Images in Anesthesiology: Carotid Sinus Reflex From Neck Mass and Opioids.

Surgery on head and neck masses presents unique challenges to overcome, especially in relation to preoperative anesthesia induction. Tumor proximity to the carotid sinus can result in extreme hemodynamic depression, by way of compression or direct invasion of the node. Neck hyperextension required for endotracheal intubation can worsen the underlying compression. Additionally, many anesthetic agents have sympatholytic properties that can exacerbate this imbalance further toward the parasympathetic response. We present a case of a patient with non-Hodgkin lymphoma whose tumor compression of the carotid sinus precipitated an exaggerated vagal reflex response following fentanyl administration.

Carotid Sinus Syndrome With Convulsive Syncope in a Patient With Head and Neck Cancer.

This case report provides a comprehensive overview of a unique case of a 64-year-old male patient with head and neck (H&N) cancer who initially presented with compressive convulsive syncope, an initial manifestation of carotid sinus syndrome (CSS). CSS is an autonomic nervous system disease that often manifests as hypotension, dizziness, cerebral ischemia, or syncope, usually in elderly patients. In this case, the patient's laryngeal cancer led to lymphedema and encasement of the bilateral carotid arteries, inducing CSS and resulting in recurrent episodes of hypotension and bradycardia. These symptoms were managed through the administration of atropine and transcutaneous pacemaker placement, suggesting a probable mixed type of CSS. The patient was discharged on long-term theophylline treatment for symptomatic control of bradycardia episodes. Despite the promising outcomes of CSS cases treated with pacemakers, the efficacy is not universal and limitations may arise, particularly in H&N cancer patients. Therefore, the patient was managed with theophylline rather than a pacemaker due to its non-invasiveness and effectiveness in temporarily managing CSS. Although rare, CSS should be considered in patients experiencing convulsive syncope alongside H&N malignancies. As the evidence and consensus regarding CSS treatment in H&N cancer patients are scarce, additional research is necessary to evaluate and compare available options. This abstract concludes by emphasizing the need for further research and case reports to establish a consensus on the optimal management approach for patients affected by CSS due to compression from H&N cancers.

A Man With Progressive Chorea and Abnormal Trunk Movements.

Neuroacanthocytosis (NA) syndromes are a group of rare genetic disorders characterized by the presence of abnormally shaped red blood cells (acanthocytes) and the progressive degeneration of the basal ganglia, leading to various neurological and systemic symptoms. The "rubber man" gait, characterized by distinctive flexions of the neck (manifesting as head drops) and the trunk, is seen in advanced chorea-acanthocytosis. A 35-year-old male patient presented with progressive abnormal movements affecting his limbs and face, along with dysphagia resulting from involuntary protrusion of the tongue and biting of the cheeks and lips over the past three years. He used to place the food on the back of his tongue and throw his head back to begin swallowing. He also kept a towel in his mouth to absorb saliva and prevent cheek and lip biting. The neurologic examination revealed generalized chorea, severe orolingual dystonia (eating dystonia), and sudden loss of tone while walking, resulting in flexion of the trunk followed by extension. We believe that these features could serve as definitive clinical indicators for chorea-acanthocytosis, providing valuable diagnostic insights, especially when accompanied by self-mutilatory mouth movements or feeding-related tongue dystonia.

Less is more: Exploring neoadjuvant immunotherapy as a de-escalation strategy in head and neck squamous cell carcinoma treatment.

