A 47-year-old Chinese man presented with a 6-month history of neck pain, numbness and weakness in the left limb. In January 2019, he was admitted to the Department of Spine Surgery at our institution. His medical and family histories were unremarkable, with no prior interventions.

Neurological examination revealed deficits involving three levels of the left upper limb. Magnetic resonance imaging (MRI) revealed an extramedullary lesion at the C2-C3 level (Fig 1a to c). Following ophthalmological and dermatological assessments (including oral mucosa, external genitalia, and anus), a primary intradural extramedullary malignant melanoma (MM) was suspected. Surgical intervention was indicated to improve neurological function.

Although the tumour was in the left anterior cervical cord, its position posterior to the C2-C3 vertebral body and spindle-shaped appearance made anterior surgery less favourable, as resection of the vertebral body to access the tumour and reconstruction following removal would increase surgical trauma and risk. After discussing the risks and benefits with the patient and his family, informed consent was obtained prior to surgery.

The patient underwent posterior surgery under general anaesthesia with neuroelectrophysiological monitoring. A C2-C4 laminectomy was performed to expose the tumour, which was located on the left anterior side of the cord. The lesion was compressing and adherent to the spinal cord and dura. Using a nerve retractor and with stable intraoperative neuromonitoring, the tumour was carefully dissected and completely excised (Fig 1d to f). The dura was sutured and the laminae were re-implanted using titanium mini-plates. A drainage tube was placed, and the incision was carefully sutured.

Postoperative cervical MRI confirmed complete tumour resection (Fig 2a to c). Histopathological examination (Fig 2d to f) confirmed MM with positive staining for HMB-45 (+), S-100 (+), and a Ki-67 index of 5%.

The patient underwent postoperative rehabilitation and reported good neurological recovery at the 5-year follow-up, with minimal assistance required for certain left upper limb movements. Given the favourable outcome, the patient declined adjuvant radiochemotherapy as recommended by our team. He continues to lead a relatively active and independent life.

Malignant melanoma of the spinal region is rare and may present as either a primary or metastatic lesion, with primary cases being exceptionally uncommon.1 Primary spinal MM most frequently affects the middle and lower thoracic spine, with rare involvement of the cervical region.2 This is the first case of primary intradural extramedullary MM treated in our department in recent decades. Despite the tumour being located in the upper cervical region, satisfactory clinical outcomes were achieved.

Although MRI is the recommended and effective preoperative imaging modality to diagnose spinal MM, distinguishing it from other pigmented central nervous system tumours, such as leptomeningeal melanoma or melanocytoma,3 can be challenging. A definitive diagnosis relies on histopathological confirmation. Immunohistochemical staining using antimelanoma markers such as HMB-45 and S-100 can help confirm the diagnosis.2 In our case, positive staining for both HMB-45 and S-100 was conclusively confirmed. There are currently no established guidelines for the treatment of spinal MM, but complete surgical removal is typically recommended.4 In our case, the chief surgeon carefully removed the tumour starting on the left side and gradually accessed the anterior spinal cord. Complete resection was successfully achieved without damage to the spinal cord or nerve roots. It has been reported that patients may achieve better outcomes and prognosis with postoperative adjuvant radiotherapy and chemotherapy.5 In our case, the patient was enjoying a relatively good life at the 5-year follow-up without adjuvant therapy, indicating the importance of complete resection and consistent with the literature. However, the importance of radiotherapy or chemotherapy should not be ruled out as further follow-up is necessary to assess the final prognosis. Our team still recommends that postoperative radiotherapy or chemotherapy be routinely performed to improve patient outcomes.

Our research team reports a rare case of primary intradural extramedullary MM at the C2-C3 level with successful surgery. First, complete tumour resection is crucial for improving patient prognosis and survival, emphasising the need for careful consideration during treatment planning. Second, proper handling of the anatomical relationship between the tumour and the spinal cord or nerve roots is essential to remove the tumour as completely as possible while minimising neurological injury. Third, although our patient declined adjuvant therapy and achieved a favourable outcome at the 5-year follow-up, we continue to recommend routine postoperative radiotherapy or chemotherapy to improve prognosis. A key limitation of this case is the absence of radiological imaging at final follow-up, as the patient declined hospital visits due to perceived symptom improvement, which limits our ability to definitively exclude indolent recurrence. Our case provides valuable clinical insights, and long-term follow-up remains essential for monitoring outcomes.

