The Journal of clinical endocrinology and metabolism最新文献

{"title":"Renaming PCOS to polyendocrine metabolic ovarian syndrome: still an impediment to progress.","authors":"Andrea Dunaif, David A Ehrmann","doi":"10.1210/clinem/dgag356","DOIUrl":"10.1210/clinem/dgag356","url":null,"abstract":"","PeriodicalId":520805,"journal":{"name":"The Journal of clinical endocrinology and metabolism","volume":" ","pages":"e2439-e2440"},"PeriodicalIF":5.1,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13671764/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148868933","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The dynamic adrenal response of children to cardiac surgery and cardiac catheterization.","authors":"Daniel Paul Fudulu, Isabella Marinelli, Daniel Galvis, Eder Zavala, Terrie Walker-Smith, Jonathan Evans, Fanoula Papadopoulou, Thomas Upton, Aravind Ramesh, Filippo Rapetto, Yvonne Kershaw, Jan Fox, Angela Aramburo, Serban Constantin Stoica, Massimo Caputo, Andrew Parry, Duncan Macrae, Guido Michielon, Johann Andreas Hoschtitzky, Karen Sheehan, Martijn van Faassen, Ido Kema, Gianni Davide Angelini, Stafford Lightman, Ben Gibbison","doi":"10.1210/clinem/dgag206","DOIUrl":"10.1210/clinem/dgag206","url":null,"abstract":"<p><strong>Context: </strong>The hypothalamic-pituitary-adrenal (HPA) axis is the key homeostatic system regulating the response to surgical stress. Imbalances in HPA axis hormones increase morbidity and mortality in children after cardiac surgery. Despite this, the physiology of the HPA axis in children undergoing cardiac surgery is poorly understood, leading to controversies in clinical practice.</p><p><strong>Objective: </strong>To characterize dynamic HPA axis responses in children undergoing cardiac surgery and to determine age- and procedure-related differences in cortisol and cortisone physiology.</p><p><strong>Methods: </strong>We recruited children (0-18 years) undergoing cardiac surgery with cardiopulmonary bypass or cardiac catheterization. Tissue-free cortisol and cortisone were sampled every 20 minutes for up to 24 hours via microdialysis, alongside serum adrenocorticotropic hormone (ACTH), cortisol, cortisol-binding globulin (CBG), and inflammatory markers. We developed dynamic markers to quantify age- and procedure-dependent differences in hormonal responses and built a mathematical model to explain them.</p><p><strong>Results: </strong>Neonates undergoing surgery showed higher free cortisol and cortisone AUC and peak concentrations than catheterization patients. Neonates had higher peaks of cortisol and cortisone than older children undergoing surgery. The much higher tissue cortisone levels observed in neonates can be explained by enzymatic interconversion between cortisol and cortisone, likely due to persistent fetal high 11-βHSD2 activity and reduced 11-βHSD1 activity. Low postoperative blood cortisol and CBG values in neonates resulted in high free cortisol peaks in interstitial fluid during and after surgery.</p><p><strong>Conclusion: </strong>Neonates differ physiologically, with higher free cortisol levels that more readily diffuse into interstitial tissues, with implications for perioperative management.</p>","PeriodicalId":520805,"journal":{"name":"The Journal of clinical endocrinology and metabolism","volume":" ","pages":"3240-3249"},"PeriodicalIF":5.1,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13671769/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147937291","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bone phenotype of patients with genetic forms of lipodystrophy: a systematic review of literature.","authors":"Elif Kusgozoglu, Daniela Q C M Barge-Schaapveld, Patrick C N Rensen, Tim Roek, Hester Vlaardingerbroek, Ingrid M Jazet, Natasha M Appelman-Dijkstra","doi":"10.1210/clinem/dgag256","DOIUrl":"10.1210/clinem/dgag256","url":null,"abstract":"<p><strong>Objective: </strong>Congenital lipodystrophies (LDs), including congenital generalized LD (CGL) and familial partial LD (FPLD), are rare disorders characterized by absent or abnormal adipose tissue distribution, leading to clinical, hormonal, and metabolic complications. Although these systemic features are well described, data on bone involvement are limited. This literature review summarizes current evidence on bone manifestations in genetic LDs and potential underlying mechanisms.