Head and neck squamous cell carcinoma (HNSCC) constitutes a significant global cancer burden, given its high prevalence and associated mortality. Despite substantial progress in survival rates due to the enhanced multidisciplinary approach to treatment, these methods often lead to severe tissue damage, compromised function, and potential toxicity. Thus, there is an imperative need for novel, effective, and minimally damaging treatment modalities. Neoadjuvant treatment, an emerging therapeutic strategy, is designed to reduce tumor size and curtail distant metastasis prior to definitive intervention. Currently, neoadjuvant chemotherapy (NACT) has optimized the treatment approach for a subset of HNSCC patients, yet it has not produced a noticeable enhancement in overall survival (OS). In the contemporary cancer therapeutics landscape, immunotherapy is gaining traction at an accelerated pace. Notably, neoadjuvant immunotherapy (NAIT) has shown promising radiological and pathological responses, coupled with encouraging efficacy in several clinical trials. This potentially paves the way for a myriad of possibilities in treatment de-escalation of HNSCC, which warrants further exploration. This paper reviews the existing strategies and efficacies of neoadjuvant immune checkpoint inhibitors (ICIs), along with potential de-escalation strategies. Furthermore, the challenges encountered in the context of the de-escalation strategies of NAIT are explored. The aim is to inform future research directions that strive to improve the quality of life (QoL) for patients battling HNSCC.

The two-faced role of RNA methyltransferase METTL3 on cellular response to cisplatin in head and neck squamous cell carcinoma in vitro model.

Background: RNA methyltransferase-like 3 (METTL3) is responsible for methyl group transfer in the progression of N 6-methyladenosine (m6A) modification. This epigenetic feature contributes to the structural and functional regulation of RNA and consequently may promote tumorigenesis, tumor progression, and cellular response to anticancer treatment (chemo-, radio-, and immunotherapy). In head and neck squamous cell carcinoma (HNSCC), the commonly used chemotherapy is cisplatin. Unfortunately, cisplatin resistance is still a major cause of tumor relapse and patients' death. Thus, this study aimed to investigate the role of METTL3 on cellular response to cisplatin in HNSCC in vitro models. Materials and methods: HNSCC cell lines (H103, FaDu, and Detroit-562) with stable METTL3 knockdown (sgMETTL3) established with CRISPR-Cas9 system were treated with 0.5 tolerable plasma level (TPL) and 1 TPL of cisplatin. Further, cell cycle distribution, apoptosis, CD44/CD133 surface marker expression, and cell's ability to colony formation were analyzed in comparison to controls (cells transduced with control sgRNA). Results: The analyses of cell cycle distribution and apoptosis indicated a significantly higher percentage of cells with METTL3 knockdown 1) arrested in the G2/S phase and 2) characterized as a late apoptotic or death in comparison to control. The colony formation assay showed intensified inhibition of a single cell's ability to grow into a colony in FaDu and Detroit-562 METTL3-deficient cells, while a higher colony number was observed in H103 METTL3 knockdown cells after cisplatin treatment. Also, METTL3 deficiency significantly increased cancer stem cell markers' surface expression in all studied cell lines. Conclusion: Our findings highlight the significant influence of METTL3 on the cellular response to cisplatin, suggesting its potential as a promising therapeutic target for addressing cisplatin resistance in certain cases of HNSCC.

Heterogeneity of cancer-associated fibroblasts and tumor-promoting roles in head and neck squamous cell carcinoma.

Tumor microenvironment (TME) in head and neck squamous cell carcinoma (HNSCC) has a major influence on disease progression and therapy response. One of the predominant stromal cell types in the TME of HNSCC is cancer-associated fibroblasts (CAF). CAF constitute a diverse cell population and we are only at the beginning of characterizing and understanding the functions of various CAF subsets. CAF have been shown to interact with tumor cells and other components of the TME to shape mainly a favourable microenvironment for HNSCC progression, although some studies report existence of tumor-restraining CAF subtypes. The numerous pathways used by CAF to promote tumorigenesis may represent potential therapeutic targets. This review summarizes current knowledge on the origins, subtypes and mechanisms employed by CAF in HNSCC. The aim is to contribute to the understanding on how CAF actively influence the TME and modulate different immune cell types, as well as cancer cells, to establish a conducive setting for cancer growth. Although CAF are currently a promising therapeutic target for the treatment of other types of cancer, there is no significant therapeutic advancement in HNSCC.

