P02 - Elevated soluble alpha klotho concentrations are specific to active acromegaly among pituitary adenomas

Background Circulating levels of soluble alpha-Klotho (saKL) are known to be elevated in active acromegaly and normalize following effective treatment. However, it remains unclear whether saKL elevation is specific to excess growth hormone secretion or reflects a broader response to pituitary adenomas in general. To address this, we evaluated saKL concentrations across a range of pituitary adenoma subtypes to determine whether elevated saKL is unique to acromegaly or a common feature of pituitary tumors. Methods In this bicentric and cross-sectional study, we measured saKL by a validated immunoassay in samples from 209 patients with pituitary adenomas (acromegaly (Acro) n=87, Cushing (Cush) n=28, prolactinoma (Prol) n=54 and non- functioning pituitary adenomas (NFPA) n=40) prior and/or after surgery/medical therapy. We also correlated its concentrations to those of pituitary hormones. Results Prior to surgery, saKL (pg/mL, median (interquartile range (IQR), multiple of the upper limit of normal (xULN)) was significantly higher in Acro (5109 (2859- 10232), 4.46 (2.53-6.12)) compared to all other pituitary adenomas (Cush 728 (593-982), 0.55 (0.48-0.71), Prol 922 (786-1298), 0.69 (0.56-0.90) and NFPA (922 (782-1111), 0.71 (0.57-0.83)); (Acro vs. all pituitary adenomas, p<0.001). SaKL significantly correlated with IGF-I and IGFBP3 only in Acro (rs=0.66, p=0.0001 and rs=0.43, p=0.02, respectively vs. p>0.05 for all other pituitary adenomas). In Acro, saKL normalized after disease control (647.8 (497-917.2), 0.55 (0.38-0.74), p<0.0001), but remained high in active disease (5024 (2457-5972), 3.75 (2.34-5.24), p>0.05). In Cush, saKL slightly increased after achieving remission (Cush6m-1y 879 (657-1180), 0.71 (0.51-0.91), Cush2-3y 892 (649-1136), 0.67 (0.55-0.82); p=0.002, p=0.006, respectively). In Prol, saKL did not differ between normo- (917 (780-1292), 0.74 (0.56-0.92)) or hyperprolactinemia (972 (805-1359), 0.66 (0.52-0.85), p=0.91). In NFPA, saKL significantly decreased after surgery only in patients with IGF-I <0.5xULN (577 (424-683), 0.46 (0.36-0.68), p=0.0004). Conclusion In contrast to acromegaly—where saKL levels are elevated during active disease and return to normal with successful treatment—saKL concentrations remain within the reference range across all other types of pituitary adenomas. These findings suggest that saKL is a biomarker specifically linked to GH-IGF-I excess, rather than to the presence of a pituitary tumor itself or the hypersecretion of other pituitary hormones.