Postoperative Adrenal Crisis and Malignant Arrhythmias Associated with an Ectopic ACTH-Secreting Thymic Neuroendocrine Tumor: A Case Report and Literature Review

Postoperative Adrenal Crisis and Malignant Arrhythmias Associated with an Ectopic ACTH-Secreting Thymic Neuroendocrine Tumor: A Case Report and Literature Review | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Case Report Postoperative Adrenal Crisis and Malignant Arrhythmias Associated with an Ectopic ACTH-Secreting Thymic Neuroendocrine Tumor: A Case Report and Literature Review FeiXiang Ling, Meng Wu, Guo Yu, RiMei Zhou, LiKun Han, Jia Wang, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7969135/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 24 Jan, 2026 Read the published version in BMC Endocrine Disorders → Version 1 posted 10 You are reading this latest preprint version Abstract Background: Thymic neuroendocrine tumors associated with ectopic adrenocorticotropic hormone (ACTH) syndrome are exceedingly rare, and postoperative adrenal crisis presenting with malignant arrhythmias as the initial manifestation is even more uncommon. As a result, evidence to guide early recognition and management remains limited. Case presentation: This article reports a novel case of an ectopic ACTH-secreting thymic neuroendocrine tumor, complicated by postoperative adrenal crisis, with recurrent malignant arrhythmias. Following tumor resection, the patient developed profound shock accompanied by recurrent malignant arrhythmias, which improved significantly after prompt initiation of glucocorticoid administration and ventricular rate control. Conclusions: Adrenal crisis often presents with nonspecific clinical symptoms, predisposing it to delayed or missed diagnosis. However, during the perioperative management of ectopic ACTH-secreting neuroendocrine tumors, inappropriate glucocorticoid administration can trigger an adrenal crisis that may rapidly progress to life-threatening complications, including malignant arrhythmias, shock, and acute respiratory failure. Therefore, clinicians should aim to recognize this risk at the earliest possible stage. A multidisciplinary approach during the perioperative period remains essential to ensure timely and individualized glucocorticoid replacement therapy, thereby optimizing patient outcomes. ectopic ACTH thymic neuroendocrine tumor malignant arrhythmia adrenal crisis glucocorticoid Figures Figure 1 Figure 2 Figure 3 1 Background Neuroendocrine tumors (NETs) are a heterogeneous group of neoplasms that arise from neuroendocrine cells and peptidergic neurons. Although relatively uncommon, they account for approximately 2% of all malignancies, occurring most frequently in the gastrointestinal tract and respiratory system [ 1 ] Thymic neuroendocrine tumors (TNETs) represent the rarest and most heterogeneous subtype within this group. Classified as mediastinal epithelial tumors, they constitute only 2%–5% of thymic tumors and 0.5% of all NETs [ 2 , 3 ] . TNETs typically affect older men and are characterized by aggressive biological behavior and poor prognoses [ 4 ] . Ectopic adrenocorticotropic hormone syndrome (EAS) is a distinct form of Cushing syndrome (CS) that belongs to the adrenocorticotropic hormone (ACTH)-dependent subtype. This condition results from the excessive secretion of biologically active ACTH or ACTH analogs by non-pituitary tumors. This ectopic hormone production persistently stimulates adrenal cortex hyperplasia, leading to hypersecretion of cortisol and subsequent debilitating clinical symptoms. Among adult patients with CS, EAS accounts for 12% to 17% of cases, thymic carcinoids are exceptionally rare and represent only 2% to 4% cases [ 5 , 6 ] . Adrenal crisis (AC) is a life-threatening condition that occurs in patients with primary or secondary adrenal cortical insufficiency. Precipitating factors include surgery, stress, infection, or abrupt withdrawal of hormones, all of which can lead to a critical deficiency in adrenal hormone secretion. Glucocorticoid replacement therapy, correction of electrolyte imbalances, and symptomatic management are effective interventions for alleviating distressing symptoms. However, AC often presents acutely, with nonspecific features. This diagnostic challenge is further heightened under general anesthesia, where anesthetic agents can mask key symptoms such as nausea and abdominal pain. In addition, limited physician awareness and intraoperative complications—such as massive bleeding, hemorrhagic shock, or septic shock—frequently contribute to delayed diagnosis and treatment. Such delays can result in devastating outcomes, including malignant arrhythmias, profound shock, and death. This article reports a critical case of a patient with an ectopic ACTH-secreting thymic neuroendocrine tumor who developed postoperative AC complicated by recurrent malignant arrhythmias. Given the complexity of the case and the patient's unstable condition, timely diagnosis and aggressive management were crucial, as failure to intervene carried a grave prognosis. To our knowledge, this is the first reported case in which postoperative AC following resection of an ectopic ACTH-secreting thymic neuroendocrine tumor manifested as recurrent malignant arrhythmias, distinguishing it from previously reported cases that primarily presented with shock or respiratory failure. 2 Case presentation Patient (male, 52 years old) was admitted to the Endocrinology Department of our hospital on March 17, 2025. The main symptom was weakness in both lower limbs for 2 months. His past medical history included untreated hypokalemia diagnosed on February 24, 2025, alongside hypertension and diabetes for more than 2 months. Blood pressure was adequately controlled with daily medication, and the patient denied the use of exogenous hormones. On examination, vital signs were as follows: temperature 36.3°C, pulse 67 beats per minute, respiration rate 20 breaths per minute, and blood pressure 132/79 mmHg. His weight was 74 kg, with a BMI of 25.6 kg/m². The remainder of the physical examination was unremarkable. Laboratory evaluation showed a glycated hemoglobin level of 6.4% at admission, electrolyte potassium ion: 2.67 mmol/L. Endocrine test results are presented in Table 1 . Table 1 Preoperative Endocrine Profile Evaluation in Patients Parameter 8:00 16:00 23:59 Reference value Cortisol before the experiment 41.385 34.936 29.757 AM:4.26–24.85;4PM:2.9–17.3; 12PM:0–6.72 (µg/dL) ACTH before the experiment 278.641 226.924 181.962 7.2–63.4 (pg/mL) Low-dose dexamethasone suppression test cortisol 50.259 AM:4.26–24.85;4PM:2.9–17.3; 12PM:0–6.72 (µg/dL) 24-hour urine cortisol 1260.00 50–437 µg/24h ACTH 195.017 7.2–63.4(pg/mL) High-dose dexamethasone suppression test cortisol > 60.000 AM:4.26–24.85; 4PM:2.9–17.3; 12PM:0–6.72 (µg/dL) 24-hour urine cortisol 1320.00 50–437 µg/24h ACTH 249.933 7.2–63.4 (pg/mL) Thyroid function FT3 4.34 3.1–6.8 (pmol/L) FT4 20.6 12–22 (pmol/L) TSH 0.164 0.27–4.2 (µIU/mL) ACTH: adrenocorticotropic hormone; FT3: free triiodothyronine; FT4: free thyroxine; TSH: thyroid-stimulating hormone; Both low- and high-dose dexamethasone suppression tests failed to achieve cortisol suppression. Routine blood tests, liver and kidney function tests, cardiac echocardiography, electrocardiography, and pulmonary function testing revealed no abnormalities. However, chest computed tomography (CT) performed on March 29, 2025 (plain and contrast-enhanced) demonstrated a space-occupying lesion in the anterior superior mediastinum, highly suggestive of thymoma (Figs. 1 a, b). Cranial magnetic resonance imaging excluded the presence of a pituitary tumor, thereby ruling out pituitary ACTH secretion as a potential cause. Therefore, the endocrinology department diagnosed the patient with ectopic ACTH and considered that the source of the thymus lesion was likely to be the cause of the problem. On March 30th, the patient was reluctant to undergo the thymus lesion surgery immediately due to personal reasons. On May 22nd, the patient went to the thoracic surgery department for surgical treatment on his own. The patient underwent median thoracotomy for resection of the mediastinal tumor under general anesthesia on May 26th. The preoperative vital signs of the patient remained stable. Invasive arterial pressure monitoring was established via radial artery puncture under local anesthesia, and central venous access was obtained through right internal jugular vein cannulation. Anesthesia was induced with intravenous midazolam, fentanyl, rocuronium, etomidate, and oxycodone, followed by tracheal intubation and mechanical ventilation. Anesthesia was maintained with propofol, remifentanil, and intermittent boluses of rocuronium. Following standard disinfection and draping, the surgery was performed. The mediastinal tumor, along with surrounding adipose tissue, was meticulously dissected and completely excised. Intraoperatively, invasive blood pressure remained stable within the range of 120–170/60–90 