Association between pathological subtypes of PitNETs and postoperative biochemical remission in acromegaly

To assess whether transcription factor (TF)- and hormone-defined pathological subtypes of pituitary neuroendocrine tumors (PitNETs) are associated with postoperative biochemical remission in acromegaly.

Consecutive acromegaly patients who underwent surgery between January 2015 and October 2025 with a minimum 3-month follow-up were enrolled. Patients were classified by TF and hormone expression patterns: pure vs. non-pure PIT-1 positive, and pure vs. non-pure GH positive. Drawing on target trial emulation-derived design principles, propensity score overlap weighting (OW) balanced six prespecified confounders and covariate balance was confirmed after weighting. Associations between pathological subtypes and postoperative biochemical remission were examined using weighted Kaplan-Meier and Cox proportional hazards analyses.

Overall, 93.4% had macroadenomas; the overall remission rate was 51.0%. Pure PIT-1 positive and pure GH positive tumors represented 62.3% and 19.2%, respectively. After OW, for both TF and hormone classification, no statistically significant difference in postoperative cumulative biochemical remission was observed between the pure and non-pure groups (TF: P = 0.824; hormone: P = 0.444). Weighted Cox regression analyses confirmed that neitherthe TF-based (HR = 0.87, 95% CI: 0.53-1.42, P = 0.578) nor the hormone-based (HR = 1.52, 95% CI: 0.62-3.75, P = 0.362) classification of PitNETs predicted postoperative biochemical remission. Higher preoperative IGF-1 index was a significant negative predictor only in the TF-based group (HR = 0.51, 95%CI 0.37-0.74, P < 0.001).

Pathological subtypes of PitNETs do not independently predict surgical remission in acromegaly. The preoperative IGF-1 index showed limited, context-dependent prognostic value. Future multimodal models integrating histology, imaging, and genomics may improve prognostic accuracy.