A  neurological paraneoplastic syndrome in a patient affected by severe obesity: a case report

A neurological paraneoplastic syndrome in a patient affected by severe obesity: a case report | 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 Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article A neurological paraneoplastic syndrome in a patient affected by severe obesity: a case report Mario Caldarelli, VALERIO SPUNTARELLI, Geltrude Mingrone, ANTONIO GASBARRINI, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-3844486/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 5 You are reading this latest preprint version Abstract Introduction: Obese women experience a greater occurrence of tumors that impact the reproductive system, frequently leading to delayed diagnosis because of postponed access to medical care and unconventional manifestations. Case presentation: A 52-year-old woman was hospitalized due to an unexplained fever. After ruling out the typical reasons for fever, our patient experienced an episode of metrorrhagia she attributed to her regular menstrual cycle. Further assessments, including measurements of FSH and LH levels, as well as subsequent diagnostic imaging, revealed the existence of an abnormal growth mass affecting the uterus. Conclusion: The objective of our paper is to emphasize the significance of exploring paraneoplastic signs and symptoms in this kind of subjects, enabling prompt diagnosis and the subsequent establishment of an appropriate therapeutic approach. Body mass index fever of Unknown Origin (FUO) paraneoplastic syndrome uterine cancer visceral adipose tissue Figures Figure 1 Figure 2 INTRODUCTION Women who are obese are more likely to develop tumors affecting their reproductive system, often resulting in delayed detection due to postponed medical care access and unusual symptoms. Our case report serves as a symbol to emphasize the importance of early diagnosis, especially among individuals who often delay seeking medical attention due to obesity-related issues such as feelings of shame and transportation difficulties. In our case report, the development of endometrial tissue appears to be linked to a paraneoplastic syndrome, which presents with neurological symptoms. CASE REPORT A 52-year-old woman was admitted to the Emergency Room of the Fondazione Policlinico A. Gemelli IRCCS Hospital’s on summer 2023, due to onset of high body temperature (T: 40°C or 104°F) and confusional state over about a week. She suffered from severe obesity (height 160 cm, weight 130 kg, BMI 50.7 kg/m 2 ) associated to binge eating and anxiety disorder, bed rest syndrome and hypothyroidism. Furthermore, she complained low back pain and arthralgia at the lower limbs - she started therapy with pregabalin - and episodes of falling to the ground like drop attack. The patient was unable to precisely report the onset of symptoms due to retrograde amnesia. Once stabilized from the hemodynamic point of view, she underwent a brain CT scan and chest x-ray, both negatives. Thus, a total body CT was performed, that highlighted thickening of the gallbladder walls and hyperplastic appearance of the left adrenal gland, but with no lymphadenopathies. Blood tests documented neutrophilic leukocytosis (White Cells count 16390/L, Neutrophils 13370/L), hyponatremia (Sodium 127 mmol/L), high transaminases and creatine kinase, and increase in inflammation indices (C-reactive protein: 63 mg/l, Ferritin 411 ng/mL). The urine toxicology test was negative, as well as blood and urine cultures. According to our neurologist and infectious disease Consultants, an electroencephalogram and a cerebrospinal fluid analysis were performed, both providing negative results. However, empiric endovenous antibiotic therapy was instituted with ceftriaxone (2 grams twice a day) and vancomycin (1 gram/day). Due to the persistence of hyperpyrexia and confusional state, the patient was transferred to the intensive care unit to start invasive ventilation support. Thus, all microbiological tests (broncho wash cultures, central and peripheral blood cultures, urine cultures, urinary antigen for Legionella, and beta-glucan) resulted negative. Empiric endovenous Thiamine therapy was administered at a dose of 300 mg per day. After the improvement of the clinical conditions, the patient was transferred to our medicine ward. About medical history, she dates back the onset of fever to approximately 10 days earlier. She reported occasional xerophthalmia and xerostomia with oral aphthous stomatitis, and without any skin manifestations. Furthermore, she referred to have metrorrhagia that she associated to menstrual flow: no gynecological examination was ever carried out. As far as laboratory tests are concerned, autoimmune panel showed positive anti-citrulline antibodies (122 AU/mL) as well as extractable nuclear antigens (ENA) LA - type. However, there were no classification criteria of active autoimmune disease to justify clinical presentation. Subsequently, hormonal adjustment was required: Thyroid-stimulating hormone (TSH) 27.06 mUI/mL, free T4 6.6 pg/mL, free T3 1.5 pg/mL, Adrenocorticotropic hormone (ACTH) < 5 pg/mL, cortisol 203 ng/mL, Follicle-stimulating hormone (FSH) 1.8, LH 0.2 pg/mL. A pituitary