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

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.

Adrenal Crisis Masked as Septic Shock in a Patient With Opioid Use Disorder on Buprenorphine

“…There are no published clinical trials or randomized clinical trials on OIAI [7]. There are few reported cases of adrenal crisis among patients with opioid use, the majority of which are among patients on chronic opioids for pain management [8,[11][12][13][14][15]. Literature regarding OIAI in patients with OUD is further limited.…”

A Closer Look at Opioid-Induced Adrenal Insufficiency: A Narrative Review

“…In a case report, a 46-year-old woman who had been treated for non-cancer pain for four years with a transdermal fentanyl patch (90 to 120 MME/day) developed fatigue, decreased energy, and loss of appetite in her second year of treatment [37]. Seeking treatment for worsening opioid-induced constipation and abdominal pain, a diagnosis of OIAI was reached based on her long-term opioid exposure, laboratory tests including the corticotropin-releasing hormone stimulation test, and the exclusion of other hypothalamicpituitary disorders.…”

“…Seeking treatment for worsening opioid-induced constipation and abdominal pain, a diagnosis of OIAI was reached based on her long-term opioid exposure, laboratory tests including the corticotropin-releasing hormone stimulation test, and the exclusion of other hypothalamicpituitary disorders. Oral corticosteroid therapy was prescribed but did not relieve her constipation or abdominal pain; opioid tapering, rotation, or discontinuation was not possible because of her painful symptoms and anxiety [37].…”