Neuroendocrinology最新文献

{"title":"Upregulation of SSTR2 expression and radioligand binding of [18F]SiTATE in neuroendocrine tumour cells with combined inhibition of class I HDACs and LSD1.","authors":"Christoph J Auernhammer, Kathrin Zitzmann, Simon Lindner, Harun Ilhan, Peter Bartenstein, Umberto Maccio, Michael Orth, Lea Peischer, Julian Maurer, Gerald Spoettl, Katharina Wang, Christine Spitzweg, Alessa Fischer, Constanze Hantel, Ashley B Grossman, Felix Beuschlein, Karel Pacak, Svenja Nölting","doi":"10.1159/000545073","DOIUrl":"https://doi.org/10.1159/000545073","url":null,"abstract":"<p><strong>Introduction: </strong>Peptide receptor radionuclide therapy (PRRT) is a highly effective, targeted treatment option in advanced neuroendocrine tumours (NETs). However, NET patients expressing low levels of Somatostatin receptor type (SSTR)2 do not benefit from this powerful tool. Recently, several preclinical studies have revealed that histone deacetylase (HDAC) inhibitors can upregulate the expression of SSTR2 and enhance somatostatin ligand binding to tumour cells. In this preclinical study, we explored the effects of single and combined treatment of NET cells with the class I HDAC inhibitor entinostat and the lysine-specific demethylase 1 (LSD1) inhibitor CC-90011, on cell viability, SSTR2 expression and radioligand binding.</p><p><strong>Methods: </strong>The human NET cell lines BON1, NCI-H727, and QGP1 were treated with entinostat, CC-90011 or a combination of both. Cell viability was measured with a cell viability assay. SSTR2 expression was assessed by quantitative PCR, Western blot analysis, and immunohistochemistry. [18F]SiTATE uptake was investigated by a radioligand binding assay.</p><p><strong>Results: </strong>Treatment of NET cells with entinostat, CC-90011 and especially with the combination of both reduced tumour cell viability and strongly induced SSTR2 expression resulting in potently enhanced radioligand binding of [18F]SiTATE.</p><p><strong>Conclusion: </strong>Combined inhibition of class I HDACs and LSD1 potently increases SSTR2 expression and consequently radioligand binding and might thus be a putative strategy to improve the outcome of PRRT therapy in patients with NETs.</p>","PeriodicalId":19117,"journal":{"name":"Neuroendocrinology","volume":" ","pages":"1-25"},"PeriodicalIF":3.2,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143795853","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The effect of metformin on prolactin concentration in women with hyperprolactinemia and subclinical hyperthyroidism.","authors":"Robert Krysiak, Karolina Kowalcze, Bogusław Okopień","doi":"10.1159/000545525","DOIUrl":"https://doi.org/10.1159/000545525","url":null,"abstract":"<p><strong>Introduction: </strong>Because prolactin excess and hyperthyroidism are often complicated by hyperglycemia and impaired insulin sensitivity, many patients with both these disorders are treated with metformin. This drug inhibits secretory function of overactive anterior pituitary cells, including lactotrophs. The purpose of the current study was to investigate whether metformin action on prolactin oversecretion is impacted by coexisting hyperthyroidism.</p><p><strong>Methods: </strong>Our prospective, cohort study included two groups of women in reproductive age requiring metformin therapy with mild or moderate hyperprolactinemia. Patients with concomitant grade 1 subclinical hyperthyroidism (group A) and individuals without thyroid pathology (group B) were matched for age, insulin sensitivity and total prolactin levels. Glucose homeostasis markers, TSH, free thyroid hormones, total and monomeric prolactin, FSH, LH, estradiol, ACTH, IGF-1 and peripheral markers of thyroid hormone action (ferritin and osteocalcin) were measured before and after six-month metformin therapy.</p><p><strong>Results: </strong>At baseline, both groups differed in levels of TSH, free thyroid hormones, ferritin and osteocalcin. Although metformin reduced glucose, improved insulin sensitivity and reduced total and monomeric prolactin in both groups, these effects were more pronounced in group A than group B. The impact on prolactin in group A correlated with concentrations of free thyroid hormones. Only in group A, did metformin slightly increase FSH and LH concentrations. In women with hyperthyroidism and without thyroid pathology, there were no statistical differences between baseline and follow-up levels of the remaining variables.</p><p><strong>Conclusion: </strong>The study results suggest that hyperthyroidism potentiates the impact of metformin on secretory function of overactive lactotrophs in reproductive-age women.