Concept or design: L Tang, Y Chen.
Acquisition of data: L Tang, H Liu, M Wang, Y Zhou.
Analysis or interpretation of data: L Tang, Y Chen, J He, M Chen.
Drafting of the manuscript: L Tang, H Liu.
Critical revision of the manuscript for important intellectual content: Y Chen, J Zheng, F Wang.

All authors had full access to the data, contributed to the study, approved the final version for publication, and take responsibility for its accuracy and integrity.

All authors have disclosed no conflicts of interest.

The authors are grateful to the clinical staff of the Department of Spine Surgery at Suining Central Hospital for their assistance in completing this article. The authors also thank Bullet Edits Limited for providing language editing and proofreading services.

This study received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

The study was approved by Suining Central Hospital's Ethics Committee for Biomedical Research Involving Human Beings, China (Ref No.: KYLLMC20240019). Written informed consent was obtained from the patient for the publication of this case report.

1. Hastings-James R. Melanoma of the central nervous system. Radiology 1973;109:357-60. Crossref

2. Lee CH, Moon KY, Chung CK, et al. Primary intradural extramedullary melanoma of the cervical spinal cord: case report. Spine (Phila Pa 1976) 2010;35:E303-7. Crossref

3. Smith AB, Rushing EJ, Smirniotopoulos JG. Pigmented lesions of the central nervous system: radiologic-pathologic correlation. Radiographics 2009;29:1503-24. Crossref

4. Nakamae T, Kamei N, Tanaka N, et al. Primary spinal cord melanoma: a two-case report and literature review. Spine Surg Relat Res 2022;6:717-20. Crossref

5. Kim MS, Yoon DH, Shin DA. Primary spinal cord melanoma. J Korean Neurosurg Soc 2010;48:157-61. Crossref

A 49-year-old man with a history of poorly controlled diabetes for over 10 years was hospitalised 6 months earlier, on 2 April 2023, for severe COVID-19 infection. He was discharged after 3 weeks but later developed right-sided facial pain and diplopia. He was diagnosed with sino-orbital mucormycosis based on the clinical symptoms and imaging features (Fig a). Histopathological examination of a sinus biopsy revealed invasive ribbon-like hyphae, confirming the diagnosis. The patient underwent sinus and surgical debridement of the orbit and was prescribed antifungal treatment. After two surgical debridements of necrotic tissue and 6 weeks of combination antifungal treatment with liposomal amphotericin B (400 mg daily via infusion) plus posaconazole (300 mg twice daily on the first day and 300 mg daily intravenously thereafter), the patient was discharged in good general health but with right eye blindness. He was advised to continue treatment with oral posaconazole (300 mg twice daily on the first day, then 300 mg daily thereafter) for a duration of 12 weeks and to control his blood sugar with insulin.

In September 2023, 2 months after discharge, the patient presented to the hospital for follow-up, complaining of increased bilateral breast volume, particularly in the right breast (Fig b and c). He had first noticed this increase in volume approximately 1 month after hospitalisation, and it had gradually intensified.

Clinical examination revealed bilateral breast swelling with increased breast adipose tissue volume, more pronounced on the right side. No tenderness or palpable mass was detected. Ultrasound findings were consistent with gynaecomastia. Hormone testing showed a normal prolactin level and pituitary axes but markedly decreased testosterone and elevated oestrogen levels (Table).

In view of these results and the possible association of gynaecomastia with azole use, posaconazole was discontinued. The patient was prescribed liposomal amphotericin B 400 mg daily and monitored daily to ensure compliance with medication and to evaluate any possible side-effects. He exhibited minor hypokalaemia while receiving amphotericin B, which resolved with the administration of potassium supplements. There was no evidence of hyperaldosteronism during treatment with posaconazole. Following the discontinuation of posaconazole, the patient’s gynaecomastia improved significantly over 4 weeks (Fig d).

At the time of writing, this report represents the second documented case of posaconazole-induced gynaecomastia. Information on this adverse effect is limited, despite its recognised association with azole use. Given the common use of posaconazole for the prevention and treatment of mucormycosis, other patients may be at risk of similar complications. Disseminating this information is essential for clinical pharmacists to manage such cases effectively

Our case was a middle-aged man with a history of diabetes and COVID-19, who developed gynaecomastia following the prescription of posaconazole for mucormycosis. Gynaecomastia is a benign enlargement of the breast tissue that may occur in many adult men.1 Physiological gynaecomastia in infants, adolescents, and older adult men is usually unilateral. Non-physiological gynaecomastia may arise in patients with chronic diseases such as hypogonadism, cirrhosis, neoplasms or uraemia, or as a consequence of drug use. Additionally, non-physiological gynaecomastia may cause localised pain.2 In our patient, bilateral and painless non-physiological gynaecomastia developed as a consequence of azole use.

