Excessively high soluble Klotho in patients with acromegaly

Abstract

Objectives. 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.Patients and design. 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.Results. 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 lg L )1 , P < 0.0001, and from 588 ± 35 to 193 ± 12 lg L )1 , P < 0.001, 0.0001, respectively). Creatinine increased from 71 ± 3 to 80 ± 3 lmol 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).Conclusions. 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.

Rozpuszczalne białko α-Klotho — nowy marker aktywności akromegalii?

“…Our present study confirms the earlier findings of highly significant difference in sKlotho levels in patients with active acromegaly to other groups [11][12][13]. The difference was statistically significant when we compared the AA group to the SCA and WCA groups as well as to the CG group, so it was independent of methods of therapy or health conditions.…”

“…It is known that in acromegaly there are high levels of FGF-23, phosphate, and calcitriol and also FGF-23 resistance [13][14]16]. On the other hand, it was shown that the high level of sKlotho is a consequence of increased pituitary GH secretion, and higher pituitary transmembrane Klotho expression was not observed [7,12] . The aim of our case-control study was to assess the serum levels of soluble a-Klotho in acromegalic patients in relation to the activity of disease and to compare it with the control group (CG).…”

“…Recently, decreased sKlotho levels have been observed in children with organic growth hormone deficiency (GHD) [9], and also a strong association between sKlotho and IGF-1 was revealed in a study comprising 159 healthy children [10]. On the other hand, it was also found that soluble a-Klotho is increased in patients with active acromegaly and normalised after successful removal of GH-producing pituitary adenoma, at least as quickly as IGF-1 [11,12]. What is more, the level of sKlotho depends on gender and it is higher in women with acromegaly [13].…”

“…Additionally, the normal range for serum levels of sKlotho cannot be known. Neidert et al measured the level of sKlotho in the sera of 26 volunteers and the median was 596 pg/mL (506-734) [12]. On the other hand, Yamazaki et al reported the reference serum of sKlotho levels in 142 volunteers: the range of values was from 239 to 1266 pg/mL (mean ± SD: 526 ± 146 pg/mL).…”

Soluble α-Klotho: a novel serum biomarker for the activity of GH-producing pituitary adenomas

“…We recently found that serum-soluble aKL is markedly elevated in patients with acromegaly and that this aKL excess reversed following adenoma removal (22). In order to assess whether high serum levels of soluble aKL are specific to patients with GH-producing pituitary adenomas, we now present a prospective controlled study that documents the baseline serum levels of aKL in patients with acromegaly compared with a control group of patients with other pituitary adenomas.…”