Opioid misuse is a national public health crisis that has contributed to a decrease in life expectancy in men and women in the US. From 1999-2017, the rate of drug overdose deaths tripled, largely due to the rise in opioid use1. Despite widespread misuse, chronic opioid therapy still has a role in the clinical setting. Adverse effects include dizziness, nausea, vomiting, respiratory depression, and dependence2. While these side effects are well- documented, other effects of opioids are less explored, including opioidinduced adrenal insufficiency3,7. The typical presentation of adrenal insufficiency from any cause can include fatigue, nausea, vomiting, weight loss, abdominal pain and muscle aches. Laboratory findings might include hyponatremia and hyperkalemia. This case, however, presents a patient with atypical presentation but confirmed diagnosis of adrenal insufficiency in the setting of chronic opioid use. Ultimately, given chronic opioid use both prescribed and unprescribed, it is imperative that healthcare providers understand the endocrine effects of opioids as adrenal insufficiency is associated with higher morbidity and mortality3.

The adrenal gland is made up of a cortex and medulla which each produce vital hormones. Specifically, the cortex is responsible for producing glucocorticoids, mineralocorticoids, and androgens. Destruction or dysfunction of the adrenal gland may lead to deficiency of these hormones. Adrenal insufficiency can be classified into primary, secondary, or tertiary types. Primary adrenal insufficiency denotes malfunctioning of the adrenal gland itself. Secondary adrenal insufficiency is characterized by a decreased level of adrenocorticotropin (ACTH) released by the pituitary gland. Tertiary adrenal insufficiency is defined by a decreased level of corticotropin-releasing hormone (CRH) from the hypothalamus15. Opioids bind to mu, kappa, and delta opioid receptors to create effects throughout the body, including on the hypothalamus and pituitary. This is the proposed mechanism for opioid-induced suppression of the hypothalamus-pituitary-adrenal (HPA) axis noted in some studies3.