</p>","PeriodicalId":19117,"journal":{"name":"Neuroendocrinology","volume":" ","pages":"1-16"},"PeriodicalIF":3.2,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143753696","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neurotrophic effects of GH and GnRH in a full sciatic nerve transection model in male rats.","authors":"Jorge J A Baca-Alonso, Denisse Calderón-Vallejo, Irma Hernández-Jasso, David Epardo, Jerusa E Balderas-Márquez, Maricela Luna, Carlos Arámburo, J Luis Quintanar, Carlos G Martínez-Moreno","doi":"10.1159/000545129","DOIUrl":"https://doi.org/10.1159/000545129","url":null,"abstract":"<p><p>Peripheral nerve injuries, such as sciatic nerve transection (SNT), are associated with significant sensory and motor deficits. Growth hormone (GH) and gonadotropin-releasing hormone (GnRH) have been shown to exert neurotrophic effects that can promote nerve regeneration and functional reinnervation. However, the combined impact of these hormones on peripheral nerve repair remains poorly understood. This study aimed to analyze the individual and combined effects of GH and GnRH in a rat model of SNT, using orchiectomized male rats to prevent steroid-mediated neuroregeneration and neuroprotection. Treatments included GH, GnRH, or a combination of both, with subsequent assessments of motor and sensory function, as well as histological and molecular analyses of the nerve tissue and associated muscles. The results revealed that both GH and GnRH significantly enhanced nerve regeneration and neural function when administered individually. Treated animals exhibited improved axonal growth, myelination, as well as sensory and motor functional recovery. In addition, GH and GnRH reduced neuroinflammation/reactive gliosis, as evidenced by the downregulation of TNFα IL-1β, Iba-1 and GFAP, which are typically elevated following nerve injury. These findings indicate that each hormone independently supports critical aspects of nerve repair and functional restoration after injury. Surprisingly, when GH and GnRH were administered together, their beneficial effects were not additive. Instead, the combination of the two treatments led to diminished outcomes in comparison to either treatment alone. Specifically, animals receiving the combined therapy showed reduced axonal organization, impaired myelination, and less functional improvement. In conclusion, GH and GnRH demonstrate potential as individual therapeutic agents for promoting nerve regeneration, each providing significant benefits in terms of axonal growth, functional recovery, and reduction of neuroinflammation.</p>","PeriodicalId":19117,"journal":{"name":"Neuroendocrinology","volume":" ","pages":"1-32"},"PeriodicalIF":3.2,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143657871","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical and Genetic Factors Associated with Neuroendocrine Neoplasms - a UK Biobank Study.","authors":"Harry David Green, Marie Line El-Asmar, Brian Rous, Gareth Hawkes, Maria Trinidad Moreno-Montilla, Christina Thirlwell, John Ramage","doi":"10.1159/000545114","DOIUrl":"https://doi.org/10.1159/000545114","url":null,"abstract":"<p><p>Background Incidence of neuroendocrine neoplasms (NEN) is rising globally, yet clinical and genetic factors remain poorly understood. Evidence for the role of obesity is conflicted and studies on prospectively collected data is sparse. We aimed to identify clinical and germline genetic risk factors associated with NEN in the UK Biobank. Methods Cases of NEN were identified in the UK Biobank's cancer registry data (N~500,000). Using a combination of ICD-O3 codes for cancer site and histology, NEN cases were stratified into neuroendocrine tumour (NET), neuroendocrine carcinoma (NEC) and small / large cell lung cancer (SLCLC). A Cox-proportional hazards model was used to test for an association between clinical phenotypes and increased NEN risk, and a gene burden test in Regenie was used to test for causal variants in the exome sequencing data. Results We identified 704 NET, 340 NEC, and 550 SLCLC cases. Obesity (body mass index or waist-hip-ratio) and lower cholesterol (LDL, HDL or total) had a significantly significant association with NEN risk, however the effect size was marginal. Smoking and HbA1c associated only with SLCLC. Air pollution was not significantly associated when adjustment was made for socio-economic status. We replicated a known germline association between loss of function variants in MEN-1 and NEC, but did not detect any novel association in exome variants. Discussion This is the first large prospective population-based study to identify potential clinical and genetic risk factors for NEN and defined a novel phenotype in the UK Biobank. More research is needed to establish whether these relationships are causal. The exome study was underpowered, and future work in this area should focus on meta-analysing multiple large datasets.