magnetic resonance (MRI) showed no significant results. Thus, a transvaginal ultrasound showed a bicornuate uterus and hyperechoic endometrium (13 mm), with a no-homogeneous and no-vascularized echo structure (Fig. 1 ). An MRI of the pelvis documented at the level of the body-cervix passage the presence of an elongated formation with a posterior peduncle and endocervical and endo-vaginal development, with evidence of multiple lymph nodes increased in size in the right external iliac, right obturator, bilateral common iliac and bilateral external iliac sites (Fig. 2 ). Cancer antigen-125 level was in the normal range, while human epididymis protein 4 (HE4) was increased (445 pmol/L). Therefore, she was entrusted to our Gynecologists to perform diagnostic hysteroscopy, that she was unable to perform due to poor compliance. A diagnosis of heteroformation of the uterine cavity was then made, to be characterized histologically by hysteroscopy. DISCUSSION Our case report can be used as a symbol to highlight the significance of early diagnosis, particularly in individuals who frequently seek medical attention late due to issues related to obesity, including feelings of shame and transportation challenges. There is strong epidemiologic evidence on the association between obesity and endometrial cancer risk and mortality [ 1 ]. Obesity defined as a BMI value from a 30 to 35 kg/m 2 was associated with a 2.6-fold increase in endometrial cancer risk, while severe obesity (BMI > 35 kg/m 2 ) was associated with a 4.7-fold increase compared to normal-weight women [ 2 ]. The pivotal role in the association of obesity to cancer is played by increate visceral adipose tissue, that was shown to increase endometrial cancer risk by 1.5- to twofold [ 1 , 2 ]. The adipocyte tissue and its surrounding microenvironment might contribute to carcinogenesis, the formation of metastases, and the advancement of the disease [ 3 ]. The excessive accumulation of fat leads to dysfunction in adipose tissue, resulting in an elevated production of proinflammatory cytokines, sex hormones, and lipid metabolites. Additionally, there is a disturbance in adipocyte-derived cytokines or adipokines profiles, coupled with insulin resistance. The modified adipose tissue becomes a source of extracellular matrix (ECM) remodeling, fibrosis, cancer-associated adipocytes, impaired microbial metabolism, adipocyte progenitors, inflammation, and an altered microenvironment. These factors collectively contribute to the initiation, growth, and recurrence of tumors [ 4 ]. Among post-menopausal women, the risk of breast, endometrial, and ovarian cancers exhibit a notable rise with the escalation of BMI classification from normal to class II obesity [ 5 ]. According to the Italian association of medical oncology (AIOM), endometrial cancer (EC) represents the sixth most common cancer in women worldwide [ 6 ]. Risk factors include obesity and metabolic syndrome, excess estrogen, exposure to tamoxifen for at least 5 years. Nevertheless, oral contraceptives and parity are considered protective factors [ 7 ]. EC is typically divided into type 1 and type 2. Type 1 endometrial endometrioid carcinoma (EECs) is the most common low-grade tumor, usually expressing hormone receptors, and with a good prognosis [ 8 ]. Type 2 non-endometrioid carcinomas (NEECs) that doesn’t express hormone receptors [ 8 ]. The histological classification divides the nets into endometrial serous carcinoma (ESC), clear cell carcinoma (ECCC), carcinosarcoma, gastrointestinal carcinoma, squamous cell carcinoma, dedifferentiated carcinoma, undifferentiated carcinoma, mesonephric-like adenocarcinoma (MLA), and mixed endometrioid with serous or clear cell carcinomas [ 8 , 9 ]. The typical clinical presentation of EC is abnormal vaginal bleeding. Abdominal, pelvic, lumbosacral and buttock pain, sub occlusive syndromes, bone pain and leucoxanthorrhea are typical signs and symptoms of advanced disease [ 6 ]. Trans-Vaginal Sonography is the first test to be performed that allows to evaluate the endometrial thickness (suspicious if > 5mm postmenopausal). The diagnosis of EC is based on targeted biopsy samples. Staging is performed using MRI medium with paramagnetic contrast medium [ 6 ]. EC is associated with two biomarkers: Cancer Antigen 125 (CA125) and Human Epididymis 4 (HE4) [ 10 ]. A meta-analysis including a total of 1980 patients and 2345 controls from 25 studies, analyzed the diagnostic value of single CA125 and HE4 or association between CA125 + HE4 [ 11 ]. Results underlined a greater diagnostic efficacy of HE4, whether dosed individually or coupled with CA125. In our case report, endometrial formation seems to be associated to paraneoplastic syndrome, with neurological signs. Paraneoplastic syndromes of nervous system associated with EC are rare. Clinical manifestations include encephalitis or encephalomyelitis usually linked to autoantibodies such as anti-Hu, Ma2-associated, anti-CRMP5, anti-Ri, anti-KLHL1 that are generally secreted by neuroendocrine tumors [ 12 ]. Thus, it can also reveal as a subacute sensory neuronopathy associated with anti-Hu or anti-collapsin-responsive mediator protein 5 (CRMP5) antibodies, or as sensory-motor neuropathy. A different way of presentation