Azole antifungals are the mainstay of prevention and treatment for invasive fungal infections such as mucormycosis.3 Most reported cases of azole-induced gynaecomastia have involved patients taking ketoconazole and, to a lesser extent, itraconazole. Both inhibit cytochrome P450 enzymes involved in steroidogenesis.4 In-vitro evidence suggests that posaconazole can inhibit cytochrome P450 17A1, an enzyme involved in the lyase reaction required for androgen production. In addition, posaconazole, similar to ketoconazole, may inhibit hepatic oestrogen metabolism.5 Accordingly, our patient’s serum testosterone level was lower than normal, while the oestradiol level was significantly elevated. This is comparable to the first reported case of posaconazole-induced gynaecomastia by Thompson et al.6 In that patient, who was prescribed long-term posaconazole for coccidioidomycosis (300 mg/day slow-release formulation), the oestradiol level was raised despite a normal testosterone level. Notably, gynaecomastia did not improve following a switch from posaconazole to voriconazole. In contrast, our patient showed improvement after the complete discontinuation of azole agents.

The main limitation of this report is the absence of a serum posaconazole level, as testing was unavailable due to economic constraints affecting resource availability. This limits the ability to draw a definitive conclusion regarding the association of posaconazole with the development of gynaecomastia, or the observed improvement following its discontinuation.

Concept or design: M Salehi, H Khalili.
Acquisition of data: A Kazemzadeh, M Alaei.
Drafting of the manuscript: All authors.
Critical revision of the manuscript for important intellectual content: M Salehi, A Tabari.

All authors had full access to the data, contributed to the study, approved the final version for publication, and take responsibility for its accuracy and integrity.

All authors have disclosed no conflicts of interest.

The authors thank Mrs Fariba Zamani for language editing of the manuscript.

This study received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

This study was approved of by the institutional review board of Tehran University of Medical Sciences, Iran (Ref No.: IR.TUMS.IKHC.REC.1403.165). Written consent was obtained from the patient for publication of this case report.

1. Fagerlund A, Lewin R, Rufolo G, Elander A, Santanelli di Pompeo F, Selvaggi G. Gynecomastia: a systematic review. J Plast Surg Hand Surg 2015;49:311-8. Crossref

2. Jin Y, Fan M. Treatment of gynecomastia with prednisone: case report and literature review. J Int Med Res 2019;47:2288-95. Crossref

3. Benitez LL, Carver PL. Adverse effects associated with long-term administration of azole antifungal agents. Drugs 2019;79:833-53. Crossref

4. Satoh T, Fujita KI, Munakata H, et al. Studies on the interactions between drugs and estrogen: analytical method for prediction system of gynecomastia induced by drugs on the inhibitory metabolism of estradiol using Escherichia coli coexpressing human CYP3A4 with human NADPH-cytochrome P450 reductase. Anal Biochem 2000;286:179-86. Crossref

5. Yates CM, Garvey EP, Shaver SR, Schotzinger RJ, Hoekstra WJ. Design and optimization of highly-selective, broad spectrum fungal CYP51 inhibitors. Bioorg Med Chem Lett 2017;27:3243-8. Crossref

6. Thompson GR 3rd, Surampudi PN, Odermatt A. Gynecomastia and hypertension in a patient treated with posaconazole. Clin Case Rep 2020;8:3158-61. Crossref

A 56-year-old man was presented to the emergency department of our institution in June 2023 and has had been followed up in our medical clinic for 1 year prior to his current hospital admission. He had been diagnosed with frequent symptomatic premature ventricular complexes with an ectopic burden of 8.2% on extended ambulatory rhythm monitoring. There were also multiple recorded episodes of non-sustained ventricular tachycardia. Beta-blocker was initiated and uptitrated according to clinical symptoms. His family history was remarkable for the sudden cardiac death of his father at the age of 64 years. Subsequent transthoracic echocardiogram of the patient revealed a global hypokinetic left ventricle with a biplane-measured left ventricular ejection fraction (LVEF) of 45%. There was mild left atrial enlargement with a two-dimensional area of 25.7 cm² but no other structural abnormalities. Computed tomography coronary angiogram showed mild to moderate coronary artery disease in three vessels and guideline-directed medical treatment was initiated. Cardiac magnetic resonance imaging (CMR) was scheduled to assess cardiac structures and function, as well as tissue characterisation for features of non-ischaemic cardiomyopathy. He had been scheduled to undergo catheter ablation for frequent symptomatic premature ventricular complexes.