</p><p><strong>Methods: </strong>A systematic search was performed in PubMed, EMBASE, and the Cochrane Library using terms related to LD and bone outcomes. No restrictions on date, language, or study design were applied. Studies reporting bone-related outcomes in genetic LD in humans were included. Study quality was assessed using PRISMA guidelines and the JBI checklist.</p><p><strong>Results: </strong>Of 2632 studies identified, 15 met the inclusion criteria. Most focused on CGL1 and CGL2; no studies were found on CGL3 or CGL4. Reported bone abnormalities in CGL1 and CGL2 included osteolytic lesions, bone cysts, osteosclerosis, and pseudo-osteopoikilosis, predominantly in long bones. Bone mineral density (BMD) was generally normal to high at trabecular sites. In contrast, FPLD2 was characterized by reduced BMD at cortical sites and lower trabecular bone score, suggesting impaired bone quality. Proposed mechanisms include reduced bone marrow adipose tissue, disrupted marrow fat conversion, and altered endocrine signaling.</p><p><strong>Conclusion: </strong>Bone abnormalities are characteristic yet often underrecognized features of genetic LDs, particularly CGL1 and CGL2. Current evidence underlines the broad skeletal impact of adipose dysfunction and highlights the need for standardized, genetically stratified studies to clarify bone risk and guide clinical management in congenital LD.</p>","PeriodicalId":520805,"journal":{"name":"The Journal of clinical endocrinology and metabolism","volume":" ","pages":"3005-3011"},"PeriodicalIF":5.1,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13671773/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148393293","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Classification of glucose profile in Japanese patients with type 1 diabetes and its association with complications.","authors":"Takafumi Masuda, Naoto Katakami, Naohiro Taya, Kazuyuki Miyashita, Mitsuyoshi Takahara, Ken Kato, Iichiro Shimomura","doi":"10.1210/clinem/dgag224","DOIUrl":"10.1210/clinem/dgag224","url":null,"abstract":"<p><strong>Context: </strong>The importance of utilizing continuous glucose monitoring (CGM) to optimize glycemic profiles and thereby prevent the onset of diabetic complications in patients with type 1 diabetes has been increasingly recognized. Nevertheless, studies evaluating the risk of diabetic complications in patients with type 1 diabetes through machine learning approaches based on CGM data remain limited.</p><p><strong>Objective: </strong>To classify the glycemic profiles of Japanese patients with type 1 diabetes using a data-driven cluster analysis based on CGM and clarify the association between these clusters and diabetic complications.</p><p><strong>Methods: </strong>In this cross-sectional study, a cluster analysis using glycemic metrics from CGM of 153 Japanese patients with type 1 diabetes was performed. Logistic regression analysis adjusted for age, sex, and duration of diabetes was performed to compare the risk of diabetic complications by cluster.</p><p><strong>Results: </strong>The cluster analysis identified four clusters. Cluster 1 (n = 53) exhibited an optimal glycemic profile. Cluster 2 (n = 46) demonstrated an extended duration of hyperglycemia and a higher risk of elevated brachial-ankle pulse wave velocity than Cluster 1. Cluster 3 (n = 39) demonstrated an extended duration of hypoglycemia and a higher risk of severe hypoglycemia than Cluster 1. Cluster 4 (n = 15) demonstrated large glycemic variability associated with hyperglycemia and hypoglycemia. Cluster 4 had higher risks of polyneuropathy, elevated brachial-ankle pulse wave velocity, and higher cardiovascular disease risk scores than Cluster 1.</p><p><strong>Conclusion: </strong>High-risk diabetic complications were identified for each cluster classified by glycemic profile.</p>","PeriodicalId":520805,"journal":{"name":"The Journal of clinical endocrinology and metabolism","volume":" ","pages":"3085-3093"},"PeriodicalIF":5.1,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13671772/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148207644","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hippocampal volume and white matter impairments in patients with congenital adrenal hyperplasia.","authors":"Alice Savoia, Diana Kancsar, Anna Nordenström, Annelies Van't Westeinde, Svetlana Lajic","doi":"10.1210/clinem/dgag312","DOIUrl":"10.1210/clinem/dgag312","url":null,"abstract":"<p><strong>Context: </strong>Patients with congenital adrenal hyperplasia (CAH) have lifelong imbalances in adrenal hormones that may result in changes in structure and function of the brain that can impair cognitive performance. The hippocampus might be especially sensitive to cortisol and androgen disturbances but has not been systematically investigated in this patient group.