The Journal Of Clinical Endocrinology And Metabolism[JOURNAL]
Sun
200 papers
Pancreatic Fat and the Risk of Future Dysglycemia: A Systematic Review and Meta-analysis.
Yang J, Zhang X, Luo L … +4 more , Zheng Z, Tan C, Liu X, Chen Y
J Clin Endocrinol Metab · 2026 Jun · PMID 42258632 · Publisher ↗
CONTEXT: Pancreatic fat has emerged as a metabolically relevant ectopic fat depot, but its longitudinal association with future dysglycemic outcomes remains incompletely defined. OBJECTIVE: To evaluate the longitudinal a...
CONTEXT: Pancreatic fat has emerged as a metabolically relevant ectopic fat depot, but its longitudinal association with future dysglycemic outcomes remains incompletely defined. OBJECTIVE: To evaluate the longitudinal association of pancreatic fat with incident type 2 diabetes (T2D) and glycemic progression, with exploratory narrative synthesis of evidence in lean populations. DATA SOURCES: PubMed, Embase, Web of Science, and the Cochrane Library were searched from inception to March 1, 2026. STUDY SELECTION: Longitudinal observational studies assessing pancreatic fat at baseline and reporting subsequent incident T2D, glycemic progression, or both were included. DATA EXTRACTION: Two reviewers independently screened studies and extracted data. Methodological quality was assessed using the Newcastle-Ottawa Scale. DATA SYNTHESIS: Ten studies were included. In the primary binary meta-analysis (5 studies), higher pancreatic fat burden was associated with incident T2D (pooled effect estimate, 2.56; 95% CI, 1.27-5.14; I2 = 93.3%). Exclusion of 1 influential ultrasound-based study attenuated heterogeneity while preserving the association (pooled effect estimate, 1.45; 95% CI, 1.23-1.73; I2 = 10.2%). A separate continuous analysis (3 studies) also supported an association with incident T2D (1.17; 95% CI, 1.04-1.32; I2 = 79.2%), although exposure scales were not directly comparable. Pancreatic fat was also associated with glycemic progression (2 studies; 1.96; 95% CI, 1.10-3.48; I2 = 73.2%). Exploratory lean-population evidence was limited to 2 analytical contexts, synthesized narratively, and directionally consistent with the overall findings. CONCLUSIONS: Pancreatic fat was associated with adverse future glycemic outcomes across multiple analytical contexts. These findings support pancreatic fat as a potentially meaningful imaging-derived marker of future dysglycemia, while suggesting that heterogeneity is partly explained by differences in exposure ascertainment.
Impact of Alert Systems on Glucocorticoid Administration for Adrenal Insufficiency in the Emergency Department.
Greeviroj P, Anakepeerasak R, Thavaraputta S … +6 more , Kerr SJ, Saoraya J, Buranasupkajorn P, Parksook WW, Snabboon T, Sunthornyothin S
J Clin Endocrinol Metab · 2026 Jun · PMID 42249512 · Publisher ↗
CONTEXT: Inappropriate glucocorticoid management in adrenal insufficiency (AI) can lead to adrenal crises, particularly in an emergency setting. Clinical decision support (CDS) can be helpful, but its impact on AI manage...
CONTEXT: Inappropriate glucocorticoid management in adrenal insufficiency (AI) can lead to adrenal crises, particularly in an emergency setting. Clinical decision support (CDS) can be helpful, but its impact on AI management in emergency departments (EDs) remains limited. OBJECTIVE: To evaluate the efficacy of CDS on glucocorticoid administration time in known AI patients presenting to the ED. DESIGN: Quasi-experimental (pre- and post- intervention) design. SETTING: Tertiary academic hospital. PATIENTS: A total of 211 patients with AI; 145 had no ED visits, 66 patients had 187 ED encounters. MAIN OUTCOME MEASURES: Time from ED arrival to intravenous hydrocortisone administration pre- versus post-CDS implementation. RESULTS: The incidence of ED visits was 42 events per 100 patient-years, and the incidence of ED visits presenting with hypotension was 7 events per 100 patient-years. Among patients with ED visits, the number of visits was 73 before and 114 after CDS implementation. Events requiring intravenous hydrocortisone were 19 before and 24 after implementation, with treatment given in 89% vs. 92%, respectively (p=0.81). The median time from ED arrival to hydrocortisone administration decreased from 202 (IQR: 99-306) minutes to 77 (IQR: 45-153) minutes (p=0.01). The proportion of patients receiving hydrocortisone within 1 hour increased from 0% to 42% (p=0.002). New-onset hypotension occurred in 4 cases (21%) before implementation and in 1 case (4%) after implementation. CONCLUSIONS: Following CDS implementation, the time to hydrocortisone administration was significantly shorter among patients with known AI. These findings highlight the value of CDS in improving AI recognition and management in high-risk settings.
GLP-1 Receptor Agonist Exposure and Malignancy Risk in Patients With Endogenous Cushing's Syndrome.
