Prolactin secreting pituitary neuroendocrine tumors treated by dopamine agonists: predictors of response

Purpose: To date, no specific criteria have been clearly established to predict the response to dopamine agonists (DA), and a universally accepted definition of DA resistance remains lacking. This study aimed to analyze the clinical, hormonal, and radiological characteristics of patients with prolactin (PRL)-secreting PitNETs, also known as pituitary adenomas, treated with DA, in order to identify potential predictive factors of hormonal and radiological response to medical therapy. Methods: This retrospective cohort study included 62 patients consecutively admitted to our institution over a 20-year period (2004 – 2024). Seven patients underwent transsphenoidal surgery as first-line treatment before starting DA therapy. Demographic, clinical, hormonal, and radiological data were collected at diagnosis and during follow-up (6, 12, and 24 months, and at the last visit). DA resistance was defined as the failure to normalize PRL levels and to achieve at least a 50% reduction in the tumor’s major diameter or volume. Results: The median age at diagnosis was 37 years (IQR 26.5 – 45.3), with a male-to-female ratio of 1:1.7. Microprolactinomas were observed in 48.4% of patients. All patients were treated with cabergoline (median dose 1.0 mg/week) and followed for a median of 84 months (IQR 35.3 – 114.0). Macroprolactinomas were more frequent in males, who also showed higher baseline PRL levels. Early PRL response to DA treatment was a significant predictor of long-term hormonal response, independent of sex, age, and DA dosage (OR = 11.29; 95% CI 1.10 – 60.74). Tumor response assessment revealed low agreement between classifications based on diameter versus volume reduction. Diameter-based evaluation was more effective in identifying clinical responders at 6 months and at final follow-up, while volumetric measurements provided greater accuracy at 12 and 24 months. Conclusion: Normalization of PRL levels is a practical and reliable predictor of treatment response. A combined radiological assessment using both tumor diameter and volume is advisable: diameter offers greater insight in the early stages, while volume becomes more informative in the mid- to long-term follow-up. In patients with persistently elevated PRL levels and lack of radiological response, alternative management strategies—including surgical resection—should be considered, especially in light of recent evidence supporting the cost-effectiveness of surgery in enclosed prolactinomas.