Assessment of the effect of 21-day head-down bed rest on the cardiovascular system by blood protein composition.

Head-down bed rest (HDBR) is one of the models of the physiological effects of weightlessness used, among other things, to assess the effect of hypokinesia on the physiological systems of the human body and, first of all, on the cardiovascular system. The aim of the work was to study the effect of 21 days of HDBR factors on the cardiovascular system based on blood proteomic profile data. It was revealed that HDBR conditions led to an increase in the levels of proteins of the complement and the coagulation cascade systems, platelet degranulation, fibrinolysis, acute phase proteins, post-translational modification of proteins, retinol-binding protein 4 (RBP4), apolipoprotein B, which are associated with cardiovascular diseases, and other proteins that affect the functions of endothelial cells. Blood levels of proteins involved in cytoskeletal remodelling, oxygen transport, heme catabolism, etc. have been shown to decrease during HDBR.

Impact of Treatment Delay in Head and Neck Mucosal Melanoma on Overall Patient Survival.

Objectives Head and neck mucosal melanoma (HNMM) is a rare malignancy with high mortality. This study evaluates the impact of treatment delays on overall survival in HNMM. Design/Setting/Participants A retrospective review of patients with surgically managed HNMM treated with adjuvant radiation was performed from the 2004-2016 National Cancer Database. Main Outcome Measures Durations of diagnosis-to-treatment initiation (DTI), surgery-to-radiotherapy initiation (SRT), duration of radiotherapy (RTD), surgery-to-immunotherapy initiation (SIT), diagnosis-to-treatment end (DTE), and total treatment package (TTP) were calculated. Results A total of 1,011 patients (50.7% female, 90.5% Caucasian) met inclusion criteria. Median DTI, SRT, RTD, SIT, DTE, and TTP were 30, 49, 41, 102, 119, and 87 days, respectively. Only longer DTE was associated with decreased mortality (hazard ratio, 0.720; 95% confidence interval, 0.536-0.965; p = 0.028). Conclusion DTI, SRT, RTD, SIT, and TTP do not significantly affect overall survival in patients with HNMM who undergo surgery and adjuvant radiation. Longer DTE is associated with improved survival in this population. Level of Evidence 4.

Juvenile Nasopharyngeal Angiofibroma: A Case Study on the Diagnostic and Surgical Challenges in an Adolescent Male.

A rare and locally aggressive vascular tumor, juvenile nasopharyngeal angiofibroma (JNA) mostly affects male teenagers. This paper describes a 14-year-old male patient who presented with lethargy and recurrent nasal bleeding, which are symptoms of JNA. CT and MRI scans confirmed a vascular mass with a significant local invasion originating from the sphenopalatine foramen. After a CT angiography, which revealed the tumor's large blood supply and helped with efficient excision, a focused surgical strategy was designed. Histopathology verified the benign nature of the tumor, and the operation was successful and the patient had a smooth recovery. This case adds to the little literature on JNA. It highlights the need for healthcare professionals to be aware of the requirement of early identification and careful presurgical preparation in managing the illness.

Brusatol improves the efficacy of an anti-mouse-PD-1 antibody via inhibiting programmed cell death 1 ligand 1 expression in a murine head and neck squamous cell carcinoma model.