Dotan I, Shochat T, Kushnir S … +5 more , Diker-Cohen T, Rudman Y, Reincke M, Fleseriu M, Akirov A
J Clin Endocrinol Metab · 2026 Jun · PMID 42233686 · Publisher ↗
CONTEXT: Patients with endogenous Cushing's syndrome (CS) have increased malignancy risk. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are increasingly used for diabetes and obesity, yet their oncologic outcomes...
CONTEXT: Patients with endogenous Cushing's syndrome (CS) have increased malignancy risk. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are increasingly used for diabetes and obesity, yet their oncologic outcomes in CS remains limited. OBJECTIVE: Evaluate association between GLP-1RA exposure and incident malignancy in patients with CS. DESIGN: Nationwide cohort study using the Clalit Health Services database in Israel, including patients with endogenous CS diagnosed between 2000-2023. Patients with adrenal carcinoma or ectopic CS were excluded. GLP-1RA exposure was defined as ≥3 prescription dispensations and modeled as a time-varying variable. MAIN OUTCOME: Incident malignancy following a CS diagnosis in GLP-1RA-exposed vs non-exposed patients. Sensitivity analyses included a 12-month lag-period approach and stratification by remission. RESULTS: The cohort included 609 patients with CS (mean age±SD, 48.05±17.17 years; 65.02% women). During mean follow-up of 14.7±6.4 years, 116 patients developed cancer and 141 died. Overall, 137 patients (22.5%) received GLP-1RA therapy. A total of 8,159.69 non-exposed and 795.88 exposed person-years were accrued, with cancer incidence rates of 12.50 and 17.59 per 1,000 person-years, respectively. In time-varying competing-risk analysis, GLP-1RA exposure was not associated with increased malignancy risk (hazard ratio [HR] 1.65; 95% CI, 0.94-2.90), with consistent results after adjustment (adjusted HR 1.22; 95% CI, 0.45-3.29). Findings were similar in lag-period and remission-stratified analyses. CONCLUSION: In this nationwide cohort of patients with CS, GLP-1RA exposure was not associated with altered malignancy risk. These findings provide reassuring evidence regarding the oncologic safety of GLP-1RAs in this high-risk population.
Anti-inflammatory effects of GLP1-RA drugs.
Quintana L, Tabaza N, Kurt B … +1 more , Kahles F
J Clin Endocrinol Metab · 2026 Jun · PMID 42219869 · Publisher ↗
Glucagon-like peptide-1 receptor agonists (GLP-1RA) are established treatment options for type 2 diabetes and obesity. This class of medications has redefined care by lowering glucose, reducing body weight, and improving...
Glucagon-like peptide-1 receptor agonists (GLP-1RA) are established treatment options for type 2 diabetes and obesity. This class of medications has redefined care by lowering glucose, reducing body weight, and improving cardiovascular outcomes. Beyond metabolic benefits, accumulating evidence indicates that GLP-1RA exert direct anti-inflammatory effects across multiple organ systems. Chronic inflammation is a driving force behind many prevalent diseases, including diabetes, cardiovascular disease, neurodegenerative disorders, and inflammatory bowel disease. This review summarizes the current evidence of the anti-inflammatory effects of GLP-1RA, highlighting data from preclinical models and clinical trials across different diseases. By targeting both metabolic and inflammatory pathways, GLP-1RA may offer dual cardiometabolic and immunomodulatory protection, positioning these agents as promising candidates for broader therapeutic applications. However, several key questions remain regarding causality, the precise molecular mechanisms involved, and the extent to which these anti-inflammatory effects can be translated into effective therapies for non-metabolic inflammatory diseases.
Approach to the Patient: Investigation of Postmenopausal Androgen Excess.
Madden-Doyle L, Bowers K, Sherlock M … +1 more , O'Reilly MW
J Clin Endocrinol Metab · 2026 May · PMID 42216566 · Publisher ↗
Androgen excess in postmenopausal women presents a challenging clinical conundrum. A crucial component in management involves identification of the underlying aetiology with a focus on detection of potentially malignant...
Androgen excess in postmenopausal women presents a challenging clinical conundrum. A crucial component in management involves identification of the underlying aetiology with a focus on detection of potentially malignant pathology or underlying genetic syndromes. A basic understanding of androgen physiology in women and the associated alterations during the menopausal transition is required to accurately risk stratify this cohort and streamline investigations. Over the course of this article, we will propose an approach to investigation and management of postmenopausal androgen excess that focuses on clinical, biochemical and radiological cues. Additionally, we will suggest an algorithmic approach to clinical and biochemical diagnostics that is underpinned by identification of red flag features of underlying pathology.
Correction to: "International real-world study on osilodrostat efficacy and safety in adrenal Cushing syndrome".
J Clin Endocrinol Metab · 2026 May · PMID 42213428 · Publisher ↗
Abstract loading — click title to view on PubMed.
Determinants of Quality of Life in Patients with Immune-Checkpoint-Inhibitor Induced Secondary Adrenal Insufficiency.