of EC is also dermatomyositis or polymyositis. Dermatomyositis is an inflammatory myopathy that presents with proximal muscle weakness and skin rashes [ 13 ]. Polymyositis is characterized by myalgia with progressive and symmetric involvement. Furthermore, systemic symptoms such as loss of appetite, weakness and mild fever may be present [ 14 ]. Laboratory tests usually underline rhabdomyolysis and chronic inflammation, as happens in our patients [ 15 ]. Meningoencephalitis might be linked to cerebral salt wasting (CSW) [ 16 ]. CSW presents with hypovolemia and hyponatremia responsive to supplement treatment, as well as our patient. CONCLUSIONS This case report describes a rare case of paraneoplastic syndrome involving nervous system associated with a probable endometrial cancer, not yet well documented in medicine literature. The relevant implications of this case report are on one side the association with severe obesity, that acts as a risk factor of gynecological tumors especially in the post-menopausal state, and on the other, the importance of considering paraneoplastic syndromes when present as key diagnostic tools with respect to gynecological symptoms alone. Declarations 1. Funding: Not Applicable 2. Conflicts of interest/Competing interests: Nothing 3. Ethics approval: Not Applicable 4. Consent to participate: patient signed the Informed Consent forms before the entrance to the ward 5. Written Consent for publication: patient signed a written Consent for publication 6. Availability of data and material: data is retained in hospitals’ computers, available at reasonable request form lead author. 7. Code availability: each inverstigator used his password 8. Authors' contributions: All authors materially participated in the research.VS, MC, GM, AG, and EC participated in data collection, study design and in article preparation. VS and MC participated in acquisition of patient’s data. All authors have approved the final article. References Shaw E, Farris M, McNeil J, Friedenreich C. Obesity and Endometrial Cancer. Recent Results Cancer Res Fortschritte Krebsforsch Progres Dans Rech Sur Cancer. 2016;208:107–36. 10.1007/978-3-319-42542-9_7 . Bosch AAS, Werner HM. ; Pijnenborg, J.M.A.; Romano, A.; Winkens, B.; Putten, L.J.M. van der; Kruitwagen, R.F.P.M.; Werner, H.M.J. The Impact of Adipose Tissue Distribution on Endometrial Cancer: A Systematic Review. Front. Oncol. 2023, 13 . Lengyel E, Makowski L, DiGiovanni J, Kolonin MG. Cancer as a Matter of Fat: The Crosstalk between Adipose Tissue and Tumors. Trends Cancer. 2018;4:374–84. 10.1016/j.trecan.2018.03.004 . Pati S, Irfan W, Jameel A, Ahmed S, Shahid RK. Obesity and Cancer: A Current Overview of Epidemiology, Pathogenesis, Outcomes, and Management. Cancers 2023, 15 , 485, 10.3390/cancers15020485 . Park IS, Kim SI, Han Y, Yoo J, Seol A, Jo H, Lee J, Wang W, Han K, Song YS. Risk of Female-Specific Cancers According to Obesity and Menopausal Status in 2•7 Million Korean Women: Similar Trends between Korean and Western Women. Lancet Reg Health - West Pac. 2021;11:100146. 10.1016/j.lanwpc.2021.100146 . LG-486. -AIOM_Ca-Cervice-Endometrio.Pdf. Lu KH, Broaddus RR, Endometrial Cancer. N Engl J Med. 2020;383:2053–64. 10.1056/NEJMra1514010 . Makker V, MacKay H, Ray-Coquard I, Levine DA, Westin SN, Aoki D, Oaknin A. Endometrial Cancer. Nat Rev Dis Primer. 2021;7:88. 10.1038/s41572-021-00324-8 . Zheng W. Molecular Classification of Endometrial Cancer and the 2023 FIGO Staging: Exploring the Challenges and Opportunities for Pathologists. Cancers. 2023;15:4101. 10.3390/cancers15164101 . Barr CE, Njoku K, Jones ER, Crosbie EJ. Serum CA125 and HE4 as Biomarkers for the Detection of Endometrial Cancer and Associated High-Risk Features. Diagnostics. 2022;12:2834. 10.3390/diagnostics12112834 . Wu Q, Bai S, Song L, Wu W, Han L. Diagnostic Value of Serum Human Epididymis Protein 4, Carbohydrate Antigen 125 and Their Combination in Endometrial Cancer: A Meta-Analysis. Med (Baltim). 2023;102:e34737. 10.1097/MD.0000000000034737 . Svarna A, Liontos M, Reppas G, Fiste O, Andrikopoulou A, Dimopoulos MA, Zagouri F. What to Expect from Paraneoplastic Syndromes of the Nervous System in Uterine Cancer: A Review of the Literature. Gynecol Oncol Rep. 2023;45:101136. 10.1016/j.gore.2023.101136 . Lim D, Landon-Cardinal O, Belisle A, Davar SA. Case of Dermatomyositis with Anti-TIF1γ Antibodies Revealing Isolated Para-Aortic Lymphadenopathy Metastatic Recurrence of Endometrial Cancer: A Case Report. SAGE Open Med Case Rep. 2020;8(2050313X20961977). 10.1177/2050313X20961977 . Strauss KW, Gonzalez-Buritica H, Khamashta MA, Hughes GR. Polymyositis-Dermatomyositis: A Clinical Review. Postgrad Med J. 1989;65:437–43. 10.1136/pgmj.65.765.437 . Sarwar A, Dydyk AM, Jatwani S. Polymyositis. In StatPearls ; StatPearls Publishing: Treasure Island (FL), 2023. Ramesh R, Kanagasingam A, Sabrina S, Anushanth UA. Probable Association of Aseptic Meningoencephalitis, Complicated With Cerebral Salt Wasting Syndrome Following COVID-19 Vaccination: A Case Report. Cureus 15 , e41106, 10.7759/cureus.41106 . Cite Share Download PDF Status: Under Review Version 1 posted Reviewers agreed at journal 13 Apr, 2024 Reviewers invited by journal 08 Feb, 2024 Editor assigned by journal 31 Jan, 2024 First submitted to journal 26 Jan, 2024 Editorial decision: Minor revisions 23 Jan, 2024 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. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-3844486","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":272064710,"identity":"bbda0bf6-7879-4257-ae6b-7f13691470f8","order_by":0,"name":"Mario Caldarelli","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA8UlEQVRIiWNgGAWjYHACxgM8QJKPnbHxAYMBAwMbO2MDA4iBD4C1sDEzNhuAtTCDteDXA9XCwCYB5jKDSdxadNsPPzjwpuaeHBszc1s1T8E9uz5mZqALC/7g1GJ2Js3g4JxjxcZA97Td5jEoTm6DuBC3LWY3GAwO87AlJAJVtt2cYZCQDNIrgV8L+4fDPP8S6kFaConUwmNwmLctIQGkkuGDQYIdYS1ncgoOzu1LMAR5QQKoJQEc2gkGxri1HD++8cGbbwny/OztDz8k/Emwl29vf/jgwx85nFowQGIDiEwgXgMDgz0pikfBKBgFo2BkAAC84Us6LCbsMgAAAABJRU5ErkJggg==","orcid":"","institution":"Università Cattolica del Sacro Cuore: Universita Cattolica del Sacro Cuore","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Mario","middleName":"","lastName":"Caldarelli","suffix":""},{"id":272064711,"identity":"68a425d7-4c02-456a-8407-7d12792f5d37","order_by":1,"name":"VALERIO SPUNTARELLI","email":"","orcid":"","institution":"Policlinico Universitario Agostino Gemelli","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"VALERIO","middleName":"","lastName":"SPUNTARELLI","suffix":""},{"id":272064712,"identity":"4366e6ce-8718-46d2-a1e6-11ffaa407fae","order_by":2,"name":"Geltrude Mingrone","email":"","orcid":"","institution":"Policlinico Universitario Agostino Gemelli","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Geltrude","middleName":"","lastName":"Mingrone","suffix":""},{"id":272064713,"identity":"bba2cf0a-f977-44ab-9d68-947329054b3e","order_by":3,"name":"ANTONIO GASBARRINI","email":"","orcid":"","institution":"Policlinico Universitario Agostino Gemelli","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"ANTONIO","middleName":"","lastName":"GASBARRINI","suffix":""},{"id":272064714,"identity":"7821056f-2033-49be-89ec-45e4dcc5bbfb","order_by":4,"name":"Esmeralda Capristo","email":"","orcid":"","institution":"Policlinico Universitario Agostino Gemelli","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Esmeralda","middleName":"","lastName":"Capristo","suffix":""}],"badges":[],"createdAt":"2024-01-08 04:09:15","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-3844486/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-3844486/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":51085410,"identity":"5d8e70b2-9591-4b1b-9050-472ee8cb82e1","added_by":"auto","created_at":"2024-02-13 19:52:22","extension":"jpeg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":212598,"visible":true,"origin":"","legend":"\u003cp\u003eTransvaginal ultrasound showed a bicornuate uterus and hyperechoic endometrium (13 mm), with a no-homogeneous and no-vascularized echo structure.\u003c/p\u003e","description":"","filename":"floatimage1.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-3844486/v1/e79aec6ea402ef7bb985b4fd.jpeg"},{"id":51085403,"identity":"b1951fbc-50c7-48b2-91df-c877afc42c7c","added_by":"auto","created_at":"2024-02-13 19:52:20","extension":"jpeg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":477447,"visible":true,"origin":"","legend":"\u003cp\u003eMagnetic Resonance T2 FSI image of the uterine body.\u003c/p\u003e","description":"","filename":"floatimage2.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-3844486/v1/380e0b65b4cb11820868908e.jpeg"},{"id":51085413,"identity":"1b7142c3-c8fa-42b8-9d76-349fafc836a3","added_by":"auto","created_at":"2024-02-13 19:52:27","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":370388,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-3844486/v1/f569e0ed-bd22-4718-aa17-cb63f70655c6.pdf"}],"financialInterests":"","formattedTitle":"A neurological paraneoplastic syndrome in a patient affected by severe obesity: a case report","fulltext":[{"header":"INTRODUCTION","content":"\u003cp\u003eWomen who are obese are more likely to develop tumors affecting their reproductive system, often resulting in delayed detection due to postponed medical care access and unusual symptoms.\u003c/p\u003e \u003cp\u003eOur case report serves as a symbol to emphasize the importance of early diagnosis, especially among individuals who often delay seeking medical attention due to obesity-related issues such as feelings of shame and transportation difficulties.\u003c/p\u003e \u003cp\u003eIn our case report, the development of endometrial tissue appears to be linked to a paraneoplastic syndrome, which presents with neurological symptoms.\u003c/p\u003e"},{"header":"CASE REPORT","content":"\u003cp\u003eA 52-year-old woman was admitted to the Emergency Room of the Fondazione Policlinico A. Gemelli IRCCS Hospital\u0026rsquo;s on summer 2023, due to onset of high body temperature (T: 40\u0026deg;C or 104\u0026deg;F) and confusional state over about a week.\u003c/p\u003e \u003cp\u003eShe suffered from severe obesity (height 160 cm, weight 130 kg, BMI 50.7 kg/m\u003csup\u003e2\u003c/sup\u003e) associated to binge eating and anxiety disorder, bed rest syndrome and hypothyroidism. Furthermore, she complained low back pain and arthralgia at the lower limbs - she started therapy with pregabalin - and episodes of falling to the ground like drop attack.