OBJECTIVE: Combing PD-1/PD-L1 immune checkpoint inhibitors with natural products has exhibited better efficacy than monotherapy. Hence, the purpose of this research was to examine the anti-cancer effects of brusatol, a natural quassinoid-terpenoid derived from Brucea javanica, when used in conjunction with an anti-mouse-PD-1 antibody in a murine head and neck squamous cell carcinoma (HNSCC) model and elucidate underlying mechanisms. DESIGN: A murine HNSCC model and an SCC-15 cell xenograft nude mouse model were established to investigate the anti-cancer effects of brusatol and anti-PD-1 antibody. Mechanistic studies were performed using immunohistochemistry. Cell proliferation, migration, colony formation, and invasion were evaluated by MTT, migration, colony formation, and transwell invasion assays. PD-L1 levels in oral squamous cell carcinoma (OSCC) cells were assessed through qRT-PCR, flow cytometry, and western blotting assays. The impact of brusatol on Jurkat T cell function was assessed by an OSCC/Jurkat co-culture assay. RESULTS: Brusatol improved tumor suppression by anti-PD-1 antibody in HNSCC mouse models. Mechanistic studies revealed brusatol inhibited tumor cell growth and angiogenesis, induced apoptosis, increased T lymphocyte infiltration, and reduced PD-L1 expression in tumors. Furthermore, in vitro assays confirmed brusatol inhibited PD-L1 expression in OSCC cells and suppressed cell migration, colony formation, and invasion. Co-culture assays indicated that brusatol's PD-L1 inhibition enhanced Jurkat T cell-mediated OSCC cell death and reversed the inhibitory effect induced by OSCC cells. CONCLUSIONS: Brusatol improves anti-PD-1 antibody efficacy by targeting PD-L1, suggesting its potential as an adjuvant in anti-PD-1 immunotherapy.

Fluorescence confocal microscopy can accelerate diagnosis of cervical lymphadenopathy.

Fluorescence confocal microscopy (FCM) is an optical technique that uses laser light sources of different wavelengths to generate real-time images of fresh, unfixed tissue specimens. Unlike conventional histological evaluation methods, FCM is able to assess fresh tissue samples without the associated cryo artifacts typically observed after frozen sectioning. The purpose of this study was to evaluate the utility of FCM imaging in the differential diagnosis of cervical lymphadenopathy. Twenty-two cervical lymph node specimens from patients with lymphadenopathy of unknown origin were imaged by FCM. Two pathologists independently evaluated the scans for suspicion of malignancy and preliminary diagnosis. Malignancy was reliably excluded or confirmed by both pathologists with a sensitivity of 90.9% for pathologist 1 and 100% for pathologist 2. The specificity was 100% for both pathologists. For the preliminary diagnosis, almost perfect agreement with the final diagnosis was observed for both pathologists (κ= 0.94 for pathologist 1 and κ= 1.00 for pathologist 2). This is the first study to investigate lymph node specimens with different diagnoses, including lymphoma, using FCM. Our results indicate that differential diagnosis of lymph node specimens is feasible in FCM images, thus encouraging further exploration of FCM imaging in lymph node specimens to accelerate diagnosis and open the possibility of digitizing diagnosis on fresh, unfixed tissue.

Dihydroartemisinin inhibits HNSCC invasion and migration by controlling miR-195-5p expression.

Objectives: Dihydroartemisinin (DHA), an artemisinin derivative extracted from the traditional Chinese medicinal herb Artemisia annua, has the potential to suppress head and neck squamous cell carcinoma (HNSCC) progression. However, the mechanisms underlying these effects remain unclear. Therefore, we aimed to examine the mechanisms underlying the effects of DHA on tumor invasion and migration. Methods: Human HNSCC cell lines CAL-27 and FaDu were exposed to varying DHA concentrations (0, 5, 20, and 80 µM) for 24 h. Cell proliferation, invasion, and migration were assessed using CCK8, transwell, and wound-healing assays, respectively. Quantitative real-time PCR, western blotting, and immunofluorescence were used to assess the expression levels of the target genes and proteins. Results: DHA suppressed the invasion and migration of CAL-27 and FaDu cells. Additionally, miR-195-5p suppressed the invasion and migration of HNSCC cells. This study revealed significant differences in the expression of miR-195-5p and TENM2 between clinical samples and multiple public databases. DHA treatment and miR-195-5p overexpression significantly reduced TENM2 expression in HNSCC cells, which suggested that miR-195-5p overexpression enhanced the inhibitory effect of DHA on TENM2. Conclusions: This study provides the first evidence that DHA inhibits cell invasion and migration by regulating the miR-195-5p/TENM2 axis in HNSCC cells, suggesting it as a potentially effective treatment strategy for HNSCC.

