From the Division of Endocrinology and Diabetes, University Hospital, Zurich, Switzerland.
J Intern Med. 2012 Jul;272(1):93-7. doi: 10.1111/j.1365-2796.2012.02542.x. Epub 2012 Apr 23.
Klotho-deficient mice develop a syndrome resembling accelerated ageing, and genetic variants of Klotho have been associated with human ageing. In humans, serum levels of soluble Klotho decrease with age and with chronic renal failure. The aim of our study was to examine the relationship between excess growth hormone (GH) and serum levels of Klotho in patients with acromegaly, a disease usually caused by a pituitary adenoma, which is associated with high phosphate levels and reduced life expectancy.
We determined the levels of soluble Klotho, GH and insulin-like growth factor 1 (IGF-1) in serum samples from 24 consecutive patients with acromegaly (nine women/15 men, age 28-76 years) before and after transsphenoidal surgery.
Soluble Klotho levels were excessively high at baseline (mean ± SEM, 4.2 ± 0.7 ng mL(-1) ) and correlated with GH (r = 0.64), IGF-1 (r = 0.57) and tumour size (r = 0.5). In multiple regression analysis, soluble Klotho was associated with GH after correction for age, gender and levels of creatinine and phosphate (P = 0.029). After surgery, GH and IGF-1 levels decreased in all patients (from 26.3 ± 5.2 to 2.6 ± 0.6 μg L(-1) , P <0.0001, and from 588 ± 35 to 193 ± 12 μg L(-1) , P < 0.001, 0.0001, respectively). Creatinine increased from 71 ± 3 to 80 ± 3 μmol L(-1) (P < 0.001), and phosphate decreased from 1.37 ± 0.04 to 1.06 ± 0.02 mmol L(-1) (P < 0.001). The markedly increased preoperative levels of soluble Klotho returned towards normal after surgery (0.7 ± 0.1 ng mL(-1) , P < 0.0001).
This is the first study to show dramatically increased soluble Klotho levels in an acquired disease in humans. Reversal following tumour removal suggests a causal relation between the GH-producing adenoma and high serum Klotho concentration in acromegaly.
Klotho 缺陷小鼠表现出类似于加速衰老的综合征，Klotho 的遗传变异与人类衰老有关。在人类中，可溶性 Klotho 的血清水平随年龄增长和慢性肾衰竭而降低。本研究旨在探讨肢端肥大症患者中过量生长激素 (GH) 与血清 Klotho 水平之间的关系，肢端肥大症通常由垂体腺瘤引起，与高磷水平和预期寿命缩短有关。
我们测定了 24 例连续肢端肥大症患者（9 名女性/15 名男性，年龄 28-76 岁）术前和经蝶窦手术后血清中可溶性 Klotho、GH 和胰岛素样生长因子 1 (IGF-1) 的水平。
基线时可溶性 Klotho 水平过高（平均值±SEM，4.2±0.7ng/mL），与 GH（r=0.64）、IGF-1（r=0.57）和肿瘤大小（r=0.5）相关。多元回归分析显示，可溶性 Klotho 在校正年龄、性别以及肌酐和磷水平后与 GH 相关（P=0.029）。手术后，所有患者的 GH 和 IGF-1 水平均降低（从 26.3±5.2 降至 2.6±0.6μg/L，P<0.0001，从 588±35 降至 193±12μg/L，P<0.001，0.0001）。肌酐从 71±3 增至 80±3μmol/L（P<0.001），磷从 1.37±0.04 降至 1.06±0.02mmol/L（P<0.001）。术前明显升高的可溶性 Klotho 水平在手术后恢复正常（0.7±0.1ng/mL，P<0.0001）。
这是首次在人类获得性疾病中显示可溶性 Klotho 水平显著升高的研究。肿瘤切除后逆转表明，GH 分泌腺瘤与肢端肥大症患者血清高 Klotho 浓度之间存在因果关系。
