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Resistant prolactinomas: a case series of 26 patients

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Abstract

Purpose

Prolactin (PRL)-secreting tumors are the most common functional pituitary adenomas. They usually respond to dopamine agonist (DA) treatment, with PRL normalization and adenoma shrinkage. Our aim was to characterize patients with prolactinoma resistant to DA treatment.

Methods

This retrospective case series included patients diagnosed with DA-resistant prolactinomas between 1993–2017 in three medical centers. Resistance was defined as PRL levels above three times the upper limit of normal (ULN) despite a weekly dose of ≥2 mg cabergoline (CAB). Clinical and biochemical information, and response to treatment, were retrieved from medical records.

Results

Twenty-six patients were identified; 20 males. Of 25 macroadenomas, three were giant tumors (>40 mm) and 15 (57.7%) were invasive. The mean age at diagnosis was 31.8 ± 14.9 years (range: 13–62). The median maximal CAB dose was 3.5 mg/week (IQR, 2.5–5). Half the patients received only CAB in escalating doses, nine received CAB and underwent transsphenoidal surgery, and four underwent surgery and radiotherapy in addition to CAB treatment. PRL levels at baseline between patients treated only with CAB and those operated were (91.6 [51.1–296.7] vs. 73.1 [22.6–170.9] XULN p = 0.355), and under maximal CAB dose PRL levels between patients treated only with CAB and those operated were similar (5.77 [1.27–11.27] vs 5.27 (2.9–26) XULN p = 0.317). At the last visit patients who received combined therapy achieved lower PRL levels than those treated with DA only (5.22 [1.7–21.6] vs 1.1 [0.44–3.99] XULN p = 0.017) PRL normalization was attained in seven patients and levels below 3 × ULN in fourteen patients; the overall response was 56%.

Conclusions

Resistant prolactinomas usually require a multi-modal treatment strategy. We were able to control 14/25 (56%) of resistant tumors.

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Data availability

The datasets generated analyzed during the current study are available from the corresponding author on reasonable request.

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Author contributions

All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by Tamar Eshkoli, Dana Zaid, Yona Greenman and Ilan Shimon. The first draft of the manuscript was written by Tamar Eshkoli and Merav Fraenkel and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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Author notes

  1. These authors contributed equally: Tamar Eshkoli, Merav Fraenkel, Yona Greenman, Ilan Shimon

Authors and Affiliations

  1. Endocrine Unit, Soroka Medical Center, Beer-Sheva, Israel

    Tamar Eshkoli, Merav Fraenkel, Dayana Cohen & Uri Yoel

  2. Ben-Gurion University of the Negev, Beer-Sheva, Israel

    Tamar Eshkoli, Merav Fraenkel, Uri Yoel & Adi Goldbart

  3. Institute of Endocrinology, Diabetes, Metabolism and Hypertension, Tel Aviv-Sourasky Medical Center, Tel Aviv, Israel

    Dana Zaid & Yona Greenman

  4. Endocrine Institute, Rabin-Beilinson Medical Center, Petah-Tiqva, Israel

    Gloria Tsvetov, Alexander Gorshtein & Ilan Shimon

  5. Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel

    Alexander Gorshtein, Yona Greenman & Ilan Shimon

Authors
  1. Tamar Eshkoli
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  2. Merav Fraenkel
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  3. Dana Zaid
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  4. Dayana Cohen
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  5. Uri Yoel
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  10. Ilan Shimon
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Corresponding author

Correspondence to Tamar Eshkoli.

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The authors declare no competing interests.

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The local IRB of each institution approved the study.

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Eshkoli, T., Fraenkel, M., Zaid, D. et al. Resistant prolactinomas: a case series of 26 patients. Endocrine 77, 349–356 (2022). https://doi.org/10.1007/s12020-022-03080-1

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  • DOI: https://doi.org/10.1007/s12020-022-03080-1

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