</p>","PeriodicalId":19117,"journal":{"name":"Neuroendocrinology","volume":" ","pages":"1-10"},"PeriodicalIF":3.2,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143625348","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Review for the Clinician: Classifications, Genetics, and Treatment for Neuroendocrine Neoplasms of the Thymus (Thymic Carcinoids).","authors":"Matthias Lang, Chrysanthi Anamaterou, Isabelle Mohr, Mária Černá, Manuel Röhrich, Christine Tjaden","doi":"10.1159/000544982","DOIUrl":"10.1159/000544982","url":null,"abstract":"<p><strong>Background: </strong>Thymic carcinoids or neuroendocrine neoplasms (t-NEN) are a rare entity with a dismal prognosis. About 25% of the tumors are related to multiple endocrine neoplasia type I (MEN-1), where they contribute significantly to mortality. The tumors are classified according to the WHO classification, TNM classification and Masaoka-Koga staging system, although none of the classifications have been developed for t-NEN. A recently proposed t-NEN specific morphomolecular classification is based on copy number instability scores. Its role is yet to be defined. The prognosis depends on resectability, histological features, metastasis, the amount of copy number instabilities and mitotic activity.</p><p><strong>Summary: </strong>No study-based therapies exist. The mainstay of therapy is surgical resection as it is associated with significantly improved long-term survival. Based on published cases and small series, for non-resectable and recurring disease, platinum-based chemotherapies are preferred in neuroendocrine carcinoma, while everolimus and temozolomide are recommended in thymic neuroendocrine tumors.</p><p><strong>Key messages: </strong>This review covers current classification systems and the knowledge of genetic disorders and medical therapies.</p>","PeriodicalId":19117,"journal":{"name":"Neuroendocrinology","volume":" ","pages":"1-12"},"PeriodicalIF":3.2,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143605378","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Are Neuroendocrine Neoplasms No Longer a Rare Cancer?","authors":"Catherine Bouvier Ellis, Nicola Jervis","doi":"10.1159/000544984","DOIUrl":"10.1159/000544984","url":null,"abstract":"<p><strong>Background: </strong>Neuroendocrine neoplasms (NENs) are consistently referred to as a \"relatively\" rare heterogenous group of \"tumours\" with variability in their disease course and outcomes. However, there is a lack of consensus on (a) the group membership, that is, a lack of consistency in which \"subtypes\" of NEN are included in the group; (b) whether they should continue to be seen as a \"heterogenous group,\" or as separate entities; and (c) whether the term and current definitions of \"rare\" accurately reflects the true patient population and healthcare requirement.</p><p><strong>Summary: </strong>This opinion article explores the concept of rare, as applied to NENs: the significance of a rare cancer label and what this means for awareness, healthcare provision and, tangentially, those diagnosed. It briefly explores rare cancer definitions, including incidence thresholds and interpretation of definition as demonstrated in the variability in what subtypes are included in databanks or registries, and it also asks whether the currently utilised rare cancer definitions reflect an accurate representation of the true disease burden and fully inform disease-appropriate healthcare planning and provision.</p><p><strong>Key messages: </strong>The current definition of \"rare cancer\" based on incidence alone fails to reflect the true disease burden of NENs and is therefore inadequate, to fully inform healthcare policy, planning and provision for this patient population. This requires either a revision in definition or an alteration in how and what decision-makers utilise and include in their deliberations when assessing and planning service provision.</p>","PeriodicalId":19117,"journal":{"name":"Neuroendocrinology","volume":" ","pages":"1-5"},"PeriodicalIF":3.2,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143586406","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cocaine Self-Administration Differentially Modulates the Content of Cholesterol, Progesterone, and Testosterone in the Brain and Plasma of Male Rats.","authors":"William B Inabinett, Shiyu Wang, Paige M Estave, Emily G Peck, Sara R Jones, Rong Chen","doi":"10.1159/000544983","DOIUrl":"10.1159/000544983","url":null,"abstract":"<p><strong>Introduction: </strong>Chronic cocaine exposure results in changes in circulating steroid hormones, which is known to be associated with cocaine-seeking and cocaine-taking behavior. However, whether cocaine also alters the brain content of these steroid hormones and cholesterol, a precursor to all steroid hormones, has yet to be extensively investigated. Thus, the goal of this study was to determine whether cocaine self-administration (SA) altered the content of cholesterol and steroid hormones (progesterone and testosterone) in both the plasma and the brain of animals.