The Occurrence of Dropped Head Syndrome After a Cervical Medial Branch Nerve Block in a Patient With Cervicothoracic Kyphotic Deformity: A Case Report.

Complications from medial branch blocks (MBBs) are rare when following proper procedural protocol. Dropped head syndrome (DHS) is characterized by profound muscle weakness in the cervical spine, resulting in a failure to maintain a level horizontal gaze and, in the worst cases, a chin-on-chest deformity. In this case report, we described DHS developing after cervical MBBs using short-acting anesthetic agents and subsequent management. A 69-year-old woman with a previous C6-C7 anterior cervical discectomy and fusion (ACDF) underwent bilateral posterior cervical MBBs targeting the C4-C5 and C5-C6 levels. Immediately following the injection, she reported a sudden inability to lift her head and was subsequently diagnosed with DHS. This condition continued with minimal improvement for over six months. After weighing the risks, the patient elected to avoid surgery, and she was provided a soft cervical collar and prescribed physical therapy. DHS is a debilitating condition more commonly associated with neurodegenerative conditions and inflammatory myopathy, which has received limited attention due to its rarity as a complication of cervical radiofrequency neurotomy. Surgery for this condition, when considered, typically involves long-segment posterior cervical instrumented fusion. Undergoing such a surgery is a complicated discussion that should consider patient clinical factors and preferences. The clinical impact of loss of strength in paraspinal musculature in this patient population is clearly deserving of further study.

Racial difference in receiving computed tomography for head injury patients in emergency departments.

STUDY OBJECTIVE: Prior studies have suggested potential racial differences in receiving imaging tests in emergency departments (EDs), but the results remain inconclusive. In addition, most prior studies may only have limited racial groups for minority patients. This study aimed to investigate racial differences in head computed tomography (CT) administration rates in EDs among patients with head injuries. METHODS: Patients with head injuries who visited EDs were examined. The primary outcome was patients receiving head CT during ED visits, and the primary exposure was patient race/ethnicity, including Asian, Hispanic, Non-Hispanic Black (Black), and Non-Hispanic White (White). Multivariable logistic regression analyses were performed using the National Hospital Ambulatory Medical Care Survey database, adjusting for patients and hospital characteristics. RESULTS: Among 6130 patients, 51.9% received a head CT scan. Asian head injury patients were more likely to receive head CT than White patients (59.1% versus 54.0%, difference 5.1%, p < 0.001). This difference persisted in adjusted results (odds ratio, 1.52; 95% CI, 1.06-2.16, p = 0.022). In contrast, Black and Hispanic patients have no significant difference in receiving head CT than White patients after the adjustment. CONCLUSIONS: Asian head injury patients were more likely to receive head CT than White patients. This difference may be attributed to the limited English proficiency among Asian individuals and the fact that there is a wide variety of different languages spoken by Asian patients. Future studies should examine rates of receiving other diagnostic imaging modalities among different racial groups and possible interventions to address this difference.

Persistent depression of the lambda site with progressive skull deformity may be a sign of suture closure: Case series and pathological consideration.

