Impact of Acromegaly Subtypes on Survival: Results from a Large Multicenter Cohort

Abstract Background Acromegaly, characterized by excess growth hormone (GH) and insulin-like growth factor-1 production, is typically caused by a pituitary somatotroph adenoma. Disease activity and treatment responses vary widely according to its structural-functional classification comprising clinical, pathologic, morphologic, and biochemical features, particularly adenoma size and invasiveness on pituitary MRI and GH-granulation pattern. Objective To evaluate the association between clinicopathologic acromegaly subtypes and long-term survival. Material and methods This multicenter, bidirectional cohort study assessed all-cause mortality in adults with somatotroph adenomas classified into three different subtypes. Patients with Type 1 acromegaly have non-invasive or invasive microadenomas that are densely granulated; Type 2 non-invasive macroadenomas are densely or sparsely granulated; and Type 3 invasive macroadenomas are sparsely granulated. The primary outcome was all-cause mortality, analyzed by subtype. Results The cohort comprised 550 patients, including 50.5% women, with a mean age at diagnosis of 42.3 years (SD 13.7) and a median follow-up after diagnosis of 11.3 years (IQR 4.1-19.8). 172 patients (31.2%) had type 1, 143 (26%) type 2, and 235 (42.7%) type 3. Overall mortality was 12.9%. Rates varied significantly across subtypes (p=0.003): type 1 had the lowest mortality at 7.0%, followed by type 2 at 12.0%, and type 3 at 17.9%. On multivariate Cox regression, type 2 (HR=2.76, 95% CI: 1.86-7.81, p=0.009), and type 3 (HR=4.69, 95% CI: 1.65-13.3, p=0.004) exhibited significantly higher mortality risk versus type 1, independent of treatment modalities and presence of comorbidities. Conclusions Applying a structural-functional acromegaly classification enables distinction of significant differences in long-term survival outcomes.