The Relationship of Clinical Outcomes to Biochemical and Tissues Markers of Acromegaly in Ireland
Acromegaly is a rare, chronic condition that is associated with reduced life expectancy. In this thesis I have described the current landscape of acromegaly in Ireland including epidemiological and clinical outcomes. Furthermore, I have performed in-depth analysis of the cardio-metabolic effects of raised plasma IGf-1 concentrations in the setting of plasma GH concentrations controlled for normal life expectancy.
In the acromegaly registry study, we reported a prevalence for acromegaly in Ireland of 68.7/1,000,000 population. We found that mortality is not increased for Irish patients with acromegaly in comparison to the background population. Discordance of biochemical control was common in our registry study, 38% of patients in our series had elevated plasma IGF-1 concentrations with controlled GH at last follow up of <2ng/ml. This led us to investigate the clinical significance of raised plasma IGF-1 concentrations in the setting of controlled GH concentrations. To explore this common clinical problem, we examined patients with discordant biochemical control from a metabolic and cardiovascular perspective.
In the metabolic assessment of discordant IGF-1 patients in comparison to controlled GH and IGF-1 patients, we found no difference in clinical markers of glucose homeostasis (hba1c, fasting glucose, 2 hour glucose or HOMA-IR). We also found no difference in blood pressure control on 24 hour ambulatory blood pressure recordings. With the exception of FMD, we detected no difference in predictors of future cardiovascular disease, between patients with discordant plasma IGF-1 and GH concentrations in comparison to patients with controlled plasma GH and IGF-1 concentrations. In fact, the FMD (measure of endothelial function) was slightly higher in the discordant group indicating healthier endothelium. There was also no difference in left ventricular mass or left ventricular hypertrophy between discordant and controlled patients. Furthermore, our study found that there was no correlation between IGF %ULN or plasma GH concentrations and left ventricular mass indexed to body surface area (LVMi).
Our data, from both metabolic and cardiovascular outcomes challenges the current expert guidelines that recommend plasma IGF-1 normalization should be achieved as a key goal of treatment. Instead, we would argue that plasma IGF-1 concentrations in the monitoring of acromegaly occur as a spectrum and not a binary outcome of control or uncontrolled disease. Discordance of biochemical control is a frequently encountered conundrum in the management of acromegaly. Our data suggests that there is no additional cardiovascular or metabolic risk with mild elevations in plasma IGF-1 concentrations with controlled GH concentrations. However, further longitudinal prospective studies (with reduced IGF-1 assay variability) will be required to define a threshold at which raised plasma IGF-1 concentrations confer increased cardio-metabolic risk
First SupervisorProf. Christopher J Thompson
Second SupervisorProf. Mark Sherlock
CommentsSubmitted for the Award of Doctor of Philosophy to the Royal College of Surgeons in Ireland, 2020
Published CitationHannon AM,. The Relationship of Clinical Outcomes to Biochemical and Tissues Markers of Acromegaly in Ireland [PhD Thesis] Dublin: Royal College of Surgeons in Ireland; 2020
Degree NameDoctor of Philosophy (PhD)
Date of award31/05/2020
- Doctor of Philosophy (PhD)