The patient presented to our emergency department with out-of-hospital cardiac arrest. He had been found collapsed adjacent to a swimming pool and a bystander had initiated cardiopulmonary resuscitation. Spontaneous circulation was restored shortly after a single defibrillation delivered by an automated external defibrillator and he was transferred to our hospital immediately. On arrival at the emergency department, he was hemodynamically stable with a Glasgow Coma Scale score of 15. High-sensitive troponin I level was elevated at 44.9 ng/L. Electrocardiogram showed sinus rhythm of 71 beats/min with occasional premature ventricular complexes. There was no ST-segment elevation or significant conduction abnormalities. Bedside echocardiogram showed a similar biplane-measured LVEF of 43% with global hypokinesia. Urgent coronary angiogram showed non-occlusive moderate to severe coronary artery disease in three vessels. Given his current presentation, together with angiographic progression in coronary artery disease, complete revascularisation was performed uneventfully. He was then transferred to our cardiac care unit postoperatively for close monitoring. Inpatient CMR revealed a non-dilated left ventricle with mildly reduced LVEF of 43% with global hypokinesia. There was multifocal patchy mid-wall and subepicardial late gadolinium enhancement (LGE) at the mid-ventricular anterior, anteroseptal and anterolateral walls, as well as basal to mid-ventricular inferior and inferolateral walls (Fig 1). There was no evidence of myocardial infarct. Parametric mapping showed a mild increase in myocardial T1 with values up to 1067 ms to 1080 ms (native T1 values in healthy subjects obtained in our Aera 1.5T magnetic resonance imaging scanner [Siemens, Munich, Germany] is 996±26 ms for males), suggestive of mild diffuse interstitial fibrosis (Fig 2). Prior to hospital discharge, a transvenous implantable cardioverter defibrillator (ICD) was implanted for secondary prevention. Subsequent genetic testing identified a heterozygous pathogenic truncating variant NM_001458.5(FLNC):c.3279del p.(Gly1094Alafs^*4) in the filamin-C gene. The final clinical diagnosis was sudden cardiac arrest secondary to filamin-C variant–associated cardiomyopathy in a patient with non-dilated left ventricular cardiomyopathy (NDLVC) and mid-range ejection fraction.

The filamin-C gene encodes the filamin-C protein that plays essential roles in the sarcomere stability in cardiac muscles. Filamin-C variants have been increasingly recognised as an important cause of cardiomyopathy. It has been identified in approximately 3% to 4% of patients with dilated cardiomyopathy and commonly presents in early-to-mid adulthood with high arrhythmic risks.1

According to the 2021 European Society of Cardiology (ESC) Guidelines for the diagnosis and treatment of acute and chronic heart failure,2 primary prevention ICD is indicated in patients with symptomatic heart failure with an LVEF of lower than 35% despite optimal medical treatment and a reasonable quality of life. Such recommendation is supported by numerous landmark trials including MADIT (Multicenter Automatic Defibrillator Implantation Trial),3 DEFINITE (DEFibrillators In Non-Ischemic Cardiomyopathy Treatment Evaluation),4 and SCD-HeFT (the Sudden Cardiac Death in Heart Failure Trial).5 In addition, several additional clinical risk factors should also be considered in sudden cardiac death risk assessment, especially in patients with non-ischaemic cardiomyopathy.2 These risk factors include significant LGE on CMR, younger age, and specific genotypes. Nonetheless these recommendations are ambiguous, and the guideline has not defined, for example, the burden of LGE and variant mechanisms in several high-risk genes that would warrant ICD implantation. Moreover, there are limited recommendations for primary prevention ICD in patients with heart failure with mid-range or preserved ejection fraction.

