally classified based on calcium dose-response curve profiles, and clinical parameters were compared among the respective classes. Changes in the relative expression of 3 key components in the calcium/parathyroid hormone (PTH) signaling axis-CASR, RGS5, and RCAN1-were evaluated as potential mechanisms for calcium-sensing failure. RESULTS: Parathyroid adenomas grouped into 3 distinct functional classes. Tumors with diminished calcium sensitivity were the most common (18 of 39) and were strongly associated with reduced bone mineral density (P = 0.0009). Tumors with no calcium-sensing deficit (11 of 39) were associated with higher preoperative PTH (P = 0.036). A third group (6/39) displayed a nonsigmoid calcium/PTH response curve; 4 of these 6 tumors expressed elevated RCAN1. CONCLUSION: Calcium-sensing capacity varies among parathyroid tumors but downregulation of the calcium-sensing receptor (CASR) is not an obligate underlying mechanism. Differences in tumor calcium responsiveness may contribute to variations in PHPT clinical presentation.","journal":"The Journal of Clinical Endocrinology & Metabolism","year":2021,"id":202593,"datarank":0.29188652235829704,"base_score":1.9459101490553132,"endowment":1.9459101490553132,"self_citation_contribution":0.29188652235829704,"citation_network_contribution":0.0,"self_endowment_contribution":0.29188652235829704,"citer_contribution":0.0,"corpus_percentile":43.9,"corpus_rank":7203,"citation_count":6,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":true,"is_dataset_confidence":0.5346,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":782701,"name":"Run Zhang","orcid":"0000-0003-4876-810X","position":1,"is_corresponding":false},{"id":451746,"name":"Sanziana A. Roman","orcid":"0000-0002-6911-2508","position":2,"is_corresponding":false},{"id":761130,"name":"Quan‐Yang Duh","orcid":"0000-0002-7947-4393","position":3,"is_corresponding":false},{"id":759787,"name":"Jessica E. Gosnell","orcid":"0000-0002-0640-5418","position":4,"is_corresponding":false},{"id":451563,"name":"Wen T. Shen","orcid":"0000-0001-7531-1450","position":5,"is_corresponding":false},{"id":390042,"name":"Insoo Suh","orcid":"0000-0001-6911-2324","position":6,"is_corresponding":false},{"id":263809,"name":"Julie Ann Sosa","orcid":"0000-0002-3356-7316","position":7,"is_corresponding":false},{"id":604551,"name":"James Koh","orcid":"0000-0001-6853-8606","position":0,"is_corresponding":true}],"reference_count":56,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T23:51:10.291262Z","pmid":"34272844","pmcid":"PMC8530711","fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}