Y.T. Cheung¹, C.Y. Lau², P.L.Chen², Y.K. Chong¹

¹Hospital Authority Toxicology Reference Laboratory, Hong Kong SAR
²Chemical Pathology Laboratory, Department of Pathology, Queen Elizabeth Hospital, Hong Kong SAR

Introduction: Etomidate, a general anaesthetic, is known to inhibit 11β-hydroxylase at subanaesthetic concentrations. An emerging trend of abuse of etomidate and its analogue, (iso)propoxate, is recently noted. Their effects on steroidogenesis as drugs of abuse are unknown. We investigated the effects of etomidate and (iso)propoxate abuse on steroidogenesis, and characterised urine steroid profiles of users of the drugs.

Method: Urine specimens tested positive for etomidate, (iso)propoxate and/or their metabolites were analysed for urine steroid profile. Results were compared against normal profiles between 1/1/2022 and 24/6/2024. Steroids were measured by gas chromatography-mass spectrometry. Clinical and biochemical information was retrieved from electronic patient records for review.

Results: Twenty users of etomidate/(iso)propoxate aged 18 to 54 years were analysed for urine steroid profile. Results were compared against 567 normal profiles. Multiple metabolites, in particular tetrahydro-11-deoxycortisol and tetrahydro-deoxycorticosterone, were elevated. The urine steroid pattern confirmed 11β-hydroxylase inhibition. 

Conclusion: 11β-hydroxylase inhibition was demonstrated in recreational users of etomidate and (iso)propoxate. Such activity contributes to the clinical features of hypokalaemia, and hyperandrogenism in female patients. Etomidate/(iso)propoxate misuse could be a harbinger of an increasing prevalence of acquired 11β-hydroxylase deficiency.

Author contribution statement: YTC conceptualised the study and performed data analyses. CYL coordinated urine steroid profile analyses. PLC and YKC provided supervision on the study and offered advices.