Herndon J, Hleibiehova Y, Achenbach SJ … +4 more , Bancos AN, Atkinson EJ, Donegan D, Bancos I
J Clin Endocrinol Metab · 2026 May · PMID 42212516 · Publisher ↗
CONTEXT: Limited data are available on quality of life (QoL) and adrenal crises in patients with immune checkpoint inhibitor-induced secondary adrenal insufficiency (ICI-SAI). OBJECTIVE: To 1) characterize the presentati...
CONTEXT: Limited data are available on quality of life (QoL) and adrenal crises in patients with immune checkpoint inhibitor-induced secondary adrenal insufficiency (ICI-SAI). OBJECTIVE: To 1) characterize the presentation, management, and outcomes of patients with ICI-SAI; 2) compare outcomes of ICI-SAI with other etiologies of secondary adrenal insufficiency (oSAI); and 3) identify variables associated with QoL and adrenal crisis. METHODS: In this single-center cross-sectional study, adults with ICI-SAI or oSAI (2018-2025) completed questionnaires assessing symptoms, management, adrenal crises, and the Addison disease-specific QoL survey (AddiQoL).Outcomes AddiQoL score and adrenal crisis events. RESULTS: Patients with ICI-SAI (n=109) were older (median age 66 vs 60 years), more often women (59% vs 43%), and more frequently diagnosed within one year of symptom onset (88% vs 42%, P<0.001), compared to patients with oSAI (n=139). Patients with ICI-SAI had higher AddiQoL scores (median 87 vs 85, P=0.020). In a multivariable analysis of age, sex, glucocorticoid dose and type, insurance support and duration of SAI, ICI-SAI remained independently associated with higher AddiQoL (estimate 5.4, P=0.010). The prevalence of reported adrenal crises within the prior year was similar between groups (15% vs 14%, P=0.782). In a multivariable analysis, higher AddiQoL scores were independently associated with lower odds of adrenal crisis (OR of 0.57, 95% CI 0.42-0.76). CONCLUSION: Patients with ICI-SAI report better QoL compared with patients with other causes of SAI, despite similar adrenal crisis rates. These differences may be related to earlier diagnosis and differing clinical contexts, underscoring the importance of timeline recognition and patient-centered management.
First large-scale screening of Notch biallelic variants implicates novel candidate genes in congenital hypothyroidism.
Wu FY, Wu CY, Wang Z … +21 more , Tian ZG, Song YK, Cui RJ, Yang RF, Zhang HY, Li MY, Liu XY, Zhan M, Yang L, Wu J, Dong M, Nulali JY, Zhang FX, Bao Y, Song SY, Song SH, Li R, Peng MF, Yang RM, Zhao SX, Song HD
J Clin Endocrinol Metab · 2026 May · PMID 42192612 · Publisher ↗
CONTEXT: Congenital hypothyroidism (CH) is a major preventable cause of developmental and cognitive impairment. Current genetic testing identifies causative variants for only half of cases, leaving the majority without a...
CONTEXT: Congenital hypothyroidism (CH) is a major preventable cause of developmental and cognitive impairment. Current genetic testing identifies causative variants for only half of cases, leaving the majority without a molecular diagnosis. Although animal studies implicate Notch signaling in thyroid development, its role in human CH remains unexplored. OBJECTIVE: To investigate whether Notch pathway variants contribute to genetically unexplained CH. DESIGN: Genetic screening using whole-exome sequencing with zebrafish functional validation. SETTING: Endocrinology outpatient clinic at Shanghai Ninth People's Hospital. PATIENTS OR OTHER PARTICIPANTS: 781 unrelated Chinese patients with CH. After identifying variants in 21 known causative genes in 364 patients, the remaining 417 unsolved cases were screened for variants in 77 Notch signaling pathway genes. MAIN OUTCOME MEASURE(S): Identification of biallelic Notch pathway variants; functional validation through zebrafish morpholino knockdown experiments assessing thyroid morphology and hormone production; clinical phenotype including thyroid function parameters, thyroid morphology, and levothyroxine dosage requirements; comparison with 267 DUOX2 patients. RESULTS: We identified biallelic variants in 11 Notch pathway genes (NEURL1, CNTN6, NOTCH3, DTX1, DVL1, DTX2, ATXN1, SPEN, CTBP2, NCOR2, MAMLD1) in 21 patients. Zebrafish knockdown provided functional support for the potential pathogenic role of these genes, showing reduced thyroglobulin expression, abnormal morphology, elevated tsh levels, and decreased T4. Notch-variant patients showed higher initial FT4 but required significantly higher levothyroxine doses than DUOX2 patients. CONCLUSIONS: Notch pathway variants may contribute to approximately 5% of genetically unexplained CH. Variants across multiple pathway components collectively impair thyroid function. These findings suggest a potential expansion of CH genetic architecture and suggest that Notch-variant patients may require enhanced hormone replacement despite milder initial presentation, warranting pathway-specific screening.
Post-Transplant Diabetes Mellitus Requiring Insulin Identifies High-Risk Outcomes After Solid Organ Transplantation.