mmHg. Electrolyte analysis revealed a potassium level of 2.90 mmol/L, while blood glucose and other biochemical parameters showed no significant changes. Estimated blood loss was approximately 100 mL. Two hours postoperatively, intravenous hydrocortisone (100 mg daily) was initiated, and electrolyte imbalances were actively corrected. Pathological examination (Figs. 2 a, b) identified a neuroendocrine tumor within the mediastinal fat, displaying histological features suggestive of an atypical carcinoid. The tumor measured 10 cm × 7 cm × 5 cm. Immunohistochemistry showed the following profile: CK(+); CgA(+); Syn(+); CD56(+); CD117(+-); TTF-1(-); CD5(-); P63(-); Ki67 (positive in 20% of tumor cells). On postoperative day two, the patient experienced three distinct episodes of malignant arrhythmia, with heart rate surging to 200 beats per minute (electrocardiograms shown in Figs. 3 a, b). During the third episode, heart rate again reached 200 bpm and was accompanied by an alarming fall in blood pressure to 60/48 mmHg. Urgent blood gas analysis revealed no abnormalities in electrolyte concentrations, lactate levels, body temperature, or pathogen screening. The results of the infection indicators test for the patient at that time showed an elevated leukocyte count (12.81×10 9 /L) and an elevated high sensitivity C-reactive protein (57.18 mg/L) level, and a procalcitonin ( 2.96 ng/mL) level. Aggressive management included amiodarone for ventricular rate control, fluid resuscitation with 3,000 mL, and vasopressor support. Despite these interventions, the patient showed no clinical improvement. Consciousness deteriorated significantly, and peripheral oxygen saturation decreased to 88%. Urgent consultations with Endocrinology and the Intensive Care Unit (ICU) were requested, leading to a critical diagnosis of AC, supported by profoundly low serum cortisol (3.803 nmol·L⁻¹) and ACTH < 1 ng/L. With the family's consent, the patient was swiftly transferred to the ICU. On admission, emergent interventions were initiated, including tracheal intubation, mechanical ventilation, sedation and analgesia, norepinephrine infusion to stabilize blood pressure, intravenous hydrocortisone (300 mg/24 hours), piperacillin-tazobactam for infection control, strict glycemic management, and comprehensive organ function support. Following admission, the patient experienced three recurrent episodes of atrial fibrillation accompanied by hypotension. Sinus rhythm was restored promptly with electrical cardioversion, after which blood pressure stabilized (Figs. 3 c, d). Blood gas, electrolyte and lactate levels, rechecked during each episode, revealed no abnormalities. Intravenous hydrocortisone (300 mg/24 hours) was continued for 5 days, after which the dose was gradually tapered to 100 mg once daily, then 40 mg every 12 hours, and subsequently 30 mg every 12 hours via intravenous drip. Therapy was later transitioned to oral hydrocortisone, with standard replacement dosing of 20 mg, 10 mg, and 10 mg administered at breakfast, lunch, and dinner, respectively. The vital signs of the patient progressively stabilized. Comprehensive medical interventions were carried out to correct internal environmental disorders, strengthen anti-infection therapy, and support organ function alongside comprehensive nutritional care. Hydrocortisone dosing was gradually tapered, and vasoactive medications were carefully adjusted based on continuous blood pressure monitoring. Following a demanding 12-day ICU course characterized by steady clinical improvement, the patient was transferred to a general ward and eventually discharged. 3 Discussion and Conclusions Clinical studies have identified more than 15 distinct tumor types of diverse origins associated with ectopic ACTH syndrome [ 7 ] . Most of these tumors arise in the lungs, pancreas, or thymus, most commonly as NETs [ 8 , 9 ] . The typical manifestations include lung and thymic carcinoids, with occasional reports of multiple small pulmonary lesions [ 6 ] . NETs originate from neuroendocrine cells and may secrete hormones or bioactive substances such as ACTH, thereby inducing ectopic ACTH syndrome. Patients with this syndrome frequently present with clinical features such as central obesity, purple striae on the skin, hirsutism, refractory hypertension, hypokalemia with muscle weakness, hyperlipidemia, and diabetes [ 10 ] . This patient presented the following characteristics: (i) middle-aged male, with a short disease course and acute onset; (ii) the typical clinical manifestations of Cushing's syndrome were relatively few, mainly presenting as hypokalemia and weakness in the lower extremities. (iii) markedly elevated cortisol levels with loss of circadian rhythm; failure of cortisol suppression with low-dose dexamethasone testing; persistently elevated ACTH levels without suppression after high-dose dexamethasone testing; (iv) enhanced CT scan demonstrating a well-defined thymic mass; and (v) pathological confirmation of a thymic NET. Collectively, these findings establish the diagnosis of a thymic NET associated with ectopic ACTH syndrome. EAS represents a rare subtype of CS, yet recent years have witnessed a marked increase in reported cases. Global medical consensus now recognizes this condition [ 10 ] . Current expert recommendations emphasize that early detection and complete resection of the ectopic tumor remain the optimal therapeutic strategy [ 11 , 12 ] . When the primary lesion is unresectable, treatment options include pharmacological intervention or surgical resection of the target glands, followed by essential glucocorticoid replacement therapy [ 11 , 13 ] . However, medical therapy is frequently limited by poor patient tolerance to adverse effects, and in such cases, surgical excision of the affected glands has emerged as a practical alternative [ 13 ] . Excessive ACTH secretion in patients with EAS results in a precipitous decline of both cortisol and ACTH levels following resection of the ectopic tumor. At this point, due to the insufficient supplementation of exogenous hydrocortisone and the increased demand of the body caused by surgical stress, the large amount of endogenous cortisol (stored in the circulation) remaining in the body before the surgery can still meet the basic needs. However, within 12–66 hours after the surgery, the remaining cortisol is basically depleted, and the serum cortisol often drops below 20 µg/L. This stage is the peak period for adrenal crisis, and intensified glucocorticoid replacement therapy is required [ 14 ] . Secondary adrenal insufficiency due to ACTH deficiency, though rare, affects approximately one in every ten thousand children and can arise from either congenital or acquired causes [ 15 ] . Rushworth et al. reported that the incidence of AC increases with advancing age, with annual hospitalization rates reaching 24.3 per 100,000 individuals aged 60–69 years [ 16 ] . Similarly, a prospective two-year German study involving 400 patients revealed an incidence of 8.3 AC events per 100 patient-years, with an associated mortality rate of 6.3% [ 17 ] . Early identification of AC is critical to improving patient outcomes. Allolio et al [ 18 ] defined AC as the presence of two or more symptoms, such as nausea, vomiting, profound fatigue, fever, drowsiness, hyponatremia, hyperkalemia, or hypotension. However, manifestations, such as hypotension, fever, and shock, lack specificity and are frequently misdiagnosed as septic shock. In the present case, the patient's blood tests revealed only mild elevations in infection markers, including white blood cells and procalcitonin. These findings align with typical postoperative reactive changes and do not support the profile of severe infection-induced septic shock. Furthermore, patients with septic shock often develop oliguria due to impaired renal perfusion. In contrast, despite profound hypotension, this patient maintained a daily urine output of 2000–5000 mL, which was inconsistent with septic shock. No unified diagnostic standard exists for AC. Its onset is abrupt, and its clinical manifestations are diverse and nonspecific [ 19 ] . To date, only one case of AC following surgery for a thymic neuroendocrine tumor has been reported in the English-language literature [ 20 ] ; that case manifested as acute respiratory failure and shock. What distinguishes the present report is the unusual recurrence of atrial tachycardia. Previous studies have shown that adrenal insufficiency can prolong the QT interval and trigger polymorphic ventricular tachycardia [ 21 , 22 ] . However, the exact mechanism through which AC influences atrial electrophysiology and precipitates atrial tachycardia remains unclear [ 23 ] . Two potential pathways may have contributed to the clinical course in this case. First, preoperatively, the ectopic ACTH-secreting tumor induced hypercortisolism and hypokalemia, leading to myocardial injury and increased susceptibility to arrhythmias. Second, following tumor resection, ACTH levels dropped