ECE2024 Poster Presentations Pituitary and Neuroendocrinology (120 abstracts)
Clinical and radiological predictive factors of dopamin agonist resistance in prolactinoma
Sandra Pekic Djurdjevic 1,2 , Marko Stojanovic 1,2 , Mirjana Doknic 1,2 , Dragana Miljic 1,2 , Toplica Milojevic 3 , Mihailo Milicevic 1,3 , Aleksandar Stanimirovic 1,3 , Vuk Scepanovic 1,3 , Emilija Manojlovic Gacic 1,4 , Ivana Cekic 2 , Ivan Jevtic 2 , Zvezdana Jemuovic 2 , Marina Nikolic Djurovic 1,2 , Danica Grujicic 1,3 , Vera Popovic 1 & Milan Petakov 1,2
1Faculty of Medicine, University of Belgrade, Belgrade, Serbia; 2Clinic for Endocrinology, Diabetes and Diseases of Metabolism, University Clinical Center of Serbia, Department of Neuroendocrinology, Belgrade, Serbia; 3Clinic for Neurosurgery, University Clinical Center of Serbia, Belgrade, Serbia; 4Institute of Pathology, Belgrade, Serbia
Background: A subset of patients with prolactinomas does not respond satisfactorily to first-line medical therapy with dopamine agonists (DA). DA resistance is defined as failure to normalize prolactin (PRL) levels and/or to achieve ≥50% reduction in maximal tumor diameter under maximally tolerated doses (or a weekly cabergoline dose of ≥3mg). The predictive factors for DA resistance are male gender and tumor invasiveness.
Aim: To characterize patients with DA resistant prolactinoma patients.
Methods: We retrospectively analysed clinical, hormonal and radiological features, management and outcome of DA therapy of 527 patients with prolactinoma who were treated at the Department of Neuroendocrinology of a tertiary hospital between 2005 and 2023.
Results: Thirteen prolactinoma patients with cabergoline resistance were identifed (2.5%). The mean age at diagnosis was 36.5±3.3years (range: 17-64) and seven patients (53.8%) were male. PRL level at baseline was 70.110±41.425mIU/l (range: 1796-505.978). The average tumor size was 27.3±7.0mm (range: 9-58), ten (76.9%) were macroadenomas. Of ten macroadenomas, all were invasive and three were giant tumors (>40mm). Males had larger tumors than females (40.0±6.8mm vs 10.3±0.9mm; P<0.001) and higher PRL levels at baseline (137.562±75.700 vs 2657±380mIU/l; P<0.01) Prolactinomas were graded as KNOSP-3 in 2 (15.4%), and KNOSP-4 in 3 (23.1%) patients, more frequent in males (P<0.01). The mean maximal cabergoline dose was 4.1±0.4 mg/week (range: 3-7), higher in males (5.0±0.6 mg/week vs 3.0±0.8 mg/week; P<0.01). The median follow-up was 86.8±17.0months (range: 18-233). Nine patients were treated only with cabergoline in escalating doses, two underwent transsphenoidal surgery combined with cabergoline, one underwent surgery and radiotherapy combined with cabergoline and one patient was treated with all these modalities plus temozolomide. PRL level after therapy (only cabergoline, or multimodal therapy) was 9383±7099mIU/l (range: 400-94.000). Two patients developed apoplexy during cabergoline therapy and two patients had nasoliquorrhea. One patient treated with multimodal therapy and temozolomide died after eighth operation. At the last visit five patients had controlled PRL levels and most of them had a stable tumor size.
Conclusion: The prevalence of cabergoline resistance in our series was around 2.5%. Our data support a male gender, large tumor size and tumor invasiveness as the risk factors for DA resistance. We were able to control 5/12 (41.6%, 1 patient died) of resistant prolactinomas. Resistant prolactinomas usually require a multi-modal treatment strategy.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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