</p><p><strong>Methods: </strong>Male Sprague-Dawley rats were allowed to self-administer cocaine (1.5 mg/kg/infusion) for a maximum of 40 injections within 6 h per day for 5 consecutive days followed by cue reactivity test and cocaine SA under the progressive ratio schedule as a measure of motivation to acquire cocaine. Eighteen hours after the last behavior test, the blood and brain tissue, including the prefrontal cortex (PFC) and dorsal striatum (CPu), were collected for biochemical assays.</p><p><strong>Results: </strong>While cocaine SA did not alter the content of cholesterol and progesterone in the plasma, it reduced cholesterol content and almost completely abolished progesterone content in both the PFC and CPu. Further, testosterone levels were reduced in the CPu and plasma. Notably, plasma testosterone was positively correlated with its content in the PFC and CPu.</p><p><strong>Conclusions: </strong>Cholesterol and progesterone in the brain are more sensitive to changes induced by cocaine SA than those in the plasma. Future studies should focus on understanding the functional consequence of altered brain steroids on neurotransmission and cocaine-seeking and cocaine-taking behavior.</p>","PeriodicalId":19117,"journal":{"name":"Neuroendocrinology","volume":" ","pages":"1-10"},"PeriodicalIF":3.2,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143542629","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Doppler Assessment of the Uterine Arteries Is a Valuable Adjunct Tool for the Evaluation of Efficacy of Gonadotropin-Releasing Hormone Agonist Therapy in Girls with Central Precocious Puberty.","authors":"Amanda Veiga Cheuiche, Letícia Guimarães da Silveira, Iara Regina Siqueira Lucena, Márcia Puñales, Fabiola Costenaro, Cristiane Kopacek, Gustavo Monteiro Escott, Sandra Pinho Silveiro, Leila Cristina Pedroso de Paula","doi":"10.1159/000544985","DOIUrl":"10.1159/000544985","url":null,"abstract":"<p><strong>Introduction: </strong>Pelvic ultrasound has been studied for the follow-up of girls with precocious puberty during gonadotropin-releasing hormone agonists (GnRHa) therapy. The addition of Doppler evaluation of uterine arteries needs to be further investigated. We aimed to evaluate the accuracy of the uterine artery pulsatility index (PI) for monitoring GnRHa therapy in girls with precocious puberty.</p><p><strong>Methods: </strong>This is a retrospective cohort study of girls with central precocious puberty (CPP) and early and fast puberty (EFP) treated with GnRHa. We included girls who underwent pelvic ultrasound and Doppler imaging of the uterine arteries before and during therapy. Analyses included uterine artery PI and uterine, endometrial, and ovarian measurements. Receiver operating characteristic (ROC) curves with cutoffs determined by the Youden index were used for data analysis.</p><p><strong>Results: </strong>In total, 28 pairs of PI measurements (54% of girls with CPP, 46% with EFP) before and during GnRHa therapy were included in the paired-sample analysis. The median duration of treatment at the time of ultrasound was 11.5 (7; 19) months. The mean PI was significantly higher during GnRHa therapy than at baseline (6.5 ± 1.8 vs. 4.0 ± 1.6, respectively, p < 0.001). A total of three girls met clinical and laboratory criteria for treatment failure. ROC curve analysis showed that the PI was able to identify an effective GnRHa therapy with a mean area under the curve of 0.967 ± 0.04 (p < 0.001), and the PI cutoff point of 5.4 held a sensitivity of 84%, specificity of 100%, and accuracy of 86%.</p><p><strong>Conclusion: </strong>We found a significant increase in the PI during GnRHa therapy, which reflects higher resistance in the blood flow to the uterus, indicating effective pubertal hormone suppression.</p>","PeriodicalId":19117,"journal":{"name":"Neuroendocrinology","volume":" ","pages":"1-10"},"PeriodicalIF":3.2,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143542631","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Involvement of the AVP/OT System and Lateral Septum in the Modulation of Anxiety/Depression Caused by 14-Week and 20-Week Social Isolation.","authors":"Jing Liu, Weizheng Zhang, Yuting Bai, Rui Fu, Miao Lin, Jialong Li, Liangteng Nie, Xiaohui Dang, Qiao Wang, Yunmeng Zhu, Lu Li, Xing Guo, Lizi Zhang, Yishan Qu, Kaizhe Huang, Xiao Han, Shufeng Shang, Jiayu Xiao, Yin Li, Caihong Huang, Rui Jia, Zhixiong He, Fadao Tai","doi":"10.1159/000544839","DOIUrl":"10.1159/000544839","url":null,"abstract":"<p><strong>Introduction: </strong>Chronic social isolation (CSI) stress leads to numerous maladaptive changes in physiology and psychology, however, very little is known about the effects of longer time-scale CSI and there are divergent views regarding the underlying mechanisms. This study aimed to elucidate the common neuroendocrine mechanisms underlying the maladaptive changes caused by 14-week (14wk) and 20-week (20wk) CSI.