Department of Neurosurgery, University Hospital Zurich, University of Zurich, Zurich, Switzerland.
Eur J Endocrinol. 2013 Mar 15;168(4):575-83. doi: 10.1530/EJE-12-1045. Print 2013 Apr.
Klotho is a lifespan-influencing gene expressed mainly in the kidneys. Soluble α-Klotho (αKL) is released into the circulation. In this study, we present baseline αKL serum levels of patients with acromegaly compared with controls with other pituitary adenomas and assess changes following transsphenoidal surgery.
Prospective controlled study.
We measured soluble αKL (sandwich ELISA) and IGF1 (RIA) in sera of 14 patients (eight females and six males) with active acromegaly and in 22 control patients (13 females and nine males) operated for non-GH-producing pituitary adenomas. Immunohistochemical staining for Klotho was performed in resected adenomas and in normal pituitary tissue samples.
Soluble αKL was high in the acromegaly group preoperatively (median 4217 pg/ml, interquartile range (IQR) 1812-6623 pg/ml) and declined after surgery during early follow-up (2-6 days; median 645 pg/ml, IQR 550-1303 pg/ml) (P<0.001) and during late follow-up (2-3 months post-operatively; median 902 pg/ml, IQR 497-1340 pg/ml; P<0.001). In controls, preoperative soluble αKL was significantly lower than in acromegalics, 532 pg/ml (400-677 pg/ml; P<0.001). Following surgery, soluble αKL remained low during early and late follow-up - changes over time within the control group were not statistically significant. These results were independent of age, sex and kidney function. Klotho staining was equal or slightly decreased in GH-positive adenomas compared with controls.
High soluble αKL serum levels were specific to GH-producing adenomas and decreased rapidly following adenoma removal. Thus, soluble αKL appears to be a new specific and sensitive biomarker reflecting disease activity in acromegaly. Similar Klotho staining patterns in controls and acromegalics suggest that the rise in serum αKL is caused by systemic actions of pituitary GH rather than due to increased expression of Klotho by the pituitary (adenoma).
Klotho 是一种主要在肾脏中表达的影响寿命的基因。可溶性α-Klotho（αKL）被释放到循环中。在这项研究中，我们比较了肢端肥大症患者与其他垂体腺瘤患者的基线αKL 血清水平，并评估了经蝶窦手术治疗后的变化。
前瞻性对照研究。
我们测量了 14 例活动性肢端肥大症患者（8 名女性和 6 名男性）和 22 例因非生长激素分泌性垂体腺瘤而接受手术的对照患者（13 名女性和 9 名男性）的血清可溶性αKL（夹心 ELISA）和 IGF1（RIA）。在切除的腺瘤和正常垂体组织样本中进行 Klotho 免疫组织化学染色。
术前肢端肥大症组可溶性αKL 水平较高（中位数 4217pg/ml，四分位距（IQR）1812-6623pg/ml），术后早期（2-6 天）下降（中位数 645pg/ml，IQR 550-1303pg/ml）（P<0.001）和术后晚期（2-3 个月）下降（中位数 902pg/ml，IQR 497-1340pg/ml；P<0.001）。在对照组中，术前可溶性αKL 明显低于肢端肥大症患者，为 532pg/ml（400-677pg/ml；P<0.001）。手术后，早期和晚期可溶性αKL 均较低-对照组的时间变化无统计学意义。这些结果与年龄、性别和肾功能无关。与对照组相比，GH 阳性腺瘤中的 Klotho 染色相等或略有减少。
高可溶性αKL 血清水平是 GH 分泌性腺瘤的特异性，并在腺瘤切除后迅速下降。因此，可溶性αKL 似乎是反映肢端肥大症疾病活动的新的特异性和敏感的生物标志物。对照组和肢端肥大症患者的 Klotho 染色模式相似，提示血清αKL 的升高是由垂体 GH 的全身作用引起的，而不是由垂体（腺瘤）中 Klotho 的表达增加引起的。
