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Opioids and pituitary function: expert opinion

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Abstract

Purpose

Opioids are highly addictive potent analgesics and anti-allodynics whose use has dramatically increased in recent decades. The precipitous rise in opioid dependency and opioid use disorder is an important public health challenge given the risks for severely adverse health outcomes. The long-term opioid impact on hypothalamic–pituitary axes is particularly underappreciated among both endocrinologists and primary care physicians. We review the effects of opioids on hypothalamic–pituitary-target gland function and their implications for clinical practice.

Methods

Experts in hypothalamic–pituitary disorders and opioid pharmacology reviewed recently published literature and considered strategies for diagnosing and managing these opioid-induced endocrine effects.

Results

Opioid suppression of hypothalamic–pituitary axes can lead to hypogonadotropic hypogonadism, central adrenal insufficiency, and hyperprolactinemia. These important clinical manifestations are often under-estimated, poorly evaluated, and typically either untreated or not optimally managed. Data on biochemical testing for diagnosis and on the effect of hormone replacement in these patients is limited and prospective randomized controlled studies for guiding clinical practice are lacking.

Conclusions

Patients should be informed about risks for hypogonadism, adrenal insufficiency, and hyperprolactinemia, and encouraged to report associated symptoms. Based on currently available evidence, we recommend clinical and biochemical evaluation for potential central adrenal insufficiency, central hypogonadism, and/or hyperprolactinemia in patients chronically treated with opioids as well as the use of current expert guidelines for the diagnosis and treatment of these conditions.

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Acknowledgements

The authors thank Shira Berman for her expert editorial assistance.

Funding

The authors did not receive support from any organization for the submitted work.

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Authors and Affiliations

  1. Endocrine Unit and Neuroendocrinology Research Center, Medical School and Hospital Universitário Clementino Fraga Filho - Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil

    Mônica R. Gadelha

  2. Neuroendocrine Unit - Instituto Estadual do Cérebro Paulo Niemeyer, Secretaria Estadual de Saúde, Rio de Janeiro, Brazil

    Mônica R. Gadelha

  3. Neuropathology and Molecular Genetics Laboratory, Instituto Estadual do Cérebro Paulo Niemeyer, Secretaria Estadual de Saúde, Rio de Janeiro, Brazil

    Mônica R. Gadelha

  4. Institute of Metabolism and Systems Research, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK

    Niki Karavitaki

  5. Centre for Endocrinology, Diabetes and Metabolism, Birmingham Health Partners, Birmingham, UK

    Niki Karavitaki

  6. Department of Endocrinology, Queen Elizabeth Hospital, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK

    Niki Karavitaki

  7. President, Remitigate Therapeutics, Delmar, NY, USA

    Jeffrey Fudin

  8. Department of Pharmacy Practice, Albany College of Pharmacy & Health Sciences, Albany, NY, USA

    Jeffrey Fudin

  9. Department of Pharmacy Practice, Western New England University College of Pharmacy, Springfield, MA, USA

    Jeffrey Fudin

  10. Department of Pharmacy and Pain Management, Stratton VA Medical Center, Albany, NY, USA

    Jeffrey Fudin

  11. Pain Management and Addiction Medicine, Saratoga Hospital Medical Group, Saratoga Springs, NY, USA

    Jeffrey J. Bettinger

  12. Division of Endocrinology and Molecular Medicine, Departments of Medicine, Surgery, and Physiology, Medical College of Wisconsin, Milwaukee, WI, USA

    Hershel Raff

  13. Endocrine Research Laboratory, Aurora St. Luke’s Medical Center, Advocate Aurora Research Institute, 2801 W KK River Pky Suite 260, Milwaukee, WI, 53215, USA

    Hershel Raff

  14. Pituitary Center, Division of Endocrinology, Diabetes and Metabolism, Cedars-Sinai Medical Center, Los Angeles, CA, USA

    Anat Ben-Shlomo

  15. Multidisciplinary Adrenal Program, Departments of Medicine and Surgery, Cedars-Sinai Medical Center, Los Angeles, CA, USA

    Anat Ben-Shlomo

Authors
  1. Mônica R. Gadelha
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  2. Niki Karavitaki
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  3. Jeffrey Fudin
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  4. Jeffrey J. Bettinger
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  5. Hershel Raff
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  6. Anat Ben-Shlomo
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Corresponding author

Correspondence to Hershel Raff.

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Conflict of interest

The interests listed below were not directly related to the work submitted for publication but are provided for completeness. Mônica R. Gadelha: Speaker for Recordati Rare Diseases, Novartis, Ipsen and Crinetics; Principal Investigator—Clinical trials for Recordati Rare Diseases, Novartis and Crinetics; Scientific advisory board for Novartis, Crinetics, Ipsen and Novo Nordisk. Niki Karavitaki: Speaker for Pfizer, Ipsen, HRA Pharma, Recordati Rare Diseases,—Investigator for Pfizer, Ipsen, Shire—Scientific Advisory Board for Pfizer, Ipsen, Recordati Rare Diseases. Jeffrey Fudin: Lecturer (non-speakers’ bureau) for Abbott Laboratories; Speakers bureau, consulting, advisory boards for AcelRx Pharmaceuticals; Collaborative publications, consulting, advisory boards for BioDelivery Sciences International; Educational studio recording for Collegium Pharmaceutical; Consulting for Firstox Laboratories; Collaborative non-paid poster presentations for GlaxoSmithKline (GSK); Advisory Board for Hisamitsu America; Advisory Board for Hikma Pharmaceuticals; Collaborative non-paid publications for Scilex Pharmaceuticals; Speakers’ bureau, consultant, advisory boards for Salix Pharmaceuticals; Lecture, non-speakers’ bureau for Torrent Pharmaceuticals. Jeffrey Bettinger: National Advisory Board: Hisamitsu America, Inc; Scientific Advisory Board: PainScript. Hershel Raff: Consultant for Corcept Therapeutics; Consultant for Cerium Pharmaceuticals. Anat Ben-Shlomo: Consultant for Recordati Rare Diseases. Principal investigator, Precision Health in the Diagnosis and Treatment of Adrenal Insufficiency, Cedars Sinai Medical Center.

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Gadelha, M.R., Karavitaki, N., Fudin, J. et al. Opioids and pituitary function: expert opinion. Pituitary 25, 52–63 (2022). https://doi.org/10.1007/s11102-021-01202-y

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