Opting for first-line surgery in carefully selected patients with microprolactinomas provides the advantage of avoiding long-term dopamine agonist (DA) medication and potential associated side effects. However, the lack of comprehensive long-term data poses a challenge in identifying those patients who would benefit the most from upfront surgery. To improve guidance in the selection process for microprolactinoma patients in clinical practice, we aimed to establish simple clinical and biochemical parameters predicting non-dependence on DAs. Retrospective analysis of a prospectively maintained database, focusing on patients with microprolactinomas who underwent upfront surgery. We assessed clinical and biochemical risk factors for the patients' reliance on DAs at their latest follow-up using regression analysis. We next proceeded to conduct Receiver Operating Characteristic (ROC) analysis to determine the optimal threshold cutoff prolactin (PRL) level for practical application in clinical settings that best differentiates between surgical long-term remission status and long-term dependence on DAs. A microadenoma was observed in 46 patients, of whom 12 (26%) exhibited long-term dependence on DAs at a median follow-up of 78 months. Baseline PRL values were significantly higher in patients with long-term DA dependence compared to those without (p = 0.05). High baseline PRL values (HR 23.9, 95% CI 1.0-593.7, p = 0.05), but not the presence of headache or male gender, were identified as independent predictors of long-term dependence on DAs. PRL thresholds for discriminating long-term DA dependence were estimated to be 290µg/L (AUROC = 0.73, 95% CI 0.55-0.92, p = 0.03; sensitivity = 90%, specificity = 80%). In patients with microprolactinomas, first-line surgery presents a favorable prospect for reducing reliance on DAs. However, for those with high PRL levels ≥ 290µg/L at diagnosis, first-line surgery is not recommended, as the majority of them require adjuvant DA therapy in the long term.
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