The Journal of clinical endocrinology and metabolism最新文献

{"title":"Incretin Receptor Agonism, Fat-free Mass, and Cardiorespiratory Fitness: A Narrative Review.","authors":"Zhenqi Liu, Nathan R Weeldreyer, Siddhartha S Angadi","doi":"10.1210/clinem/dgaf335","DOIUrl":"https://doi.org/10.1210/clinem/dgaf335","url":null,"abstract":"<p><strong>Context: </strong>Individuals with obesity often exhibit low muscle quality and are at risk of reduced muscle mass and diminished cardiorespiratory fitness (CRF). Glucagon-like peptide 1 (GLP-1) receptor agonists (GLP-1RA) and dual GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) receptor agonist (GLP-1/GIPRA) promote significant loss in adipose tissue but are also associated with notable reductions in fat-free mass (FFM). It is not yet understood how these drugs affect CRF which is an independent predictor of all-cause and cardiovascular mortality.</p><p><strong>Evidence description: </strong>People with obesity frequently have low CRF which is defined by the Fick principle - the product of cardiac output and peripheral oxygen extraction. Cardiovascular dysfunction and reduced muscle quality, due to lipid infiltration, relatively low muscle mass, and dysfunctional microvasculature, work in concert to affect the determinants of the Fick equation and cause low CRF in this population. Weight loss interventions, including GLP-1RAs and dual GLP-1/GIPRA, may improve these measures. However, recent trials show GLP-1RAs and dual GLP-1/GIPRA therapy accelerates FFM loss. Evidence indicates that approximately 25-40% of weight loss attributed to GLP-1RAs and dual GLP-1/GIPRA comes from FFM loss, a rate far exceeding the annual age-related decline of FFM in adults. While these therapies have revolutionized obesity and glycemic management by inducing significant weight loss, reducing blood glucose levels, and demonstrating cardiovascular benefits in individuals with or without type 2 diabetes, clinical studies have failed to show improvements in CRF, a critical determinant of long-term cardiovascular health, and the long-term implications of FFM loss in these individuals remain unknown.</p><p><strong>Conclusion: </strong>GLP-1RAs and dual GLP-1/GIPRA significantly reduce body weight and adiposity, along with a substantial FFM loss but with no clear evidence of CRF enhancement. Further research is needed to elucidate the complex interplay among GLP-1 and dual GLP-1/GIP receptor agonism, FFM, direct cardiovascular measures, and determinants of CRF to optimize clinical outcomes in obesity and type 2 diabetes.</p>","PeriodicalId":520805,"journal":{"name":"The Journal of clinical endocrinology and metabolism","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144251924","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":"Cardiomyopathy in patients with acromegaly - not truly a concern anymore?","authors":"Peter Wolf, Luigi Maione, Peter Kamenický, Philippe Chanson","doi":"10.1210/clinem/dgaf338","DOIUrl":"https://doi.org/10.1210/clinem/dgaf338","url":null,"abstract":"<p><p>Acromegaly is associated with increased mortality rates if not adequately treated. Cardiovascular and metabolic comorbidities are highly prevalent and have long been considered the main cause of death among patients with acromegaly. However, substantial advances in GH/IGF-I-lowering treatment, together with increased awareness and optimized management of other risk factors, have led to major improvements in mortality rates in the 2-3 past decades. Here we review the effects of chronic excessive GH/IGF-I production and the successful treatment of this condition on relevant classical cardiovascular risk factors. and on morphological and functional changes in the heart and discuss differences in reported prevalence rates over time according to different imaging methodologies used. While morphological alterations, i.e., myocardial hypertrophy as well as increased atrial and ventricular volumes, are common in patients with acromegaly, overt clinically relevant dysfunction is rare. Valvular cardiac disease and arrhythmia are also reviewed. Clinically relevant cardiomyopathy is currently less common than previously estimated. Recent epidemiological studies have shown that the risk of heart failure is comparable to that of the general population after adjusting for biochemical disease control and other risk factors.