Caldara R, Catarinella D, Gremizzi C … +5 more , Tentori S, Paloschi V, Williford S, Rusconi F, Piemonti L
J Clin Endocrinol Metab · 2026 May · PMID 42186204 · Publisher ↗
AIMS/HYPOTHESIS: Post-transplant diabetes mellitus (PTDM) is a common complication after solid organ transplantation, but its long-term prognostic significance and the clinical implications of post-transplant antidiabeti...
AIMS/HYPOTHESIS: Post-transplant diabetes mellitus (PTDM) is a common complication after solid organ transplantation, but its long-term prognostic significance and the clinical implications of post-transplant antidiabetic treatment patterns remain incompletely understood. We aimed to evaluate PTDM incidence, determinants, treatment patterns, and associated long-term outcomes using large-scale real-world data. METHODS: We analyzed adult solid organ transplant recipients without pre-existing diabetes within the TriNetX Global Collaborative Network (2006-2024). PTDM incidence and risk factors were assessed using time-to-event analyses. Clinical outcomes were evaluated using propensity score-matched cohorts. Antidiabetic treatment patterns were characterized using treatment pathway analyses, and outcomes were compared according to insulin versus non-insulin-based management among recipients with PTDM. RESULTS: Among 263,325 recipients, PTDM incidence increased over time and varied markedly by transplanted organ, transplant era, and geographic region. Older age, male sex, adiposity, baseline dysglycaemia, dyslipidaemia, reduced renal function, and immunosuppressive exposure were independently associated with PTDM. After matching, PTDM was associated with higher long-term risks of mortality, graft failure, graft rejection, cardiovascular events, infections, malignancies, and renal-metabolic complications, while early post-transplant risks were largely comparable. Antidiabetic treatment patterns were heterogeneous and organ-specific. Insulin-treated PTDM recipients experienced substantially worse graft and patient outcomes than non-insulin-treated recipients, despite similar long-term glycaemic control, indicating that insulin requirement identifies a high-risk metabolic phenotype. Findings were consistent in single organ transplant-specific sensitivity analyses. CONCLUSIONS/INTERPRETATION: PTDM acts as a chronic modifier of long-term outcomes after solid organ transplantation. Insulin-treated PTDM identifies a subgroup at particularly high risk, underscoring the need for improved metabolic risk stratification and tailored management strategies in transplant recipients.
Sleeve Gastrectomy in Paediatric and Transition Age Patients with Prader-Willi Syndrome: A 5-Year Longitudinal Study.
Aureli A, Carlomagno F, Crinò A … +11 more , Bocchini S, Battaglia S, Camanni D, Ceriati E, Mariani M, Delli Noci S, Manco M, De Peppo F, Isidori AM, Cianfarani S, Fintini D
J Clin Endocrinol Metab · 2026 May · PMID 42178926 · Publisher ↗
OBJECTIVE: To evaluate the long-term effectiveness of laparoscopic sleeve gastrectomy (LSG) in paediatric and transition-age patients with Prader-Willi syndrome (PWS). DESIGN: Single-centre, longitudinal, retrospective c...
OBJECTIVE: To evaluate the long-term effectiveness of laparoscopic sleeve gastrectomy (LSG) in paediatric and transition-age patients with Prader-Willi syndrome (PWS). DESIGN: Single-centre, longitudinal, retrospective cohort study. METHODS: We reviewed EHRs of 110 patients with PWS and 268 subjects undergoing LSG. We included 16 patients with PWS and severe obesity (PWS-LSG) and 32 matched non-syndromic patients with obesity (OB-LSG), both undergoing LSG, and 16 patients with PWS receiving lifestyle intervention only (PWS-LS). The primary endpoint was ΔBMI-SDS% at 5 years. RESULTS: In PWS-LSG, BMI-SDS decreased from 5.18 to an early nadir at 1-2 years (median ΔBMI-SDS% ∼-26%), then partially rebounded to 4.75 at 5 years, with ΔBMI-SDS% -16.9% (p= 0.012). Conventional metrics confirmed this attenuated response, with %BMI change -2.8% and absolute ΔBMI-SDS -1.10 at 5 years. In OB-LSG, BMI-SDS declined from 4.95 to 2.24, with larger and more sustained improvement (ΔBMI-SDS% -57.4%; p<0.001 within-group; p=0.002 vs PWS-LSG), corresponding to a %BMI change -40.1% and absolute ΔBMI-SDS -2.81 at 5 years. In PWS-LS, BMI-SDS increased from 2.25 to 3.19 (ΔBMI-SDS% +36.4%, p=0.003). The mean number of obesity-related comorbidities decreased in PWS-LSG (2.69±1.66 to 1.94±1.18; p=0.041) and in OB-LSG (1.25±0.88 to 0.56±0.76; p<0.001), but increased in PWS-LS (1.56±0.96 to 2.44±1.32; p=0.004). CONCLUSION: In PWS, LSG produces clinically relevant early weight loss with partial maintenance at 5 years, but markedly attenuated long-term benefit compared with non-syndromic peers. Nevertheless, when interpreted against the progressive worsening of obesity and cardiometabolic comorbidities observed with lifestyle intervention alone, LSG appears to modify disease trajectory in PWS.
