Journal of Clinical Endocrinology & Metabolism最新文献

{"title":"The natural history of cytologically low-risk indeterminate thyroid nodules.","authors":"Marsida Teliti, Spyridon Chytiris, Francesca Coperchini, Matteo Cerutti, Beatrice Grillini, Maria Gallo, Benedetto Calì, Giovanni Arpa, Mario Rotondi, Flavia Magri","doi":"10.1210/clinem/dgaf052","DOIUrl":"https://doi.org/10.1210/clinem/dgaf052","url":null,"abstract":"<p><strong>Background: </strong>Thyroid nodules classified cytologically as low-risk indeterminate lesions (TIR3A) on fine-needle aspiration biopsy (FNAB) present a clinical challenge due to their uncertain malignancy risk. This single-center study aimed to evaluate the natural history of TIR3A nodules.</p><p><strong>Materials and methods: </strong>FNABs performed between July 2017 and December 2019 were retrospectively retrieved and patients with TIR3A nodules were evaluated at baseline and throughout a follow-up based on ultrasound (US) parameters and clinical data.</p><p><strong>Results: </strong>The final study group encompassed 371 patients with an initial TIR3A cytological result. Among them 102 were addressed to surgery after the first endocrinological evaluation, and 269 were addressed to conservative follow-up. Repeat FNAB was performed in 120 out of 269 and 13 further patients underwent surgery following FNAB repetition. The malignancy rate among TIR3A nodules was 16.5%, with most interventions being performed for reasons unrelated to the TIR3A result. Repeat FNAB provided a more definitive diagnosis in 40% of cases, with a 5% increase in malignancy risk. The remaining patients were monitored with clinical and US follow-up. Among all patients with TIR3A cytology managed conservatively (149 without FNAB repetition and 66 with at least one FNAB repetition), no significant changes in nodule size and/or US pattern were observed during a median follow-up of 3.3 years.</p><p><strong>Conclusions: </strong>These findings suggest that active surveillance is a safe option for managing TIR3A nodules, particularly when no additional risk factors are present. The study highlights the role of repeat FNAB in reducing unnecessary surgeries and underscores the generally indolent nature of TIR3A nodules.</p>","PeriodicalId":50238,"journal":{"name":"Journal of Clinical Endocrinology & Metabolism","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143069408","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Endocrine alterations in patients with pachydermoperiostosis.","authors":"Maria Stelmachowska-Banaś, Sayka Barry, Ishita Angurala, Tom Rice, Kesson Magid, Ana Carreira, Ashutosh Rai, Amy Evans, Mark Bollington, Vaishali Kaur, Shallu Singhmar, Cristina Alina Silaghi, Kudakwashe Mandisodza, Alan McGregor, Jayaprakash Sahoo, Rahul Gupta, Kishore Kumar Behera, Ayan Roy, Ian Carr, Paul Benjamin Loughrey, Pinaki Dutta, Márta Korbonits","doi":"10.1210/clinem/dgaf050","DOIUrl":"https://doi.org/10.1210/clinem/dgaf050","url":null,"abstract":"<p><strong>Context: </strong>Pachydermoperiostosis (primary hypertrophic osteoarthropathy, PHO) usually due to biallelic loss-of-function variants in HPGD and SLCO2A1, has some features overlapping with acromegaly and often referred to endocrinologists. A detailed endocrine assessment is not available for these patients.</p><p><strong>Objective: </strong>To assess the genetic and endocrine characteristics of PHO patients referred to endocrine centres with a possible diagnosis of acromegaly.</p><p><strong>Methods: </strong>Seventeen patients from 14 families in which acromegaly was excluded based on lack of elevated IGF-1 levels and/or GH suppression on an oral glucose tolerance test were assessed for HPGD and SLCO2A1 variants.</p><p><strong>Results: </strong>Age at diagnosis was 26.2±9.0 years (mean±standard deviation, range 9-43). Digital clubbing was present in all patients. Periostosis (94%), arthralgia (88%), periarticular oedema (77%), pachydermia (82%) and coarsened facial features resembling acromegaly (71%) was present in the vast majority of the patients, while eyelash trichomegaly, blepharoptosis, high-arched palate, gingival hypertrophy, gastrointestinal symptoms and marfanoid habitus was seen in some. Nine patients (53%) had low IGF-1 levels, the rest of the patients had IGF-1 levels in the lowest quartile of the reference range. Oestradiol concentration was increased above the normal range in eight male patients (62%) with normal testosterone and prolactin levels. Biallelic HPGD (2/14 kindreds) or SLCO2A1 (eight novel) variants (12/14 kindreds) were found. Two patients had no identifiable pathogenic/likely pathogenic variant in HPGD or SLCO2A1. Their phenotype was not different from the other patients.