precipitously, and the long-suppressed hypothalamic-pituitary-adrenal axis could not immediately compensate, resulting in adrenal atrophy and insufficient cortisol secretion. Cortisol plays a critical role in regulating intracellular calcium homeostasis. Rao et al. [ 24 ] demonstrated that adrenalectomized rats showed impaired sarcoplasmic reticulum calcium uptake, which was restored with exogenous cortisol supplementation. In the present patient, paroxysmal atrial tachycardia accompanied by profuse sweating occurred repeatedly during postoperative transfer to the ICU. Prompt treatment with high-dose glucocorticoids (with increased dosage and frequency), aggressive fluid resuscitation to correct dehydration, and electrical cardioversion rapidly normalized physiological parameters and terminated the tachycardia. This response not only confirmed the diagnosis of AC but also demonstrated that AC can serve as a reversible cause of atrial tachycardia. Following resection of ectopic ACTH-secreting tumors, consensus supports the use of glucocorticoid supplementation to prevent AC. However, no unified standard currently exists for hormone replacement plans in the perioperative period [ 10 ] . Hydrocortisone remains the preferred drug because of its combined glucocorticoid and mineralocorticoid activity. Studies have shown that daily cortisol secretion in healthy individuals is approximately 15–30 mg, but secretion can rise to 100–300 mg under stress to meet metabolic demands. When adrenal function is impaired or the gland is surgically removed, the body cannot mount this compensatory increase, thereby predisposing patients to AC. In this patient, long-term hypercortisolemia caused severe disturbances in metabolism, immune function, and electrolyte balance. These pathological and physiological changes were not fully assessed and corrected before surgery. The tumor exhibited extensive adhesion to surrounding tissues, which made resection technically challenging, prolonged operative time, and increased intraoperative bleeding. However, the plasma half-life of hydrocortisone is only about 1.5 hours, yet supplementation during surgery was neither timely nor adequate. In addition, limited awareness among surgeons of the increased demand for glucocorticoids during surgical stress was also a contributing factor. The combined effect of these elements ultimately led to AC and recurrent malignant arrhythmias. The combined effect of these elements ultimately led to AC and recurrent malignant arrhythmias. Therefore, perioperative guidelines for glucocorticoid management in patients with adrenal cortical insufficiency recommend that adults with any underlying cause of the condition receive a 100 mg intravenous hydrocortisone bolus at induction of anesthesia, followed by a continuous infusion of 200 mg over 24 hours [ 15 ] . Mishra et al [ 25 ] further proposed administering hydrocortisone at 30 mg/h for the first 6 hours after surgery, supplemented with 200 mg at 10 mg/h on the first postoperative day. However, a recent systematic review of 71 studies demonstrated that cortisol fluctuations during the perioperative period were highest in patients undergoing open surgery or general anesthesia [ 26 ] . Moreover, significant interindividual variability in glucocorticoid responses means that some patients remain undertreated and fail to achieve target cortisol concentrations [ 27 ] . Woodcock et al [ 15 ] emphasized that, beyond continuous perioperative treatment, a balanced and individualized supplementation strategy is essential, requiring careful consideration of dosage, frequency, treatment duration, and stress levels. Given the plasma half-life of hydrocortisone, continuous intravenous administration during surgery is critical, followed by sequential oral dosing with gradual postoperative tapering [ 28 ] . In conclusion, for patients with ectopic ACTH syndrome undergoing thymic tumor resection, glucocorticoid supplementation must be meticulously individualized to prevent an abrupt postoperative cortisol decline, which can precipitate relative cortisol deficiency and AC. Regardless of the supplementation plan selected, comprehensive perioperative monitoring of endocrine hormone levels is mandatory. If relevant clinical symptoms emerge, AC due to insufficient glucocorticoid supplementation should be a primary consideration, warranting immediate adjustment of therapy. Finally, large-scale clinical studies to establish the optimal glucocorticoid dosage and frequency in patients with ectopic ACTH syndrome after tumor resection remain limited. High-quality research is urgently needed to provide stronger evidence-based guidance. In conclusion, when ectopic ACTH syndrome is suspected, comprehensive endocrine hormone level assessments and targeted imaging are critical for accurate diagnosis and for establishing a solid foundation for preoperative planning. Prophylactic suppression of ACTH is of paramount importance. Surgical management of ectopic ACTH-secreting tumors requires multidisciplinary collaboration. During the perioperative period, glucocorticoid dosing must be administered precisely and adjusted according to the patient's clinical status. Clinicians should remain aware that the manifestations of AC are often subtle. In patients with EAS undergoing resection of ectopic ACTH tumors who develop sudden, life-threatening arrhythmias or shock, a high index of suspicion for AC is essential. Immediate initiation of glucocorticoid replacement therapy is critical to preserve life. Abbreviations AC adrenal crisis ACTH adrenocorticotropic hormone CS Cushing's syndrome CT computed tomography EAS ectopic adrenocorticotropic hormone syndrome ECG electrocardiograph FT3 free triiodothyronine FT4 free thyroxine HB hemoglobin ICU intensive care unit NET neuroendocrine tumor TNET thymic neuroendocrine tumors TSH thyroid-stimulating hormone Declarations Clinical trial number: Not applicable. Ethics approval and consent to participate: Not applicable. Consent for publication: Written informed consent was obtained for the publication of this case report and accompanying images. Conflict of Interest The authors declare that they have no competing interests. Funding This study was supported by the Guangxi Medical and Health Key Cultivation Discipline Construction Project. Author Contribution 1. FX-L: Conceptualization & study design, Writing—original draft.LB-M: Corresponding author responsibilities, supervision, Writing—review & editing. A-JJ: Corresponding author responsibilities, supervision, Writing—review & editing. MW and GY: Data collection & curation. LK-H,W-J and RM-Z: Writing – review & editing. All authors read and approved the final version of the manuscript. Acknowledgement We express our gratitude to colleagues from the Intensive Care Unit of the First Affiliated Hospital of Guilin Medical University for their valuable suggestions, which strengthened this paper. Availability of data and materials The datasets used and analyzed in this study are available from the corresponding author upon reasonable request. 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Supplementary Files CAREchecklistEnglish2013.pdf Cite Share Download PDF Status: Published Journal Publication published 24 Jan, 2026 Read the published version in BMC Endocrine Disorders → Version 1 posted Editorial decision: Revision requested 02 Dec, 2025 Reviews received at journal 28 Nov, 2025 Reviews received at journal 13 Nov, 2025 Reviewers agreed at journal 13 Nov, 2025 Reviewers agreed at journal 13 Nov, 2025 Reviewers invited by journal 11 Nov, 2025 Editor invited by journal 06 Nov, 2025 Editor assigned by journal 30 Oct, 2025 Submission checks completed at journal 30 Oct, 2025 First submitted to journal 28 Oct, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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16:42:55","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-7969135/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7969135/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s12902-026-02171-8","type":"published","date":"2026-01-24T15:58:45+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":96555598,"identity":"ef180294-9d7a-47be-b127-7965c1551158","added_by":"auto","created_at":"2025-11-23 11:39:06","extension":"jpg","order_by":0,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":3786144,"visible":true,"origin":"","legend":"","description":"","filename":"Figure1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7969135/v1/b21f250a526570d6e3799c49.jpg"},{"id":96555597,"identity":"1fa80841-6117-44a2-a333-448f9fb32a8c","added_by":"auto","created_at":"2025-11-23 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11:39:07","extension":"xml","order_by":13,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":76739,"visible":true,"origin":"","legend":"","description":"","filename":"1afded8840a2444eac1879b5b880fb9a1structuring.xml","url":"https://assets-eu.researchsquare.com/files/rs-7969135/v1/885c7214bdc10806766f80fb.xml"},{"id":96605002,"identity":"298a1153-5ef3-4a1f-a372-b8c7ef0e2733","added_by":"auto","created_at":"2025-11-24 09:17:20","extension":"html","order_by":14,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":83341,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-7969135/v1/cd0ea252e515cfe983055b0c.html"},{"id":96555599,"identity":"5b813e62-5b18-4202-a755-1fdd86cdec37","added_by":"auto","created_at":"2025-11-23 11:39:06","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":3786144,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003e(a, b)\u003c/strong\u003eAn enhanced CT scan of the chest vividly revealed a thymic mass extending into the anterior mediastinum and producing a pronounced mass effect.