IGF-1 and recovery in anorexia nervosa: evidence from population-based and clinical cohorts.
Dani C, Tarchi L, Bonacchi L … +9 more , Haydar S, Cassioli E, Rossi E, Fanelli A, De Logu F, Nassini R, Micali N, Ricca V, Castellini G
J Clin Endocrinol Metab · 2026 May · PMID 42177039 · Publisher ↗
CONTEXT: Anorexia nervosa (AN) is associated with severe metabolic and endocrine alterations, including growth hormone (GH) resistance and reduced insulin-like growth factor 1 (IGF-1). The longitudinal behavior of IGF-1...
CONTEXT: Anorexia nervosa (AN) is associated with severe metabolic and endocrine alterations, including growth hormone (GH) resistance and reduced insulin-like growth factor 1 (IGF-1). The longitudinal behavior of IGF-1 during treatment remains incompletely characterized. OBJECTIVE: To evaluate IGF-1 levels in current and weight restored AN, determine metabolic correlates, and examine longitudinal changes during clinical treatment. DESIGN: Cross-sectional analysis in a population-based cohort and longitudinal analysis in a clinical cohort. SETTING: UK Biobank (UKB) and a specialist eating disorder clinic. PARTICIPANTS: (i) UKB: 129 adult women with current AN, 2,380 weight restored AN, and 2,380 healthy controls (HC) matched for age, sex, and BMI. (ii) Clinical cohort: 189 adult women with AN assessed at baseline and 12-month follow-up. MAIN OUTCOMES MEASURES: Plasma IGF-1 levels; secondary metabolic and reproductive hormones including GH, insulin, glucose, FT3, and gonadal hormones. RESULTS: Across the UKB groups, IGF-1 levels showed a graded pattern: lowest in current AN, medium in weight restored AN, and highest in HC. In the clinical cohort, IGF-1 correlated positively with insulin, glucose, and FT3, and negatively with GH, consistent with GH resistance. IGF-1 levels increased significantly over 12 months of treatment (p = 0.003), with higher BMI at baseline predicting greater increases. Higher IGF-1 levels were associated with greater likelihood of menstrual function independent of BMI (p < 0.001). CONCLUSIONS: IGF-1 appears reduced in current AN and may only partly normalize with weight restoration. IGF-1 may reflect metabolic state and reproductive function, suggesting value as an indicator of severity and treatment response.
APPROACH TO THE PATIENT: Genetics and Management of Congenital Hypothyroidism.
Nguyen Quoc A, Kariyawasam D, Polak M … +2 more , Carré A, Stoupa A
J Clin Endocrinol Metab · 2026 May · PMID 42170892 · Publisher ↗
Congenital hypothyroidism (CH) encompasses a diverse spectrum of disorders with diverse genetic etiologies and variable clinical courses, ranging from transient neonatal hyperthyrotropinemia to permanent thyroid hormone...
Congenital hypothyroidism (CH) encompasses a diverse spectrum of disorders with diverse genetic etiologies and variable clinical courses, ranging from transient neonatal hyperthyrotropinemia to permanent thyroid hormone or thyrotropin deficiency. Advances in molecular genetics have substantially expanded the catalog of genes implicated in CH; however, the translation of this knowledge into everyday clinical practice remains challenging. In this Approach to the Patient, we use selected clinical vignettes to illustrate how genetic information can substantiate the diagnosis, management, and counseling of patients with CH. Rather than providing an exhaustive genetic review, this paper focuses on clinically relevant scenarios and pragmatic decision points-when to perform genetic testing, how results influence treatment duration and intensity, and how they guide prognostication and family counseling. This case-based framework emphasizes a pragmatic, patient-centered approach to the use of genetics in the management of CH.
68Ga-DOTA-exendin-4 PET/CT for Insulinoma Localization in Patients with Negative or Inconclusive Conventional Imaging.
Fricke JG, Laubner K, Schildmeijer M … +7 more , Menz L, Wojsa C, Meyer PT, Seufert J, Wild D, Christ E, Freitag MT
J Clin Endocrinol Metab · 2026 May · PMID 42168767 · Publisher ↗
CONTEXT: Insulinomas are the main cause of endogenous hyperinsulinemic hypoglycemia (EHH) in adults, with surgery as the only cure. Pancreas-preserving surgery is preferred, making precise preoperative localization cruci...
