The Journal of clinical endocrinology and metabolism最新文献

{"title":"Development of a Machine Learning-Based Model for Methimazole Dosage Adjustment in Youth with Hyperthyroidism.","authors":"Joon Young Kim, Kanghyuck Lee, Eunsik Choi, Jun Suk Oh, Eun Byoul Lee, Hyun Wook Chae, Taehoon Ko, Kyungchul Song","doi":"10.1210/clinem/dgaf542","DOIUrl":"https://doi.org/10.1210/clinem/dgaf542","url":null,"abstract":"<p><strong>Context: </strong>Accurate methimazole (MMI) dose adjustment in pediatric hyperthyroidism is crucial, but individualized titration relies on clinician experience due to a lack of validated predictive tools.</p><p><strong>Objective: </strong>This study aimed to develop and validate machine learning-based models for predicting optimal MMI dosage in pediatric hyperthyroidism.</p><p><strong>Design: </strong>This was a retrospective, multicenter, model-development study. Machine learning models, including linear regression, decision tree, support vector regression, eXtreme Gradient Boosting (XGBoost), and feed-forward neural networks, were trained and validated.</p><p><strong>Setting: </strong>Data were collected from a primary center for model training, with two separate centers providing data for external validation.</p><p><strong>Patients or other participants: </strong>Data were derived from 1,512 visits for the training set, and 666 and 31 visits for two external validation cohorts, respectively. All data were from youth aged ≤18 years with hyperthyroidism.</p><p><strong>Interventions: </strong>The models were trained to predict the optimal daily dosage of MMI based on variables including age, sex, anthropometric measures, prior MMI dosage, treatment duration, current and previous results of thyroid function tests.</p><p><strong>Main outcome measures: </strong>Model performance was evaluated by the mean absolute error (MAE) between the predicted and actual MMI dosages. Feature importance was determined using Shapley additive explanations (SHAP) analysis.</p><p><strong>Results: </strong>The XGBoost model demonstrated the best performance in both internal validation (MAE, 1.72 mg) and external validation (MAE, 1.08 mg). SHAP analysis identified previous MMI dose, triiodothyronine, and free thyroxine levels as key predictors.</p><p><strong>Conclusions: </strong>This study introduces the first data-driven tool to guide MMI dosing in pediatric hyperthyroidism which can improve clinical efficiency.</p>","PeriodicalId":520805,"journal":{"name":"The Journal of clinical endocrinology and metabolism","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145246199","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":"Osilodrostat-associated Adrenal Gland Shrinkage: a Case Series of Patients with ACTH-Dependent Cushing's Syndrome.","authors":"Elena V Varlamov, Brian J Park, Maria Fleseriu","doi":"10.1210/clinem/dgaf552","DOIUrl":"https://doi.org/10.1210/clinem/dgaf552","url":null,"abstract":"<p><strong>Context: </strong>Medical therapy for Cushing's syndrome (CS) is increasingly used. A potent adrenal steroidogenesis inhibitor, osilodrostat, has been rarely linked to prolonged adrenal insufficiency (AI).</p><p><strong>Objective: </strong>We hypothesized that osilodrostat-induced adrenal insufficiency could be associated with adrenal gland shrinkage.</p><p><strong>Design: </strong>Non-interventional, retrospective, longitudinal, IRB-approved study of patients with CS treated at Oregon Health and Science University between January 1, 2000 and July 1, 2025.</p><p><strong>Setting: </strong>Ambulatory and inpatient, academic, quaternary medical center.</p><p><strong>Patients or other participants: </strong>Patients with ACTH-dependent CS, treated with osilodrostat for >3 months, and CT imaging before and after osilodrostat available for adrenal volume (AV) measurement.</p><p><strong>Intervention(s): </strong>Age, sex, osilodrostat doses and duration, laboratory data and AI were recorded. AV was calculated using manual segmentation on CT images by a board-certified radiologist.</p><p><strong>Main outcome measure(s): </strong>AV before and after initiation of osilodrostat was expressed as percent reduction.</p><p><strong>Results: </strong>10 patients (5 ectopic CS, 4 unknown ACTH source, 1 Cushing's disease) were included. Osilodrostat mean starting, maximum and final doses: 7.7, 13.8 and 5.9 mg/day, respectively, over 23 months. Four patients received block-and-replace regimen, AI developed in 5. Adrenal gland volume decreased by 46.7±22.2% from 25.5±9.9 ml to 12.7±6.4 ml, p<0.001 over a median of 19 months. AV reduction positively correlated with maximum osilodrostat dose, r=0.626, p=0.027.