</p><p><strong>Methods: </strong>We investigated the impacts of 14wk and 20wk CSI on anxiety-/depression-like behaviors in male C57BL/6N mice with classical behavioral tests, and the immunofluorescence (IF) method was used for quantification of the arginine vasopressin (AVP)/oxytocin (OT) positive neurons in the PVN and screening out the differential activation brain regions (DABrs) on exposure of tail suspension. The expression of Avpr1a and Oxtr in the lateral septum (LS) was assessed by quantitative RT-PCR (qPCR), and the function of LSD Avpr1a+/+ neurons in emotion regulation was verified with pharmacological approaches. The concentration of AVP/OT in plasma was examined with the enzyme-linked immunosorbent assay (ELISA).</p><p><strong>Results: </strong>14wk and 20wk CSI increased anxiety-/depression-like behaviors and altered levels of exploratory locomotion in opposite directions, which are likely due to an imbalance of the AVP/OT system within the PVN and peripheral plasma, differential activation of LSD and thalamic brain regions, and abnormal expression of Avpr1a in LS. Pharmacological results demonstrated that Avpr1a+/+ neurons in the LSD were involved in emotion regulation.</p><p><strong>Conclusion: </strong>This study suggests that the imbalance of the AVP/OT system and the dysfunction of Avpr1a+/+ neurons in the LSD were engaged in common neuroendocrinology mechanisms for anxiety/depression induced by long-term CSI.</p>","PeriodicalId":19117,"journal":{"name":"Neuroendocrinology","volume":" ","pages":"1-27"},"PeriodicalIF":3.2,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143502867","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ectopic Corticotropin-Releasing Hormone/Adrenocorticotropic Hormone-Co-Secreting Neuroendocrine Tumors Leading to Cushing's Disease: A Case Presentation and Literature Review.","authors":"Jasmin Ewert, Maximilian Seidl, Jann Achim Hommen, Matthias Schott, Norbert Gattermann","doi":"10.1159/000544727","DOIUrl":"10.1159/000544727","url":null,"abstract":"<p><strong>Background: </strong>Adrenocorticotropic hormone (ACTH) and corticotropin-releasing hormone (CRH) are essential regulators of cortisol production within the hypothalamic-pituitary-adrenal (HPA) axis. Elevated cortisol levels, resulting from excessive ACTH, can lead to Cushing's syndrome, a condition associated with significant morbidity. Neuroendocrine tumors (NETs) can ectopically produce both ACTH and CRH, a rare phenomenon that further contributes to this syndrome.</p><p><strong>Summary: </strong>This review discusses the pathophysiology, types, clinical presentation, diagnosis, and management of NETs that ectopically secrete CRH and ACTH. Particular emphasis is placed on the importance of identifying dual CRH/ACTH secretion, which complicates diagnosis and treatment. Furthermore, the review highlights the prognosis, common complications, and future directions for research in this area. We further report the case of a 53-year-old female patient who presented with severe Cushing's syndrome and was diagnosed with ectopic ACTH syndrome. Despite initial findings suggesting pituitary-dependent hypercortisolism, further investigations revealed the presence of a highly differentiated, atypically located tumor in the lung. Immunohistochemistry of the tumor tissue demonstrated not only ACTH but also CRH and CRH-R1 expression. The simultaneous expression of these molecules supports the hypothesis of a positive endocrine feedback loop within the NET, in which the release of CRH stimulates ACTH expression via binding to CRH-R1.</p><p><strong>Key messages: </strong>This case report highlights the challenges in diagnosing and managing ectopic ACTH syndrome, emphasizing the importance of a comprehensive diagnostic approach to identify secondary factors influencing cortisol production, such as CRH secretion and other contributing neuroendocrine mechanisms. Recognizing the dual secretion of CRH and ACTH in NETs is crucial for accurate diagnosis and optimizing patient management.</p>","PeriodicalId":19117,"journal":{"name":"Neuroendocrinology","volume":" ","pages":"1-13"},"PeriodicalIF":3.2,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143433554","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}