CONTEXT: Insulinomas are the main cause of endogenous hyperinsulinemic hypoglycemia (EHH) in adults, with surgery as the only cure. Pancreas-preserving surgery is preferred, making precise preoperative localization crucial. GLP-1R-targeted imaging, such as [68Ga]Ga-DOTA-exendin-4 PET/CT, outperforms other imaging procedures for insulinoma localization. OBJECTIVE: To investigate the performance and clinical impact of [68Ga]Ga-DOTA-exendin-4 PET/CT for the detection of insulinomas in patients with EHH and prior negative or inconclusive conventional imaging. METHODS: In this retrospective, real-world, dual-center imaging study, 101 patients with biochemically proven EHH and/or a positive Whipple's triad underwent [68Ga]Ga-DOTA-exendin-4 PET/CT at two tertiary centers between April 2017 and March 2024. Among these, 58 patients with prior negative or inconclusive conventional imaging constituted the primary analysis cohort. Endpoints: Insulinoma detection rate and sensitivity by [68Ga]Ga-DOTA-exendin-4 PET/CT after negative or inconclusive conventional imaging and impact on clinical management. RESULTS: Among the 58 patients with prior negative or inconclusive conventional imaging, [68Ga]Ga-DOTA-exendin-4 PET/CT was positive in 42 patients, corresponding to a detection rate of 72% (95% CI, 59-83%). Thirty patients subsequently underwent PET/CT-guided surgery. Overall, 32 patients had histological verification (including two PET/CT-negative cases), corresponding to a sensitivity of 93.8% (95% CI, 79-99%). CONCLUSION: In real-world clinical practice, [68Ga]Ga-DOTA-exendin-4 PET/CT provides a high detection rate of 72% for localizing insulinomas, including one case of diffuse nesidioblastosis in patients with EHH and prior negative or inconclusive conventional imaging, thereby enabling PET/CT-guided surgical approaches. These findings underscore the substantial clinical impact of GLP-1R-targeted PET/CT on patient management and prognosis.GLP-1 receptor.
Dysregulation of glycogen metabolism in cardiomyopathy caused by glycogenin-1 (GYG1) missense variants.
Visuttijai K, Hedberg-Oldfors C, Braun O … +8 more , Englund E, Glamuzina E, Turner C, Vukusic K, Sandstedt J, Dellgren G, Karason K, Oldfors A
J Clin Endocrinol Metab · 2026 May · PMID 42165248 · Publisher ↗
CONTEXT: Glycogen storage diseases are inherited disorders of glycogen metabolism and are commonly associated with hypoglycaemia, hepatic dysfunction, or skeletal and cardiac myopathy, depending on the affected enzyme. G...
CONTEXT: Glycogen storage diseases are inherited disorders of glycogen metabolism and are commonly associated with hypoglycaemia, hepatic dysfunction, or skeletal and cardiac myopathy, depending on the affected enzyme. Glycogen storage disease type 15 (GSD15) is caused by pathogenic variants in GYG1, which encodes glycogenin-1, the auto-glucosylating primer required for glycogen synthesis. GSD15 is characterized by cardiomyopathy and storage of abnormal glycogen and polyglucosan in cardiomyocytes. OBJECTIVE: To understand the pathobiology of GSD15, we investigated the storage material in heart explants from two previously reported patients and describe a new case of GSD15. METHODS: The characteristic storage material was investigated using laser capture microdissection followed by quantitative mass spectrometry (MS) and immunohistochemistry comparing differentially abundant proteins in the storage material with normal-appearing cytoplasmic regions from the same patient. Global protein dysregulation in GSD15 was assessed by quantitative MS of whole-myocardial tissue samples from patients and normal controls. RESULTS: The storage material was enriched in proteins involved in glycogen metabolism, including glycogen synthase, UDP-glucose pyrophosphorylase 2, glycogenin-1, glycogen phosphorylase, and glycogen debranching enzyme. Sequestosome 1 (p62) and desmin were also enriched, without evidence of increased autophagocytosis. Whole-tissue analyses revealed upregulation of cardiomyopathy-associated biomarkers and downregulation of mitochondrial proteins, suggesting impaired energy metabolism contributing. to congestive heart failure. CONCLUSIONS: In GSD15, storage of abnormal glycogen in cardiomyocytes is associated with enrichment of specific proteins involved in glycogen metabolism, contributing to dysregulation of glycogen turnover. This dysregulation results in polyglucosan accumulation, disruption of sarcomeric and mitochondrial architecture, and progressive fibrosis. No disease-modifying therapy currently exists for GSD15; future strategies based on substrate reduction, enhancement of autophagy, or gene therapy require further investigation.
Fibrous Dysplasia in Hospitalized Patients in France: Prevalence and Associated Manifestations from a Health Database.
Levaillant L, Coutant R, Rodien P … +2 more , Levaillant M, Briet C
J Clin Endocrinol Metab · 2026 May · PMID 42161884 · Publisher ↗
INTRODUCTION: Fibrous dysplasia (FD)/McCune-Albright syndrome (MAS) is a rare mosaic disorder involving the skeleton and/or extraskeletal manifestations, particularly endocrine features. Population-based estimates of pre...