In the updated 2023 ESC Guidelines for the management of cardiomyopathies,6 a new entity of NDLVC is introduced. An algorithm for consideration of primary prevention ICD similar to that for patients with dilated cardiomyopathy is recommended in this patient population. Patient genotype and imaging features on CMR have been proposed in the early sudden cardiac death risk assessment for patients with NDLVC. A previous study has demonstrated a higher rate of malignant arrhythmic events in patients who are genotype-positive, compared with their genotype-negative counterparts.7 Such association has been observed irrespective of LVEF. Variants in certain genes including lamin A/C, phospholamban, filamin-C, RNA-binding motif protein 20, desmoplakin and plakophilin-2 are associated with a high risk of malignant ventricular arrhythmias and sudden cardiac death. Apart from genotype information, the presence and distribution of LGE on CMR, such as a ring-like pattern of LGE, has also been shown to be a strong risk marker for ventricular arrhythmias.8 Hence, based on the current ESC Guidelines,6 primary prevention ICD should be considered in patients with NDLVC and high-risk genotype and in the presence of additional risk factors such as syncope and LGE on CMR, irrespective of LVEF.

Our case highlights the need to incorporate a patient’s genotype and imaging features on CMR into the personalised risk assessment for sudden cardiac death in patients with NDLVC. This will facilitate a more comprehensive and informative discussion about the indication for primary prevention ICD and improve the clinical outcome for patients with cardiomyopathy.

Concept or design: KWC Lun, DPH Lee.
Acquisition of data: All authors.
Analysis or interpretation of data: KWC Lun, DPH Lee.
Drafting of the manuscript: KWC Lun, DPH Lee.
Critical revision of the manuscript for important intellectual content: All authors.

All authors had full access to the data, contributed to the study, approved the final version for publication, and take responsibility for its accuracy and integrity.

All authors have disclosed no conflicts of interest.

This study received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

The patient was treated in accordance with the Declaration of Helsinki. The patient provided consent for all treatments and procedures, and consent for publication of the case report.

1. Agarwal R, Paulo JA, Toepfer CN, et al. Filamin C cardiomyopathy variants cause protein and lysosome accumulation. Circ Res 2021;129:751-66. Crossref

2. McDonagh TA, Metra M, Adamo M, et al. 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J 2021;42:3599-726. Crossref

3. Moss AJ, Zareba W, Hall WJ, et al. Prophylactic implantation of a defibrillator in patients with myocardial infarction and reduced ejection fraction. N Engl J Med 2002;346:877-83. Crossref

4. Kadish A, Dyer A, Daubert JP, et al. Prophylactic defibrillator implantation in patients with nonischemic dilated cardiomyopathy. N Engl J Med 2004;350:2151-8. Crossref

5. Bardy GH, Lee KL, Mark DB, et al. Amiodarone or an implantable cardioverter-defibrillator for congestive heart failure. N Engl J Med 2005;352:225-37. Crossref

6. Arbelo E, Protonotarios A, Gimeno JR, et al. 2023 ESC Guidelines for the management of cardiomyopathies. Eur Heart J 2023;44:3503-626. Crossref

7. Escobar-Lopez L, Ochoa JP, Mirelis JG, et al. Association of genetic variants with outcomes in patients with nonischemic dilated cardiomyopathy. J Am Coll Cardiol 2021;78:1682-99. Crossref

8. Meier C, Eisenblätter M, Gielen S. Myocardial late gadolinium enhancement (LGE) in cardiac magnetic resonance imaging (CMR)—an important risk marker for cardiac disease. J Cardiovasc Dev Dis 2024;11:40. Crossref

Etomidate is a non-barbiturate intravenous anaesthetic agent commonly used in emergency and critical care settings, due to its rapid onset, short duration of action, and minimal cardiorespiratory suppression. Adrenal suppression is a known side-effect. From April to May 2024, three adolescents presented to the paediatric departments of local hospitals with adrenal insufficiency due to etomidate inhalation via electronic cigarette (e-cigarette) vaping, a novel form of drug misuse emerging in Hong Kong.

In Case 1, a 17-year-old male with attention deficit hyperactivity disorder was admitted with ketamine cystitis. He had mild hypokalaemia, hypertension (137/84 mm Hg), and a positive urine toxicology screen by liquid chromatography–tandem mass spectrometry for cocaine, ketamine, and etomidate (Table). He reported daily vaping of ‘space oil’ via e-cigarettes for 4 months. Adrenal insufficiency was diagnosed based on elevated adrenocorticotropic hormone (ACTH) and a suboptimal response in a low-dose short Synacthen test. In Case 2, a 16-year-old male with autistic spectrum disorder presented with confusion, insomnia, and unsteady gait after vaping ‘space oil’ weekly for 1 month. Blood pressure and electrolytes were normal. Urine toxicology revealed etomidate and its analogue propoxate. Adrenal insufficiency was confirmed. In Case 3, a 15-year-old male with substance abuse–induced psychosis presented with emotional instability under drug effects. He reported vaping ‘space oil’ via e-cigarettes weekly for several months. Blood pressure and electrolytes were normal. Partial adrenal insufficiency was diagnosed with borderline results in the low-dose short Synacthen test. Two patients (Cases 1 and 2) required regular hydrocortisone replacement. In Case 1, repeated testing 5 months after cessation of etomidate revealed persistent adrenal insufficiency, likely due to second-hand smoke exposure from peers who used etomidate. For Cases 2 and 3, follow-up tests were planned after etomidate cessation. All patients received psychiatric follow-up.