\u003c/p\u003e","description":"","filename":"Figure1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7969135/v1/1c512e2417d170b5f4f07a72.jpg"},{"id":96604735,"identity":"7e0b32a2-f98b-476f-9778-d8c7a0b51a70","added_by":"auto","created_at":"2025-11-24 09:14:43","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":10090298,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003e(a, b)\u003c/strong\u003e Pathological findings of the mediastinal mass biopsy stained with Hematoxylin and Eosin (100×). Immunohistochemistry showed the following profile: CK(+); CgA(+); Syn(+); CD56(+); CD117(+-); TTF-1(-); CD5(-); P63(-); Ki67(positive in 20% of tumor cells).\u003c/p\u003e","description":"","filename":"Figure2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7969135/v1/d77d1610f4032977de40cfd9.jpg"},{"id":96555613,"identity":"c90b3a92-50b1-41f3-87fd-9978fab4e138","added_by":"auto","created_at":"2025-11-23 11:39:07","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":13238720,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003e(a, b)\u003c/strong\u003eRecurrent ECG manifestations of atrial flutter were observed on the patient's second postoperative day. \u003cstrong\u003e(c)\u003c/strong\u003eThe ECG demonstrates the reemergence of atrial fibrillation after transfer to the ICU. \u003cstrong\u003e(d)\u003c/strong\u003eThe ECG captured following electrical cardioversion successfully restored hemodynamic stability after the patient's sixth episode of atrial fibrillation.\u003c/p\u003e","description":"","filename":"Figure3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7969135/v1/77a76a406009b4b810796e23.jpg"},{"id":101152559,"identity":"fc59dadb-339b-4a97-839e-0629ef53f618","added_by":"auto","created_at":"2026-01-26 16:12:21","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":27676103,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7969135/v1/c93c750e-84d8-48d4-b561-774f60062160.pdf"},{"id":96555596,"identity":"a7e547d1-25e9-4bc8-8dc8-1b1cbb178864","added_by":"auto","created_at":"2025-11-23 11:39:06","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":783360,"visible":true,"origin":"","legend":"","description":"","filename":"CAREchecklistEnglish2013.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7969135/v1/0eee7c833edb77a6e4d74c48.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Postoperative Adrenal Crisis and Malignant Arrhythmias Associated with an Ectopic ACTH-Secreting Thymic Neuroendocrine Tumor: A Case Report and Literature Review","fulltext":[{"header":"1 Background","content":"\u003cp\u003eNeuroendocrine tumors (NETs) are a heterogeneous group of neoplasms that arise from neuroendocrine cells and peptidergic neurons. Although relatively uncommon, they account for approximately 2% of all malignancies, occurring most frequently in the gastrointestinal tract and respiratory system\u003csup\u003e[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]\u003c/sup\u003e Thymic neuroendocrine tumors (TNETs) represent the rarest and most heterogeneous subtype within this group. Classified as mediastinal epithelial tumors, they constitute only 2%\u0026ndash;5% of thymic tumors and 0.5% of all NETs \u003csup\u003e[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]\u003c/sup\u003e. TNETs typically affect older men and are characterized by aggressive biological behavior and poor prognoses \u003csup\u003e[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eEctopic adrenocorticotropic hormone syndrome (EAS) is a distinct form of Cushing syndrome (CS) that belongs to the adrenocorticotropic hormone (ACTH)-dependent subtype. This condition results from the excessive secretion of biologically active ACTH or ACTH analogs by non-pituitary tumors. This ectopic hormone production persistently stimulates adrenal cortex hyperplasia, leading to hypersecretion of cortisol and subsequent debilitating clinical symptoms. Among adult patients with CS, EAS accounts for 12% to 17% of cases, thymic carcinoids are exceptionally rare and represent only 2% to 4% cases \u003csup\u003e[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eAdrenal crisis (AC) is a life-threatening condition that occurs in patients with primary or secondary adrenal cortical insufficiency. Precipitating factors include surgery, stress, infection, or abrupt withdrawal of hormones, all of which can lead to a critical deficiency in adrenal hormone secretion. Glucocorticoid replacement therapy, correction of electrolyte imbalances, and symptomatic management are effective interventions for alleviating distressing symptoms. However, AC often presents acutely, with nonspecific features. This diagnostic challenge is further heightened under general anesthesia, where anesthetic agents can mask key symptoms such as nausea and abdominal pain. In addition, limited physician awareness and intraoperative complications\u0026mdash;such as massive bleeding, hemorrhagic shock, or septic shock\u0026mdash;frequently contribute to delayed diagnosis and treatment. Such delays can result in devastating outcomes, including malignant arrhythmias, profound shock, and death. This article reports a critical case of a patient with an ectopic ACTH-secreting thymic neuroendocrine tumor who developed postoperative AC complicated by recurrent malignant arrhythmias. Given the complexity of the case and the patient's unstable condition, timely diagnosis and aggressive management were crucial, as failure to intervene carried a grave prognosis. To our knowledge, this is the first reported case in which postoperative AC following resection of an ectopic ACTH-secreting thymic neuroendocrine tumor manifested as recurrent malignant arrhythmias, distinguishing it from previously reported cases that primarily presented with shock or respiratory failure.\u003c/p\u003e"},{"header":"2 Case presentation","content":"\u003cp\u003ePatient (male, 52 years old) was admitted to the Endocrinology Department of our hospital on March 17, 2025. The main symptom was weakness in both lower limbs for 2 months. His past medical history included untreated hypokalemia diagnosed on February 24, 2025, alongside hypertension and diabetes for more than 2 months. Blood pressure was adequately controlled with daily medication, and the patient denied the use of exogenous hormones. On examination, vital signs were as follows: temperature 36.3\u0026deg;C, pulse 67 beats per minute, respiration rate 20 breaths per minute, and blood pressure 132/79 mmHg. His weight was 74 kg, with a BMI of 25.6 kg/m\u0026sup2;. The remainder of the physical examination was unremarkable. Laboratory evaluation showed a glycated hemoglobin level of 6.4% at admission, electrolyte potassium ion: 2.67 mmol/L. Endocrine test results are presented in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003ePreoperative Endocrine Profile Evaluation in Patients\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"5\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eParameter\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003e8:00\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003e16:00\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003e23:59\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eReference value\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCortisol before the experiment\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e41.385\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e34.936\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e29.757\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eAM:4.26\u0026ndash;24.85;4PM:2.9\u0026ndash;17.3; 12PM:0\u0026ndash;6.72 (\u0026micro;g/dL)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eACTH before the experiment\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e278.641\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e226.924\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e181.962\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e7.2\u0026ndash;63.4 (pg/mL)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLow-dose dexamethasone suppression test\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ecortisol\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e50.259\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eAM:4.26\u0026ndash;24.85;4PM:2.9\u0026ndash;17.3; 