The Journal of clinical endocrinology and metabolism最新文献

{"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}

{"title":"Clinical Significance of Successful Ablation in Follicular Thyroid Carcinoma.","authors":"Haruhiko Yamazaki, Kiminori Sugino, Ryohei Katoh, Kenichi Matsuzu, Wataru Kitagawa, Mitsuji Nagahama, Aya Saito, Koichi Ito","doi":"10.1210/clinem/dgaf326","DOIUrl":"https://doi.org/10.1210/clinem/dgaf326","url":null,"abstract":"<p><strong>Objective: </strong>The purpose of this study is to investigate the clinical characteristics of follicular thyroid carcinoma (FTC) patients who received postoperative ablation, the predictive factors for successful ablation, and the association between successful ablation and the clinical outcomes of FTC.</p><p><strong>Patients: </strong>The study included 428 patients with FTC (216 in ablation group and 212 in observation group). A multivariate logistic regression model was used to identify factors independently associated with successful ablation.</p><p><strong>Results: </strong>Patients in the ablation group were significantly older (p < 0.001), had a higher prevalence of widely invasive-FTC histology (p < 0.001), had vascular invasion ≥ 2, and had a higher rate of anti-thyroglobulin antibody positivity (p = 0.007) in comparison to patients in the observation group. Among the 116 patients with postoperative ablation following diagnostic I-131 scintigraphy, 65 (56%) achieved successful ablation. In the multivariate analysis, the thyroglobulin level at ablation as the only independent predictor successful ablation (odds ratio, 0.952; 95% confidence interval, 0.909-0.996; p = 0.034). Among the ablation group, the 10-year cause-specific survival (CSS) rates of patients with (n = 65) and without successful ablation (n = 151) were 100% and 98.4% (p = 0.246), respectively. None of the patients with successful ablation died during the follow-up period. The 10-year distant-metastasis free survival (DMFS) rates of patients with and without successful ablation were 100% and 81.7% (p < 0.001), respectively. None of the patients with successful ablation experienced distant metastatic recurrence during the follow-up period.</p><p><strong>Conclusions: </strong>FTC patients with successful ablation achieved excellent 10-year CSS and DMFS rates of 100%. Therefore, careful follow-up may be unnecessary for these patients even if they have negative prognostic factors.</p>","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":"144218595","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 Lai: The beneficial effects of sodium-glucose cotransporter 2 inhibitors on anemia in type 2 diabetes-a real world study.","authors":"Shih-Wei Lai","doi":"10.1210/clinem/dgaf325","DOIUrl":"https://doi.org/10.1210/clinem/dgaf325","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":"144218597","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":"Diabetes Progression and Its Impact on Kidney Cancer Risk: Insights From a Longitudinal Korean Cohort Study.","authors":"Jin Yu, Bongseong Kim, Kyungdo Han, Mee Kyoung Kim","doi":"10.1210/clinem/dgaf249","DOIUrl":"https://doi.org/10.1210/clinem/dgaf249","url":null,"abstract":"<p><strong>Context: </strong>The incidence of kidney cancer is rising in Korea, with lifestyle and metabolic factors such as smoking, obesity, and hypertension contributing to this trend.</p><p><strong>Objective: </strong>This study assessed the relationship between diabetes progression and kidney cancer risk.</p><p><strong>Methods: </strong>Using data from the National Health Information Database in South Korea, analyzing 2 365 294 patients with type 2 diabetes mellitus who underwent health examinations in 2015 and 2016, excluding those with pre-existing cancer or who died within a year. Patients were monitored until 2022 to determine the incidence of kidney cancer, defined by ICD-10 code C64. Diabetes progression was assessed using a scoring system (range 0-6) based on the number of oral glucose-lowering drugs (GLDs), diabetes duration, insulin use, and the presence of chronic kidney disease (CKD), diabetic retinopathy (DR), or cardiovascular disease.</p><p><strong>Results: </strong>Among the indicators of diabetes progression, prolonged diabetes duration and the presence of CKD or DR were linked to higher hazard ratios (HRs) for kidney cancer. The risk of kidney cancer increased progressively with higher diabetes progression scores. Compared to participants with a score of 0, the adjusted HRs for kidney cancer were 1.21 (95% CI 1.13-1.30) for a score of 1, 1.28 (1.18-1.38) for a score of 2, 1.37 (1.23-1.51) for a score of 3, and 1.73 (1.49-2.01) for scores of 4 or higher.</p><p><strong>Conclusion: </strong>Diabetes progression is strongly associated with an increased risk of kidney cancer. These findings underscore the importance of targeted screening and awareness programs for kidney cancer in individuals with advanced diabetes.</p>","PeriodicalId":520805,"journal":{"name":"The Journal of clinical endocrinology and metabolism","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144210759","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}