Opioid-induced adrenal insufficiency in transdermal fentanyl treatment: a revisited diagnosis in clinical setting

Aki Kondo; Takaaki Murakami; Toshihito Fujii; Makiko Tatsumi; Yoriko Ueda-Sakane; Yohei Ueda; Ichiro Yamauchi; Masahito Ogura; Daisuke Taura; Nobuya Inagaki

doi:10.1507/endocrj.EJ21-0359

NOTE

Opioid-induced adrenal insufficiency in transdermal fentanyl treatment: a revisited diagnosis in clinical setting

Aki Kondo, Takaaki Murakami, Toshihito Fujii, Makiko Tatsumi, Yoriko Ueda-Sakane, Yohei Ueda, Ichiro Yamauchi, Masahito Ogura, Daisuke Taura, Nobuya Inagaki

Author information

Aki Kondo
Department of Diabetes, Endocrinology and Nutrition, Kyoto University Graduate School of Medicine, Kyoto 606-8507, Japan
Takaaki Murakami
Department of Diabetes, Endocrinology and Nutrition, Kyoto University Graduate School of Medicine, Kyoto 606-8507, Japan
Toshihito Fujii
Department of Diabetes, Endocrinology and Nutrition, Kyoto University Graduate School of Medicine, Kyoto 606-8507, Japan
Makiko Tatsumi
Department of Diabetes, Endocrinology and Nutrition, Kyoto University Graduate School of Medicine, Kyoto 606-8507, Japan
Yoriko Ueda-Sakane
Department of Diabetes, Endocrinology and Nutrition, Kyoto University Graduate School of Medicine, Kyoto 606-8507, Japan
Yohei Ueda
Department of Diabetes, Endocrinology and Nutrition, Kyoto University Graduate School of Medicine, Kyoto 606-8507, Japan
Ichiro Yamauchi
Department of Diabetes, Endocrinology and Nutrition, Kyoto University Graduate School of Medicine, Kyoto 606-8507, Japan
Masahito Ogura
Department of Diabetes, Endocrinology and Nutrition, Kyoto University Graduate School of Medicine, Kyoto 606-8507, Japan
Daisuke Taura
Department of Diabetes, Endocrinology and Nutrition, Kyoto University Graduate School of Medicine, Kyoto 606-8507, Japan
Nobuya Inagaki
Department of Diabetes, Endocrinology and Nutrition, Kyoto University Graduate School of Medicine, Kyoto 606-8507, Japan

Keywords: Opioid, Secondary adrenal insufficiency, Opioid-induced adrenal insufficiency, Fentanyl, Transdermal

JOURNAL FREE ACCESS FULL-TEXT HTML

2022 Volume 69 Issue 2 Pages 209-215

DOI https://doi.org/10.1507/endocrj.EJ21-0359

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Abstract

Opioids are widely used for treatment of acute and chronic pain. However, opioids have several well-known clinical adverse effects such as constipation, nausea, respiratory depression and drowsiness. Endocrine dysfunctions are also opioid-induced adverse effects but remain under-diagnosed in clinical settings, especially opioid-induced adrenal insufficiency (OIAI). A 46-year-old woman was treated with transdermal fentanyl at a dose of 90–120 mg daily morphine milligram equivalent for non-malignant chronic pain for four years. Fatigue, loss of appetite and decrease in vitality began about two years after starting fentanyl. Subsequently, constipation and abdominal pain appeared and became worse, which led to suspicion of adrenal insufficiency. Clinical diagnosis of OIAI was established based on laboratory findings of secondary adrenal insufficiency, including corticotropin-releasing hormone stimulation test, clinical history of long-term fentanyl use, and exclusion of other hypothalamic-pituitary diseases. Oral corticosteroid replacement therapy was unable to relieve her abdominal pain and constipation; opioid-rotation and dose-reduction of fentanyl were not feasible because of her persistent pain and severe anxiety. While her clinical course clearly suggested that long-term, relatively high-dose transdermal fentanyl treatment may have contributed to the development of secondary adrenal insufficiency, the symptoms associated with OIAI are generally non-specific and complex. Together with under-recognition of OIAI as a clinical entity, the non-specific, wide range of symptoms can impede prompt diagnosis. Thus, vigilance for early symptoms enabling treatments including corticosteroid replacement therapy is necessary for patients taking long-term and/or high dose opioid treatment.

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