Journal of the Endocrine Society最新文献

{"title":"The Loss of Estradiol by Androgen Deprivation in Prostate Cancer Patients Shows the Importance of Estrogens in Males.","authors":"Herjan J T Coelingh Bennink, Amanda Prowse, Jan F M Egberts, Frans M J Debruyne, Ilpo T Huhtaniemi, Bertrand Tombal","doi":"10.1210/jendso/bvae107","DOIUrl":"10.1210/jendso/bvae107","url":null,"abstract":"<p><p>The role of estradiol (E2; an estrogen) in men needs to be more appreciated. In this review, we address the clinical situations that allow the study of the clinical consequences of E2 deficiency in men and discuss the effects of restoration of levels of this reproductive steroid hormone. In men with advanced prostate cancer (PCa) undergoing androgen deprivation therapy (ADT), E2 is suppressed along with testosterone, leading to side effects affecting the quality of life. These include hot flashes, arthralgia, fatigue, mood changes, cognition problems, weight gain, bone loss, and increased risk of cardiovascular disease. Transdermal E2 alone for ADT has shown equivalent testosterone suppression compared to gonadotropin-releasing hormone (GnRH) agonists while also preventing estrogen-deficiency side effects, including hot flashes and bone loss. Co-treatment of ADT with fetal estrogen estetrol (E4) has shown significant improvements of estrogen-deficiency symptoms. These observations emphasize the need to raise awareness of the importance of estrogens in men among clinicians and the lay public.</p>","PeriodicalId":17334,"journal":{"name":"Journal of the Endocrine Society","volume":"8 7","pages":"bvae107"},"PeriodicalIF":3.0,"publicationDate":"2024-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11177789/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141331234","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":"Systemic Inflammatory Indices and Liver Dysfunction in Turner Syndrome Patients: A Retrospective Case-control Study.","authors":"Nadia Zaegel, Rigleta Brahimaj, Shyuefang Battaglia-Hsu, Zohra Lamiral, Eva Feigerlova","doi":"10.1210/jendso/bvae099","DOIUrl":"10.1210/jendso/bvae099","url":null,"abstract":"<p><strong>Context: </strong>Liver function abnormalities have been reported in patients with Turner syndrome (TS); however, the pathophysiological mechanisms have not been well elucidated. Low-grade inflammation has been associated with metabolic dysfunction-associated steatotic liver disease.</p><p><strong>Objective: </strong>We studied systemic inflammatory indices [aspartate transaminase to lymphocyte ratio index (ALRI), aspartate transaminase to platelet ratio index (APRI), gamma-glutamyl transferase to platelet ratio (GPR), neutrophil-lymphocyte-ratio (NLR), and platelet lymphocyte ratio and examined their associations with the hepatic abnormalities observed in these subjects.</p><p><strong>Methods: </strong>We performed a retrospective analysis of the medical records of 79 patients with TS (mean age 32.5 ± 9.2 SD years) who were treated at the University Hospital of Nancy. Using matched-pair analyses based on age and body mass index (BMI), we compared 66 patients with TS (25.6 ± 7.3 years; BMI 25.9 ± 6.3 kg/m²) to 66 healthy control participants (24.7 ± 6.8 years; BMI 26 ± 6.7 kg/m²).</p><p><strong>Results: </strong>Liver function abnormalities were present in 57% of the patients with TS. The ALRI, APRI, GPR, and NLR were significantly greater in patients with TS who presented with liver dysfunction than in patients with TS who had normal liver function. According to the matched-pair analyses, the ALRI, APRI, and GPR were greater in patients with TS than in healthy control participants. Logistic regression revealed that a diagnosis of TS was significantly associated with ALRI, APRI, and GPR and liver dysfunction.</p><p><strong>Conclusion: </strong>Noninvasive inflammatory indices (ALRI, APRI, and GPR) might be a promising indicators of liver dysfunction in patients with TS. Future prospective studies are needed to confirm our findings and to explore the clinical significance and prognostic value of systemic inflammatory indices in Turner syndrome.