Insulin-like growth factor-I and symptoms of acromegaly according to time since somatostatin receptor ligand injection
Ilan Remba-Shapiro, Júnia Ribeiro de Oliveira Longo Schweizer, Alberto Moscona-Nissan, Karen J. P. Liebert, Pamela S. Jones, Katharina Schilbach, Jessica Naredo Rojas, Michelle M. Adams, Vicky O Cheng, Nicholas A. Tritos, Martin Bidlingmaier, Lisa B. Nachtigall
Abstract
BACKGROUND: Somatostatin receptor ligands (SRLs) are the mainstay of pharmacotherapy for acromegaly. Patients report symptoms toward the end of the injection cycle. However, the correlation between insulin-like growth factor-I (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 2 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 = .045) and IDS-iSYS (201.2 ± 86.3 ng/mL vs 165.5 ± 75.8 ng/mL, P = .023) assays. In cycle 1, PASQ scores worsened in week 4 (18.10 ± 11.96) compared to week 2 (15.53 ± 9.94; P = .011) and week 3 (15.00 ± 12.49; P = .021). SRL concentrations were lower during late phase (3563 ± 1444 pg/mL vs 2588 ± 1085 pg/mL; P = .008). Change in (Δ)SRL negatively correlated with ΔIGF-I IDS-iSYS (r = -0.385, P = .047). ΔACROQoL physical significantly correlated with ΔIGF-I. Δsoluble alpha-klotho (sαKL) correlated with ΔPASQ score (r = 0.337, P = .034) and swelling (r = 0.335, P = .035). CONCLUSIONS: IGF-I concentrations increased according to time since SRL injection. Patient-reported outcomes 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.