The Pituitary Is a Candidate Organ That Modulates Circulating Klotho Levels

CONTEXT: The antiaging protein Klotho is shed and released into the blood stream (soluble Klotho). Growth hormone (GH) is considered an active Klotho regulator, because growth retardation is described in Klotho-deficient mice. The origin of circulating Klotho is, however, not fully understood. OBJECTIVES: Our objective was to analyze a possible role of the pituitary in regulating soluble Klotho in patients with pituitary adenomas. PATIENTS, DESIGN, AND SETTING: We analyzed serum levels of soluble Klotho, GH, and insulin-like growth factor 1 (IGF-1) from 21 consecutive patients in our center with pituitary tumor, 7 with GH-producing adenomas (GHomas), and 14 with non–GH-producing pituitary adenomas (non-GHomas), before and after endoscopic transsphenoidal surgery (eTSS). MAIN OUTCOME MEASURE: Soluble Klotho levels were determined by ELISA with antihuman Klotho antibodies. RESULTS: Baseline soluble Klotho levels in all patients, those with GHoma and those with non-GHoma, were 542 (median) (interquartile range: 403, 652), 1083 (425, 1213), and 525 (399, 590), respectively. A drastic reduction in Klotho levels was identified in those with GHoma, accompanied by decreases in GH and IGF-1 levels, after eTSS. Interestingly, patients with non-GHoma had significant declines in soluble Klotho without any significant changes in GH levels. Moreover, an oral glucose tolerance test revealed that soluble Klotho levels decreased, whereas a paradoxical GH peak was observed after glucose intake in a patient with GHoma. CONCLUSIONS: Our data suggest that the pituitary may be a key organ that regulates circulating Klotho concentrations, implying that the pituitary possibly controls circulating Klotho through GH-dependent and/or GH-independent mechanisms.