Ex vivo intact tissue analysis reveals alternative calcium-sensing behaviors in parathyroid adenomas.
Ex vivo intact tissue analysis reveals alternative calcium-sensing behaviors in parathyroid adenomas.
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DOI：
10.1210/clinem/dgab524
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发表时间：
2021-07
期刊：
影响因子：
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通讯作者：
J. Koh;Run Zhang;S. Roman;Q. Duh;J. Gosnell;W. Shen;Insoo Suh;J. Sosa
中科院分区：
文献类型：
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作者：
J. Koh;Run Zhang;S. Roman;Q. Duh;J. Gosnell;W. Shen;Insoo Suh;J. Sosa
背景：原发性甲状旁腺功能亢进症(PHPT)临床变异的生化基础尚不清楚。目的明确甲状旁腺肿瘤的生化特征与PHPT患者钙感觉障碍的关系，并将这些特征的不同与临床表现的差异联系起来。设计术前临床数据评估与甲状旁腺肿瘤生化行为的相关性。在一家大型公立大学医院设立内分泌手术转诊中心。患者和其他参与者39名接受PHPT手术的患者进行了连续的系列研究。主要观察指标甲状旁腺腺瘤与正常供体腺体相比，采用完整的组织体外询问试验评价甲状旁腺腺瘤的钙敏感性。根据钙剂量-反应曲线对肿瘤进行功能分类，并比较不同类别之间的临床参数。钙/甲状旁腺素信号轴的三个关键成分CaSR、RGS5和RCAN1相对表达的变化被评估为钙敏感失败的潜在机制。结果甲状旁腺腺瘤可分为三种不同的功能类型。钙敏感性降低的肿瘤是最常见的(18/39)，并且与骨密度降低密切相关(p=0.0009)。无钙感知缺陷的肿瘤(11/39)与术前甲状旁腺激素升高有关(p=0.036)。第三组(6/39)显示非乙状结肠钙化/甲状旁腺素反应曲线；这六种肿瘤中有四种表达RCAN1升高。结论不同的甲状旁腺肿瘤的钙敏感能力不同，但钙敏感受体(CaSR)的下调不是主要的潜在机制。肿瘤钙反应的差异可能是PHPT临床表现不同的原因之一。
CONTEXT The biochemical basis for clinical variability in primary hyperparathyroidism (PHPT) is poorly understood. OBJECTIVES 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. DESIGN Pre-operative clinical data were evaluated for correlation to parathyroid tumor biochemical behavior. SETTING An endocrine surgery referral center at a large, public university hospital. PATIENTS AND OTHER PARTICIPANTS A sequential series of 39 patients undergoing surgery for PHPT. MAIN OUTCOME MEASURES 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 CASR, RGS5, and RCAN1, three key components in the calcium/PTH signaling axis were evaluated as potential mechanisms for calcium-sensing failure. RESULTS Parathyroid adenomas grouped into three 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 pre-operative PTH (p = 0.036). A third group (6/39) displayed a non-sigmoid calcium/PTH response curve; four of these six tumors expressed elevated RCAN1. CONCLUSIONS Calcium-sensing capacity varies among parathyroid tumors but down-regulation 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.