Severe Hypoglycaemia Secondary to Chronic Opioid‐Induced Hypothalamic–Pituitary–Adrenal Axis Suppression: An Under‐Recognised Phenomenon

I thank Do and colleagues for their lessons from practice article addressing the importance of opioid-induced central adrenal insufficiency resulting in severe hypoglycaemia [1]. A minor point is that in addition to causing cortisol deficiency and impairment of counter-regulatory responses, opioids may cause hypoglycaemia due to endogenous hyperinsulinaemia and reduction in hepatic glycogen. Hyperinsulinaemic, hypoketotic hypoglycaemia with elevated C-peptide and normal cortisol levels mimicking insulinoma has been reported in individuals exposed to methadone, tramadol and propoxyphene [2, 3]. An important message from the article is the need for greater awareness of the possibility of opioid-induced adrenal insufficiency (OIAI) among health professionals and among individuals with chronic opioid use, and the potential for this to be life-threatening without glucocorticoid therapy in the setting of intercurrent illness. OIAI has been described in 9%–29% of individuals with chronic opioid use [4]. Central adrenal insufficiency may be more difficult to consider than primary adrenal insufficiency as mineralocorticoid production remains intact, and hypotension is less likely to occur. Health professionals working in correctional institutions, in pain and addiction medicine, and those working in acute care, such as paramedics and emergency physicians in particular, need to be aware of the possibility of OIAI. Individuals with chronic opioid use also need to be made aware of the potential need for glucocorticoid supplementation during minor illness, and of the need for urgent parenteral therapy with more severe illness, particularly with vomiting. Adam Morton: conceptualization, writing – original draft, writing – review and editing. The author has nothing to report. The author declares no conflicts of interest. The author has nothing to report.