</p>","PeriodicalId":17334,"journal":{"name":"Journal of the Endocrine Society","volume":"8 7","pages":"bvae099"},"PeriodicalIF":3.0,"publicationDate":"2024-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11145559/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141237926","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":"Apelin and Copeptin Levels in Patients With Chronic SIAD Treated With Empagliflozin.","authors":"Sophie Monnerat, Nikolaos Drivakos, Fiona A Chapman, Neeraj Dhaun, Julie Refardt, Mirjam Christ-Crain","doi":"10.1210/jendso/bvae106","DOIUrl":"10.1210/jendso/bvae106","url":null,"abstract":"<p><strong>Background: </strong>Empagliflozin increases sodium levels in patients with a chronic syndrome of inappropriate antidiuresis (SIAD), and dapagliflozin increases apelin levels in patients with diabetes mellitus. Exogenous apelin increases sodium levels in rats with SIAD. We aimed to investigate whether an increase in plasma apelin concentration may contribute to the efficacy of empagliflozin in SIAD.</p><p><strong>Methods: </strong>Post hoc secondary analysis of a double-blind, crossover, placebo-controlled trial performed from December 2017 to August 2021 at the University Hospital Basel, Switzerland, investigating the effect of 4-week treatment with empagliflozin 25 mg/day as compared to placebo in 14 outpatients with chronic SIAD (NCT03202667). The objective was to investigate the effect of empagliflozin on plasma apelin and copeptin concentrations and their ratio.</p><p><strong>Results: </strong>Fourteen patients, 50% female, with a median [interquartile range] age of 72 years [65-77] were analyzed. Median apelin concentration was 956 pmol/L [853, 1038] at baseline. Median [interquartile range] apelin relative changes were +11% [0.7, 21] and +8% [-5, 25] (<i>P</i> = .672) at the end of the placebo and empagliflozin phases, respectively. Median copeptin concentration was 2.6 [2.2, 4.5] pmol/L at baseline and had a relative change of +5 [-2. 11]% and +25% [10, 28] (<i>P</i> = .047) over the placebo and empagliflozin phases, respectively.</p><p><strong>Conclusion: </strong>Empagliflozin did not lead to significant changes in apelin or the apelin/copeptin ratio in patients with chronic SIAD but led to an increase in copeptin. This suggests that the efficacy of empagliflozin in SIAD is independent of apelin and is not blunted by the adaptative increase in copeptin.</p>","PeriodicalId":17334,"journal":{"name":"Journal of the Endocrine Society","volume":"8 7","pages":"bvae106"},"PeriodicalIF":3.0,"publicationDate":"2024-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11170659/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141317646","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 Effect of Apalutamide on Thyroid Function in Prostate Cancer Patients.","authors":"Clare Moffatt, Melissa G Lechner, Trevor E Angell, John Shen, Alexandra Drakaki, Gonzalo J Acosta, Tom Z Liang, Karen Tsai","doi":"10.1210/jendso/bvae105","DOIUrl":"10.1210/jendso/bvae105","url":null,"abstract":"<p><strong>Context: </strong>Apalutamide (APT) is a nonsteroidal antiandrogen medication used to treat metastatic castrate-sensitive and nonmetastatic castrate-resistant prostate cancer. Early clinical trials of APT identified thyroid dysfunction as a common adverse effect of therapy, but the clinical presentation and management of APT-induced hypothyroidism has not been studied.</p><p><strong>Objective: </strong>The objective of our study is to elucidate the clinical presentation and treatment approach of APT-associated thyroid dysfunction in prostate cancer patients.</p><p><strong>Methods: </strong>We report a case series of 16 patients with APT-associated thyroid dysfunction during prostate cancer treatment at 2 academic medical centers. Patient clinical parameters, thyroid function laboratory data, and thyroid hormone requirements over the course of APT treatment were analyzed.</p><p><strong>Results: </strong>Among the 16 patients in our case series with APT-associated hypothyroidism, 3 had no prior thyroid disease and 13 had preexisting hypothyroidism. The patterns of thyroid dysfunction included overt and subclinical hypothyroidism. The median time from APT initiation to thyroid function test abnormality was 19 weeks, but occurred in some cases as early as 2 to 4 weeks. Hypothyroidism was effectively managed with thyroid hormone replacement using levothyroxine (LT4), though some patients with preexisting hypothyroidism required a 2- to 3-fold dose increase while on APT to achieve a euthyroid state. In the subset of patients who completed or stopped APT therapy, thyrotropin levels fell at a median of 11 weeks post APT therapy and thyroid hormone requirements decreased to near pre-APT levels.