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The combination of doxazosin and metyrosine as a preoperative treatment for pheochromocytomas and paragangliomas

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Abstract

Purpose

Preoperative medical management is critical to prevent intraoperative cardiovascular complications in patients with pheochromocytomas and paragangliomas (PPGLs). Initial treatment involves α-adrenergic receptor blockers. However, while the routine use of metyrosine alongside these blockers is not strongly recommended due to a lack of evidence supporting its efficacy and associated safety concerns, there are previous studies on combination therapy with phenoxybenzamine and metyrosine. There are few reports on combination therapy with the selective α1-adrenergic receptor blocker doxazosin. Therefore, we investigated this combination treatment, which theoretically can affect perioperative outcomes in patients with PPGLs. To our knowledge, this is the first such study.

Methods

This retrospective single-center observational study involved 51 patients who underwent surgical resection of PPGLs at Kobe University Hospital between 2014 and 2022. All patients received doxazosin at maximum doses. Fourteen patients received concomitant metyrosine, while 37 received doxazosin alone. Their perioperative outcomes were compared.

Results

No severe event, such as acute coronary syndrome, was observed in either group. Intraoperatively, the doxazosin + metyrosine group exhibited a lower median minimum systolic blood pressure (56 [54–60] vs. 68 [59–74] mmHg, P = 0.03) and required lower median remifentanil (P = 0.04) and diltiazem (P = 0.02) doses than the doxazosin-alone group.

Conclusion

The combination of metyrosine and doxazosin as a preoperative treatment for PPGLs affects intraoperative circulatory hemodynamics, such as a reduced occurrence of blood pressure elevation during surgery. Further research is necessary to identify patients who will benefit most from this combination treatment.

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Data availability

All relevant data are presented in the manuscript.

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Acknowledgements

We thank Ms. Kayo Imura, Hitomi Satoura, Yuriko Shindo, and Michiko Sakoda for their valuable assistance and dedication to excellent patient care.

Author information

Authors and Affiliations

  1. Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan

    Yuka Ohmachi, Masaaki Yamamoto, Shin Urai, Yasutaka Tsujimoto, Yuma Motomura, Yuriko Sasaki, Yuka Oi-Yo, Naoki Yamamoto, Masaki Suzuki & Wataru Ogawa

  2. Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Hospital, Kobe, Japan

    Yuiko Inaba, Risa Matsumoto, Hironori Bando, Keitaro Kanie, Michiko Takahashi, Genzo Iguchi & Hidenori Fukuoka

  3. Department of Internal Medicine (I), Osaka Medical and Pharmaceutical University, Osaka, Japan

    Yuiko Inaba

  4. Division of Anesthesiology, Department of Surgery Related, Kobe University Graduate School of Medicine, Kobe, Japan

    Shohei Makino & Satoshi Mizobuchi

  5. Department of Nutrition, Kobe University Hospital, Kobe, Japan

    Michiko Takahashi

  6. Medical Center for Student Health, Kobe University, Kobe, Japan

    Genzo Iguchi

  7. Division of Biosignal Pathophysiology, Kobe University, Kobe, Japan

    Genzo Iguchi

  8. Department of Diagnostic Pathology, Kobe University Hospital, Kobe, Japan

    Maki Kanzawa

  9. Division of Urology, Department of Surgery Related, Faculty of Medicine, Kobe University Graduate School of Medicine, Kobe, Japan

    Junya Furukawa & Katsumi Shigemura

Authors
  1. Yuka Ohmachi
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  2. Masaaki Yamamoto
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Contributions

Y.Oh. and M.Y.: Conceptualization; Y.Oh. and Y.I.: Data curation and investigation; Y.Oh., M.Y., Y.I., S.U., R.M., H.B., K.K., Y.T., Y.M., Y.S., Y.Oi., N.Y., M.S., M.T., G.I., J.F., K.S., S.M., W.O., and H.F.: Resources and formal analysis; M.K.: Performing pathological diagnosis; Y.Oh.: Writing—original draft preparation and Visualization; M.Y., M.K., S.U. and H.F.: Writing—review and editing; M.Y.: Project administration and Supervision. All the authors contributed to the discussion and approved the final version of the manuscript.

Corresponding author

Correspondence to Masaaki Yamamoto.

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The authors declare no competing interests.

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This retrospective observational study was approved by the Institutional Review Board of the Kobe University Hospital (#B220221) and performed in accordance with the Declaration of Helsinki.

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Informed consent was obtained from the participants using an opt-out approach.

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Ohmachi, Y., Yamamoto, M., Inaba, Y. et al. The combination of doxazosin and metyrosine as a preoperative treatment for pheochromocytomas and paragangliomas. Endocrine 84, 694–703 (2024). https://doi.org/10.1007/s12020-023-03681-4

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  • DOI: https://doi.org/10.1007/s12020-023-03681-4

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