12PM:0\u0026ndash;6.72 (\u0026micro;g/dL)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e24-hour urine cortisol\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e1260.00\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e50\u0026ndash;437 \u0026micro;g/24h\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eACTH\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e195.017\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e7.2\u0026ndash;63.4(pg/mL)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHigh-dose dexamethasone suppression test\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ecortisol\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e\u0026gt;\u0026thinsp;60.000\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eAM:4.26\u0026ndash;24.85; 4PM:2.9\u0026ndash;17.3; 12PM:0\u0026ndash;6.72 (\u0026micro;g/dL)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e24-hour urine cortisol\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e1320.00\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e50\u0026ndash;437 \u0026micro;g/24h\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eACTH\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e249.933\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e7.2\u0026ndash;63.4 (pg/mL)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eThyroid function\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eFT3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e4.34\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e3.1\u0026ndash;6.8 (pmol/L)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eFT4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e20.6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e12\u0026ndash;22 (pmol/L)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTSH\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0.164\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.27\u0026ndash;4.2 (\u0026micro;IU/mL)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"5\"\u003eACTH: adrenocorticotropic hormone; FT3: free triiodothyronine; FT4: free thyroxine; TSH: thyroid-stimulating hormone;\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eBoth low- and high-dose dexamethasone suppression tests failed to achieve cortisol suppression. Routine blood tests, liver and kidney function tests, cardiac echocardiography, electrocardiography, and pulmonary function testing revealed no abnormalities. However, chest computed tomography (CT) performed on March 29, 2025 (plain and contrast-enhanced) demonstrated a space-occupying lesion in the anterior superior mediastinum, highly suggestive of thymoma (Figs.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003ea, b). Cranial magnetic resonance imaging excluded the presence of a pituitary tumor, thereby ruling out pituitary ACTH secretion as a potential cause. Therefore, the endocrinology department diagnosed the patient with ectopic ACTH and considered that the source of the thymus lesion was likely to be the cause of the problem. On March 30th, the patient was reluctant to undergo the thymus lesion surgery immediately due to personal reasons. On May 22nd, the patient went to the thoracic surgery department for surgical treatment on his own. The patient underwent median thoracotomy for resection of the mediastinal tumor under general anesthesia on May 26th. The preoperative vital signs of the patient remained stable. Invasive arterial pressure monitoring was established via radial artery puncture under local anesthesia, and central venous access was obtained through right internal jugular vein cannulation. Anesthesia was induced with intravenous midazolam, fentanyl, rocuronium, etomidate, and oxycodone, followed by tracheal intubation and mechanical ventilation. Anesthesia was maintained with propofol, remifentanil, and intermittent boluses of rocuronium. Following standard disinfection and draping, the surgery was performed. The mediastinal tumor, along with surrounding adipose tissue, was meticulously dissected and completely excised. Intraoperatively, invasive blood pressure remained stable within the range of 120\u0026ndash;170/60\u0026ndash;90 mmHg. Electrolyte analysis revealed a potassium level of 2.90 mmol/L, while blood glucose and other biochemical parameters showed no significant changes. Estimated blood loss was approximately 100 mL. Two hours postoperatively, intravenous hydrocortisone (100 mg daily) was initiated, and electrolyte imbalances were actively corrected. Pathological examination (Figs.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003ea, b) identified a neuroendocrine tumor within the mediastinal fat, displaying histological features suggestive of an atypical carcinoid. The tumor measured 10 cm \u0026times; 7 cm \u0026times; 5 cm. Immunohistochemistry showed the following profile: CK(+); CgA(+); Syn(+); CD56(+); CD117(+-); TTF-1(-); CD5(-); P63(-); Ki67 (positive in 20% of tumor cells). On postoperative day two, the patient experienced three distinct episodes of malignant arrhythmia, with heart rate surging to 200 beats per minute (electrocardiograms shown in Figs.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003ea, b). During the third episode, heart rate again reached 200 bpm and was accompanied by an alarming fall in blood pressure to 60/48 mmHg. Urgent blood gas analysis revealed no abnormalities in electrolyte concentrations, lactate levels, body temperature, or pathogen screening. The results of the infection indicators test for the patient at that time showed an elevated leukocyte count (12.81\u0026times;10\u003csup\u003e9\u003c/sup\u003e/L) and an elevated high sensitivity C-reactive protein (57.18 mg/L) level, and a procalcitonin ( 2.96 ng/mL) level. Aggressive management included amiodarone for ventricular rate control, fluid resuscitation with 3,000 mL, and vasopressor support. Despite these interventions, the patient showed no clinical improvement. Consciousness deteriorated significantly, and peripheral oxygen saturation decreased to 88%. Urgent consultations with Endocrinology and the Intensive Care Unit (ICU) were requested, leading to a critical diagnosis of AC, supported by profoundly low serum cortisol (3.803 nmol\u0026middot;L⁻\u0026sup1;) and ACTH\u0026thinsp;\u0026lt;\u0026thinsp;1 ng/L. With the family's consent, the patient was swiftly transferred to the ICU. On admission, emergent interventions were initiated, including tracheal intubation, mechanical ventilation, sedation and analgesia, norepinephrine infusion to stabilize blood pressure, intravenous hydrocortisone (300 mg/24 hours), piperacillin-tazobactam for infection control, strict glycemic management, and comprehensive organ function support. Following admission, the patient experienced three recurrent episodes of atrial fibrillation accompanied by hypotension. Sinus rhythm was restored promptly with electrical cardioversion, after which blood pressure stabilized (Figs.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003ec, d). Blood gas, electrolyte and lactate levels, rechecked during each episode, revealed no abnormalities. Intravenous hydrocortisone (300 mg/24 hours) was continued for 5 days, after which the dose was gradually tapered to 100 mg once daily, then 40 mg every 12 hours, and subsequently 30 mg every 12 hours via intravenous drip. Therapy was later transitioned to oral hydrocortisone, with standard replacement dosing of 20 mg, 10 mg, and 10 mg administered at breakfast, lunch, and dinner, respectively. The vital signs of the patient progressively stabilized. Comprehensive medical interventions were carried out to correct internal environmental disorders, strengthen anti-infection therapy, and support organ function alongside comprehensive nutritional care. Hydrocortisone dosing was gradually tapered, and vasoactive medications were carefully adjusted based on continuous blood pressure monitoring. Following a demanding 12-day ICU course characterized by steady clinical improvement, the patient was transferred to a general ward and eventually discharged.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003e\u003c/p\u003e"},{"header":"3 Discussion and Conclusions","content":"\u003cp\u003eClinical studies have identified more than 15 distinct tumor types of diverse origins associated with ectopic ACTH syndrome\u003csup\u003e[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]\u003c/sup\u003e. Most of these tumors arise in the lungs, pancreas, or thymus, most commonly as NETs \u003csup\u003e[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]\u003c/sup\u003e. The typical manifestations include lung and thymic carcinoids, with occasional reports of multiple small pulmonary lesions \u003csup\u003e[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]\u003c/sup\u003e. NETs originate from neuroendocrine cells and may secrete hormones or bioactive substances such as ACTH, thereby inducing ectopic ACTH syndrome. Patients with this syndrome frequently present with clinical features such as central obesity, purple striae on the skin, hirsutism, refractory hypertension, hypokalemia with muscle weakness, hyperlipidemia, and diabetes\u003csup\u003e[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]\u003c/sup\u003e. This patient presented the following characteristics: (i) middle-aged male, with a short disease course and acute onset; (ii) the typical clinical manifestations of Cushing's syndrome were relatively few, mainly presenting as hypokalemia and weakness in the lower extremities. (iii) markedly elevated cortisol levels with loss of circadian rhythm; failure of cortisol suppression with low-dose dexamethasone testing; persistently elevated ACTH levels without suppression after high-dose dexamethasone testing; (iv) enhanced CT scan demonstrating a well-defined thymic mass; and (v) pathological confirmation of a thymic NET. Collectively, these findings establish the diagnosis of a thymic NET associated with ectopic ACTH syndrome.