\u003c/p\u003e \u003cp\u003eThe patient was unable to precisely report the onset of symptoms due to retrograde amnesia.\u003c/p\u003e \u003cp\u003eOnce stabilized from the hemodynamic point of view, she underwent a brain CT scan and chest x-ray, both negatives. Thus, a total body CT was performed, that highlighted thickening of the gallbladder walls and hyperplastic appearance of the left adrenal gland, but with no lymphadenopathies.\u003c/p\u003e \u003cp\u003eBlood tests documented neutrophilic leukocytosis (White Cells count 16390/L, Neutrophils 13370/L), hyponatremia (Sodium 127 mmol/L), high transaminases and creatine kinase, and increase in inflammation indices (C-reactive protein: 63 mg/l, Ferritin 411 ng/mL).\u003c/p\u003e \u003cp\u003eThe urine toxicology test was negative, as well as blood and urine cultures.\u003c/p\u003e \u003cp\u003eAccording to our neurologist and infectious disease Consultants, an electroencephalogram and a cerebrospinal fluid analysis were performed, both providing negative results.\u003c/p\u003e \u003cp\u003eHowever, empiric endovenous antibiotic therapy was instituted with ceftriaxone (2 grams twice a day) and vancomycin (1 gram/day).\u003c/p\u003e \u003cp\u003eDue to the persistence of hyperpyrexia and confusional state, the patient was transferred to the intensive care unit to start invasive ventilation support. Thus, all microbiological tests (broncho wash cultures, central and peripheral blood cultures, urine cultures, urinary antigen for Legionella, and beta-glucan) resulted negative.\u003c/p\u003e \u003cp\u003eEmpiric endovenous Thiamine therapy was administered at a dose of 300 mg per day.\u003c/p\u003e \u003cp\u003eAfter the improvement of the clinical conditions, the patient was transferred to our medicine ward.\u003c/p\u003e \u003cp\u003eAbout medical history, she dates back the onset of fever to approximately 10 days earlier.\u003c/p\u003e \u003cp\u003eShe reported occasional xerophthalmia and xerostomia with oral aphthous stomatitis, and without any skin manifestations.\u003c/p\u003e \u003cp\u003eFurthermore, she referred to have metrorrhagia that she associated to menstrual flow: no gynecological examination was ever carried out.\u003c/p\u003e \u003cp\u003eAs far as laboratory tests are concerned, autoimmune panel showed positive anti-citrulline antibodies (122 AU/mL) as well as extractable nuclear antigens (ENA) LA - type. However, there were no classification criteria of active autoimmune disease to justify clinical presentation.\u003c/p\u003e \u003cp\u003eSubsequently, hormonal adjustment was required: Thyroid-stimulating hormone (TSH) 27.06 mUI/mL, free T4 6.6 pg/mL, free T3 1.5 pg/mL, Adrenocorticotropic hormone (ACTH)\u0026thinsp;\u0026lt;\u0026thinsp;5 pg/mL, cortisol 203 ng/mL, Follicle-stimulating hormone (FSH) 1.8, LH 0.2 pg/mL.\u003c/p\u003e \u003cp\u003eA pituitary magnetic resonance (MRI) showed no significant results.\u003c/p\u003e \u003cp\u003eThus, a transvaginal ultrasound showed a bicornuate uterus and hyperechoic endometrium (13 mm), with a no-homogeneous and no-vascularized echo structure (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eAn MRI of the pelvis documented at the level of the body-cervix passage the presence of an elongated formation with a posterior peduncle and endocervical and endo-vaginal development, with evidence of multiple lymph nodes increased in size in the right external iliac, right obturator, bilateral common iliac and bilateral external iliac sites (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eCancer antigen-125 level was in the normal range, while human epididymis protein 4 (HE4) was increased (445 pmol/L).\u003c/p\u003e \u003cp\u003eTherefore, she was entrusted to our Gynecologists to perform diagnostic hysteroscopy, that she was unable to perform due to poor compliance.\u003c/p\u003e \u003cp\u003eA diagnosis of heteroformation of the uterine cavity was then made, to be characterized histologically by hysteroscopy.\u003c/p\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003eOur case report can be used as a symbol to highlight the significance of early diagnosis, particularly in individuals who frequently seek medical attention late due to issues related to obesity, including feelings of shame and transportation challenges.\u003c/p\u003e \u003cp\u003eThere is strong epidemiologic evidence on the association between obesity and endometrial cancer risk and mortality [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Obesity defined as a BMI value from a 30 to 35 kg/m\u003csup\u003e2\u003c/sup\u003e was associated with a 2.6-fold increase in endometrial cancer risk, while severe obesity (BMI\u0026thinsp;\u0026gt;\u0026thinsp;35 kg/m\u003csup\u003e2\u003c/sup\u003e) was associated with a 4.7-fold increase compared to normal-weight women [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. The pivotal role in the association of obesity to cancer is played by increate visceral adipose tissue, that was shown to increase endometrial cancer risk by 1.5- to twofold [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe adipocyte tissue and its surrounding microenvironment might contribute to carcinogenesis, the formation of metastases, and the advancement of the disease [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe excessive accumulation of fat leads to dysfunction in adipose tissue, resulting in an elevated production of proinflammatory cytokines, sex hormones, and lipid metabolites. Additionally, there is a disturbance in adipocyte-derived cytokines or adipokines profiles, coupled with insulin resistance. The modified adipose tissue becomes a source of extracellular matrix (ECM) remodeling, fibrosis, cancer-associated adipocytes, impaired microbial metabolism, adipocyte progenitors, inflammation, and an altered microenvironment. These factors collectively contribute to the initiation, growth, and recurrence of tumors [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eAmong post-menopausal women, the risk of breast, endometrial, and ovarian cancers exhibit a notable rise with the escalation of BMI classification from normal to class II obesity [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eAccording to the Italian association of medical oncology (AIOM), endometrial cancer (EC) represents the sixth most common cancer in women worldwide [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eRisk factors include obesity and metabolic syndrome, excess estrogen, exposure to tamoxifen for at least 5 years. Nevertheless, oral contraceptives and parity are considered protective factors [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eEC is typically divided into type 1 and type 2. Type 1 endometrial endometrioid carcinoma (EECs) is the most common low-grade tumor, usually expressing hormone receptors, and with a good prognosis [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Type 2 non-endometrioid carcinomas (NEECs) that doesn\u0026rsquo;t express hormone receptors [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe histological classification divides the nets into endometrial serous carcinoma (ESC), clear cell carcinoma (ECCC), carcinosarcoma, gastrointestinal carcinoma, squamous cell carcinoma, dedifferentiated carcinoma, undifferentiated carcinoma, mesonephric-like adenocarcinoma (MLA), and mixed endometrioid with serous or clear cell carcinomas [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe typical clinical presentation of EC is abnormal vaginal bleeding. Abdominal, pelvic, lumbosacral and buttock pain, sub occlusive syndromes, bone pain and leucoxanthorrhea are typical signs and symptoms of advanced disease [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eTrans-Vaginal Sonography is the first test to be performed that allows to evaluate the endometrial thickness (suspicious if\u0026thinsp;\u0026gt;\u0026thinsp;5mm postmenopausal). The diagnosis of EC is based on targeted biopsy samples. Staging is performed using MRI medium with paramagnetic contrast medium [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eEC is associated with two biomarkers: Cancer Antigen 125 (CA125) and Human Epididymis 4 (HE4) [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eA meta-analysis including a total of 1980 patients and 2345 controls from 25 studies, analyzed the diagnostic value of single CA125 and HE4 or association between CA125\u0026thinsp;+\u0026thinsp;HE4 [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eResults underlined a greater diagnostic efficacy of HE4, whether dosed individually or coupled with CA125.\u003c/p\u003e \u003cp\u003eIn our case report, endometrial formation seems to be associated to paraneoplastic syndrome, with neurological signs.\u003c/p\u003e \u003cp\u003eParaneoplastic syndromes of nervous system associated with EC are rare. Clinical manifestations include encephalitis or encephalomyelitis usually linked to autoantibodies such as anti-Hu, Ma2-associated, anti-CRMP5, anti-Ri, anti-KLHL1 that are generally secreted by neuroendocrine tumors [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. Thus, it can also reveal as a subacute sensory neuronopathy associated with anti-Hu or anti-collapsin-responsive mediator protein 5 (CRMP5) antibodies, or as sensory-motor neuropathy.\u003c/p\u003e \u003cp\u003eA different way of presentation of EC is also dermatomyositis or polymyositis. Dermatomyositis is an inflammatory myopathy that presents with proximal muscle weakness and skin rashes [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Polymyositis is characterized by myalgia with progressive and symmetric involvement.\u003c/p\u003e \u003cp\u003eFurthermore, systemic symptoms such as loss of appetite, weakness and mild fever may be present [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. Laboratory tests usually underline rhabdomyolysis and chronic inflammation, as happens in our patients [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eMeningoencephalitis might be linked to cerebral salt wasting (CSW) [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eCSW presents with hypovolemia and hyponatremia responsive to supplement treatment, as well as our patient.\u003c/p\u003e"},{"header":"CONCLUSIONS","content":"\u003cp\u003eThis case report describes a rare case of paraneoplastic syndrome involving nervous system associated with a probable endometrial cancer, not yet well documented in medicine literature.