</p><p><strong>Conclusion: </strong>APT-associated thyroid dysfunction presents as new or worsening hypothyroidism and should prompt initiation or increase in thyroid hormone replacement. Monitoring of thyroid function tests is recommended every 1 to 2 months for all patients on APT and 2 to 3 months after completion of APT.</p>","PeriodicalId":17334,"journal":{"name":"Journal of the Endocrine Society","volume":"8 7","pages":"bvae105"},"PeriodicalIF":3.0,"publicationDate":"2024-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11156616/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141296243","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":"Key Considerations for Studying the Effects of High-Fat Diet on the Nulligravid Mouse Endometrium.","authors":"Hilary J Skalski, Amelia R Arendt, Shannon K Harkins, Madison MacLachlan, Cody J M Corbett, Robinson W Goy, Amita Kapoor, Galen Hostetter, Ronald L Chandler","doi":"10.1210/jendso/bvae104","DOIUrl":"10.1210/jendso/bvae104","url":null,"abstract":"<p><p>The obesity epidemic continues to increase, with half of US women predicted to be obese by 2030. Women with obesity are at increased risk for not only cardiovascular and liver disease, but also reproductive disorders. Although mouse models are useful in studying the effects of obesity, there is inconsistency in obesity-induction methods, diet composition, and mouse strains, and studies using female mice are limited. In this study, we sought to compare the effects of a 45% high-fat diet (HFD) versus a 60% HFD on the uterine estrous cycle of nulligravid C57BL/6J mice. For 22 weeks, we placed a total of 20 mice on either a 60% HFD, 45% HFD, or each HFD-matched control diet (CD). Both HFDs produced significant weight gain, with 60% HFD and 45% HFD gaining significant weight after 2 weeks and 15 weeks, respectively. Additionally, both HFDs led to glucose intolerance, fatty liver, and adipocyte hypertrophy. Mice fed 60% HFD displayed hyperphagia in the first 12 weeks of HFD treatment. Moreover, 60% HFD-treated mice had a longer estrous cycle length and an increased percentage of estrus stage samplings compared to CD-treated mice. Estrous cycle stage-controlled 60% HFD-treated mice displayed an increased estrogen-to-progesterone ratio and decreased ovarian corpora lutea compared to CD-treated mice, which may underlie the observed estrous cycle differences. There was no significant difference between diets regarding endometrial morphology or the percent of endometrial CD45+ immune cells. Our results indicate that consideration is needed when selecting a HFD-induced obesity mouse model for research involving female reproductive health.</p>","PeriodicalId":17334,"journal":{"name":"Journal of the Endocrine Society","volume":"8 7","pages":"bvae104"},"PeriodicalIF":3.0,"publicationDate":"2024-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11156617/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141296242","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":"Clinical and Molecular Characterization of Hyperinsulinism in Kabuki Syndrome.","authors":"Elizabeth Rosenfeld, Lauren M Mitteer, Kara Boodhansingh, Victoria R Sanders, Heather McKnight, Diva D De Leon","doi":"10.1210/jendso/bvae101","DOIUrl":"10.1210/jendso/bvae101","url":null,"abstract":"<p><strong>Context: </strong>Kabuki syndrome (KS) is associated with congenital hyperinsulinism (HI).</p><p><strong>Objective: </strong>To characterize the clinical and molecular features of HI in children with KS.</p><p><strong>Design: </strong>Retrospective cohort study of children with KS and HI evaluated between 1998 and 2023.</p><p><strong>Setting: </strong>The Congenital Hyperinsulinism Center of the Children's Hospital of Philadelphia.</p><p><strong>Patients: </strong>Thirty-three children with KS and HI.</p><p><strong>Main outcome measures: </strong>HI presentation, treatment, course, and genotype.