INTRODUCTION: Fibrous dysplasia (FD)/McCune-Albright syndrome (MAS) is a rare mosaic disorder involving the skeleton and/or extraskeletal manifestations, particularly endocrine features. Population-based estimates of prevalence and incidence are scarce, including in France, and data on associated manifestations mainly derive from specialized centres. This study aimed to estimate the prevalence and incidence of FD/MAS in hospitalized patients in France and to evaluate the frequency of associated manifestations. METHODS: This retrospective cohort study used the French National Health Insurance Database, to identify all patients hospitalized between 2012 and 2024 with a primary or associated diagnosis of monostotic FD (MFD; ICD-10 M85.0) or polyostotic FD/MAS (PFD/MAS; ICD-10 Q78.1). Prevalence and incidence were calculated for 2024. Associated manifestations were assessed using hospitalization diagnoses and outpatient drug dispensing data. RESULTS: Over the 2012-2024 period, 2249 patients were hospitalized in France; 60% had PFD/MAS, 63% were female, and 26% were children. The 2024 prevalence was 5.36 per 1,000,000 inhabitants (95% CI: 4.83-5.94), and the 2024 incidence was 2.58 patients per 1,000,000 inhabitants (95% CI: 2.21-2.99). Regarding associated manifestations, 27% of patients per year received bisphosphonates, 7.4% received phosphate supplements, 3.3% aromatase inhibitors, 8% pituitary treatments and 2.2% antithyroid agents. CONCLUSION: This nationwide study provides the first estimates of the prevalence and incidence of hospitalized FD/MAS in France, although estimates based on hospitalization data likely underestimate the true frequency of monostotic FD. Treatment-based proxies offer valuable insights into associated manifestations. Improved outpatient coding and integration of clinical data are needed to better capture the full spectrum of FD/MAS at the population level.
Evidence for actions of estrone distinct from those of estradiol.
Santen RJ, Gompel A, Klein KO … +4 more , Lumsden MA, Pinkerton JV, Stuenkel CA, Yue W
J Clin Endocrinol Metab · 2026 May · PMID 42161325 · Publisher ↗
CONTEXT: Recent studies challenge the traditional view that estrone (E1) must be converted to estradiol (E2) to be biologically active. The prior view was based on several findings: E2 binds to ERα and ERβ, and their nuc...
CONTEXT: Recent studies challenge the traditional view that estrone (E1) must be converted to estradiol (E2) to be biologically active. The prior view was based on several findings: E2 binds to ERα and ERβ, and their nuclear coactivators, with 4 to 25 times greater affinity than E1. 17β-hydroxysteroid dehydrogenases can efficiently convert E1 to E2 in vivo. Observations from cell culture, animal models, and clinical studies have supported the idea that E1's biological effects depend on its conversion to E2. EVIDENCE ACQUISITION: A systematic search was conducted using PubMed, Ovid Medline, Embase, Web of Science and bibliographies of manuscripts to obtain pertinent data. EVIDENCE SYNTHESIS: In postmenopausal women, plasma levels of E1 are 4-fold higher than those of E2, and the E1 production through peripheral aromatization is 8-fold higher. Recent research has shown that E1 has distinct effects on brain function, gene expression, breast tissue inflammation, immune modulation, epithelial to mesenchymal cell transformation (EMT), stem cells, and vascular endothelial cells. The specific recruitment of coactivators to enhancer complexes during nuclear transcription may explain these unique actions of E1. Collectively, these findings provide evidence that E1 can act independently of conversion to E2. Extensive study is now required regarding clinical implications for the selection of type of estrogen therapy after menopause, especially regarding cognitive function, mood disorders, and effects on breast inflammation '. CONCLUSION: Current evidence indicates that E1 is a biologically significant estrogen in its own right. Further preclinical and clinical studies are needed to clarify E1's unique effects.
Heterogeneity of MGMT expression in corticotroph adenomas and mechanism of acquired temozolomide resistance.
Paes T, Feelders RA, Dogan F … +5 more , Iyer AM, Kros JM, Schwarz Y, van Koetsveld PM, Hofland LJ
J Clin Endocrinol Metab · 2026 May · PMID 42149504 · Publisher ↗
CONTEXT: 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...
CONTEXT: 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. OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.
The germline landscape of pituitary adenomas: established and emerging predisposition genes.
Mignone E, Sorvina A, Torpy DJ … +2 more , Scott HS, De Sousa SMC
J Clin Endocrinol Metab · 2026 May · PMID 42141904 · Publisher ↗
Pituitary adenomas are increasingly recognised to have a germline genetic component in a subset of patients, particularly those with young-onset disease, familial clustering or syndromic features. The spectrum of germlin...
Pituitary adenomas are increasingly recognised to have a germline genetic component in a subset of patients, particularly those with young-onset disease, familial clustering or syndromic features. The spectrum of germline variants implicated in pituitary tumorigenesis has broadened considerably, with evidence of both established predisposition genes and a growing number of emerging candidate genes. Established germline predisposition genes - namely, MEN1, PRKAR1A, AIP, CDKN1B, GPR101, SDHx and MAX - remain central to our understanding of familial pituitary adenoma predisposition and have defined roles in specific clinical contexts which influence adenoma phenotype, age at presentation, surveillance strategies and family screening. Beyond this, a set of less prevalent variants in other genes - for example, CABLES1, CDH23, PAM, CHEK2 and the mismatch repair (MMR) genes - are emerging as potential contributors, although the pathogenicity and clinical relevance of these genes remain to be fully established. Identifying causative germline variants in people with pituitary adenomas offers the opportunity of personalised care via gene-specific surveillance strategies, prognostication, cascade testing and reproductive planning to the potential benefit of the individual as well as their families. In this review, we provide a clinically-orientated overview of the established and emerging genes implicated in the germline predisposition to pituitary adenomas. We also present a contemporary clinical approach to germline genetic testing in patients with pituitary adenomas.
