Impact of acromegaly subtypes on survival: results from a large multicenter cohort

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.

To evaluate the association between clinicopathologic acromegaly subtypes and long-term survival.

This multicenter, bidirectional cohort study assessed all-cause mortality in adults with somatotroph adenomas classified into 3 different subtypes. Patients with Type 1 acromegaly have noninvasive or invasive microadenomas that are densely granulated; Type 2 noninvasive macroadenomas are densely or sparsely granulated; and Type 3 invasive macroadenomas are sparsely granulated. The primary outcome was all-cause mortality, analyzed by subtype.

The cohort comprised 550 patients, including 50.5% women, with a mean age at diagnosis of 42.3 years (standard deviation 13.7) and a median follow-up after diagnosis of 11.3 years (interquartile range 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 = .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 (hazard ratio [HR] = 2.76, 95% CI: 1.86-7.81, P = .009), and Type 3 (HR = 4.69, 95% CI: 1.65-13.3, P = .004) exhibited significantly higher mortality risk vs Type 1, independent of treatment modalities and presence of comorbidities.

Applying a structural-functional acromegaly classification enables distinction of significant differences in long-term survival outcomes.