\u003c/p\u003e\u003cp\u003eEAS represents a rare subtype of CS, yet recent years have witnessed a marked increase in reported cases. Global medical consensus now recognizes this condition \u003csup\u003e[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]\u003c/sup\u003e. Current expert recommendations emphasize that early detection and complete resection of the ectopic tumor remain the optimal therapeutic strategy \u003csup\u003e[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]\u003c/sup\u003e. When the primary lesion is unresectable, treatment options include pharmacological intervention or surgical resection of the target glands, followed by essential glucocorticoid replacement therapy\u003csup\u003e[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]\u003c/sup\u003e. However, medical therapy is frequently limited by poor patient tolerance to adverse effects, and in such cases, surgical excision of the affected glands has emerged as a practical alternative\u003csup\u003e[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]\u003c/sup\u003e. Excessive ACTH secretion in patients with EAS results in a precipitous decline of both cortisol and ACTH levels following resection of the ectopic tumor. At this point, due to the insufficient supplementation of exogenous hydrocortisone and the increased demand of the body caused by surgical stress, the large amount of endogenous cortisol (stored in the circulation) remaining in the body before the surgery can still meet the basic needs. However, within 12\u0026ndash;66 hours after the surgery, the remaining cortisol is basically depleted, and the serum cortisol often drops below 20 \u0026micro;g/L. This stage is the peak period for adrenal crisis, and intensified glucocorticoid replacement therapy is required\u003csup\u003e[\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]\u003c/sup\u003e. Secondary adrenal insufficiency due to ACTH deficiency, though rare, affects approximately one in every ten thousand children and can arise from either congenital or acquired causes \u003csup\u003e[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]\u003c/sup\u003e. Rushworth et al. reported that the incidence of AC increases with advancing age, with annual hospitalization rates reaching 24.3 per 100,000 individuals aged 60\u0026ndash;69 years\u003csup\u003e[\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]\u003c/sup\u003e. Similarly, a prospective two-year German study involving 400 patients revealed an incidence of 8.3 AC events per 100 patient-years, with an associated mortality rate of 6.3%\u003csup\u003e[\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eEarly identification of AC is critical to improving patient outcomes. Allolio et al\u003csup\u003e[\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]\u003c/sup\u003e defined AC as the presence of two or more symptoms, such as nausea, vomiting, profound fatigue, fever, drowsiness, hyponatremia, hyperkalemia, or hypotension. However, manifestations, such as hypotension, fever, and shock, lack specificity and are frequently misdiagnosed as septic shock. In the present case, the patient's blood tests revealed only mild elevations in infection markers, including white blood cells and procalcitonin. These findings align with typical postoperative reactive changes and do not support the profile of severe infection-induced septic shock. Furthermore, patients with septic shock often develop oliguria due to impaired renal perfusion. In contrast, despite profound hypotension, this patient maintained a daily urine output of 2000\u0026ndash;5000 mL, which was inconsistent with septic shock. No unified diagnostic standard exists for AC. Its onset is abrupt, and its clinical manifestations are diverse and nonspecific \u003csup\u003e[\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]\u003c/sup\u003e. To date, only one case of AC following surgery for a thymic neuroendocrine tumor has been reported in the English-language literature \u003csup\u003e[\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]\u003c/sup\u003e; that case manifested as acute respiratory failure and shock. What distinguishes the present report is the unusual recurrence of atrial tachycardia. Previous studies have shown that adrenal insufficiency can prolong the QT interval and trigger polymorphic ventricular tachycardia \u003csup\u003e[\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]\u003c/sup\u003e. However, the exact mechanism through which AC influences atrial electrophysiology and precipitates atrial tachycardia remains unclear \u003csup\u003e[\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]\u003c/sup\u003e. Two potential pathways may have contributed to the clinical course in this case. First, preoperatively, the ectopic ACTH-secreting tumor induced hypercortisolism and hypokalemia, leading to myocardial injury and increased susceptibility to arrhythmias. Second, following tumor resection, ACTH levels dropped precipitously, and the long-suppressed hypothalamic-pituitary-adrenal axis could not immediately compensate, resulting in adrenal atrophy and insufficient cortisol secretion. Cortisol plays a critical role in regulating intracellular calcium homeostasis. Rao et al.\u003csup\u003e[\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]\u003c/sup\u003e demonstrated that adrenalectomized rats showed impaired sarcoplasmic reticulum calcium uptake, which was restored with exogenous cortisol supplementation. In the present patient, paroxysmal atrial tachycardia accompanied by profuse sweating occurred repeatedly during postoperative transfer to the ICU. Prompt treatment with high-dose glucocorticoids (with increased dosage and frequency), aggressive fluid resuscitation to correct dehydration, and electrical cardioversion rapidly normalized physiological parameters and terminated the tachycardia. This response not only confirmed the diagnosis of AC but also demonstrated that AC can serve as a reversible cause of atrial tachycardia.\u003c/p\u003e\u003cp\u003eFollowing resection of ectopic ACTH-secreting tumors, consensus supports the use of glucocorticoid supplementation to prevent AC. However, no unified standard currently exists for hormone replacement plans in the perioperative period \u003csup\u003e[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]\u003c/sup\u003e. Hydrocortisone remains the preferred drug because of its combined glucocorticoid and mineralocorticoid activity. Studies have shown that daily cortisol secretion in healthy individuals is approximately 15\u0026ndash;30 mg, but secretion can rise to 100\u0026ndash;300 mg under stress to meet metabolic demands. When adrenal function is impaired or the gland is surgically removed, the body cannot mount this compensatory increase, thereby predisposing patients to AC. In this patient, long-term hypercortisolemia caused severe disturbances in metabolism, immune function, and electrolyte balance. These pathological and physiological changes were not fully assessed and corrected before surgery. The tumor exhibited extensive adhesion to surrounding tissues, which made resection technically challenging, prolonged operative time, and increased intraoperative bleeding. However, the plasma half-life of hydrocortisone is only about 1.5 hours, yet supplementation during surgery was neither timely nor adequate. In addition, limited awareness among surgeons of the increased demand for glucocorticoids during surgical stress was also a contributing factor. The combined effect of these elements ultimately led to AC and recurrent malignant arrhythmias. The combined effect of these elements ultimately led to AC and recurrent malignant arrhythmias. Therefore, perioperative guidelines for glucocorticoid management in patients with adrenal cortical insufficiency recommend that adults with any underlying cause of the condition receive a 100 mg intravenous hydrocortisone bolus at induction of anesthesia, followed by a continuous infusion of 200 mg over 24 hours \u003csup\u003e[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]\u003c/sup\u003e. Mishra