BACK GROUND: Flat head syndrome (FHS) sometimes occurs when a baby maintains the same head position during the first several months of life causing a skull deformity. FHS usually improves with time and natural growth, however, some shows aggravation against conservative treatment. We reviewed pathologically proved early closure of skull suture that may have seen secondary to FHS. METHODS: The clinical and radiological findings of the patients who showed progressive skull deformity resembling FHS were retrospectively reviewed. All the patients underwent surgical treatment and pathological specimens were obtained. RESULTS: The detected patients included two 5-month-old infants and one 1-year-old infant. The formers were conservatively treated without any obvious premature suture closure on computed tomography (CT), and later developed progressive tower-like skull deformities. The infants were diagnosed with possible premature fusion of Lambda site and underwent removal around lambda depression (LD). The latter showed evident sagittal suture closure on CT with digital markings, and was diagnosed with increased intracranial pressure and underwent cranioplasty of posterior expansion. Histopathological specimens obtained from the patients' resected sutures showed irregularly narrowed suture structure with ossification and fibrous tissue proliferation within them, supporting the diagnosis of premature closure of the sagittal sutures. Their postoperative courses were uneventful, and their skull deformities subsequently improved. CONCLUSIONS: Conservative therapy-resistant progressive occipital skull deformity with LD may be a sign of early suture closure, even if CT does not show obvious suture closure. The findings are helpful for early diagnosis and might lead to minimal invasive surgery if needed.

A retrospective study of Monteggia fractures in 8 dogs and 1 cat.

Monteggia fractures (MFs) are proximal ulnar fractures with concurrent dislocation of the radial head. This retrospective study aims to report the clinical findings and discuss the treatments and outcomes in MFs cases of 9 cases. Previous medical records of the animals were reviewed for history, clinical features, radiographic findings and choice of treatment. Treatment follow-up was evaluated over the telephone by discussion with the owners. Six animals included in the study were presented 2 days after the initial trauma. Five dogs were presented after common road traffic accidents and two after unknown traumas. All dogs had type I MFs, while the cat had a type III MF. Radiographical findings showed that six animals had extra-articular ulnar fractures, while three animals had intra-articular ulnar fractures. All animals were treated with open reduction of the ulna and internal fixation surgical methods. Six ulnar fractures were stabilized with intramedullary pin(s) with cerclage wire. The clinical outcome was assessed by the owners as full function in 3 dogs, acceptable function in 2 dogs and unacceptable function in 2 dogs with intraarticular ulnar fractures. The cat case was rated as full function. One dog died from a pulmonary fat embolism. The findings presented here provide some support that cerclage wire placement could be a satisfactory method for annular ligament reconstruction as a simple and economical treatment option. Also, to the authors' knowledge, this is the third report of MFs with intraarticular ulnar fractures. In this series, comminuted, intraarticular fractures were related to major postoperative complications.

Primary hyperparathyroidism caused by a tiny mediastinal parathyroid adenoma with non-localising imaging studies.

Variations in parathyroid gland positions often cause failure in initial parathyroid adenoma surgery, especially when imaging fails to localise the adenoma. This report describes a female patient with primary hyperparathyroidism for which preoperative localisation studies did not determine the position of the hyperfunctioning gland. The initial approach with bilateral cervical exploration and intraoperative parathyroid hormone monitoring was performed unsuccessfully. A mediastinal adenoma was suspected due to meticulous negative neck exploration and repeated negative images for a neck adenoma. Subsequently, a second approach involving mediastinal exploration was performed. After the removal of remnant thymic tissue in the mediastinal space, a significant drop in intraoperative parathyroid hormone levels was achieved. The pathological result confirmed the presence of a tiny pathological parathyroid adenoma within the thymus. At 6 months follow-up, postoperative biochemical assessment was consistent with normal calcium and parathyroid hormone levels.

Heading during the season and its potential impact on brain structure and neurocognitive performance in high-level male football players: An observational study.