</p><p><strong>Conclusions: </strong>We establish that low IGF-1 and elevated oestradiol levels are frequent features of PHO. Nine novel and five known pathogenic/likely pathogenic genetic variants were identified.</p>","PeriodicalId":50238,"journal":{"name":"Journal of Clinical Endocrinology & Metabolism","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143060987","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Glucose Metabolic Abnormalities and Their Interaction With Defective Phosphate Homeostasis in Tumor-induced Osteomalacia.","authors":"RuoTong Zhou, Ruizhi Jiajue, Xiaolin Ni, Qianqian Pang, Yue Chi, Yan Jiang, Ou Wang, Mei Li, Xiaoping Xing, Lijia Cui, Xiang Li, Yong Liu, Huanwen Wu, Jin Jin, Wei Lv, Yu Xia, Li Huo, Lian Zhou, Wei Yu, XunWu Meng, Weibo Xia","doi":"10.1210/clinem/dgae886","DOIUrl":"https://doi.org/10.1210/clinem/dgae886","url":null,"abstract":"<p><strong>Context: </strong>Phosphate homeostasis was compromised in tumor-induced osteomalacia (TIO) due to increased fibroblast growth factor 23 (FGF23) secretion. Nevertheless, the glucose metabolic profile in TIO patients has not been investigated.</p><p><strong>Objectives: </strong>This work aimed to clarify the glucose metabolic profiles in TIO patients and explore their interaction with impaired phosphate homeostasis.</p><p><strong>Methods: </strong>20 TIO patients, 20 individuals with normal glucose tolerance, and 20 patients with type 2 diabetes mellitus (DM) were enrolled and underwent an oral glucose tolerance test (OGTT). Serum phosphate and FGF23 concentration were monitored during OGTT.</p><p><strong>Results: </strong>In patients with TIO, 60% (12/20) exhibited impaired glucose tolerance (IGT) and 5% (1/20) had type 2 DM. Those with IGT or type 2 DM experienced more ambulatory difficulties (69.2% vs 42.9%), lower phosphate concentrations (0.43 ± 0.10 vs 0.53 ± 0.10, P = .042), and lower calcium concentrations (2.20 ± 0.08 vs 2.30 ± 0.40, P = .001) compared to TIO patients without these conditions. According to correlation analysis, serum phosphate levels were negatively correlated with plasma glucose levels at 60 minutes (P < .001), fasting plasma insulin levels (P < .05), and homeostasis model assessment for insulin resistance (P < .05). Those with high FGF23 levels had a higher glucose level at 60 minutes (10.5 [9.3, 12.3] vs 7.3 [6.4, 10.1], P = .048) than that of low group. After glucose loading, both FGF23 and phosphate levels exhibited a decreasing trend.</p><p><strong>Conclusion: </strong>The development of diabetes in TIO patients may be predisposed by ambulatory issues, low phosphate, and elevated FGF23 levels. Dysglycemia might further aggravate hypophosphatemia.</p>","PeriodicalId":50238,"journal":{"name":"Journal of Clinical Endocrinology & Metabolism","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143053830","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Searching for monogenic autoimmune etiology in patients with type 1 diabetes onset under 30 months of age.","authors":"Laura Saso-Jiménez, Inés Urrutia, Begona Calvo, José Ramón Bilbao, Ana Lucía Gómez-Gila, Isabel Leiva-Gea, Andrea Jiménez-Sanchis, Itxaso Rica, Luis Castano, Rosa Martínez","doi":"10.1210/clinem/dgaf049","DOIUrl":"https://doi.org/10.1210/clinem/dgaf049","url":null,"abstract":"<p><strong>Introduction: </strong>The most frequent form of diabetes in pediatric patients is polygenic autoimmune diabetes (T1D), but single-gene variants responsible for autoimmune diabetes have also been described. Both disorders share clinical features, which can lead to monogenic forms being misdiagnosed as T1D. However, correct diagnosis is crucial for therapeutic choice, prognosis and genetic counseling. The aim of this study was to search for monogenic autoimmune diabetes in Spanish pediatric patients with early-onset T1D.