</p>","PeriodicalId":520805,"journal":{"name":"The Journal of clinical endocrinology and metabolism","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144251902","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":"Fragility of Evidence for the Efficacy of Anti-fracture Medications.","authors":"Nick Tran, Thach S Tran, Tuan V Nguyen","doi":"10.1210/clinem/dgaf332","DOIUrl":"https://doi.org/10.1210/clinem/dgaf332","url":null,"abstract":"<p><strong>Context: </strong>A P-value and statistical significance, conventionally considered for assessing an intervention's effectiveness are usually misused and misinterpreted.</p><p><strong>Objective: </strong>To quantify fragility of randomized controlled trial (RCT) evidence for anti-fracture efficacy.</p><p><strong>Design: </strong>This retrospective analysis included 27 phase 3/4 RCTs in high-impact medical journals which assessed anti-fracture efficacy, allocated participants in a 1:1 ratio to pharmacological intervention or control and reported a statistically significant result. Fragility of the results were assessed using the Fragility Index (FI) and Fragility Quotient (FQ). FI is the minimum number of participants in a positive analysis result for whom reversing the reported status would eliminate statistical significance, while FQ is a function of FI to the sample size.</p><p><strong>Results: </strong>The median FI was 9 (IQR: 4, 19), indicating that adding 9 fracture patients (∼0.51% of the study size) to the intervention group would eliminate the documented evidence of anti-fracture efficacy. Notably, the number of participants lost to follow-up exceeded the corresponding FI in 60% of analyses. The most robust evidence for anti-fracture efficacy was documented for romosozumab (FI: 19.5; IQR: 7.0, 31.5); whereas the least found for denosumab (4; 3, 17) and calcium/vitamin D supplementation (7.0; 2.3, 16.8). Anti-fracture efficacy evidence improved among the results that considered fractures the primary endpoint measure (14; 11, 33) or those with P-value< 0.001 (26; 18, 42).</p><p><strong>Conclusion: </strong>The existing RCT evidence of anti-fracture efficacy is highly fragile. The FI, its comparison with loss to follow-up and FQ should be incorporated into clinical guideline development and doctor-patient risk communication.</p>","PeriodicalId":520805,"journal":{"name":"The Journal of clinical endocrinology and metabolism","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144251904","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":"Coproporphyrinogen oxidase deficiency causes primary adrenal insufficiency and 46,XY DSD.","authors":"Misa Honda, Satoshi Narumi, Kosei Hasegawa, Yoshimitsu Goto, Yusuke Kawashima, Osamu Ohara, Ryuji Fukuzawa, Tomohiro Ishii, Tomonobu Hasegawa","doi":"10.1210/clinem/dgaf329","DOIUrl":"https://doi.org/10.1210/clinem/dgaf329","url":null,"abstract":"<p><strong>Context: </strong>Primary adrenal insufficiency (PAI) is a rare, life-threatening condition, and at times is associated with differences of sexual differentiation (DSD). Cytochrome P450 enzymes, which are essential for steroidogenesis in adrenals and gonads, have heme in their active center. CPOX encodes an enzyme coproporphyrinogen oxidase (CPOX) that is involved in the synthesis of heme.</p><p><strong>Objective: </strong>This study aims to report the identification of biallelic inactivating CPOX variants in three unrelated patients with PAI and their clinical characteristics.</p><p><strong>Methods: </strong>We reported three patients with childhood-onset PAI, including two patients with 46,XY DSD. All three had adrenal hypoplasia. Additionally, they commonly had severe neonatal jaundice; two of them developed skin blisters in the areas exposed to phototherapy, and two showed severe neonatal anemia requiring transfusions. Exome sequencing was performed to explore the genetic basis of the patients. The pathogenicity of the identified variants was confirmed with targeted mRNA and proteomic analyses of the patient-derived peripheral blood cells.</p><p><strong>Results: </strong>We identified biallelic rare CPOX variants in each patient, including c.2T>G, p.Arg426*, c.1277G>A and p.Tyr429Cysfs33*. The three patients commonly had the start codon-altering c.2T>G variant. Analysis of the mRNA and proteome of peripheral blood cells from one patient (c.2T>G and p.Arg426*) showed that CPOX mRNA expression was comparable to controls, however CPOX protein expression was significantly decreased to 1%.</p><p><strong>Conclusion: </strong>We provided genetic evidence linking CPOX deficiency and PAI with 46,XY DSD, suggesting that the heme synthesis pathway plays an important role in human steroidogenesis.