MON-066 Overcoming Cabergoline Resistance in a Macroprolactinoma: Diagnostic and Therapeutic Challenges

Abstract Disclosure: M.V. Lopes: None. J. Rocha: None. M.D. Severino: None. C.R. Peixe: None. C.I. Lopes: None. M. Duarte: None. M.I. Alexandre: None. A. Gomes: None. C.C. Faria: None. E.L. Nobre: None. Introduction: Dopamine agonists (DA), particularly cabergoline, are effective in treating prolactinomas in most cases. However, DA resistance may rarely occur, requiring surgical intervention. Case report: A 14-year-old female was referred to the Endocrinology Clinic for secondary amenorrhea and frequent headaches. Examination showed normal secondary sexual characters and no signs of hyperandrogenism. Initial work-up revealed hypogonadotropic hypogonadism and hyperprolactinemia [113.4ng/mL (normal range: <25ng/mL)]. Sellar magnetic resonance imaging (MRI) showed a pituitary lesion measuring 1.2x1.1cm, without stalk deviation or invasion of adjacent structures. Neuro-ophthalmology evaluation was normal. A diagnosis of macroprolactinoma was presumed and cabergoline therapy was started and titrated up to 3mg/week, leading to reduction of prolactin levels to 39ng/mL and tumor size to 0.9x0.85cm, at 12 months follow-up. However, normoprolactinemia was never achieved and, at 24 months follow-up, a new rise in prolactin was detected, reaching 1184ng/mL over the following several months. At this point, sellar MRI showed tumor growth (2.1x1.6cm), and the patient admitted to partial non-compliance with her medication. However, even after the patient resumed adhering to the prescribed medication (which was confirmed by directly observed therapy), prolactin levels remained high (1264ng/mL) and there was no further tumor shrinkage. At this time, it was revealed that the patient had recently been diagnosed with severe depression and therefore had started therapy with fluoxetine 20mg/day, quetiapine 50mg/day, lamotrigine 200mg/day and sodium valproate 1000mg/day a few months earlier. Despite the potential interference of these psychotropic drugs with prolactin levels, given the sustained rise in both tumor size and prolactin levels under cabergoline therapy, transsphenoidal surgery was performed. Postoperatively, sellar MRI showed complete removal of the tumor and prolactin levels were 141ng/mL. Non-normalization of prolactin was attributed to psychotropic medications. At last follow-up, the patient maintains a prolactin level of 156ng/mL with no associated symptoms and no hypogonadism. Conclusions: We present a rare case of a cabergoline-resistant macroprolactinoma requiring surgical treatment. This case also highlights the challenges of diagnosing DA resistance in the presence of patient non-adherence and concomitant psychotropic medications with influence on prolactin levels. A multidisciplinary approach proved essential in achieving a favorable outcome, emphasizing the importance of individualized management in complex cases. Presentation: Monday, July 14, 2025