\u003c/p\u003e \u003cp\u003eThe relevant implications of this case report are on one side the association with severe obesity, that acts as a risk factor of gynecological tumors especially in the post-menopausal state, and on the other, the importance of considering paraneoplastic syndromes when present as key diagnostic tools with respect to gynecological symptoms alone.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e1. Funding: Not Applicable\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e2. Conflicts of interest/Competing interests: Nothing\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e3. Ethics approval: Not Applicable\u003c/p\u003e\n\u003cp\u003e4. Consent to participate: patient signed the Informed Consent forms before the entrance to the ward\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e5. Written Consent for publication: patient signed a written Consent for publication\u003c/p\u003e\n\u003cp\u003e6. Availability of data and material: data is retained in hospitals\u0026rsquo; computers, available at reasonable request form lead author.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e7. Code availability: each inverstigator used his password\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e8. Authors\u0026apos; contributions: All authors materially participated in the research.VS, MC, GM, AG, and EC participated in data collection, study design and in article preparation. VS and MC participated in acquisition of patient\u0026rsquo;s data. All authors have approved the final article.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eShaw E, Farris M, McNeil J, Friedenreich C. Obesity and Endometrial Cancer. Recent Results Cancer Res Fortschritte Krebsforsch Progres Dans Rech Sur Cancer. 2016;208:107\u0026ndash;36. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1007/978-3-319-42542-9_7\u003c/span\u003e\u003cspan address=\"10.1007/978-3-319-42542-9_7\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBosch AAS, Werner HM. ; Pijnenborg, J.M.A.; Romano, A.; Winkens, B.; Putten, L.J.M. van der; Kruitwagen, R.F.P.M.; Werner, H.M.J. The Impact of Adipose Tissue Distribution on Endometrial Cancer: A Systematic Review. \u003cem\u003eFront. Oncol.\u003c/em\u003e 2023, \u003cem\u003e13\u003c/em\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLengyel E, Makowski L, DiGiovanni J, Kolonin MG. Cancer as a Matter of Fat: The Crosstalk between Adipose Tissue and Tumors. Trends Cancer. 2018;4:374\u0026ndash;84. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.trecan.2018.03.004\u003c/span\u003e\u003cspan address=\"10.1016/j.trecan.2018.03.004\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePati S, Irfan W, Jameel A, Ahmed S, Shahid RK. Obesity and Cancer: A Current Overview of Epidemiology, Pathogenesis, Outcomes, and Management. \u003cem\u003eCancers\u003c/em\u003e 2023, \u003cem\u003e15\u003c/em\u003e, 485, \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3390/cancers15020485\u003c/span\u003e\u003cspan address=\"10.3390/cancers15020485\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePark IS, Kim SI, Han Y, Yoo J, Seol A, Jo H, Lee J, Wang W, Han K, Song YS. Risk of Female-Specific Cancers According to Obesity and Menopausal Status in 2\u0026bull;7 Million Korean Women: Similar Trends between Korean and Western Women. Lancet Reg Health - West Pac. 2021;11:100146. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.lanwpc.2021.100146\u003c/span\u003e\u003cspan address=\"10.1016/j.lanwpc.2021.100146\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLG-486. -AIOM_Ca-Cervice-Endometrio.Pdf.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLu KH, Broaddus RR, Endometrial Cancer. N Engl J Med. 2020;383:2053\u0026ndash;64. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1056/NEJMra1514010\u003c/span\u003e\u003cspan address=\"10.1056/NEJMra1514010\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMakker V, MacKay H, Ray-Coquard I, Levine DA, Westin SN, Aoki D, Oaknin A. Endometrial Cancer. Nat Rev Dis Primer. 2021;7:88. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1038/s41572-021-00324-8\u003c/span\u003e\u003cspan address=\"10.1038/s41572-021-00324-8\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZheng W. Molecular Classification of Endometrial Cancer and the 2023 FIGO Staging: Exploring the Challenges and Opportunities for Pathologists. Cancers. 2023;15:4101. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3390/cancers15164101\u003c/span\u003e\u003cspan address=\"10.3390/cancers15164101\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBarr CE, Njoku K, Jones ER, Crosbie EJ. Serum CA125 and HE4 as Biomarkers for the Detection of Endometrial Cancer and Associated High-Risk Features. Diagnostics. 2022;12:2834. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3390/diagnostics12112834\u003c/span\u003e\u003cspan address=\"10.3390/diagnostics12112834\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWu Q, Bai S, Song L, Wu W, Han L. Diagnostic Value of Serum Human Epididymis Protein 4, Carbohydrate Antigen 125 and Their Combination in Endometrial Cancer: A Meta-Analysis. Med (Baltim). 2023;102:e34737. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1097/MD.0000000000034737\u003c/span\u003e\u003cspan address=\"10.1097/MD.0000000000034737\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSvarna A, Liontos M, Reppas G, Fiste O, Andrikopoulou A, Dimopoulos MA, Zagouri F. What to Expect from Paraneoplastic Syndromes of the Nervous System in Uterine Cancer: A Review of the Literature. Gynecol Oncol Rep. 2023;45:101136. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.gore.2023.101136\u003c/span\u003e\u003cspan address=\"10.1016/j.gore.2023.101136\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLim D, Landon-Cardinal O, Belisle A, Davar SA. Case of Dermatomyositis with Anti-TIF1γ Antibodies Revealing Isolated Para-Aortic Lymphadenopathy Metastatic Recurrence of Endometrial Cancer: A Case Report. SAGE Open Med Case Rep. 2020;8(2050313X20961977). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1177/2050313X20961977\u003c/span\u003e\u003cspan address=\"10.1177/2050313X20961977\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eStrauss KW, Gonzalez-Buritica H, Khamashta MA, Hughes GR. Polymyositis-Dermatomyositis: A Clinical Review. Postgrad Med J. 1989;65:437\u0026ndash;43. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1136/pgmj.65.765.437\u003c/span\u003e\u003cspan address=\"10.1136/pgmj.65.765.437\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSarwar A, Dydyk AM, Jatwani S. Polymyositis. In \u003cem\u003eStatPearls\u003c/em\u003e; StatPearls Publishing: Treasure Island (FL), 2023.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRamesh R, Kanagasingam A, Sabrina S, Anushanth UA. Probable Association of Aseptic Meningoencephalitis, Complicated With Cerebral Salt Wasting Syndrome Following COVID-19 Vaccination: A Case Report. \u003cem\u003eCureus 15\u003c/em\u003e, e41106, \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.7759/cureus.41106\u003c/span\u003e\u003cspan address=\"10.7759/cureus.41106\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\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":"sn-comprehensive-clinical-medicine","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"sncm","sideBox":"Learn more about [SN Comprehensive Clinical Medicine](https://www.springer.com/journal/42399)","snPcode":"42399","submissionUrl":"https://submission.nature.com/new-submission/42399/3","title":"SN Comprehensive Clinical Medicine","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"Body mass index, fever of Unknown Origin (FUO), paraneoplastic syndrome uterine cancer, visceral adipose tissue","lastPublishedDoi":"10.21203/rs.3.rs-3844486/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-3844486/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eIntroduction: \u003c/strong\u003eObese women experience a greater occurrence of tumors that impact the reproductive system, frequently leading to delayed diagnosis because of postponed access to medical care and unconventional manifestations.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCase presentation:\u003c/strong\u003e A 52-year-old woman was hospitalized due to an unexplained fever. After ruling out the typical reasons for fever, our patient experienced an episode of metrorrhagia she attributed to her regular menstrual cycle. Further assessments, including measurements of FSH and LH levels, as well as subsequent diagnostic imaging, revealed the existence of an abnormal growth mass affecting the uterus.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion:\u003c/strong\u003e The objective of our paper is to emphasize the significance of exploring paraneoplastic signs and symptoms in this kind of subjects, enabling prompt diagnosis and the subsequent establishment of an appropriate therapeutic approach.\u003c/p\u003e","manuscriptTitle":"A neurological paraneoplastic syndrome in a patient affected by severe obesity: a case report","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-02-13 19:52:15","doi":"10.21203/rs.3.rs-3844486/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"reviewerAgreed","content":"","date":"2024-04-13T20:11:34+00:00","index":0,"fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-02-08T18:56:17+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-01-31T08:12:34+00:00","index":"","fulltext":""},{"type":"submitted","content":"SN Comprehensive Clinical Medicine","date":"2024-01-26T14:05:11+00:00","index":"","fulltext":""},{"type":"decision","content":"Minor revisions","date":"2024-01-23T05:05:42+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"sn-comprehensive-clinical-medicine","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"sncm","sideBox":"Learn more about [SN Comprehensive Clinical Medicine](https://www.springer.com/journal/42399)","snPcode":"42399","submissionUrl":"https://submission.nature.com/new-submission/42399/3","title":"SN Comprehensive Clinical Medicine","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"4c36483f-31b5-4eeb-b8ee-957baeafe2a0","owner":[],"postedDate":"February 13th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2024-05-08T09:04:24+00:00","versionOfRecord":[],"versionCreatedAt":"2024-02-13 19:52:15","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-3844486","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-3844486","identity":"rs-3844486","version":["v1"]},"buildId":"CiT4i_kKBbxQbnFL0ufpk","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}