</p><p><strong>Methods: </strong>Among 500 Spanish pediatric patients with T1D, those with disease onset between 9 and 30 months of age were selected for screening for monogenic autoimmune diabetes (n=44). Genetic testing was performed by NGS with a customized panel that included the major causative genes for monogenic autoimmune syndromes, including early-onset diabetes: AIRE, CTLA4, FOXP3, IL2RA, ITCH, LRBA, STAT1, STAT3, STAT5B. RT-PCR and cDNA sequencing of the RNA isolated from whole blood were used to analyze splicing variants.</p><p><strong>Results: </strong>Genetic screening identified, in two patients with diabetes onset under one year of age, two likely pathogenic novel variants affecting canonical splicing sites: c.286-12_290del in STAT5B and c.-22-2delA in FOXP3. RNA analyses demonstrated that both variants modify mRNA splicing. The variant in STAT5B induced exon 4 skipping and the variant in FOXP3 caused a deletion of 16 nucleotides before the transcription start-site.</p><p><strong>Conclusions: </strong>T1D onset in the first year of life may indicate monogenic autoimmune diabetes and molecular testing may be recommended.</p>","PeriodicalId":50238,"journal":{"name":"Journal of Clinical Endocrinology & Metabolism","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143054039","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Insulitis and exocrinitis in autoantibody-positive non-diabetic individuals: role of HLA genotypes.","authors":"Marc Diedisheim, Roberto Mallone, Alberto Pugliese, Danièle Dubois-Laforgue, Etienne Larger","doi":"10.1210/clinem/dgaf039","DOIUrl":"https://doi.org/10.1210/clinem/dgaf039","url":null,"abstract":"<p><strong>Context: </strong>Type 1 diabetes (T1D) is characterized by the presence of autoantibodies on a genetic background largely determined by HLA class II haplotypes. Stage 1 T1D is characterized by the presence of multiple autoantibodies and normoglycemia.</p><p><strong>Objective: </strong>To investigate the prevalence of high-risk HLA-DQB1 haplotypes and the extent of islet autoimmunity in pancreatic tissues from non-diabetic organ donors with autoantibodies.</p><p><strong>Design: </strong>We analyzed 117 virtual pancreatic slides from 30 antibody-positive non-diabetic donors, from the Network for Pancreatic Organ Donors with Diabetes (nPOD).</p><p><strong>Patients: </strong>30 non-diabetic individuals positive for ≥1 autoantibody. HLA haplotypes were classified as at risk (DQ2, namely DQB1*02:01 and/or DQ8, namely DQB1*03:02), protective (DQ6, namely DQB1*06:02) or neutral (other HLA-DQ alleles).</p><p><strong>Main outcome measure: </strong>CD3+ lymphocyte infiltration of both endocrine and exocrine pancreas, according to HLA.</p><p><strong>Results: </strong>Among these 30 individuals with a median age of 25 years (interquartile range 21-39); median BMI 24 kg/m² (21-30), 23 were single autoantibody-positive and 7 were positive for 2 autoantibodies. β-cell mass was normal in all. HLA-DQ allele distribution was similar to that of autoantibody-negative non-diabetic nPOD donors, and differed from that of nPOD donors with stage 3 T1D. Insulitis was identified only in one case. CD3+ lymphocyte densities did no correlate with HLA status or autoantibody number or titers, neither in islets nor in the exocrine pancreas.</p><p><strong>Conclusions: </strong>Contrary to stage 3 T1D, autoantibody-positive donors had normal β-cell mass and no significant insulitis, suggesting heterogeneity in the progression of autoimmunity, even in the presence of genetic risk, rather than a uniform slow-progressing process.</p>","PeriodicalId":50238,"journal":{"name":"Journal of Clinical Endocrinology & Metabolism","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143054034","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Utility of the C-peptide/insulin molar ratio for distinguishing type A insulin resistance syndrome from type 2 diabetes.","authors":"Seiji Nishikage, Yushi Hirota, Tomofumi Takayoshi, Kai Yoshimura, Takehito Takeuchi, Tetsushi Hamaguchi, Mariko Ueda, Akane Yamamoto, Kazuhiko Sakaguchi, Wataru Ogawa","doi":"10.1210/clinem/dgaf043","DOIUrl":"https://doi.org/10.1210/clinem/dgaf043","url":null,"abstract":"<p><strong>Objective: </strong>Type A insulin resistance syndrome (IRS), characterized by impaired insulin receptor function due to variants of the insulin receptor gene, manifests as severe insulin-resistant diabetes. Differentiation of type A IRS from type 2 diabetes on the basis of hyperinsulinemia can be challenging. Given the association between insulin receptor dysfunction and reduced insulin clearance, we evaluated the potential of the circulating C-peptide reactivity (CPR)/immunoreactive insulin (IRI) molar ratio, a marker of insulin clearance, for distinguishing type A IRS from type 2 diabetes.