A Paradigm Shift in the Monitoring of Patients With Acromegaly: Last Available Growth Hormone May Overestimate Risk

Context: Acromegaly is associated with reduced life expectancy, which has been reported to be normalized if treatment is successful in controlling GH/IGF-I levels. Objective: Most previous studies have invariably used the last available GH/IGF-I, which may be biased as it only assesses exposure at a single point in time. We compared the last available GH/IGF-I analysis to a time-dependent and cumulative method, during follow-up to assess risk of mortality in the West Midlands Acromegaly study (n = 501). Results: Using the last available GH, there was a statistically significant increase in mortality comparing groups as low as GH <= 1 mu g/L vs > 1 mu g/L (relative risks [RR] 1.8, P = .03). This was not the case when using the time-dependent method, where only comparisons of GH values of GH <= 5 mu g/L vs > 5 mu g/L were suggestive of being associated with an increased risk of mortality (RR = 1.5, P = .08). When the time-dependent GH method of analysis was used, the RR of mortality at each level was lower and the associated P value was less significant. Irrespective of using the last available or time-dependent method, when IGF-I was divided into levels according to quartile or arbitrary cutoffs, there was no significant increase in mortality with higher levels. Conclusions: This study emphasizes the potential bias of using the latest available GH/IGF-I levels to predict mortality. Our study again highlights the limitations of IGF-I in predicting mortality.