</p><p><strong>Objective: </strong>In this study, we assessed hippocampal subfield volumes, mean diffusivity, and resting-state functional connectivity along with memory performance in patients with CAH and healthy controls using structural magnetic resonance imaging.</p><p><strong>Design: </strong>Cohort study; patients were recruited and tested as part of the PREDEX study.</p><p><strong>Setting: </strong>Single research institute.</p><p><strong>Participants: </strong>Twenty-nine patients with CAH (20 females, 9 males) and 33 healthy controls (19 females, 14 males).</p><p><strong>Intervention(s): </strong>No intervention was performed.</p><p><strong>Main outcome measure(s): </strong>Hippocampal subfield volumes, mean diffusivity, resting-state functional connectivity, and memory performance.</p><p><strong>Results: </strong>Patients with CAH had reduced left CA4 and left and right subiculum volumes. In the group by sex interaction analyses, males presented higher mean diffusivity in left CA3 and CA4 compared to controls. When looking at males and females separately, it was identified that females had reduced volumes of the bilateral subiculum, CA1, and left CA3 and CA4. Hippocampal structural alterations were not associated with memory performance.</p><p><strong>Conclusions: </strong>Patients with CAH had structural alterations in several hippocampal subfield volumes, but there might be a discrepancy between males and females in sensitivity to white or gray matter impairments. The findings warrant further investigation into sex-specific differences in treatment sensitivity to optimize brain health in both men and women with CAH.</p>","PeriodicalId":520805,"journal":{"name":"The Journal of clinical endocrinology and metabolism","volume":" ","pages":"e2392-e2402"},"PeriodicalIF":5.1,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13671783/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148633386","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to: \"Prevalence of Psychiatric Comorbidities in Females with Classic Congenital Adrenal Hyperplasia\".","authors":"","doi":"10.1210/clinem/dgag333","DOIUrl":"10.1210/clinem/dgag333","url":null,"abstract":"","PeriodicalId":520805,"journal":{"name":"The Journal of clinical endocrinology and metabolism","volume":" ","pages":"e2450-e2451"},"PeriodicalIF":5.1,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13671778/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148805600","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gestational hypothyroidism and pregnancy outcomes following hemithyroidectomy: a nationwide matched cohort study.","authors":"Dor Atias, Raviv Allon, Nofar Ben-Basat, Michal Kovo, Guy Melamed, Yaki Saciuk, Tal Patalon","doi":"10.1210/clinem/dgag235","DOIUrl":"10.1210/clinem/dgag235","url":null,"abstract":"<p><strong>Background: </strong>Hemithyroidectomy is increasingly performed in women of reproductive age, but its implications for thyroid function during pregnancy and obstetric outcomes remain unclear.</p><p><strong>Objective: </strong>To assess gestational hypothyroidism and the risks of preterm birth and pregnancy loss among pregnancies in women with prior hemithyroidectomy vs matched pregnancies in women without thyroid surgery.</p><p><strong>Methods: </strong>We conducted a retrospective matched cohort study using anonymized electronic medical records from Maccabi Healthcare Services, Israel, from 2002 to 2023. Pregnancies with at least one thyroid-stimulating hormone (TSH) measurement were included. Pregnancies after hemithyroidectomy were matched to pregnancies without thyroid surgery using exact matching on maternal age, gravidity, and pregnancy year, followed by propensity-score matching on sociodemographic and clinical covariates. Gestational hypothyroidism was defined as TSH >4.0 mIU/L or levothyroxine initiation during pregnancy and analyzed using generalized estimating equations. Pregnancy loss and preterm birth were analyzed using a weighted time-varying Cox model with gestational age as the time scale, incorporating thyroid status and levothyroxine treatment as time-varying covariates and a hemithyroidectomy-by-trimester interaction.