Codeine-Associated Secondary Adrenal Insufficiency: A Case Report

We report the case of a 47-year-old woman who presented with a two-month history of significant lethargy, dizziness, and weakness. Blood tests showed a significantly low 9:00 am cortisol level of 52 nmol/L (normal: >275 nmol/L), an abnormal Synacthen test, and low adrenocorticotropic hormone (ACTH) levels. The remaining pituitary function tests and MRI of the pituitary and hypothalamus were normal. Interestingly, she had been taking the maximum licensed dose of codeine for back pain for 12 weeks before the blood tests. Adrenal insufficiency was thought to be induced by codeine, and the medication was stopped immediately. Her symptoms resolved spontaneously without steroid replacement, and repeat investigations six months later showed full recovery of adrenal function. Opioids suppress cortisol secretion, mainly through negative feedback on the hypothalamus and pituitary gland. The literature suggests that opioids also interact with other endocrine functions. Although hypogonadotropic hypogonadism is the most reported endocrine effect, opioids also exert inhibitory effects on the corticotropic axis.