et al\u003csup\u003e[\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]\u003c/sup\u003e further proposed administering hydrocortisone at 30 mg/h for the first 6 hours after surgery, supplemented with 200 mg at 10 mg/h on the first postoperative day. However, a recent systematic review of 71 studies demonstrated that cortisol fluctuations during the perioperative period were highest in patients undergoing open surgery or general anesthesia\u003csup\u003e[\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]\u003c/sup\u003e. Moreover, significant interindividual variability in glucocorticoid responses means that some patients remain undertreated and fail to achieve target cortisol concentrations \u003csup\u003e[\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]\u003c/sup\u003e. Woodcock et al\u003csup\u003e[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]\u003c/sup\u003e emphasized that, beyond continuous perioperative treatment, a balanced and individualized supplementation strategy is essential, requiring careful consideration of dosage, frequency, treatment duration, and stress levels. Given the plasma half-life of hydrocortisone, continuous intravenous administration during surgery is critical, followed by sequential oral dosing with gradual postoperative tapering\u003csup\u003e[\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]\u003c/sup\u003e. In conclusion, for patients with ectopic ACTH syndrome undergoing thymic tumor resection, glucocorticoid supplementation must be meticulously individualized to prevent an abrupt postoperative cortisol decline, which can precipitate relative cortisol deficiency and AC. Regardless of the supplementation plan selected, comprehensive perioperative monitoring of endocrine hormone levels is mandatory. If relevant clinical symptoms emerge, AC due to insufficient glucocorticoid supplementation should be a primary consideration, warranting immediate adjustment of therapy. Finally, large-scale clinical studies to establish the optimal glucocorticoid dosage and frequency in patients with ectopic ACTH syndrome after tumor resection remain limited. High-quality research is urgently needed to provide stronger evidence-based guidance.\u003c/p\u003e\u003cp\u003eIn conclusion, when ectopic ACTH syndrome is suspected, comprehensive endocrine hormone level assessments and targeted imaging are critical for accurate diagnosis and for establishing a solid foundation for preoperative planning. Prophylactic suppression of ACTH is of paramount importance. Surgical management of ectopic ACTH-secreting tumors requires multidisciplinary collaboration. During the perioperative period, glucocorticoid dosing must be administered precisely and adjusted according to the patient's clinical status. Clinicians should remain aware that the manifestations of AC are often subtle. In patients with EAS undergoing resection of ectopic ACTH tumors who develop sudden, life-threatening arrhythmias or shock, a high index of suspicion for AC is essential. Immediate initiation of glucocorticoid replacement therapy is critical to preserve life.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eAC\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eadrenal crisis\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eACTH\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eadrenocorticotropic hormone\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eCS\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eCushing's syndrome\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eCT\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003ecomputed tomography\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eEAS\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eectopic adrenocorticotropic hormone syndrome\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eECG\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eelectrocardiograph\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eFT3\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003efree triiodothyronine\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eFT4\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003efree thyroxine\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eHB\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003ehemoglobin\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eICU\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eintensive care unit\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eNET\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eneuroendocrine tumor\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eTNET\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003ethymic neuroendocrine tumors\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eTSH\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003ethyroid-stimulating hormone\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eClinical trial number:\u003c/strong\u003e Not applicable.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate:\u003c/strong\u003e\u003cp\u003eNot applicable.\u003c/p\u003e\u003c/p\u003e\u003cp\u003e\u003ch2\u003eConsent for publication:\u003c/h2\u003e\u003cp\u003e Written informed consent was obtained for the publication of this case report and accompanying images.\u003c/p\u003e\u003c/p\u003e\u003cp\u003e\u003ch2\u003eConflict of Interest\u003c/h2\u003e\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\u003c/p\u003e\u003ch2\u003eFunding\u003c/h2\u003e\u003cp\u003eThis study was supported by the Guangxi Medical and Health Key Cultivation Discipline Construction Project.\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003e1. FX-L: Conceptualization \u0026amp;amp; study design, Writing\u0026mdash;original draft.LB-M: Corresponding author responsibilities, supervision, Writing\u0026mdash;review \u0026amp;amp; editing. A-JJ: Corresponding author responsibilities, supervision, Writing\u0026mdash;review \u0026amp;amp; editing. MW and GY: Data collection \u0026amp;amp; curation. LK-H,W-J and RM-Z: Writing \u0026ndash; review \u0026amp;amp; editing. All authors read and approved the final version of the manuscript.\u003c/p\u003e\u003ch2\u003eAcknowledgement\u003c/h2\u003e\u003cp\u003eWe express our gratitude to colleagues from the Intensive Care Unit of the First Affiliated Hospital of Guilin Medical University for their valuable suggestions, which strengthened this paper.\u003c/p\u003e\u003ch2\u003eAvailability of data and materials\u003c/h2\u003e\u003cp\u003eThe datasets used and analyzed in this study are available from the corresponding author upon reasonable request. The data and materials, including all the clinical data of the patient, are included within the article.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eAguilar M, Rose RA, Takawale A, et al. New aspects of endocrine control of atrial fibrillation and possibilities for clinical translation[J]. Cardiovasc Res. 2021;117(7):1645\u0026ndash;61.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eAllolio B. Extensive expertise in endocrinology. Adrenal crisis[J]. Eur J Endocrinol. 2015;172(3):R115\u0026ndash;24.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eArioglu E, Doppman J, Gomes M, et al. Cushing's syndrome caused by corticotropin secretion by pulmonary tumorlets[J]. N Engl J Med. 1998;339(13):883\u0026ndash;6.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBiller BM, Grossman AB, Stewart PM, et al. Treatment of adrenocorticotropin-dependent Cushing's syndrome: a consensus statement[J]. J Clin Endocrinol Metab. 2008;93(7):2454\u0026ndash;62.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eChunharojrith P, Pradniwat K, Kongmalai T. A rare case of ectopic ACTH syndrome caused by primary renal neuroendocrine tumor[J]. Endocrinol Diabetes Metab Case Rep, 2021,2021.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eCui X, Yang L, Li J, et al. Perioperative Endocrine Therapy for Patients with Cushing's Syndrome Undergoing Retroperitoneal Laparoscopic Adrenalectomy[J]. Int J Endocrinol. 2012;2012:983965.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eFleseriu M, Auchus R, Bancos I, et al. Consensus on diagnosis and management of Cushing's disease: a guideline update[J]. Lancet Diabetes Endocrinol. 2021;9(12):847\u0026ndash;75.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eHahner S, Spinnler C, Fassnacht M, et al. High incidence of adrenal crisis in educated patients with chronic adrenal insufficiency: a prospective study[J]. J Clin Endocrinol Metab. 2015;100(2):407\u0026ndash;16.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eHsu CH, Chan JK, Yin CH, et al. Trends in the incidence of thymoma, thymic carcinoma, and thymic neuroendocrine tumor in the United States[J]. PLoS ONE. 2019;14(12):e227197.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eIlias I, Torpy DJ, Pacak K, et al. Cushing's syndrome due to ectopic corticotropin secretion: twenty years' experience at the National Institutes of Health[J]. J Clin Endocrinol Metab. 