Poster Presentation ESA-SRB-ANZBMS 2024 in conjunction with ENSA

Severe hypoglycaemia secondary to chronic opioid-induced hypothalamic-pituitary-adrenal axis suppression: an under-recognised phenomenon (#580)

Michael Do 1 , Annabelle G Hayes 1 , Malgorzata M Brzozowska 1 2
  1. Department of Endocrinology, Sutherland Hospital, Caringbah, NSW, Australia
  2. UNSW Sydney, Sydney, NSW, Australia

Background

Hypoglycaemia in type 2 diabetes mellitus (T2DM) is often attributed to hypoglycaemic agents, yet adrenal insufficiency should be considered[1]. Chronic opioid use, an under-recognised cause of central adrenal insufficiency, occurs by suppression of corticotropin-releasing hormone via central G-coupled opiate receptors, and can be permanent[2].

Case 

A 49-year-old female with T2DM was hospitalised for critical hypoglycaemia (blood glucose 0.9 mmol/L), and required protracted intravenous dextrose therapy. Initially this was attributed to insulin use despite reduced oral intake. Comorbidities included obesity (BMI 30.4 kg/m²), hypertension on candesartan, and chronic opioids for migraines, equivalent to 80mg oral morphine/day, raising suspicion of opioid-induced central adrenal insufficiency.

Diagnosis of opioid-induced central adrenal insufficiency was supported by the presence of critically low early morning serum cortisol 9 nmol/L (RR 155-599 nmol/L), with low adrenocorticotropin hormone (ACTH) <1 ng/mL (RR 7.2-63.3 ng/mL). She had normal thyroid function tests and suppressed gonadotrophins while on the oral contraceptive pill. Her pituitary MRI demonstrated normal structural appearance, with no sellar mass or radiological features of hypophysitis.

The patient commenced hydrocortisone therapy and was counselled on sick day management. Multiple attempts to reduce her opioid intake were unsuccessful. Over six years, ACTH remained suppressed and peak cortisol level was 200 nmol/L (RR >450 nmol/L) on cosyntropin stimulation tests confirming unresolved central adrenal insufficiency. No further severe hypoglycaemic episodes occurred. The patient therefore continued hydrocortisone treatment indefinitely.

Conclusion

Given the common use of opioids, this near fatal case underscores the importance of recognising opioid-induced HPA axis suppression.  Variable susceptibility may be explained through altered opioid receptor affinity or interleukin 1β function on corticotropin-releasing hormone[3]. Further research is needed to explore the mechanisms responsible for HPA suppression in chronic opioid users and to enhance interventions to prevent HPA suppression in this patient group.

  1. Coluzzi F, et al Int J Mol Sci. 2023;24(5):4575.
  2. Donegan D, Bancos I. Mayo Clin Proc. 2018 Jul;93(7):937-944.
  3. Delitala, G et al. Neuroendocrinology vol. 37,4 (1983): 275-9