OR32-2 Alpha Klotho as a Marker of Disease Activity in Acromegaly

Abstract

Introduction: Measurements of GH and IGF-I are considered gold standard for biochemical acromegaly diagnosis and follow-up, but have limitations. Novel laboratory tools would be of interest, especially when results for GH and IGF-I are discrepant. Soluble alpha-klotho (αKL) might have endocrine functions and few studies have investigated αKLs role in acromegaly. Methods: We measured αKL in treatment-naïve patients before surgery (A; n=29), after surgery (controlled, B; n=32; not controlled, C; n=15) in postoperative patients on SSA (controlled, D; n=22; not controlled, E; n=11), in patients with non-functioning pituitary adenomas (NFPA, F; n=20) and in healthy controls (HC, G; n=31). Control was defined by IGF-I≤1.3XULN. Random GH was also measured. Agreement between categorizations based on IGF-I ≤1.3XULN, GH <1.0ng/mL and normal αKL was investigated. ROC analysis was used to define cut-offs above which αKL indicates lack of control of acromegaly. Results: As expected, GH and IGF-I significantly dropped after surgery and with pharmacological control. αKL was markedly elevated in treatment-naïve patients before surgery, decreased after surgery and normalized with biochemical control (A vs. B, D; p<0.0001). It remained higher in uncontrolled patients after surgery as compared to controlled patients, NPFA and HC (C, E vs. B, D, F, G; p<0.05) and did not differ between controlled patients, NFPA and HC (B, D vs. F, G; p>0.05). αKL was correlated with IGF-I (r=0.8) and - to a lesser degree - with random GH (r=0.6; p<0.0001 for both). High GH concentrations (>10ng/mL) still correlated significantly with αKL (r=0.50; p=0.03), but no longer with IGF-I. Concentrations of αKL were not correlated to prolactin and markers of calcium metabolism. In contrast to IGF-I, αKL did not change with sex and age in acromegaly, NFPA and HC. In patients which were controlled based on normalized IGF-I, but not on GH, αKL was also normalized in >95% of the cases. Concentrations of αKL>1617pg/mL indicate lack of control (ROC; 98.1% sensitivity, 76.3% specificity). Conclusion: Similar to GH and IGF-I, circulating αKL reflects disease activity in acromegaly. It might be useful as a surrogate parameter at diagnosis and during follow up, particularly if GH and IGF-I are discrepant. αKL has potential advantages over IGF-I as it seems to be unaffected by age and sex, and remains correlated to GH hypersecretion at very high GH concentrations.