Opioid-induced adrenal insufficiency in transdermal fentanyl treatment: a revisited diagnosis in clinical setting
Opioid-induced adrenal insufficiency in transdermal fentanyl treatment: a revisited diagnosis in clinical setting
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DOI：
10.1507/endocrj.ej21-0359
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发表时间：
2021-09-03
影响因子：
2
通讯作者：
Inagaki, Nobuya
中科院分区：
文献类型：
--
作者：
Kondo, Aki;Murakami, Takaaki;Inagaki, Nobuya
阿片类药物被广泛用于治疗急性和慢性疼痛。然而，阿片类药物有几种众所周知的临床副作用，如便秘、恶心、呼吸抑制和嗜睡。内分泌功能障碍也是阿片类药物引起的不良反应，但在临床环境中仍被低估，特别是阿片类药物诱发的肾上腺功能不全(OIAI)。一位46岁的女性接受了芬太尼透皮贴剂的治疗，剂量为每天90-120毫克的吗啡毫克当量，用于治疗非恶性慢性疼痛，为期四年。在开始使用芬太尼大约两年后，开始出现疲劳、食欲不振和活力下降。随后，便秘和腹痛出现并加重，导致怀疑肾上腺功能不全。OIAI的临床诊断是基于继发性肾上腺皮质功能不全的实验室检查结果，包括促肾上腺皮质激素释放激素刺激试验、长期使用芬太尼的临床病史和排除其他下丘脑-垂体疾病。口服糖皮质激素替代治疗无法缓解她的腹痛和便秘；由于她持续疼痛和严重焦虑，阿片类药物轮换和芬太尼减量是不可行的。虽然她的临床过程清楚地表明，长期、相对高剂量的芬太尼透皮治疗可能是导致继发性肾上腺皮质功能不全的原因之一，但与OIAI相关的症状通常是非特异性的和复杂的。再加上对OIAI作为临床实体的认识不足，非特异性、广泛的症状可能会阻碍及时诊断。因此，对于长期和/或大剂量阿片类药物治疗的患者来说，对包括皮质类固醇替代治疗在内的早期症状保持警惕是必要的。
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.