SAT-081 A Case of Aggressive Resistant Prolactinoma: Overcoming Challenges with Multimodal Therapy

Abstract Disclosure: A. Arida: None. N. Prasad: None. J. Shakil: None. R. Al-ward: None. Introduction:Prolactinomas are the most common type of pituitary adenomas (PA) which are typically benign and respond well to dopamine agonists (DAs). However, about 10% of prolactinomas exhibit resistance to DAs despite high doses. Management of resistant prolactinomas requires a combination of medical, surgical, and radiotherapeutic approaches which is outlined in this case. Case Report:A 24-year-old male presented with blurry vision, erectile dysfunction, and headaches for five years. MRI brain revealed a 3.9 × 3.5 cm sellar and suprasellar mass with optic chiasm compression and cavernous sinus invasion. Labs showed severe hyperprolactinemia (1,029 ng/mL) with hypogonadotropic hypogonadism. Subtotal transsphenoidal resection confirmed a prolactinoma with Ki-67 proliferation index of 5-7% and mitotic rate of 5 mitoses/10 HPF. Repeat MRI showed significant reduction in tumor size with a small residual tumor in the right cavernous sinus. Postoperatively, his Prolactin (PRL) level dropped to 270 ng/mL and he was started on cabergoline 2 mg weekly. Two years later, he presented with new vision changes and increased PRL level (569 ng/mL). Imaging showed large solid and cystic mass with suprasellar extension and cavernous sinus extension so he had a repeat transsphenoidal resection. Despite that and progressive dose escalation of cabergoline to 5.5 mg weekly, the tumor continued to grow leading to encasement of right internal carotid artery and compression on optic chiasm and right optic nerve. Five years from first surgery, he underwent intensity-modulated radiation therapy (54 Gy in 30 fractions) followed by a craniofacial approach for tumor debulking due to worsening central vision. Cabergoline was escalated gradually to 16 mg weekly, which he tolerated well with no side effects, and metformin was initiated. About 17 months after radiation, imagining revealed significant tumor shrinkage with PRL 12 ng/mL. The patient maintained stable endocrine function without signs of adrenal insufficiency, hypothyroidism, or AVP-D. Discussion:The management of aggressive prolactinomas requires individualized strategies beyond DAs in resistant cases. Risk factors like young age, male gender, and high Ki-67 index contribute to tumor aggressiveness. This case highlights the efficacy of multimodal therapy using high-dose cabergoline (16 mg/week), metformin (via AMPK activation), radiation, and surgical debulking in achieving biochemical and tumor control. This highlights the need for tailored interventions in refractory cases. Conclusion: This case focuses on the importance of a multidisciplinary approach in managing resistant prolactinomas. Future research should focus on identifying biomarkers predictive of DA resistance and exploring novel therapies to improve outcomes in this challenging patient population. Presentation: Saturday, July 12, 2025