</p>","PeriodicalId":520805,"journal":{"name":"The Journal of clinical endocrinology and metabolism","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144251903","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":"Influence of Preexisting Psychiatric Morbidity on Liothyronine Use in Hypothyroidism: A Swedish Nationwide Cohort Study.","authors":"Fredric Hedberg, Jonatan D Lindh, Buster Mannheimer, Tereza Planck, Jakob Skov, Mikael Lehtihet, Henrik Falhammar, Jan Calissendorff","doi":"10.1210/clinem/dgaf337","DOIUrl":"https://doi.org/10.1210/clinem/dgaf337","url":null,"abstract":"<p><strong>Background: </strong>Autoimmune hypothyroidism is a common endocrine disorder affecting 1-2% of the population in iodine sufficient areas. While levothyroxine is standard treatment, a substantial number of patients report persistent symptoms despite adequate treatment. The use of liothyronine as an adjunct to levothyroxine therapy has increased. The psychiatric characteristics of patients receiving liothyronine remain largely unknown. This study examines the association between preexisting psychiatric morbidity and subsequent liothyronine use in autoimmune hypothyroidism.</p><p><strong>Methods: </strong>This nationwide retrospective cohort study includes all adults in Sweden with autoimmune hypothyroidism and initiated on treatment with thyroid hormones between 2006 and 2020. Data were obtained from the National Patient Register and the National Prescribed Drug Register. Psychiatric morbidity prior to diagnosis was identified using ICD-10 codes and ATC-codes for psychiatric medications. Logistic models estimated associations, adjusting for sex, age, and region.</p><p><strong>Results: </strong>Among 353,708 patients, 44.8% had a history of psychiatric morbidity. These patients were more likely to receive liothyronine (adjusted odds ratio (aOR) 1.90, 95% confidence interval (95% CI) 1.83-1.97, p<0.001) compared to those without a psychiatric history. This was most evident among individuals with affective or anxiety morbidity (aOR 1.91, 95% CI 1.84-1.98, p<0.001). No association was found for psychotic morbidity (aOR 1.08, 95% CI 0.98-1.19, p=0.11).</p><p><strong>Conclusion: </strong>Patients with a psychiatric history before autoimmune hypothyroidism were more likely to receive liothyronine, especially among those with affective or anxiety morbidity. This may reflect persistent symptoms and affect subsequent decisions in the treatment of hypothyroidism.</p>","PeriodicalId":520805,"journal":{"name":"The Journal of clinical endocrinology and metabolism","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144251925","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":"TSH Receptor Antibody Test Utilization Patterns from a National Reference Laboratory: TRAb, TSI, or Both?","authors":"Heather A Nelson, Kelly Doyle, Joely A Straseski","doi":"10.1210/clinem/dgaf330","DOIUrl":"https://doi.org/10.1210/clinem/dgaf330","url":null,"abstract":"<p><strong>Background: </strong>There are currently two classes of thyroid stimulating hormone receptor (TSHR) antibody assays, namely TSHR antibody (TRAb) assays and thyroid stimulating immunoglobulin (TSI) assays. Clinical guidelines do not currently specify appropriate use of TSHR autoantibody tests in the diagnosis of hyperthyroidism which may result in paired orders for both tests with the possibility of discordant results and excessive costs.</p><p><strong>Methods: </strong>Over 189,000 patient encounters with TRAb and TSI bioassay (TSI-BA) or TSI bridge immunoassay (TSI-Br) test orders were examined to assess the frequency of paired orders and qualitative agreement of TRAB/TSI. A chart review was performed on a subset of patients for clinical correlation. Lastly, a cost analysis was performed to estimate the financial burden of unnecessary paired testing.</p><p><strong>Results: </strong>TRAb and TSI were co-ordered on the same encounter in 14.3% of TRAb/TSI-BA orders and 17.4% of TRAb/TSI-Br orders. Qualitative comparison showed discordance in 12.5% (1,590) of TRAb and TSI-BA paired orders and 6.6% (1,149) of TRAb and TSI-Br paired orders. Based on patient FT4 and TSH concentrations and disease status, the TSI assays aligned better with hyperthyroidism and confirmed Graves' disease diagnoses. Paired orders resulted in a 31-325% increase in potentially unnecessary testing costs.