</p><p><strong>Conclusions: </strong>We found that in selected patients with ACTH-dependent CS, osilodrostat can induce significant adrenal shrinkage, with or without AI. Further confirmation by larger studies of different CS types and monitoring for AI is required for all patients.</p>","PeriodicalId":520805,"journal":{"name":"The Journal of clinical endocrinology and metabolism","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145240764","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":"Antigen Presenting Cell Isolevuglandins Link Salt-Sensitivity of Blood Pressure to Insulin Resistance.","authors":"Lale A Ertuglu, Mert Demirci, Ashley L Mutchler, Cheryl L Laffer, Mohammad Saleem, T Alp Ikizler, Annet Kirabo","doi":"10.1210/clinem/dgaf556","DOIUrl":"https://doi.org/10.1210/clinem/dgaf556","url":null,"abstract":"<p><strong>Background: </strong>Insulin resistance has been associated with salt sensitivity and low sodium intake; however, the mechanisms remain elusive. Our previous studies showed that sodium-induced isolevuglandin (IsoLG) formation in antigen-presenting cells (APCs) leads to systemic inflammation and salt-sensitive hypertension and IsoLG formation in APCs is affected by acute alterations in salt intake in salt-sensitive but not salt-resistant people. In this clinical study, we investigated how acute salt loading and depletion change insulin resistance markers and whether these changes are linked with changes in IsoLGs in APCs.</p><p><strong>Methods: </strong>20 participants with hypertension underwent an inpatient protocol of salt loading and depletion for assessment of salt sensitivity. Plasma glucose and insulin levels were measured after 24 hours of salt loading and depletion and insulin resistance was measured by the homeostasis model assessment index (HOMA-IR). IsoLG-adduct accumulation in APCs (dendritic cells, classical, intermediate and non-classical monocytes) was assessed by flow cytometry.</p><p><strong>Results: </strong>Baseline insulin resistance correlated with higher salt sensitivity. Insulin resistance significantly increased from salt loading to salt depletion. Salt-depletion induced changes in IsoLG+ APCs significantly correlated with changes in HOMA-IR. This correlation was significant only in participants who were insulin resistant at baseline.</p><p><strong>Conclusion: </strong>Within 24 hours of acute salt depletion, markers of insulin resistance exhibit a significant increase, which strongly correlates with change in IsoLG formation in APCs. This finding implies that oxidative stress in APCs may be implicated in the salt-sensitive modulation of glucose metabolism.</p>","PeriodicalId":520805,"journal":{"name":"The Journal of clinical endocrinology and metabolism","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145240846","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 Importance of Disease Specific Growth Charts for Children with Congenital Adrenal Hyperplasia.","authors":"Kyriakie Sarafoglou, Yesica Mercado Munoz, Charles Sukin, Aida Lteif, Jennifer Kyllo, Bradley S Miller, O Yaw Addo, Deborah Merke","doi":"10.1210/clinem/dgaf554","DOIUrl":"https://doi.org/10.1210/clinem/dgaf554","url":null,"abstract":"<p><strong>Background: </strong>Children with congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency typically have height, weight and BMI growth patterns that differ from the general population due to increased androgen and/or glucocorticoid exposures. With the recent surge in the development of new therapies, CAH-specific growth charts are needed to evaluate the effectiveness of these new treatments.</p><p><strong>Methods: </strong>Retrospective data from patients aged 0-20 years with classic CAH, confirmed by hormonal testing and/or CYP21A2 genotyping, from two large clinical databases were analyzed. Specialized charts were developed using the Lamda-Mu-Sigma semi-parametric modeling method to generate CAH-specific percentile curves from 0-20 years. Nodal-point analyses were conducted to assess differences in incremental growth at 4, 8, 12, 16 and 20 years of age relative to CDC-2000 normative charts using one-sided quantile tests and age of adiposity rebound estimated with curve derivative solutions.</p><p><strong>Results: </strong>A total sample of 8692 visits from 515 patients were used. Growth (height-, weight-, BMI-for-age) channels of CAH patients were significantly different over the entire growing period and characterized by diminished pubertal spurt relative to the CDC reference. Onset of adiposity rebound based on BMI-for-age occurred earlier for CAH patients (females 3.3 years, males 3.9 years) compared to their normative counterparts (5-8 years).</p><p><strong>Conclusion: </strong>Our study showed that at incremental time points throughout childhood, children with CAH collectively follow specific differences in growth trajectories than unaffected children. These variations highlight the need for CAH-specific charts to assist in clinical management, appraisal of growth trajectories and to assess the impact of new therapies.