This is the first local paediatric report of adrenal insufficiency associated with etomidate misuse via e-cigarettes. Since its clinical introduction 40 years ago, recreational use via the intravenous route has been rare.1 Nonetheless, its misuse as ‘space oil’ via e-cigarette vaping has surged in Hong Kong and Mainland China since 2023. e-Cigarette use is relatively common among adolescents, with a local survey reporting that 5.3% of secondary school students have had experience with e-cigarettes.2 From May to December 2024, the Hong Kong Poison Control Centre recorded 45 cases of ‘space oil’ misuse presenting to Hospital Authority emergency departments, with a median patient age of 17 years.3 Our cases also illustrate that psychiatric co-morbidities and polysubstance misuse are not uncommon among adolescent etomidate users.

Knowledge about the pharmacology of inhaled etomidate is limited since historical studies have focused on its properties in the context of a single intravenous bolus or short-duration infusion,4 while inhalation may involve higher doses and prolonged use. Known toxicities include decreased consciousness, nausea, vomiting, myoclonus, and adrenal insufficiency. Respiratory suppression or bradycardia may develop in overdose. Long-term neurological and psychological effects, particularly dependence and withdrawal, remain poorly characterised.

Etomidate and its analogues, propoxate/isopropoxate, inhibit 11-beta-hydroxylase, causing adrenal insufficiency with consequent decreased cortisol and aldosterone production, and elevated precursors such as 11-deoxycorticosterone, 11-deoxycortisol, and 17-hydroxyprogesterone (Fig). Accumulation of deoxycorticosterone, the precursor to aldosterone, leads to mineralocorticoid excess. Marked elevation of androstenedione in Case 1 and urinary androgen metabolites in Case 3 suggested androgen excess, consistent with a recently reported local female adult case of hyperandrogenism from etomidate misuse.5

Adrenal suppression from etomidate is dose-dependent and reversible, lasting 6 to 8 hours after a single dose and up to 24 to 48 hours with continuous infusion.4 6 Effects after chronic inhalation are less clear due to the variable drug content of e-cigarettes and inconsistent inhalation routes. Adrenal hyperplasia has been observed on computed tomography examinations among chronic users,5 7 suggesting possible prolonged ACTH stimulation due to ongoing adrenal suppression beyond typical durations in clinical settings.

Etomidate-induced 11-beta-hydroxylase inhibition can resemble congenital adrenal hyperplasia due to 11-beta-hydroxylase deficiency. In addition to adrenal insufficiency, features of mineralocorticoid excess include hypertension, hypokalaemia, and suppression of endogenous renin and aldosterone, as seen in Case 2. Although mild hypokalaemia was observed in Case 1, severe hypokalaemia has been reported.7 Cases 1 and 3 demonstrated significantly elevated 11-deoxycortisol, while 17-hydroxyprogesterone was normal to mildly elevated, suggesting the former is a more sensitive marker of enzyme inhibition, as it is immediately upstream of the inhibited enzyme (Fig). Urinary steroid profiling can identify abnormal precursor-to-product ratios. A short Synacthen test should be performed to confirm adrenal insufficiency. Cases 2 and 3 demonstrated that ACTH may be normal and cortisol response may be relatively preserved despite circumstantial evidence of 11-beta-hydroxylase inhibition, possibly reflecting less drug exposure or compensation between periods of drug use.

Given the uncertainty of the duration of adrenal suppression, hydrocortisone replacement and/or stress dose precautions should be given for confirmed adrenal insufficiency. Etomidate users should receive counselling on hydrocortisone’s role, as it does not mitigate the full spectrum of etomidate toxicities. After cessation of etomidate, follow-up testing is recommended to document adrenal recovery. Persistently abnormal results should prompt suspicion of ongoing drug use, with non-classic congenital adrenal hyperplasia due to 11-beta-hydroxylase deficiency being a rare differential diagnosis. Our cases highlight the challenges of achieving complete cessation of drug misuse due to peer influence and potential dependence. A multidisciplinary approach should be adopted to address the complex medical and psychosocial issues in adolescent etomidate users.