</p><p><strong>Methods: </strong>We retrospectively analyzed CPR and IRI levels measured during a 75-g oral glucose tolerance test (OGTT) in 18 individuals with type A IRS and 126 with type 2 diabetes. Receiver operating characteristic (ROC) curve analysis was performed to determine the diagnostic performance of the CPR/IRI molar ratio and IRI levels.</p><p><strong>Results: </strong>IRI levels were significantly higher and the CPR/IRI molar ratio significantly lower in individuals with type A IRS compared with those with type 2 diabetes. The area under the ROC curve for the CPR/IRI molar ratio at baseline, 1 hour, and 2 hours after OGTT initiation was 0.997 (sensitivity 100%, specificity 99.2%), 0.999 (sensitivity 100%, specificity 97.6%), and 0.997 (sensitivity 100%, specificity 95.1%), respectively. The CPR/IRI molar ratio demonstrated robust diagnostic performance regardless of body mass index or hyperinsulinemia severity.</p><p><strong>Conclusions: </strong>The CPR/IRI molar ratio, both at baseline and during OGTT, exhibited higher sensitivity and specificity than IRI levels alone for distinguishing type A IRS from type 2 diabetes. This ratio may serve as a reliable clinical marker for early and accurate diagnosis of type A IRS.</p>","PeriodicalId":50238,"journal":{"name":"Journal of Clinical Endocrinology & Metabolism","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143054044","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diagnostic value of 11C-Methionine PET-CT imaging in persistent or recurrent Cushing's disease after surgery.","authors":"Raluca Maria Furnica, France Devuyst, Céline Mathey, Stefan Matei Constantinescu, Carlien De Herdt, Orsalia Alexopoulou, Renaud Lhommel, Dominique Maiter","doi":"10.1210/clinem/dgaf047","DOIUrl":"https://doi.org/10.1210/clinem/dgaf047","url":null,"abstract":"<p><strong>Introduction: </strong>Equivocal or negative pituitary magnetic resonance imaging (MRI) findings raise a significant challenge in the management of persistent or recurrent Cushing's disease (CD), compromising the chances of success of a further transsphenoidal surgery (TSS). The aim of our study was to determine the diagnostic utility of 11C-methionine (MET) positron emission tomography coupled with computerized tomography (PET/CT) in localizing the residual or relapsing corticotroph adenoma.</p><p><strong>Methods: </strong>We retrospectively analyzed the results of 11C-MET PET/CT performed in two tertiary medical centers between May 2002 and November 2023 in 22 patients with a persisting or recurrent CD after initial TSS and equivocal or negative pituitary MRI findings. In 15 cases, images obtained from MET PET/CT were also co-registered with high-resolution 3D T1 or FLAIR MRI pituitary imaging. All patients had a proven CD at the time of first surgery.</p><p><strong>Results: </strong>Twenty-two patients were included (18 females and 4 males), with a mean age of 36 years at diagnosis. Initial tumors were mostly microadenomas with a mean maximum tumor diameter of 6.5 mm. Thirteen out of the 22 patients had a suspect anomaly on conventional MRI that could however not be clearly distinguished from postsurgical changes, while the remaining 9 had a negative MRI. A maximal metabolic activity in the suspected area of the tumor residue (SUVmaxT) was found in 14 patients (63.5%; 5/9 patients with negative pituitary MRI and 9/13 with equivocal findings). On the basis of positive imaging, repeat TSS was performed in 12 patients and was successful in 7, while Gamma Knife radiosurgery (GKRS) was performed in 2 patients allowing remission in both (total remission rate of 64%). Among the 5 patients not cured by TSS, the presence of a corticotroph adenoma in the resected tissue was found in 3 cases. Therefore, when positive, 11C-MET PET/CT had a detection rate accuracy of 86% (12/14). Out of the 8 PET-negative patients, exploratory TSS was performed in 2, with no remission, and GKRS was performed in another two patients, with long-term remission in one.