MON-327 Soluble Alpha Klotho and IGF-I Before Surgery as Prognostic Factors to Acromegaly Long-term Remission

BACKGROUND: Transsphenoidal surgery is the cornerstone of acromegaly treatment. However, cure is obtained in only ~50% of the cases. Until today, no biochemical marker has been identified to preoperatively predict surgical outcome and long-term remission. Recently, soluble alpha klotho (αKL) was proposed as new biomarker for diagnosis and follow-up of acromegaly. Therefore, we aimed to evaluate the potential of pre-surgery αKL concentrations as a prognostic factor to predict remission by surgery alone. Methods: We measured αKL concentrations (IBL-ELISA) and classical biomarkers (IGF-I and GH(random), both by IDS-iSYS, GH(nadir) measured by IDS-iSYS (n=13) or DiaSorin-Liaison(®) (n=7)) in samples from a prospective study in treatment-naïve patients with acromegaly (total n=25). Patients were then followed for at least 6 months after surgery (median (range) 30.1 (6–142) months). Outcome was evaluated and classified as non-remission (NR: IGF-I>1.2xULN (n=2) or continued need for medical treatment with somatostatin analogues (n=10)) or remission (R: improvement on clinical signs and symptoms and IGF-I<1.2xULN without medical treatment, n=13). Results: Before surgery, all patients had elevated IGF-I (>1.2xULN), GH(nadir) (>0.4 ng/mL) and GH(random) (>1.0 ng/mL). As expected, αKL (pg/mL) was also high (>1.2xULN) in 92% patients. Before surgery, αKL was significantly higher in NR compared to R [6648 (4408–13951) vs. 3389 (2132–6837); p<0.05), as was IGF-I (ng/mL) [NR: 879.7 (771.8–961.5) vs. R: 640.2 (448.6–862.6); p<0.05). There was no difference in GH(nadir) and GH(random) (ng/mL) [10.42 (6.35–16.40) vs. 5.19 (1.19–10.70) and 12.39 (8.24–24.87) vs. 8.94 (4.24–15.55); p>0.05 for both comparisons). ROC analysis indicated that concentrations of αKL>4470pg/mL (~3.5xULN) (75% specificity, 62% sensitivity, AUC=0.72) and IGF-I>3.8xULN (67% specificity, 85% sensitivity, AUC=0.79) indicate lack of long-term remission. Conclusion: High αKL (>4470pg/mL, ~3.5xULN) and IGF-I (>3.8xULN) concentrations before surgery are significantly associated with persistent disease activity after surgery. However, both biomarkers alone or in combination have insufficient specificity (though acceptable sensitivity) as predictors of surgical outcome.