LAUSR

Abstract The increased cardiovascular mortality in acromegaly can be reversed by achieving plasma GH concentrations to a target of <2ng/ml and normalizing IGF-1 concentrations to within the age-related reference range. However, in approximately 30% of patients, plasma GH concentrations which are on target are associated with discordantly elevated plasma IGF-1 concentrations. It is not known whether this discordance confers excess morbidity. The aim of this study was to determine whether discordance of plasma GH and IGF-1 negatively affects parameters which predict cardiovascular morbidity. Methods: Group 1 (Concordant): 28 patients (15F,13M) with plasma GH <2ng/ml and IGF-1 concentrations within the age and sex matched reference range. Group 2 (Discordant): 27 patients (5F, 22M) with plasma GH <2ng/ml and elevated plasma IGF-1 concentrations above the age and sex-matched reference range. IGF-1 and GH concentrations were analysed in one laboratory using IDS-iSYS assay. Patients were excluded if they were receiving Pegvisomant therapy, if they had a change in therapy in the preceding 6 months or if the random GH was >2ng/ml. Parameters Measured: OGTT with GH, fasting lipid profile, HOMA-IR, Carotid Intima Thickness (CIMT), pulse wave velocity (PWV), flow mediated dilatation (FMD) and 24-hour ambulatory blood pressure. All tests were completed with a standardised protocol over one day. IGF-1 concentrations were calculated as % Upper limit of normal (%ULN) to allow comparison across different age matched reference ranges. Results: The median age (range) was similar in the two groups; 54 (32-78) years in the concordant group and 61 (34-83) years in the discordant group, p=0.45. There were no significant between group differences in BMI, smoking, hypertension, diabetes mellitus or obstructive sleep apnoea. GH nadir during OGTT (p=0.03) and basal plasma GH (p=0.03) were higher in the discordant group. HOMA-IR was also higher in the discordant group (median = 1.75, range 0.73 - 4.88) compared to the concordant group (median = 1.123, range 0.27-4.63), p=0.01. However, there were no significant differences in HbA1c and fasting glucose between the two groups. Furthermore, there were no significant differences between IMT (p=0.63), PWV (p=0.3), mean daytime (p=0.48) or night-time systolic blood pressure (p=0.54) between the two groups. Conclusion: Elevated plasma IGF-1, with controlled GH concentrations, was associated with higher basal GH, higher nadir GH on OGTT and higher markers of insulin resistance in comparison to patients with controlled GH and IGF-1 concentrations. However, we found no difference in other predictors of future cardiovascular risk between the two groups. Further investigation of these findings is warranted to determine if the differences in HOMA-IR and GH dynamics between the two groups requires intervention.