Abstract

Background

Congo red-positive material was described in normal and diseased parathyroids (adenoma and hyperplasia) 50 years ago. However, the incidence and the clinical significance of such observation are unknown, and the causal fibril protein has never been convincingly demonstrated.

Methods

We conducted the present study including an exceptional case report accompanied with a retrospective study of 105 parathyroid adenomas. We used histopathological, immunohistochemical, ultrastructural, mass spectrometry-based proteomic analysis of parathyroid adenoma tissue samples, and genetic analysis.

Results

We describe a 57-year-old man with mild hypercalcemia and elevated parathyroid hormone (PTH) level for whom histopathological analysis revealed a parathyroid adenoma associated with nodular typical amyloid deposits. Tandem mass spectrometry after laser microdissection (LMD-MS) of amyloid adenoma identified PTH as the fibril protein, and no germline mutation in the PTH gene was detected. Congo red-positive PTH-deposits were further observed in 6.6% of the parathyroid adenomas analyzed, and were associated with complete/incomplete or absent universal amyloid signature, but with fibrillar morphology at ultrastructural level.

Conclusions

Inappropriate PTH production leads to progressive disease-amyloid aggregation of PTH in a subset of parathyroid adenomas, providing new insights into the pathophysiology of this condition and adding PTH to the list of amyloid protein derived from hormones.

中文翻译：

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基于质谱的甲状旁腺腺瘤蛋白质组学分析揭示了 PTH 作为一种新的人类激素衍生的淀粉样原纤维蛋白

摘要

背景

50 年前，在正常和患病的甲状旁腺（腺瘤和增生）中描述了刚果红阳性物质。然而，这种观察的发生率和临床意义尚不清楚，也从未令人信服地证明了因果原纤维蛋白。

方法

我们进行了本研究，包括一份特殊病例报告以及对 105 例甲状旁腺腺瘤的回顾性研究。我们对甲状旁腺瘤组织样本进行了组织病理学、免疫组织化学、超微结构、基于质谱的蛋白质组学分析，以及基因分析。

结果

我们描述了一名患有轻度高钙血症和甲状旁腺激素 (PTH) 水平升高的 57 岁男性，其组织病理学分析显示甲状旁腺腺瘤与结节状典型淀粉样蛋白沉积物相关。淀粉样腺瘤激光显微切割 (LMD-MS) 后的串联质谱法将 PTH 鉴定为原纤维蛋白，并且未检测到PTH基因中的种系突变。在分析的 6.6% 的甲状旁腺腺瘤中进一步观察到刚果红阳性 PTH 沉积，并且与完整/不完整或不存在普遍的淀粉样蛋白特征相关，但在超微结构水平具有纤维形态。

结论

不适当的 PTH 产生会导致 PTH 在一部分甲状旁腺腺瘤中进行性疾病 - 淀粉样蛋白聚集，从而为这种疾病的病理生理学提供新的见解，并将 PTH 添加到源自激素的淀粉样蛋白列表中。