</p>","PeriodicalId":520805,"journal":{"name":"The Journal of clinical endocrinology and metabolism","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145240728","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 and Biochemical Phenotype Across the Genotypic Spectrum of 21-Hydroxylase Deficiency in 457 Individuals.","authors":"Qizong Lao, Annie Schulman, Sarah Kulkarni, Sarah Kollender, Daniella Bick, Amy Moon, Deepika Burkardt, Deborah P Merke","doi":"10.1210/clinem/dgaf546","DOIUrl":"https://doi.org/10.1210/clinem/dgaf546","url":null,"abstract":"<p><strong>Context: </strong>Genetic testing for 21-hydroxylase deficiency (21OHD) is advantageous when hormonal testing is equivocal, to molecularly confirm diagnosis, and for genetic counseling.</p><p><strong>Objectives: </strong>To characterize the clinical and biochemical phenotype across the genotypic spectrum of 21OHD in a large cohort using updated genetic methodology.</p><p><strong>Design: </strong>Retrospective study of 457 individuals with 21OHD enrolled in a Natural History study at the NIH Clinical Center.</p><p><strong>Results: </strong>The majority (79%) were compound heterozygous, 46% with chimeric alleles/30-kb deletions including 2.6% with attenuated chimeras, 10.1% with CAH-X (33% with cardiac defects) and 3.7% with genotype-phenotype discordance. The most common mutations among individuals with salt-wasting (SW), simple-virilizing (SV), and nonclassic (NC) phenotypes were In2G, I172N, and V281L respectively. Rare or novel mutations accounted for 4.3% alleles, 0.33% arose de novo. 17OHP levels at diagnosis varied by genotype group (Null>In2G> SV genotypes > P30L > Other NC; P<0.001); but maximum values obtained during clinical care over time were similar among all classic and among all NC genotypes. Individuals with P30L had higher 17OHP and lower cortisol at diagnosis compared to other NC genotypes (P<0.001) and were more likely to have basal 17OHP >1,000ng/dL (P<0.001). Individuals with cryptic NC had lower 17OHP post cosyntropin stimulation compared to those with symptomatic NC (P=0.02).</p><p><strong>Conclusion: </strong>A continuum of disease phenotypes exists with biochemical overlap that increases with age. Improving genotype accuracy to include chimera subtyping to identify attenuated chimeras and CAH-X and consideration of P30L as a unique group are important to guide genetic counseling and provide anticipatory guidance in disease management.</p>","PeriodicalId":520805,"journal":{"name":"The Journal of clinical endocrinology and metabolism","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145234895","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":"Sleep disturbances in patients with Cushing syndrome and mild autonomous cortisol secretion: a cross-sectional study.","authors":"Shubhangi Sharma Sharma, Jasmine Saini, Shireen R Chacko, Sarina Ahmadian, Vanessa Fell, Dana Erickson, Anina F Peersen, Sara J Achenbach, Elizabeth J Atkinson, Irina Bancos","doi":"10.1210/clinem/dgaf553","DOIUrl":"https://doi.org/10.1210/clinem/dgaf553","url":null,"abstract":"<p><strong>Context: </strong>The impact of active hypercortisolism on sleep is incompletely characterized. Studies report impaired sleep in patients with Cushing syndrome (CS). Patients with mild autonomous cortisol secretion (MACS) demonstrate mild nocturnal hypercortisolism that could impact sleep.</p><p><strong>Objectives: </strong>To characterize sleep abnormalities in patients with CS and MACS using the Pittsburgh Sleep Quality Index (PSQI), identify factors associated with poor sleep, and compare sleep abnormalities in patients with MACS versus referent subjects.</p><p><strong>Methods: </strong>We conducted a single-center cross-sectional study of adults with active CS and MACS. Clinical and biochemical severity scores for hypercortisolism were calculated. Parallelly, we enrolled referent subjects. Quality of life was assessed using 1) Short Form-36 in all participants, and 2) Cushing QoL in patients with active hypercortisolism. Sleep quality was assessed using PSQI.</p><p><strong>Results: </strong>PSQI was assessed in 154 patients with CS (mean 12, SD ±4.5), 194 patients with MACS (mean 11, SD 4.6), and 89 referents (mean 5, SD ±3.4). Patients with MACS exhibited shorter sleep duration, longer sleep latency, more severe daytime dysfunction, lower sleep efficiency, and a higher sleep medication use compared to referent subjects (P = <0.001 for all). Age-, sex, and BMI adjusted analysis demonstrated no differences in PSQI or its subcomponents between patients with CS and MACS (P >0.05 for all). In a multivariable analysis of patients with MACS, younger age, female sex and higher clinical hypercortisolism severity score were associated with impaired sleep. In patients with CS, only younger age was associated with poor sleep.