</p><p><strong>Results: </strong>The matched cohort included 463 pregnancies after hemithyroidectomy and 2293 matched controls. Prior hemithyroidectomy was associated with higher odds of gestational hypothyroidism (adjusted odds ratio, 4.2; 95% CI, 2.9-6.3; P < .01). In the time-varying outcome analysis, hemithyroidectomy was not associated with increased first-trimester pregnancy loss (hazard ratio [HR], 0.9; 95% CI, 0.7-1.1; P = .29), but was associated with higher hazard of preterm birth or pregnancy loss during the second and third trimesters (HR, 1.6; 95% CI, 1.3-2.0; P < .01).</p><p><strong>Conclusion: </strong>Prior hemithyroidectomy was associated with gestational hypothyroidism and modestly higher later-gestation hazard of preterm birth or pregnancy loss, supporting enhanced thyroid surveillance during pregnancy.</p>","PeriodicalId":520805,"journal":{"name":"The Journal of clinical endocrinology and metabolism","volume":" ","pages":"3042-3049"},"PeriodicalIF":5.1,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148221620","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of recurrent hypoglycemia on brain glucose transport kinetics in type 1 diabetes.","authors":"Elizabeth R Seaquist, Young Woo Park, Anjali Kumar, Alison Alvear, Lujun Zhang, Brent Strong, Lynn Eberly, Pierre-Gilles Henry, Gülin Öz","doi":"10.1210/clinem/dgag205","DOIUrl":"10.1210/clinem/dgag205","url":null,"abstract":"<p><strong>Context: </strong>Impaired awareness of hypoglycemia (IAH) significantly impacts efforts to maintain optimal glycemia. Impaired awareness of hypoglycemia occurs when recurrent episodes of hypoglycemia (HG) occur within a short period of time, but the mechanisms are unknown. Upregulation of glucose transport may contribute to the development of IAH.</p><p><strong>Objective: </strong>To determine if brain glucose transport is upregulated in response to recurrent HG in people with type 1 diabetes (T1D) and normal awareness of hypoglycemia.</p><p><strong>Methods: </strong>Participants were recruited from a clinical registry. Inclusion criteria were diagnosis of T1D, 18-65 years, hemoglobin A1C < 8.5%, and diabetes duration of 2-25 years. Exclusion criteria included IAH on the Clarke and Gold questionnaires. Forty-five subjects enrolled and 30 completed the entire 3-day protocol. Participants underwent magnetic resonance spectroscopy scans at 3 tesla during which they were clamped at 150, 225, or 300 mg/dL before and after exposure to three 2-hour HG (target = 50 mg/dL) clamps over 2 days between December 2020 and June 2023. The primary metabolite of interest was glucose. Brain glucose transport kinetics were measured in the hypothalamus (HTL) and prefrontal cortex (PFC) during hyperglycemic clamps using reversible symmetric Michaelis-Menten model.</p><p><strong>Results: </strong>Brain glucose transport kinetics measured during hyperglycemic clamps was not different before vs after exposure to recurrent HG clamps.</p><p><strong>Conclusion: </strong>Short-term exposure to recurrent HG does not upregulate glucose transport kinetics in the setting of T1D.</p>","PeriodicalId":520805,"journal":{"name":"The Journal of clinical endocrinology and metabolism","volume":" ","pages":"3229-3239"},"PeriodicalIF":5.1,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13671781/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147937243","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of cortisol circadian rhythm on psychological well-being in treated Cushing syndrome: a cross-sectional study.","authors":"Angeliki Theodorou, Emily C Tan, Anne S Reiner, Maria Sazo, Marc A Cohen, Andrew L Lin, Viviane Tabar, Eliza B Geer","doi":"10.1210/clinem/dgag232","DOIUrl":"10.1210/clinem/dgag232","url":null,"abstract":"<p><strong>Context: </strong>Patients with Cushing syndrome (CS) often experience impaired quality of life (QoL) and mood despite biochemical control. The relationship between late-night salivary cortisol (LNSC) and psychological outcomes remains poorly characterized.</p><p><strong>Objective: </strong>Assess QoL and mood outcomes in biochemically controlled CS patients based on circadian rhythm restoration.