TREATMENT RESISTANT PROLACTINOMA: REASONS BEYOND NON-COMPLIANCE G Farrish MD, J Hinkle MD Department of Medicine, LSU Health Sciences Center, Baton Rouge, LA INTRODUCTION Prolactinomas are the most frequently occurring pituitary tumor. Hypersecretion of prolactin from these adenomas suppresses gonadotropin function leading to deficiencies in sex hormones. Larger tumors can also suppress TSH and ACTH by mass effect. In most cases, Cabergoline therapy leads to normoprolactinemia and significant tumor shrinkage. Treatment-resistant prolactinomas require more invasive approaches like surgery and radiation which greatly increase morbidity and mortality. The Ki-67 index is a burgeoning metric that could be used to identify prolactinomas which are more likely to resist treatment and recur. CASE: A 21-year-old man with a one-year history of seizure and prolactinoma presented with a new seizure. His first and only seizure was one year prior, and brain magnetic resonance (MRI) imaging discovered a large 6 cm macroadenoma filling his pituitary fossa. Prolactin at that time was >2,000 ng/mL. He was diagnosed with prolactinoma and discharged on Cabergline, Keppra and Synthroid with regular follow-up scheduled with Endocrinology. At this present hospitalization, repeat MRI showed increased growth of the prolactinoma that was now invading the clivus, cavernous sinus and orbital apex. His prolactin level remained >2,000 ng/mL. The patient affirmed compliance with Cabergoline therapy, and past Endocrinology clinic notes corroborated his year-long usage. Because the patient failed maximum dose Cabergoline therapy, he was scheduled for endoscopic transsphenoidal resection followed by craniotomy if necessary. A tissue biopsy obtained perioperatively was sent to pathology lab and revealed a Ki-67 proliferation index of 15%. DISCUSSION: The Ki-67 index could be a useful tool to explain prolactinomas which do not respond to traditional pharmacologic or surgical treatments. Cabergoline therapy has demonstrated success in achieving normal prolactin levels and decreased tumor burden in the vast majority of patients. However, the average Ki-67 index for prolactin-secreting adenomas was measured to be 3.37 +/- 1.8%. This patient’s Ki-67 index of 15% might explain why his adenoma resisted maximum dose Cabergoline therapy, and the need for close monitoring for recurrence even after surgical resection.
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