</p><p><strong>Conclusions: </strong>We observed good clinical and analytical agreement between TRAb and TSI assays suggesting that paired orders for TRAb and TSI are redundant in the assessment of autoimmune-mediated hyperthyroidism. Use of a single test to assess TRAb would be appropriate in most scenarios and may lead to considerable savings of healthcare dollars.</p>","PeriodicalId":520805,"journal":{"name":"The Journal of clinical endocrinology and metabolism","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144251926","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":"The role of muscular fitness on bone mineral content and areal bone mineral density in youth with type 1 diabetes.","authors":"Jacinto Muñoz-Pardeza, Luis Gracia-Marco, José Francisco López-Gil, Ignacio Hormazábal-Aguayo, Nidia Huerta-Uribe, Andres Marmol-Perez, Yasmin Ezzatvar, Mikel Izquierdo, Antonio García-Hermoso","doi":"10.1210/clinem/dgaf328","DOIUrl":"https://doi.org/10.1210/clinem/dgaf328","url":null,"abstract":"<p><strong>Context: </strong>Type 1 diabetes in youth increases the risk of compromised bone health due to glycemic dysregulation. Muscular fitness may play a role in improving bone health during growth.</p><p><strong>Objective: </strong>This study aimed to investigate the association between muscular fitness and bone health in youth with type 1 diabetes.</p><p><strong>Methods: </strong>A total of 83 young individuals with type 1 diabetes (aged 6-18 years; 44.6% girls) from the Diactive-1 cohort study were followed for two years. Dual-energy X-ray absorptiometry whole-body scans were used to assess bone mineral content (BMC) and areal bone mineral density (aBMD) for the total body less head (TBLH), arms, legs, pelvis, and spine. Muscular fitness (handgrip strength, 1-RM, and muscle power) was assessed with a dynamometer and eGYM devices. Handgrip strength and TBLH bone parameters were age- and sex-standardized using the FitBack Project and BMD Childhood Study, respectively.</p><p><strong>Results: </strong>Linear mixed models showed longitudinal associations of handgrip strength with TBLH-BMC ([B]=17.18, 95%CI 12.47-21.90) and TBLH-aBMD (B=0.004, 95%CI 0.002-0.006); RM with TBLH-BMC (B=20.09, 95%CI 10.88-29.31) and TBLH-aBMD (B=0.007, 95%CI 0.004-0.011); and power with TBLH-BMC (B=26.80, 95%CI: 17.31-36.28) and TBLH-aBMD (B=0.009, 95%CI 0.005-0.012). Comparable results were observed across the other regions (p<0.05). Additionally, analyses with standardized data confirmed the relationships of handgrip z-scores with TBLH-BMC z-scores (B=0.19, 95%CI 0.08-0.30) and TBLH-aBMD z-scores (B=0.350, 95%CI: 0.210-0.490).</p><p><strong>Conclusion: </strong>In pediatric patients with type 1 diabetes, increasing muscular fitness could serve as a complementary therapeutic strategy to preserve or enhance bone health.</p>","PeriodicalId":520805,"journal":{"name":"The Journal of clinical endocrinology and metabolism","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144228431","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":"Response to Letter to the Editor from Mauvais-Jarvis and Dhindsa: \"Approach to the Patient: Low Testosterone Concentrations in Men with Obesity\".","authors":"Christopher A Muir, Gary A Wittert, David J Handelsman","doi":"10.1210/clinem/dgaf334","DOIUrl":"https://doi.org/10.1210/clinem/dgaf334","url":null,"abstract":"","PeriodicalId":520805,"journal":{"name":"The Journal of clinical endocrinology and metabolism","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144236777","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":"Letter to the Editor from Mauvais-Jarvis and Dhindsa: \"Approach to the Patient: Low Testosterone Concentrations in Men With Obesity\".","authors":"Franck Mauvais-Jarvis, Sandeep Dhindsa","doi":"10.1210/clinem/dgaf333","DOIUrl":"https://doi.org/10.1210/clinem/dgaf333","url":null,"abstract":"","PeriodicalId":520805,"journal":{"name":"The Journal of clinical endocrinology and metabolism","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144236776","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":"Predicting the effect of preventive treatment of type 2 diabetes. A further step towards precision medicine.","authors":"Massimiliano Copetti, Claudia Menzaghi, Vincenzo Trischitta","doi":"10.1210/clinem/dgaf327","DOIUrl":"https://doi.org/10.1210/clinem/dgaf327","url":null,"abstract":"","PeriodicalId":520805,"journal":{"name":"The Journal of clinical endocrinology and metabolism","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144228430","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}