Diagnostic delay, older age, and hormonal levels at diagnosis affect disease burden and mortality in acromegaly

Purpose: Acromegaly, a rare disease with peak incidence in early adulthood, is marked by significant diagnostic delay and increased mortality due to complications. While older patients often show milder disease activity, they experience longer diagnostic delay. Higher hormonal levels, advanced age, and prolonged delay are associated with more systemic complications. The interplay between hormonal levels, age at diagnosis, and diagnostic delay on disease activity and complications remains unclear. This study aimed to assess the hormonal and cardiometabolic features, as well as mortality, of acromegaly based on diagnostic delay and age at diagnosis. Methods: A retrospective study of 203 acromegalic patients, stratified by age at diagnosis (< 65 years, n = 175; ≥ 65 years, n = 28) and diagnostic delay (≤ 5 years, n = 103; > 5 years, n = 100). Data on clinical and hormonal profiles, cardiometabolic complications, and mortality were analyzed. Results: In multivariate analysis, age at diagnosis and diagnostic delay did not predict higher IGF-I SDS, which was associated only with male gender (OR 3.70, p = 0.001) and cardiometabolic burden (OR 3.36, p = 0.02). Younger age (OR 0.94, p = 0.000) and longer diagnostic delay (OR 1.15, p = 0.002) correlated with higher GH levels. Older age (OR 1.12, p = 0.000) and higher IGF-I SDS (OR 3.06, p = 0.02) were linked to greater cardiometabolic burden. Mortality was higher in older patients (OR 1.03, p = 0.03) and those with longer diagnostic delay (OR 1.10, p = 0.02). Conclusions: 1) older age at diagnosis strongly impacts cardiometabolic complications, while diagnostic delay has a lesser effect; 2) male gender, older age, diagnostic delay, and cardiometabolic burden predict hormonal disease burden; 3) older age and IGF-I SDS predict cardiometabolic complications; 4) mortality is predicted by older age and prolonged diagnostic delay.