US Patterns in Clinical Islet Autoantibody Ordering and Results Show Key Differences After Teplizumab Regulatory Approval.
Dixit SB, Marcelli M, Tong C … +3 more , Chen Z, Bare LA, Sims EK
J Clin Endocrinol Metab · 2026 May · PMID 42138126 · Publisher ↗
CONTEXT: Recent advances in disease-modifying therapies have increased emphasis on islet autoantibody screening to detect type 1 diabetes prior to clinical onset. OBJECTIVE: Test impacts of teplizumab approval on real-wo...
CONTEXT: Recent advances in disease-modifying therapies have increased emphasis on islet autoantibody screening to detect type 1 diabetes prior to clinical onset. OBJECTIVE: Test impacts of teplizumab approval on real-world US autoantibody ordering patterns. METHODS: Testing for biochemical and islet cytoplasmic autoantibodies in 28,206 nondiabetic individuals (HbA1c<6.5%) before ("PRE", November 2017-November 2018) versus after ("POST", November 2022-November 2023) teplizumab approval was analyzed. Results were stratified by age (<20 vs ≥20 years) and glycemia (normoglycemic versus dysglycemic). RESULTS: Islet autoantibody testing increased 1.9-fold from the PRE to POST period (p<0.0001 versus other testing), especially in adults and dysglycemic children. Overall testing was more common in adults, and tested adults were more commonly dysglycemic than children. In the POST period, providers were more likely to order 3/4 or 4/4 available biochemical antibodies. For both periods most orders in normoglycemic individuals came from primary care providers, while endocrinologists ordered most testing in dysglycemic groups. Provider-level testing was typically low volume in both periods, with providers ordering 1-3 tests/year accounting for >80% of orders. Among dysglycemic children, multiple antibody positivity in the POST period was 35.6% higher than expected compared to the PRE period (p=0.0003). CONCLUSION: Islet autoantibody testing in nondiabetic individuals increased following teplizumab approval, primarily among adults and dysglycemic children, suggesting that these groups allow for the easiest implementation of screening through clinical care. Despite shifts toward guideline-concordant testing, screening of normoglycemic children by primary care providers remains limited, highlighting the need to further integrate this testing into clinical care pathways.
Retatrutide And Lipid And Metabolite Profiles In Participants With Obesity With Or Without Type 2 Diabetes.
Pearson MJ, Willency JA, Lin Y … +8 more , Abadi A, Hartman ML, Coskun T, Ruotolo G, Duffin KL, Haupt A, Newgard CB, Pirro V
J Clin Endocrinol Metab · 2026 May · PMID 42135195 · Publisher ↗
CONTEXT: In phase 2 trials, retatrutide reduced body weight, hemoglobin A1c, and improved the lipid profiles of participants living with obesity, with and without T2D. OBJECTIVE: Assess plasma metabolome and lipidome cha...
CONTEXT: In phase 2 trials, retatrutide reduced body weight, hemoglobin A1c, and improved the lipid profiles of participants living with obesity, with and without T2D. OBJECTIVE: Assess plasma metabolome and lipidome changes associated with retatrutide treatment. DESIGN: Metabolomics and lipidomics were performed in fasting samples from two randomized, placebo-controlled phase 2 trials. Participants living with obesity with and without T2D were treated for 36 and 48 weeks, respectively. SETTING: Post-hoc exploratory analysis. PARTICIPANTS: 282 and 213 participants in the obesity and T2D trials, respectively. INTERVENTION(S): Obesity trial; retatrutide (1, 4, 8, 12 mg) or placebo. T2D trial: retatrutide (0.5, 4, 8, 12 mg) or placebo or dulaglutide (1.5 mg). MAIN OUTCOME MEASURE(S): Changes in metabolite and lipid levels with retatrutide treatment against baseline levels and placebo using multiplicity correction. RESULTS: At both primary and study endpoints for both populations, higher doses of retatrutide were associated with changes in a cluster of metabolites comprising 3-hydroxybutyrate, acetylcarnitine, free carnitine and fatty acid-derived long-chain acylcarnitines. Mediation analyses suggested that changes in these biomarkers mediated 23.2% of the weight-reduction response in participants without T2D and that this mediation was blunted to 12.7% in participants with T2D. Retatrutide treatment was also associated with changes in metabolites associated with insulin resistance, including branched-chain amino acids and their catabolic products, 2-aminoadipic acid, 2-hydroxybutyrate, urate, and triglycerides enriched in short-chain and saturated acyl side chains. These changes were found in both study populations and sustained across study endpoints. CONCLUSIONS: Retatrutide was associated with changes in two metabolic clusters related to fatty acid oxidation and insulin resistance in a direction associated with improved metabolic health and reduced cardiovascular risk.
About
- Frequency
- Sun
- Papers found
- 200
- RSS feed
- Subscribe