Acquired 11β-Hydroxylase deficiency in etomidate and (Iso)propoxate abusers: A nascent endocrine condition

Etomidate, a general anaesthetic, is known to possess inhibitory activity on steroid 11β-hydroxylase at subanaesthetic concentrations. An emerging trend of abuse of etomidate as well as its analogues propoxate/isopropoxate has recently been observed. Their effects on adrenal steroidogenesis as drugs of abuse remain to be elucidated. Steroid excretion patterns of etomidate and propoxate/isopropoxate users were analysed for evidence of disrupted steroidogenesis.

This is a retrospective, cross-sectional study. Urine steroid profiling by gas chromatography-mass spectrometry-based method was performed on spot urine specimens positive for etomidate, propoxate/isopropoxate and/or their metabolites by liquid chromatography-tandem mass spectrometry. Results were compared with routine clinical specimens with normal adult (≥ 18 years of age) urine steroid profiles, analysed between 1st January 2022 and 24th June 2024. Additional clinical and biochemical data were retrieved from the electronic patient records for review.

Ten male and ten female adult users, aged 18 to 54 years, were included in this study. Their steroid excretion patterns were compared against 377 normal profiles. Hypokalaemia and concomitant drugs of abuse were present in the majority of cases. Psychiatric symptoms were noted in eight out of 20 cases. Multiple metabolites, including tetrahydro-11-deoxycortisol, tetrahydro-deoxycorticosterone and multiple adrenal androgen metabolites, were elevated in etomidate and propoxate/isopropoxate abusers. The pattern indicates 11β-hydroxylase inhibition.

11β-hydroxylase inhibition was demonstrated in recreational users of etomidate and/or its analogues, explaining the clinical features of hypokalaemia, and hyperandrogenism in female patients. Misuse of the compounds could be a harbinger of an increasing prevalence of acquired 11β-hydroxylase deficiency.