</p><p><strong>Design: </strong>Cross-sectional.</p><p><strong>Setting: </strong>Tertiary-care center.</p><p><strong>Participants: </strong>Ninety treated, biochemically controlled patients with CS (84 Cushing disease (CD); 6 adrenal CS), stratified into 3 groups: normal LNSC (Group A), abnormal LNSC (Group B), on long-term GC replacement (Group C).</p><p><strong>Main outcome measures: </strong>Hospital Anxiety and Depression Scale (HADS), CushingQoL questionnaire, Nottingham Health Profile (NHP).</p><p><strong>Results: </strong>Group A had lower HADS-Anxiety (4 vs 7, A vs B; P = .006) and (HADS-Depression 2.5 vs 6 vs 9, A vs B; P = .006, A vs C; P < .001). QoL was better in Group A vs C in psychosocial (67.5 vs 39.5; P < .001) and physical (63.9 vs 44.3; P = .005) domains. Group A had better emotional reaction (0 vs 24; P = .002), A vs B; energy level (0 vs 63; P = .001), and sleep (13 vs 56; P < .001), A vs C. In multivariable analyses excluding Group C, LNSC normalization was consistently associated with better outcomes in all HADS domains, CushingQoL psychosocial, NHP emotional reaction, social isolation, physical abilities, and home relationships. Group B had the highest diabetes rate. Among patients with surgically remitted CD, 18.6% had abnormal LNSC, characterizing a previously unrecognized clinical phenotype.</p><p><strong>Conclusion: </strong>In biochemically controlled CS, LNSC normalization correlates with QoL, mood, and metabolic outcomes, and could represent a therapeutic target.</p>","PeriodicalId":520805,"journal":{"name":"The Journal of clinical endocrinology and metabolism","volume":" ","pages":"e2356-e2368"},"PeriodicalIF":5.1,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13671768/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148255460","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Heterogeneity of MGMT expression in corticotroph adenomas and mechanism of acquired temozolomide resistance.","authors":"Ticiana Paes, Richard A Feelders, Fadime Dogan, Anand M Iyer, Johan M Kros, Yair Schwarz, Peter M van Koetsveld, Leo J Hofland","doi":"10.1210/clinem/dgag170","DOIUrl":"10.1210/clinem/dgag170","url":null,"abstract":"<p><strong>Context: </strong>Temozolomide (TMZ) can be an effective medical treatment for aggressive pituitary tumors. In case of disease recurrence following TMZ treatment, however, treatment with the drug generally does not control tumor regrowth.</p><p><strong>Objective: </strong>This work aimed to better understand the mechanisms of resistance of corticotroph tumors to TMZ in the context of heterogeneity of methylguanine-DNA methyltransferase (MGMT) expression.</p><p><strong>Methods: </strong>We performed immunohistochemical analysis of the MGMT expression pattern in 25 corticotroph tumors to evaluate intratumoral heterogeneity. In addition, we created in vitro models of AtT20 corticotroph tumor cells with acquired TMZ-resistance after exposure to high- and low-dose TMZ, the latter representing a clinically achievable TMZ level.</p><p><strong>Results: </strong>MGMT immunostaining in corticotroph tumors showed a considerable heterogeneous intertumoral and intratumoral distribution pattern in 80% of tumors. In the in vitro model, high- and low-dose TMZ challenges induced a 6.3- and 3.4-fold decreased sensitivity to the growth inhibitory effect of TMZ. TMZ-induced changes in cell cycle phases were lower in TMZ-resistant cells than in vehicle-challenged cells. TMZ-resistant cells had higher Mgmt messenger RNA and protein expression and 1.8-fold higher number of Mgmt-positive cells. No difference was observed in the level of Mgmt promoter methylation.</p><p><strong>Conclusion: </strong>Corticotroph pituitary tumors demonstrate a high intertumoral and intratumoral heterogeneity in MGMT expression. In an acquired TMZ-resistant corticotroph pituitary tumor cell model, TMZ resistance was associated with strong increase in MGMT expression and percentage of MGMT-positive cells. We hypothesize that clonal selection of high MGMT-expressing cells is involved in this acquired TMZ resistance.</p>","PeriodicalId":520805,"journal":{"name":"The Journal of clinical endocrinology and metabolism","volume":" ","pages":"3196-3208"},"PeriodicalIF":5.1,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13671774/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147966977","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}