2005;90(8):4955\u0026ndash;62.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKidd M, Modlin IM, Bodei L, et al. Decoding the Molecular and Mutational Ambiguities of Gastroenteropancreatic Neuroendocrine Neoplasm Pathobiology[J]. Cell Mol Gastroenterol Hepatol. 2015;1(2):131\u0026ndash;53.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKomuro J, Kaneko M, Ueda K, et al. Adrenal insufficiency causes life-threatening arrhythmia with prolongation of QT interval[J]. Heart Vessels. 2016;31(6):1003\u0026ndash;5.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eMa K, Liu Y, Xue Z, et al. Treatment, prognostic markers, and survival in thymic neuroendocrine tumors: A single center experience of 41 patients[J]. Med (Baltim). 2017;96(43):e7842.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eMayberg M, Reintjes S, Patel A, et al. Dynamics of postoperative serum cortisol after transsphenoidal surgery for Cushing's disease: implications for immediate reoperation and remission[J]. J Neurosurg. 2018;129(5):1268\u0026ndash;77.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eMishra AK, Agarwal A, Gupta S, et al. Outcome of adrenalectomy for Cushing's syndrome: experience from a tertiary care center[J]. World J Surg. 2007;31(7):1425\u0026ndash;32.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eNeary NM, Lopez-Chavez A, Abel BS, et al. Neuroendocrine ACTH-producing tumor of the thymus\u0026ndash;experience with 12 patients over 25 years[J]. J Clin Endocrinol Metab. 2012;97(7):2223\u0026ndash;30.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eOronsky B, Ma PC, Morgensztern D, et al. Nothing But NET: A Review of Neuroendocrine Tumors and Carcinomas[J]. Neoplasia. 2017;19(12):991\u0026ndash;1002.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003ePrete A, Yan Q, Al-Tarrah K, et al. The cortisol stress response induced by surgery: A systematic review and meta-analysis[J]. Clin Endocrinol (Oxf). 2018;89(5):554\u0026ndash;67.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eRao MK, Xu A, Narayanan N. Glucocorticoid modulation of protein phosphorylation and sarcoplasmic reticulum function in rat myocardium[J]. Am J Physiol Heart Circ Physiol. 2001;281(1):H325\u0026ndash;33.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eRichardson J. Post-thymectomy collapse: an unusual case of acute adrenal insufficiency[J]. Postgrad Med J. 1995;71(834):242\u0026ndash;4.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eRushworth RL, Torpy DJ. A descriptive study of adrenal crises in adults with adrenal insufficiency: increased risk with age and in those with bacterial infections[J]. BMC Endocr Disord. 2014;14:79.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eTorpy DJ. Commentary on article: Adrenal crisis in treated patients with Cushing's syndrome[J]. Eur J Endocrinol. 2019;181(4):C13\u0026ndash;5.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eVolante M, Mete O, Pelosi G, et al. Molecular Pathology of Well-Differentiated Pulmonary and Thymic Neuroendocrine Tumors: What Do Pathologists Need to Know?[J]. Endocr Pathol. 2021;32(1):154\u0026ndash;68.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eWannachalee T, Turcu AF, Auchus RJ. Mifepristone in the treatment of the ectopic adrenocorticotropic hormone syndrome[J]. Clin Endocrinol (Oxf). 2018;89(5):570\u0026ndash;6.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eWoodcock T, Barker P, Daniel S, et al. Guidelines for the management of glucocorticoids during the peri-operative period for patients with adrenal insufficiency: Guidelines from the Association of Anaesthetists, the Royal College of Physicians and the Society for Endocrinology UK[J]. Anaesthesia. 2020;75(5):654\u0026ndash;63.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eWoods CP, Argese N, Chapman M, et al. Adrenal suppression in patients taking inhaled glucocorticoids is highly prevalent and management can be guided by morning cortisol[J]. Eur J Endocrinol. 2015;173(5):633\u0026ndash;42.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eYoung J, Haissaguerre M, Viera-Pinto O, et al. MANAGEMENT OF ENDOCRINE DISEASE: Cushing's syndrome due to ectopic ACTH secretion: an expert operational opinion[J]. Eur J Endocrinol. 2020;182(4):R29\u0026ndash;58.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eYu M, Sun L, Yang HL, et al. A rare endocrine cause of ventricular tachycardia: a case series of two patients and a literature review[J]. Cardiovasc J Afr. 2022;33(5):277\u0026ndash;81.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-endocrine-disorders","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bend","sideBox":"Learn more about [BMC Endocrine Disorders](http://bmcendocrdisord.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bend/default.aspx","title":"BMC Endocrine Disorders","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"ectopic ACTH, thymic neuroendocrine tumor, malignant arrhythmia, adrenal crisis, glucocorticoid","lastPublishedDoi":"10.21203/rs.3.rs-7969135/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7969135/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground:\u003c/strong\u003e Thymic neuroendocrine tumors associated with ectopic adrenocorticotropic hormone (ACTH) syndrome are exceedingly rare, and postoperative adrenal crisis presenting with malignant arrhythmias as the initial manifestation is even more uncommon. As a result, evidence to guide early recognition and management remains limited.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCase presentation:\u003c/strong\u003e This article reports a novel case of an ectopic ACTH-secreting thymic neuroendocrine tumor, complicated by postoperative adrenal crisis, with recurrent malignant arrhythmias. Following tumor resection, the patient developed profound shock accompanied by recurrent malignant arrhythmias, which improved significantly after prompt initiation of glucocorticoid administration and ventricular rate control.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions:\u003c/strong\u003e Adrenal crisis often presents with nonspecific clinical symptoms, predisposing it to delayed or missed diagnosis. However, during the perioperative management of ectopic ACTH-secreting neuroendocrine tumors, inappropriate glucocorticoid administration can trigger an adrenal crisis that may rapidly progress to life-threatening complications, including malignant arrhythmias, shock, and acute respiratory failure. Therefore, clinicians should aim to recognize this risk at the earliest possible stage. A multidisciplinary approach during the perioperative period remains essential to ensure timely and individualized glucocorticoid replacement therapy, thereby optimizing patient outcomes.\u003c/p\u003e","manuscriptTitle":"Postoperative Adrenal Crisis and Malignant Arrhythmias Associated with an Ectopic ACTH-Secreting Thymic Neuroendocrine Tumor: A Case Report and Literature Review","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-11-23 11:39:01","doi":"10.21203/rs.3.rs-7969135/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-12-02T08:22:39+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-11-28T19:05:46+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-11-13T20:19:12+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"265890543932163881503689722692427914482","date":"2025-11-13T19:32:30+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"310343170388032081772375846128701912198","date":"2025-11-13T18:38:08+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-11-11T17:58:58+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2025-11-06T05:14:16+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-10-31T03:16:13+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-10-31T03:15:31+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Endocrine Disorders","date":"2025-10-28T13:09:52+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-endocrine-disorders","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bend","sideBox":"Learn more about [BMC Endocrine Disorders](http://bmcendocrdisord.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bend/default.aspx","title":"BMC Endocrine Disorders","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"f78d988b-da79-4aaf-b236-cc1b778745cb","owner":[],"postedDate":"November 23rd, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2026-01-26T16:08:47+00:00","versionOfRecord":{"articleIdentity":"rs-7969135","link":"https://doi.org/10.1186/s12902-026-02171-8","journal":{"identity":"bmc-endocrine-disorders","isVorOnly":false,"title":"BMC Endocrine Disorders"},"publishedOn":"2026-01-24 15:58:45","publishedOnDateReadable":"January 24th, 2026"},"versionCreatedAt":"2025-11-23 11:39:01","video":"","vorDoi":"10.1186/s12902-026-02171-8","vorDoiUrl":"https://doi.org/10.1186/s12902-026-02171-8","workflowStages":[]},"version":"v1","identity":"rs-7969135","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7969135","identity":"rs-7969135","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}