Soluble Klotho protein as a novel serum biomarker in patients with acromegaly

Acromegaly is a chronic disease caused by overproduction of growth hormone, in most cases due to excessive secretion from a pituitary ad-enoma [1, 2]. The incidence of acromegaly is approximately 5 cases per million per year, and the prevalence is estimated to be about 60 cases per million [3]. Growth hormone (GH) induces the synthesis of insulin-like growth factor-1 (IGF-1), which leads to severe metabolic complications resulting in significant morbidity and mortality [2, 4, 5]. It has been suggested that the mortality associated with acromegaly is at least twofold higher compared to the general population, especially due to the higher prevalence of hypertension, diabetes, cardiovascular complications, and sleep apnoea, and it may be reduced after sufficient control of GH and IGF-1 levels [4, 6, 7]. Approximately 70% of acromegalic subjects have macroadenomas, and the majority of them will not be cured by surgery alone and will require adjuvant medical therapy or radiotherapy [2, 5, 8]. Klotho protein (α-Klotho), named after one of the three Fates in Greek mythology-the goddess who spins the thread of life, was first investigated in 1997 by Kuro-o et al., who found that mice with a defective Klotho gene had phenotypes of accelerated aging including atherosclerosis, os-teoporosis, ectopic calcification, skin atrophy, and pulmonary emphyse-ma, conditions resembling human premature aging syndrome [9–12]. It is well known that overexpression of Klotho leads to aging suppression and lifespan extension [9, 11, 13, 14]. There are studies which indicate that soluble Klotho (sKlotho) levels are associated with GH and IGF-1 production and thus are markedly increased in patients with acromegaly and return to normal after resection of GH-producing pituitary adenoma at least as quickly as IGF-1 [14, 15]. Moreover, acromegaly is found to be the only acquired disease charac-terised by excessively elevated serum soluble Klotho (sKlotho) concentrations [16]. In this paper we focus on sKlotho used in monitoring patients with acromegaly, based on the three studies conducted in the Zurich cohort [9, 15, 16]. In acromegaly, IGF-1 appears to be more closely related to disease activity and better correlates with morbidity than GH levels do [9]. The criteria for a biochemical cure of acromegaly include GH levels < 0.4 μg/l after oral glucose tolerance test (OGTT) and IGF-1 concentrations within the normal age range and gender-adjusted range [2, 7, 17]. Determina-tions of GH and IGF-1 are known to have biological and technical limitations [18, 19]. Similarly, results in oral glucose …