</p><p><strong>Results: </strong>Hypoglycemia was recognized on the first day of life in 25 children (76%). Median age at HI diagnosis was 1.8 months (interquartile range [IQR], 0.6-6.1 months). Median age at KS diagnosis was 5 months (IQR, 2-14 months). Diagnosis of HI preceded KS diagnosis in 20 children (61%). Twenty-four children (73%) had a pathogenic variant in <i>KMT2D</i>, 5 children (15%) had a pathogenic variant in <i>KDM6A</i>, and 4 children (12%) had a clinical diagnosis of KS. Diazoxide trial was conducted in 25 children, 92% of whom were responsive. HI treatment was discontinued in 46% of the cohort at median age 2.8 years (IQR, 1.3-5.7 years).</p><p><strong>Conclusion: </strong>Hypoglycemia was recognized at birth in most children with KS and HI, but HI diagnosis was often delayed. HI was effectively managed with diazoxide in most children. In contrast to prior reports, the frequency of variants in <i>KMT2D</i> and <i>KDM6A</i> were similar to their overall prevalence in individuals with KS. Children diagnosed with KS should undergo evaluation for HI, and, because KS features may not be recognized in infancy, <i>KMT2D</i> and <i>KDM6A</i> should be included in the genetic evaluation of HI.</p>","PeriodicalId":17334,"journal":{"name":"Journal of the Endocrine Society","volume":"8 7","pages":"bvae101"},"PeriodicalIF":3.0,"publicationDate":"2024-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11163021/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141300891","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":"Medullary Thyroid Cancer: Epidemiology and Characteristics According to Data From the Marne-Ardennes Register 1975-2018.","authors":"Sarah Caillé, Adeline Debreuve-Theresette, Géraldine Vitellius, Sophie Deguelte, Luigi La Manna, Mohamad Zalzali","doi":"10.1210/jendso/bvae084","DOIUrl":"10.1210/jendso/bvae084","url":null,"abstract":"<p><strong>Context: </strong>Medullary thyroid cancer (MTC) is a rare disease.</p><p><strong>Objective: </strong>The main objective of our study was to analyze the incidence evolution of MTC with a follow-up of more than 40 years. Further, a descriptive and survival analysis was performed according to the Kaplan-Meier analysis.</p><p><strong>Design setting and patients: </strong>This is a retrospective epidemiological study using data from the Marne-Ardennes registry from 1975 to 2018. Two hundred sixty patients with MTC were included.</p><p><strong>Main outcome measures: </strong>The incidence was calculated in the territory of the register (Marne and Ardennes departments of France) and standardized on the demographic structure of France. Patient and tumor characteristics were described. An analysis in a subgroup comparing hereditary and sporadic forms was performed. An analysis of survival was performed.</p><p><strong>Results: </strong>The standardized incidence shows an increasing trend over time. The incidence increased significantly from 0.41 to 0.57/100 000 person-years between 1986 and 1996 and 2008 and 2018. The MTC was hereditary in 21.2% of cases. The sex ratio (males:females) was 0.73. The average age at diagnosis was 53 years. Ninety-seven patients (37.3%) were N1, 26 (10%) were M1, and 56 (21.5%) developed metastases during the follow-up. Complete remission was obtained in 58.5% of patients. The disease was refractory for 18.1% of patients. The 5-year survival rate was 88.4%. Sporadic cases had a poorer prognosis than hereditary MTC.</p><p><strong>Conclusion: </strong>Our study demonstrates a moderate increase in the incidence of MTC between 1975 and 2018. The prognosis remains worse for sporadic MTC than for hereditary MTC.</p>","PeriodicalId":17334,"journal":{"name":"Journal of the Endocrine Society","volume":"8 6","pages":"bvae084"},"PeriodicalIF":4.1,"publicationDate":"2024-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11091837/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140922119","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":"Letter to the Editor From de Zegher and Ibáñez: \"Distinct Reproductive Phenotypes Segregate With Differences in Body Weight in Adolescent Polycystic Ovary Syndrome\".","authors":"Francis de Zegher, Lourdes Ibáñez","doi":"10.1210/jendso/bvae074","DOIUrl":"10.1210/jendso/bvae074","url":null,"abstract":"","PeriodicalId":17334,"journal":{"name":"Journal of the Endocrine Society","volume":"8 