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.