OBJECTIVES: To investigate potential effects of heading on the neurocognitive performance and the white matter (WM) of the brain in high-level adult male football players. DESIGN: Prospective longitudinal. METHODS: Football players engaging in the highest football leagues in Germany were included. Neurocognitive performance tests and diffusion tensor imaging (DTI) were executed before and after the observation period. Video recordings of each training session and each match play during the observation period were analyzed regarding heading exposure and characteristics. Four DTI measures from tract-based spatial statistics (fractional anisotropy, mean, axial, and radial diffusivity) were investigated. Associations between heading variables and DTI and neurocognitive parameters were tested subsequently. RESULTS: 8052 headers of 22 players (19.9 ±â€¯2.7 years) were documented in a median of 16.9 months. The individual total heading number ranged from 57 to 943 (median: 320.5). Header characteristics differed between training sessions and matches. Neurocognitive performance (n = 22) and DTI measures (n = 14) showed no significant differences from pre- to post-test. After correction for multiple comparisons, no significant correlations with the total heading number were found. However, the change in fractional anisotropy in the splenium of the corpus callosum correlated significantly with the total amount of long-distance headers (Pearson's r = -0.884; p < 0.0001). CONCLUSIONS: Over the median observation period of 16.9 months, DTI measures and neurocognitive performance remained unchanged. To elucidate the meaning of the association between individual change in fractional anisotropy and long-distance headers further investigations with larger samples, longer observations, and various cohorts regarding age and level of play are required.

Dosimetric evaluation of intensity modulated photon versus proton reirradiation of head and neck cancer.

BACKGROUND: Reirradiation of head and neck cancer (HNC) became more accessible in the last decade, owing to modern irradiation techniques which offer a reduction in treatment related toxicities. The aim of this paper was to comparatively evaluate the dosimetric aspects derived from intensity modulated photon vs. proton treatment planning in reirradiated HNC patients. METHODS: Six recurrent HNC patients were enrolled in this retrospective study. For each patient two treatment plans were created: one IMRT/VMAT and one IMPT plan. The prescribed dose for the second irradiation was between 50 and 70 Gy RBE. The study comparatively analyzed the CTV coverage, doses to organs at risk (OARs) and low doses received by the healthy tissue (other than OAR). RESULTS: Similar CTV coverage was achieved for photon vs proton plans, with the latter presenting better homogeneity in four cases. Maximum dose to CTV was generally higher for photon plans, with differences ranging from 0.3 to 1.9%. For parotid glands and body, the mean dose was lower for proton plans. A notable reduction of low dose to healthy tissue (other than OARs) could be achieved with protons, with an average of 60% and 64% for D10% and Dmean, respectively. CONCLUSION: The dosimetric comparison between photon and proton reirradiation of HNC showed a great need for treatment individualization, concluding that protons should be considered for reirradiation on an individual basis.

Increased adrenocortical activity in patients with vasovagal syncope.

OBJECTIVE: Syncope is a transient loss of consciousness resulting from cerebral hypoperfusion. Vasovagal syncope (VVS) is a form of orthostatic intolerance (OI). Its clinical signs such as dizziness and hypotension may mimic symptoms of adrenal insufficiency. The objective of this study was to evaluate the adrenal gland function in patients with vasovagal syncope after stimulation with synthetic adrenocorticotropic hormone (ACTH). DESIGN: Case-control study on patients with VVS and healthy controls. METHODS: The study involved 42 participants, including 27 patients diagnosed with VVS using the head-up tilt test and 15 healthy individuals with no history of syncope or any orthostatic symptoms. Serum cortisol and aldosterone concentrations were measured under basal conditions and at 30 and 60 min after intramuscular ACTH stimulation. RESULTS: Patients with VVS had significantly higher cortisol levels at baseline (441 ± 143 vs. 331 ± 84.7 nmol/L, p = 0.01), at 30 min (802 ± 143 vs. 686 ± 105 nmol/L, p = 0.01) and at 60 min (931 ± 141 nmol/L vs. 793 ± 147 nmol/L, p = 0.001) after ACTH administration (Synacthen 250 µg). Plasma aldosterone increased after ACTH stimulation, but did not show significant differences among groups. Furthermore, there was also no significant correlation between cortisol levels and blood pressure or heart rate. CONCLUSION: Patients diagnosed with VVS have higher cortisol levels both at baseline and after ACTH stimulation. This finding indicates that individuals with VVS have higher adrenocortical activity potentially as a response to the orthostatic stress induced by syncope, which acts as a stressful stimulus on the autonomic nervous system.