Etomidate and its three analogues—metomidate, propoxate, and isopropoxate—have been listed as dangerous drugs in Hong Kong since February 2025.8 It is expected that more stringent regulations, along with continued law enforcement on illegal drug production and distribution, may help deter etomidate misuse. Public education should also be strengthened to emphasise that substances in e-cigarettes are not harmless, even if they are not traditionally classified as drugs.

Etomidate misuse via e-cigarettes is an emerging public health issue. Clinicians should be alert to the risk of adrenal insufficiency among e-cigarette users, particularly those who present with unexplained hypertension or hypokalaemia. Additional testing, such as toxicology screening, 11-deoxycortisol measurement, and urinary steroid profiling may provide supportive evidence. Further research is warranted to understand the pharmacological properties and long-term effects of etomidate misuse.

Concept or design: All authors.
Acquisition of data: YK Chung, YT Cheung, CSY Chan, CC Wong.
Analysis or interpretation of data: All authors.
Drafting of the manuscript: YK Chung.
Critical revision of the manuscript for important intellectual content: All authors.

All authors had full access to the data, contributed to the study, approved the final version for publication, and take responsibility for its accuracy and integrity.

All authors have disclosed no conflicts of interest.

This study received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

The patients were managed in accordance with the Declaration of Helsinki and provided informed consent for all treatments, procedures, and publication.

1. Uhm J, Hong S, Han E. The need to monitor emerging issues in etomidate usage: the misuse or abuse potential. Forensic Sci Med Pathol 2024;20:249-60. Crossref

2. Health Bureau, Hong Kong SAR Government. School-based survey on smoking among students in 2022/23. 2023. Available from: https://www.censtatd.gov.hk/wbr/B1130201/B11302012024XX01/att/en/78/School-based%20Survey%20on%20Smoking%20among%20Students%20in%202022-23%20-%20Key%20findings_7.pdf. Accessed 15 Aug 2024.

3. Wong IN, Chan CK, Tse ML. Spread of ‘space oil drug’ (etomidate) abuse in Hong Kong and consequent emergency department presentations. Hong Kong Med J 2025;31:173-4. Crossref

4. Forman SA. Clinical and molecular pharmacology of etomidate. Anesthesiology 2011;114:695-707. Crossref

5. Lau CY, Cheung YT, Han TM, Chung CM, Chong YK, Chen PL. Acquired 11β-hydroxylase deficiency by inhaled etomidate and its analogues: a mimic of congenital adrenal hyperplasia. JCEM Case Rep 2024;2:luae207. Crossref

6. Vinclair M, Broux C, Faure P, et al. Duration of adrenal inhibition following a single dose of etomidate in critically ill patients. Intensive Care Med 2008;34:714-9. Crossref

7. Wu W, Xia C, Gan L, Liao S, Yan Y. Etomidate-induced hypokalemia in electronic cigarette users: two case reports and literature review. Front Endocrinol (Lausanne) 2024;15:1321610. Crossref

8. Hong Kong SAR Government. Dangerous Drugs Ordinance (Amendment of First Schedule) Order 2025. Available from: https://www.elegislation.gov.hk/hk/2025/ln13!en. Accessed 15 Feb 2025.

A 69-year-old female presented to the clinic with a 2-year history of intermittent headaches. Cranial computed tomography (CT) and magnetic resonance imaging (MRI) examination (Fig 1a and b) revealed a space-occupying lesion in the right frontal lobe, suggestive of a meningioma. Preoperatively, the patient experienced a single episode of epilepsy lasting for 2 minutes, relieved by antiepileptic medication.

Cranial surgery was performed based on the preoperative CT localisation. The tumour was completely separated and excised, measuring 4 × 3 × 2 cm³, greyish-yellow in colour, and encapsulated (Fig 1e). The encapsulated surface was rich in blood vessels. Upon opening, the tumour was yellow, and lipid droplet-like fluid was observed on the surface (Fig 1f).

Postoperative pathology indicated a hibernoma. Haematoxylin and eosin staining revealed a complete thin capsule attached to the outside of the tumour that was lobulated. A network of capillaries could be seen inside. Under the microscope, polygonal/round cells with eosinophilic granular cytoplasm were seen. The cell nuclei were round and centrally located. In addition, many small vacuolated brown adipocytes and unilocular adipocytes were seen, with a considerable amount of blood vessels, spindle cells, and collagen fibres infiltrating around the tumour cells (Fig 2).

