原发性甲状旁腺功能亢进
甲状旁腺激素
钙
内科学
内分泌学
医学
甲状旁腺功能亢进
钙敏感受体
钙代谢
离体
体内
生物
生物技术
作者
James Koh,Run Zhang,Sanziana A. Roman,Quan-Yang Duh,Jessica E. Gosnell,Wen Zhong Shen,Insoo Suh,Julie Ann Sosa
标识
DOI:10.1210/clinem/dgab524
摘要
The biochemical basis for clinical variability in primary hyperparathyroidism (PHPT) is poorly understood.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.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.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.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.
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