IGF-I and symptoms of acromegaly according to time since somatostatin receptor ligand injection

Abstract Background Somatostatin receptor ligands (SRLs) are the mainstay pharmacotherapy for acromegaly. Patients report symptoms towards the end of the injection cycle. However, the correlation between IGF-I and patient-reported outcomes (PROMs) has not been evaluated in this context. Objective To determine IGF-I, PROMs, and SRL concentration variability in patients with acromegaly receiving long-acting SRLs. Methods Quality of life surveys, early and late phase (weeks 1 and 4 after SRL injection) biochemical markers, and SRL concentrations were obtained in 20 patients receiving monthly SRLs during two injection cycles. All IGF-I levels were measured using both mass spectrometry (LC-MS) and an immunoassay (IDS-iSYS). Results IGF-I concentrations were higher during late vs. early phase of cycle 2 using LC-MS (179.5±85.6 ng/mL vs. 154.8±80.2 ng/mL, p=0.045) and IDS-iSYS (201.2±86.3 ng/mL vs. 165.5±75.8 ng/mL, p=0.023) assays. In cycle 1, PASQ scores worsened in week 4 (18.10±11.96) compared to week 2 (15.53±9.94; p=0.011) and week 3 (15.00±12.49; p=0.021). SRL concentrations were lower during late phase (3563±1444 pg/mL vs. 2588±1085 pg/mL; p=0.008). Change in (Δ)SRL negatively correlated with ΔIGF-I IDS-iSYS (r=-0.385, p=0.047). ΔACROQoL physical significantly correlated with ΔIGF-I. Δsoluble alpha-klotho (sαKL) corelated with ΔPASQ score (r=0.337, p=0.034) and swelling (r=0.335, p=0.035). Conclusions IGF-I concentrations increased according to time since SRL injection. PROMs fluctuated, correlating with IGF-I and sαKL changes. Measuring IGF-I at the end of the injection cycle is advisable. Decreases in SRL concentration suggest phase-based differences in IGF-I concentrations. These findings inform personalized approaches to acromegaly, with titration of therapy based on individual IGF-I and/or PROMs fluctuation.