</p><p><strong>Conclusions: </strong>11C-Methionine PET/CT imaging can provide valuable diagnostic information to detect a corticotroph microadenoma in more than half of patients with persistent or recurrent CD and equivocal or negative MRI findings, thereby allowing targeted TSS or radiosurgery with a global success rate of 64% in the selected subgroup with positive imaging.</p>","PeriodicalId":50238,"journal":{"name":"Journal of Clinical Endocrinology & Metabolism","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143053824","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Romosozumab Improves Tissue Thickness-Adjusted Trabecular Bone Score in Women With Osteoporosis and Diabetes.","authors":"Serge Ferrari, Donald Betah, Robert G Feldman, Bente L Langdahl, Mary Oates, Jen Timoshanko, Zhenxun Wang, Ruban Dhaliwal","doi":"10.1210/clinem/dgae862","DOIUrl":"https://doi.org/10.1210/clinem/dgae862","url":null,"abstract":"<p><strong>Context: </strong>Trabecular bone score (TBS), a gray-level texture index derived from lumbar spine (LS) dual-energy x-ray absorptiometry (DXA) scans, is decreased in patients with diabetes and is associated with increased fracture risk, independent of areal bone mineral density (aBMD), but potentially influenced by abdominal fat tissue.</p><p><strong>Objective: </strong>Evaluate effect of romosozumab (210 mg monthly) for 12 months followed by alendronate (70 mg weekly) for 24 months vs alendronate alone (70 mg weekly) for 36 months on LS aBMD and TBS in women with type 2 diabetes (T2D) enrolled in the ARCH study.</p><p><strong>Methods: </strong>This post hoc analysis included women from ARCH who had T2D at baseline and LS DXA scans at baseline and ≥1 postbaseline visit (romosozumab-to-alendronate, n = 165; alendronate-to-alendronate, n = 195). aBMD and TBS (determined by an updated tissue thickness-adjusted TBS algorithm [TBSTT]) were assessed on LS DXA scans at baseline and ≥1 postbaseline visit (months 12, 24, and 36).</p><p><strong>Results: </strong>Romosozumab led to significantly greater gains in LS aBMD and TBSTT at month 12 vs alendronate, and the greater gains with romosozumab were maintained after transition to alendronate and persisted significantly at months 24 and 36 vs alendronate alone. TBSTT percentage changes weakly correlated to LS aBMD percentage changes from baseline to month 36 (romosozumab-to-alendronate, R2 = 0.1493; alendronate-to-alendronate, R2 = 0.0429).</p><p><strong>Conclusion: </strong>In postmenopausal women with osteoporosis and T2D, 12 months of romosozumab followed by 24 months of alendronate vs alendronate alone significantly improved LS aBMD and TBSTT (independently of abdominal fat) and to a greater extent. Hence, romosozumab may improve bone strength in patients with T2D.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov-NCT01631214.</p>","PeriodicalId":50238,"journal":{"name":"Journal of Clinical Endocrinology & Metabolism","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143034538","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Using a Composite Summary of Daily Sex Hormones to Gauge Time Until Menopause: A Focus on Pregnanediol Glucuronide (PDG).","authors":"J F Winkles, Alicia Colvin, Samar R El Khoudary, Nanette Santoro, Mary Sammel, Sybil Crawford","doi":"10.1210/clinem/dgae895","DOIUrl":"https://doi.org/10.1210/clinem/dgae895","url":null,"abstract":"<p><strong>Context: </strong>The timing of a woman's final menstrual period (FMP) in relation to her age is considered a valuable indicator of overall health, being associated with cardiovascular, bone health, reproductive, and general mortality outcomes.</p><p><strong>Objective: </strong>This work aimed to evaluate the relationship between hormones and the \"time to FMP\" when daily hormone trajectories are characterized by their 1) entropy, and 2) deviation from premenopausal/stable cycle patterns (representing a textbook \"gold standard\"; GS).