Poster Presentation The Annual Scientific Meeting of the Endocrine Society of Australia and the Society for Reproductive Biology 2014

Opioid-induced transient secondary hypoadrenalism: are some clinically significant cases being overlooked? (#288)

Eddy J Tabet 1 2 , Angela ST Lee 1 2 , Elizabeth L Chua 1 2 , Stephen M Twigg 1 2
  1. Department of Endocrinology, Royal Prince Alfred Hospital, Camperdown, NSW, Australia
  2. Sydney Medical School, University of Sydney, Camperdown, NSW, Australia

Opioid-induced hypoadrenalism may be an under-recognised entity with potential serious adverse outcomes. We report a case of acute, transient secondary hypoadrenalism in a hospitalised patient who received fentanyl and tramadol.


An 18 year-old female with a long history of hollow visceral myopathy presented with small bowel obstruction. Intravenous fentanyl was administered initially followed by high dose oral tramadol in the eight subsequent days. She then had multiple episodes of documented fasting hypoglycaemia despite adjustment of parenteral carbohydrate administration. There was no history of diabetes mellitus, exogenous insulin or oral hypoglycaemic medication use. Investigation for what was determined to be non-insulin mediated hypoglycaemia revealed a low morning cortisol of 109nmol/L and an inappropriately low ACTH level of 2.2pmol/L.

A diagnosis of secondary hypoadrenalism was confirmed on repeat cortisol and ACTH testing and by a sub-normal short SynACTHen test. After cessation of opioid therapy, there was recovery of adrenal function at ~24 hours with normalisation of morning cortisol and propensity to hypoglycaemia. However, the hypocortisolaemic pattern was replicated when fentanyl was readministered 5 days later. Subsequent short SynACTHen test and ACTH level undertaken nine days after opioid cessation reflected HPA axis recovery.


This case of transient opioid-induced secondary hypoadrenalism caused secondary fasting hypoglycaemia. Opioid-induced hypoadrenalism is a likely under-recognised clinical entity with potentially serious adverse patient outcomes. There are reported cases involving commonly prescribed opioids including fentanyl, tramadol and methadone. Both ACTH and β-endorphin are peptide derivatives of proopiomelanocortin. This patient’s HPA axis was particularly susceptible to exogenous opioid causing negative feedback on ACTH, possibly via its relationship to β-endorphin. Given the widespread use of opioids, further studies are required to define what percentage of patients are affected by clinically significant acute and more long-term hypoadrenalism, and factors potentially modulating this relationship at the receptor and post-receptor level.

  1. Debono et al, Tramadol-induced adrenal insufficiency, Eur J Clin Pharmacol (2011) 67: 865-867
  2. Abs et al, Endocrine consequences of long-term intrathecal administration of opioids, J Clin Endocrinol Metab. 2000; 85(6): 2215-22