</p><p><strong>Conclusions: </strong>Patients with MACS demonstrate sleep impairment that is similar to patients with CS. Younger women with higher clinical severity of MACS are more likely to have impaired sleep.</p>","PeriodicalId":520805,"journal":{"name":"The Journal of clinical endocrinology and metabolism","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145234903","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":"Mineralocorticoid receptor antagonist pre-adrenalectomy in primary aldosteronism.","authors":"Jessica Goi, Miguel Paja Fano, Alicia Rizo Gellida, Marga González-Boillos, Patricia Martín Rojas-Marcos, Laura Caja Guayerbas, Ana María García Cano, Jorge Gabriel Ruiz-Sanchez, Almudena Vicente, Emilia Gómez-Hoyos, Mònica Recasens, Rebeca Barahona San Millan, María José Picón César, Patricia Díaz Guardiola, Carolina María Perdomo, Laura Manjón-Miguélez, Ángel Rebollo Román, Cristina Robles Lázaro, José María Recio-Cordova, María Calatayud, Noemi Jiménez López, Miguel Sampedro Nuñez, Elena Mena Ribas, Alicia Sanmartín Sánchez, Cesar Gonzalvo Diaz, Cristina Lamas, Joaquín Serrano, Theodora Michalopoulou, Susana Tenes Rodrigo, Eider Pascual-Corrales, Fernando Jaén Aguila, Nuria Muñoz Rivas, Eva María Moya Mateo, Sonsoles Gutiérrez-Medina, Felicia Alexandra Hanzu, Paola Parra Ramírez, Marta Araujo-Castro","doi":"10.1210/clinem/dgaf545","DOIUrl":"https://doi.org/10.1210/clinem/dgaf545","url":null,"abstract":"<p><strong>Background: </strong>Perioperative use of mineralocorticoid receptor antagonists (MRA) in patients with unilateral primary aldosteronism (PA) awaiting surgery is not well standardized. The aim of this study was to compare the risk of postoperative complications and surgical outcomes between PA patients treated with MRA prior to adrenalectomy and those non-pretreated.</p><p><strong>Methods: </strong>Adrenalectomized patients for unilateral PA from the SPAIN-ALDO registry, with clinical, hormonal and treatment information before and after adrenalectomy, were analyzed.</p><p><strong>Results: </strong>A total of 355 surgically-treated patients were included and 76.9% (n=273) received presurgical treatment with MRA (more commonly spironolactone [64.5%] than eplerenone [35.5%]). Adrenalectomy was guided by lateralization at AVS in 33.5% of the overall cohort, and by imaging in all the other cases. Patients pretreated with MRA had longer duration of hypertension, higher prevalence of hypokalemia and greater aldosterone concentrations than those not pretreated (n=82). No differences in the rate of postsurgical hyperkalemia, hypoaldosteronism, renal function impairment, blood pressure changes and biochemical outcomes were detected between groups in the immediate (≤30 days) and at short-term follow-up (≤90 days) following surgery. At long-term follow-up, patients pretreated with MRA exhibited better postsurgical biochemical outcomes (81.7% had complete biochemical response vs. 57.1% of non-pretreated patients; p=0.004). In the multivariable analysis, the use of MRA prior to adrenalectomy was independently associated with a successful postsurgical biochemical response.</p><p><strong>Conclusion: </strong>Preoperative MRA therapy can be safely introduced to control blood pressure and potassium levels in patients with PA awaiting surgery, without increasing the risk of postoperative hyperkalemia, hypoaldosteronism, renal impairment, or hypotension.</p>","PeriodicalId":520805,"journal":{"name":"The Journal of clinical endocrinology and metabolism","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145228712","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":"Comprehensive Molecular Studies in 88 Japanese Patients With Congenital Hypogonadotropic Hypogonadism.","authors":"Wataru Tanikawa, Shingo Okamoto, Osamu Ohara, Yohei Masunaga, Kaori Yamoto, Yasuko Fujisawa, Ibuki Ohyama, Hirotomo Saitsu, Maki Fukami, Tadashi Kaname, Tsutomu Ogata","doi":"10.1210/clinem/dgaf548","DOIUrl":"https://doi.org/10.1210/clinem/dgaf548","url":null,"abstract":"<p><strong>Background: </strong>Congenital hypogonadotropic hypogonadism (CHH) is a genetically heterogeneous disorder, with multiple causative and candidate genes identified to date.</p><p><strong>Methods: </strong>We examined 88 Japanese patients with CHH using gene panel analysis (GPA) for 14 representative causative genes and whole exome sequencing (WES) which was initially focused on 41 causative/candidate genes and subsequently expanded to other genes. We extracted rare variants (frequency of <0.01) and performed pathogenic assessment using refined ACMG/AMP criteria and registered information in ClinVar.