Department of Internal Medicine, Division of Nephrology, Robert-Bosch Hospital, Auerbachstrasse 110, 70376, Stuttgart, Germany.
Endocrine. 2013 Aug;44(1):255-63. doi: 10.1007/s12020-013-9881-6. Epub 2013 Jan 20.
The presentation of patients with primary hyperparathyroidism is often atypical and ranges from normocalcemic, primary hyperparathyroidism to severe, symptomatic hypercalcemia. G-protein-coupled, calcium-sensing receptor (CaSR), vitamin D receptor (VDR), and fibroblast growth factor receptor (FGFR)/klotho complexes seem to be involved in the development of pHPT. Parathyroid glands from 53 patients with pHPT and normal parathyroid tissue from 7 patients were obtained during parathyroidectomy. Conventional detailed morphological and immunohistochemical analyses of parathyroid glands were performed after dividing each slide in a 3 × 3 array. From morphology, the number of lipocytes was significantly lower in parathyroid tissue glands in the pHPT group (p < 0.001). Protein expressions of klotho, CaSR, and VDR were significantly reduced in the pHPT compared with the control group (p = 0.004, p = 0.007, p < 0.001). No differences were seen between the two groups (p = 0.35) regarding expression of FGFR. Correlations between expression showed significant positively correlations between klotho and CaSR and FGFR and VDR. No correlations between klotho expression and serum calcium levels could be detected (R = -0.13, p = 0.66), but there were positive correlations between expressions of CaSR/serum phosphate and klotho/serum phosphate. Impaired protein expression of CaSR and VDR seem to be involved in the development of pHPT. The role of the FGFR/klotho-axis remains still unclear. Correlations between protein expression of CaSR and serum phosphate and klotho and serum phosphate levels could be detected. Whether these findings give new insights into the pathogenesis of the disease is yet unknown and has to be elucidated.
原发性甲状旁腺功能亢进症患者的临床表现常不典型，范围从血钙正常、原发性甲状旁腺功能亢进症到严重、有症状的高钙血症。G 蛋白偶联钙敏感受体（CaSR）、维生素 D 受体（VDR）和纤维母细胞生长因子受体（FGFR）/klotho 复合物似乎参与了 pHPT 的发生发展。在甲状旁腺切除术期间获得了 53 例 pHPT 患者的甲状旁腺和 7 例正常甲状旁腺组织。在将每个幻灯片分为 3×3 阵列后，对甲状旁腺进行了常规的详细形态学和免疫组织化学分析。从形态学上看，pHPT 组的脂肪细胞数量明显低于对照组（p < 0.001）。与对照组相比，pHPT 组的 klotho、CaSR 和 VDR 蛋白表达显著降低（p = 0.004、p = 0.007、p < 0.001）。两组之间 FGFR 的表达无差异（p = 0.35）。表达之间的相关性表明，klotho 与 CaSR 和 FGFR 与 VDR 之间存在显著的正相关。klotho 表达与血清钙水平之间无法检测到相关性（R = -0.13，p = 0.66），但 CaSR/血清磷酸盐和 klotho/血清磷酸盐的表达之间存在正相关。CaSR 和 VDR 蛋白表达受损似乎参与了 pHPT 的发生发展。FGFR/klotho 轴的作用仍不清楚。可以检测到 CaSR 蛋白表达与血清磷酸盐和 klotho 蛋白表达与血清磷酸盐水平之间的相关性。这些发现是否为疾病的发病机制提供了新的见解尚不清楚，有待阐明。