Immunohistochemistry showed CD34 to be positive in the vessels, and Ki-67 scattered positive with a proportion of <1%. Immunohistochemistry results were as follows: CK (-), S-100 (-), MDM2 (-), CDK4 (-), P53 (-), CD34 (vascular +), CD117 (-), and Ki -67 (+, <1%) [Fig 2].

Postoperative re-examination confirmed complete removal of the tumour, and the patient had no further epileptic seizures. Three years later, cranial MRI follow-up revealed no tumour recurrence (Fig 1c and d).

Hibernomas are rare benign tumours composed of brown adipose tissue.1 They are asymptomatic and slow-growing. Compared with lipomas originating from white adipose tissue, hibernomas are exceedingly rare, with <200 cases reported in the literature.2 These tumours most commonly occur in the proximal axial skeleton, where fetal brown adipose tissue exists and continues into adulthood. They are most frequently found in the interscapular region, upper mediastinum, axilla, retroperitoneum, and neck. According to literature reports, hibernomas are extremely rare in the cranial cavity. In 1972, Vagn-Hansen et al3 reported a case of intracranial hibernoma. Due to medical constraints at the time, detailed case descriptions of CT and MRI images were not available. Therefore, the diagnosis of this patient has significant clinical significance and academic value. The rarity of intracranial hibernomas in clinical diagnosis can easily be overlooked or misdiagnosed as other more common intracranial tumours such as meningiomas. Clinicians and pathologists need to remain highly vigilant for this rare tumour to ensure timely and accurate diagnosis and treatment.

In radiology, differentiation between hibernomas and meningiomas is challenging. Hibernomas typically present as low- to medium-intensity on T1-weighted MRI and high intensity on T2-weighted MRI. Due to their origin from adipose tissue, hibernomas may show signal suppression in the fat-suppressed sequence of MRI. Due to the rich vascular supply inside the tumour, MRI post-contrast enhancement is evident. Also, due to the high fat content of hibernomas, they may appear as low density or iso-density lesions on CT scans.

Meningiomas typically present as iso- to high-intensity on both T1- and T2-weighted MRI and show significant uniform enhancement following contrast administration. Meningiomas often accompany the dural tail sign, an important distinguishing feature in imaging. Furthermore, the density of meningiomas on CT scans is quite uniform, with significant enhancement following contrast administration. Therefore, while there is overlap in imaging between hibernomas and meningiomas, detailed radiological analysis, especially the combination of fat-suppressed sequences and tumour enhancement characteristics, can help distinguish the two and increase diagnostic accuracy.

Pathological diagnosis is the gold standard for confirming hibernomas. Histological features include small multilocular brown adipocytes that have a rich granular cytoplasm and central or eccentric round or oval nuclei. Unlike the single large lipid droplet in white adipocytes, brown adipocytes contain multiple small lipid droplets and abundant mitochondria, giving the cytoplasm a granular appearance. In addition, hibernomas usually have a rich vascular network. Immunohistochemical staining showing vascular CD34 positivity can further confirm the diagnosis. Hibernoma cells have varying degrees of S-100 protein and CD34 expression according to the literature.4 5 Combining these pathological features can effectively distinguish hibernomas from other intracranial tumours such as meningiomas.

The diagnostic process of this case of intracranial hibernoma emphasises the importance of clinicians and pathologists when facing uncommon intracranial tumours. Detailed imaging analysis and pathological examination facilitate accurate differential diagnosis, providing the best treatment plan for patients. More case reports and research are needed to further enrich the understanding and treatment strategies of intracranial hibernomas.

All authors contributed to the concept or design, drafting of the manuscript, and critical revision of the manuscript for important intellectual content. All authors had full access to the data, contributed to the study, approved the final version for publication, and take responsibility for its accuracy and integrity.

The authors declared no conflicts of interest.

The authors thank Dr Yanqing Li and Dr Qinyi Wang from the Department of Pathology at Suzhou TCM Hospital Affiliated to Nanjing University of Chinese Medicine for their expertise and assistance in the diagnosis and analysis of the patient’s condition.

This study received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

The study was approved by the Ethics Committee of Suzhou TCM Hospital Affiliated to Nanjing University of Chinese Medicine, China (Ref No.: 2024-005). The patient was treated in accordance with the Declaration of Helsinki. The patient provided written consent for publication of this case report.

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