</p><p><strong>Methods: </strong>As part of the Study of Women's Health Across the Nation, urinary luteinizing hormone (LH), follicle-stimulating hormone (FSH), estrogen conjugates (E1C), and pregnanediol glucuronide (PDG) were measured daily from a multiracial sample of 549 mid-life women for the duration of one menstrual cycle. Hormone trajectories were mapped onto a plane with axes representing Fuzzy entropy (FuzzEn) and the normalized dynamic time warping distance (DTW) from the GS.</p><p><strong>Results: </strong>Viewing FSH, E1C, PDG, and LH through this lens reveals that, contrary to existing wisdom, PDG stands out as a powerful predictor/descriptor of \"time to FMP.\" Using cluster analyses to discretize PDG on the DTW/FuzzEn plane yields statistically different survival curves, and Cox proportional hazards analyses confirm that this separation persists in the presence of known covariates of FSH, antimüllerian hormone, age, body mass index, financial hardship, smoking status, and cycle length.</p><p><strong>Conclusion: </strong>Since PDG is generally not considered a predictor/descriptor of ovarian aging, this work validates the DTW/FuzzEn analytical framework and introduces another metric/hormone to be used in FMP-related preventive care.</p>","PeriodicalId":50238,"journal":{"name":"Journal of Clinical Endocrinology & Metabolism","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143025720","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Association between Pregnancy Complications and Long-Term Maternal Cardiometabolic Health in the MIREC Cohort Study.","authors":"Mandy Fisher, Graeme Smith, Beth K Potter, Tye E Arbuckle, Julian Little, Hope Weiler, Anne-Sophie Morisset, Bruce Lanphear, Joseph M Braun, Premkumari Kumarathasan, Mark Walker, Michael M Borghese, Jillian Ashley-Martin, Robin Shutt, Linda Dodds, Jennifer E Bruin, Jana Palaniyandi, Michael Helewa, Shayne Taback, Isabelle Massarelli, Mark R Palmert, John Krzeczkowski, William D Fraser","doi":"10.1210/clinem/dgaf041","DOIUrl":"https://doi.org/10.1210/clinem/dgaf041","url":null,"abstract":"<p><strong>Context: </strong>During pregnancy, women who experience certain pregnancy complications show elevations in biomarkers of inflammation and insulin resistance; however, few studies have examined these cardiometabolic biomarkers in the decade following pregnancy.</p><p><strong>Objective: </strong>To examine the association between pregnancy complications and cardiometabolic biomarkers 9 years postpartum including: blood pressure, blood lipids, body fat percentage, insulin resistance (glucose, insulin, proinsulin, C-peptide, HOMA-IR, HbA1c, leptin, adiponectin) and inflammation (hs-C-reactive protein).</p><p><strong>Methods: </strong>Using data from the Maternal-Infant Research on Environmental Chemicals (MIREC) cohort study (2008-2021) we determined 3 groups of pregnancy complications: 1) hypertensive disorders of pregnancy (HDP) (n=35); any pregnancy complication in the index pregnancy, defined as preterm birth, HDP, impaired glucose tolerance or gestational diabetes mellitus (GDM) (n=55); or self-reported recurrence of one of these pregnancy complications (n=19). Our comparison group included 186 women with uncomplicated pregnancies.</p><p><strong>Results: </strong>In our adjusted linear regression results, all pregnancy complication groups showed significantly higher systolic and diastolic blood pressure 9 years later. HOMA-IR was 23% (95% CI: -4.4%, 57%), 26% (95% CI: 2.0%, 55%), and 51% (95% CI: 12%, 104%) higher at follow-up in participants who had experienced a prior HDP, an index pregnancy complication, or a recurrent pregnancy complication respectively. Elevations were also seen with HbA1c, insulin, C-peptide, and leptin especially among those with recurrent complications.</p><p><strong>Conclusion: </strong>This study contributes to the body of evidence that women with a history of certain pregnancy complications merit special attention in the prevention of CVD. We recommend further exploration into these associations in larger cohorts.</p>","PeriodicalId":50238,"journal":{"name":"Journal of Clinical Endocrinology & Metabolism","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143025717","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}