Acquired 11β-hydroxylase deficiency adrenal hyperplasia associated with the use of etomidate and/or its analogues through e-cigarettes - a review of 76 cases in Hong Kong.

INTRODUCTION: Etomidate and its analogues have been abused via vaping (e-cigarettes) in Hong Kong since 2023. Clinical effects including acute neurological effects, associated injuries, hypokalaemia, menstrual disturbances, and hyperpigmentation had been reported. This study aims to examine the clinical effects and associated adrenal dysfunction resulting from etomidate abuse through the inhalation (vaping) route.

METHODS: This retrospective case series study utilised the Hong Kong Poison Control Centre database. Suspected etomidate abuse cases from 1 January 2023 to May 31, 2025 were identified from the database, by searching for "etomidate" as the poison name or for urine toxicology results positive for etomidate and/or analogues. Cases in which etomidate was prescribed during hospital admission were excluded.

RESULTS: Seventy-six cases were included, consisting of 1) Our poison centre's toxicology clinic cases, referred by social worker to us (5 cases) and 2) Our poison centre's "etomidate abuse" consultation/reporting database, consisting of suspected etomidate abusers managed by frontline clinicians of different units and consulted/reported to us (71 cases). Concerning the adrenal dysfunction, clinical features of mineralocorticoid excess (hypokalaemia, low aldosterone/renin levels), apparent glucocorticoid deficiency (low cortisol levels), adrenal androgen excess (virilisation, menstrual disturbances, elevated androstenedione and testosterone levels) and adrenocorticotropic hormone excess (hyperpigmentation, bilateral adrenal hyperplasia, elevated adrenocorticotropic hormone levels) were observed. Three associated deaths were reported.

DISCUSSION: Etomidate abuse results in an acquired form of 11β-hydroxylase deficiency adrenal hyperplasia with clinical features similar to the congenitaladrenal hyperplasia due to 11β-hydroxylase deficiency. For etomidate abusers, reversibility of hypokalaemia, low blood cortisol, and elevated ACTH had been observed in our study in a small subset of our cases.

CONCLUSION: The adrenal dysfunction in etomidate abuse manifest as an acquired 11β-hydroxylase deficiency adrenal hyperplasia, which is a pentad of mineralocorticoid excess, apparent glucocorticoid deficiency, virilisation, adrenocorticotropic hormone excess, and adrenal hyperplasia. Potentially life-threatening acute presentations include trauma sustained during the acute intoxication and severe hypokalemia. Cessation of etomidate abuse remains the cornerstone of managing the adrenal dysfunction, while glucocorticoid replacement should be considered on individual basis. In view of the local prevalence of etomidate abuse, we suggest that etomidate abuse should be considered as an important differential diagnosis in teenage and young adult patients presenting with features suggestive of congenital adrenal hyperplasia due to 11β-hydroxylase deficiency, these features include hypokalaemia, virilisation, menstrual disturbances, and hyperpigmentation.