</p><p><strong>Results: </strong>Twenty-seven pathogenic/likely pathogenic variants were identified in 30 patients through GPA performed for all the 88 patients and in four patients through WES performed for 58 patients in whom no obvious disease-causing variants were revealed by GPA. They resided in previously known ANOS1 (six variants in seven patients), CHD7 (three variants in three patients), FGFR1 (14 variants in 15 patients), PROKR2 (two variants in eight patients), and SOX10 (one variant in one patient), and hitherto unrecognized ZNF462 (one variant in one patient). One patient had two variants. Additionally, potentially CHH-related variants were detected in 12 genes including SEMA4D and CDH2 postulated on the CHH-related molecular network. Furthermore, in the 41 CHH-related genes, the frequency of oligogenicity was significantly higher and the number of rare variants per subject was significantly larger in 54 CHH patients with no discernible pathogenic/likely pathogenic variants than in 100 control subjects.</p><p><strong>Conclusion: </strong>The results support the notion that CHH occurs not only as a monogenic disorder but also as an oligogenic/multifactorial disorder, and suggest the involvement of ZNF462, SEMA4D, and CDH2 variants in the development of CHH.</p>","PeriodicalId":520805,"journal":{"name":"The Journal of clinical endocrinology and metabolism","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145226562","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 Sumi and Tominaga: \"Tolvaptan versus fluid restriction in moderate-profound hyponatremia: An open-label randomized clinical trial\".","authors":"Annabelle M Warren, Mathis Grossmann, Rudolf Hoermann, Rose Lin, Jeffrey D Zajac, Nicholas Russell","doi":"10.1210/clinem/dgaf538","DOIUrl":"https://doi.org/10.1210/clinem/dgaf538","url":null,"abstract":"","PeriodicalId":520805,"journal":{"name":"The Journal of clinical endocrinology and metabolism","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145202885","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":"Incomplete Evidence of Bone Density Normalization Following Long-Term Reproductive Hormone Treatment in Men With Hypogonadotropic Hypogonadism.","authors":"Nipun Lakshitha de Silva, Elizabeth Hyams, Bonnie Grant, Paras Dixit, Rajdeep Bassi, Paul Bassett, Alexander N Comninos, Channa N Jayasena","doi":"10.1210/clinem/dgaf488","DOIUrl":"https://doi.org/10.1210/clinem/dgaf488","url":null,"abstract":"<p><strong>Context: </strong>The prevalence and severity of low bone mineral density (BMD) in hypogonadotropic hypogonadism (HH), as well as the ability of reproductive hormone treatment to normalize BMD have not been investigated in large multicenter studies.</p><p><strong>Objective: </strong>We performed a systemic review and meta-analysis of several small, observational studies to investigate the effect of reproductive hormone treatment on BMD in men with HH compared with control groups where available.</p><p><strong>Methods: </strong>We searched OVID Medline, Embase, CINAHL, SCOPUS, Web of Science, and Cochrane Library for studies reporting BMD or fractures in men with HH (congenital [CHH] or acquired). Study selection and data extraction were performed using COVIDENCE and a prespecified tool. Results were summarized using descriptive statistics. Meta-analysis compared BMD in men with HH vs healthy controls. Meta-regression assessed relationships between treatment duration and BMD Z-scores against normative population data.</p><p><strong>Results: </strong>Of the 33 eligible studies, 24 included data specific to men with HH (n = 625). Men with HH had low lumbar spine (LS) and femoral neck BMD, improving with hormonal treatment. Meta-analysis of 5 studies found lower LS BMD in men with HH vs healthy controls (SMD -5.98; 95% CI; -11.5 to -0.47). Men with CHH may have persistently low BMD despite prolonged hormonal treatment. Higher BMD in HH was associated with younger age at treatment initiation, partial HH, and higher serum testosterone and estradiol concentrations. Fracture prevalence was high in the few studies systematically studying fractures as an outcome; in other studies, fractures were seldom reported.</p><p><strong>Conclusion: </strong>Men with HH have low BMD that improves with reproductive hormone treatment. However, current evidence suggests that incomplete BMD normalization may be common despite long-term reproductive hormone treatment in men with HH, particularly those with CHH.</p>","PeriodicalId":520805,"journal":{"name":"The Journal of clinical endocrinology and metabolism","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145208979","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}