6","pages":"bvae074"},"PeriodicalIF":4.1,"publicationDate":"2024-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11077901/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140891557","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":"Pitfalls in the Diagnostic Evaluation of Pheochromocytomas.","authors":"Gustavo F C Fagundes, Madson Q Almeida","doi":"10.1210/jendso/bvae078","DOIUrl":"10.1210/jendso/bvae078","url":null,"abstract":"<p><p>Pheochromocytomas and paragangliomas (PPGLs), rare neuroendocrine tumors arising from chromaffin cells, present a significant diagnostic challenge due to their clinical rarity and polymorphic symptomatology. The clinical cases demonstrate the importance of an integrated approach that combines clinical assessment, biochemical testing, and imaging to distinguish PPGLs from mimicking conditions, such as obstructive sleep apnea and interfering medication effects, which can lead to false-positive biochemical results. Although a rare condition, false-negative metanephrine levels can occur in pheochromocytomas, but imaging findings can give some clues and increase suspicion for a pheochromocytoma diagnosis. This expert endocrine consult underscores the critical role of evaluating preanalytical conditions and pretest probability in the biochemical diagnosis of PPGLs. Moreover, a careful differentiation of PPGLs from similar conditions and careful selection and interpretation of diagnostic tests, with focus on understanding and reducing false positives to enhance diagnostic accuracy and patient outcomes, is crucial.</p>","PeriodicalId":17334,"journal":{"name":"Journal of the Endocrine Society","volume":"8 6","pages":"bvae078"},"PeriodicalIF":4.1,"publicationDate":"2024-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11087876/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140911675","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":"Functional Analysis of a Novel <i>HNF4A</i> Variant Identified in a Patient With MODY1.","authors":"Shuntaro Morikawa, Hui Ling Ko, Ee Chee Ren, Kazuya Hara, Naoya Kaneko, Nozomi Hishimura, Akie Nakamura, Atsushi Manabe","doi":"10.1210/jendso/bvae090","DOIUrl":"10.1210/jendso/bvae090","url":null,"abstract":"<p><strong>Context: </strong>HNF4A-maturity-onset diabetes of the young (MODY1) is a relatively rare subtype of monogenic diabetes caused by loss of function of the <i>HNF4A</i> gene, which encodes the transcription factor HNF4α. HNF4α is known to form heterodimers, and the various combinations of isoforms that make up these heterodimers have been reported to result in a diversity of targeted genes. However, the function of individual HNF4α variant isoforms and the heterodimers comprising both wild-type (WT) and variant HNF4α have not yet been assessed.</p><p><strong>Objective: </strong>In this study, we analyzed the functional consequence of the <i>HNF4A</i> D248Y variant in vitro.</p><p><strong>Methods: </strong>We investigated the case of a 12-year-old Japanese girl who developed diabetes at age 11 years. Genetic sequencing detected a novel heterozygous missense <i>HNF4A</i> variant (c.742G > T, p.Asp248Tyr; referred as \"D248Y\") in the patient and her relatives who presented with diabetes.</p><p><strong>Results: </strong>Although the WT HNF4α isoforms (HNF4α2, HNF4α3, HNF4α8, HNF4α9) enhanced the <i>INS</i> gene promoter activity in HepG2 cells, the promoter activity of D248Y was consistently low across all isoforms. The presence of D248Y in homodimers and heterodimers, comprising either HNF4α8 or HNF4α3 or a combination of both isoforms, also reduced the <i>INS</i> promoter activity in Panc-1 cells.</p><p><strong>Conclusion: </strong>We report the clinical course of a patient with HNF4A-MODY and the functional analysis of novel <i>HNF4A</i> variants, with a focus on the isoforms and heterodimers they form. Our results serve to improve the understanding of the dominant-negative effects of pathogenic <i>HNF4A</i> variants.</p>","PeriodicalId":17334,"journal":{"name":"Journal of the Endocrine Society","volume":"8 6","pages":"bvae090"},"PeriodicalIF":4.1,"publicationDate":"2024-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11091833/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140922079","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}