Hormone and Metabolic Research最新文献

{"title":"Re-Evaluation of the Diagnostic Cut-Off for the Overnight Metyrapone Test Using Liquid Chromatography-Tandem Mass Spectrometry Measurement of 11-Deoxycortisol.","authors":"Jann A Hommen, Tanja Eberwein, Christiana Vogkou, Samer Albeiruty, Mareike Muchalla, Matthias Schott","doi":"10.1055/a-2976-3465","DOIUrl":"https://doi.org/10.1055/a-2976-3465","url":null,"abstract":"<p><strong>Abstract: </strong>The overnight metyrapone test is an established tool for assessing the hypothalamic-pituitary-adrenal axis. The current diagnostic cut-off for serum 11-deoxycortisol (70 µg/L) is based on older immunoassays. With the introduction of liquid chromatography-tandem mass spectrometry, concerns have arisen regarding the validity of these thresholds. This study re-evaluates 11-deoxycortisol measured by liquid chromatography-tandem mass spectrometry in the overnight metyrapone test and assesses whether current cut-offs remain appropriate. In this retrospective diagnostic study, patients undergoing single-dose metyrapone testing after pituitary surgery (2017-2025) were included. Serum 11-deoxycortisol was measured using liquid chromatography-tandem mass spectrometry. A sufficient adrenal function was classified based on the absence of glucocorticoid therapy, lack of symptoms, normotension and normal laboratory findings. Receiver operating characteristic analysis was used to determine optimal thresholds. Diagnostic performance was evaluated using sensitivity, specificity, likelihood ratios, Matthews correlation coefficient, and bootstrap validation. Receiver operating characteristic analysis showed strong discrimination for detecting secondary adrenal insufficiency (area under the curve=0.953). Multiple statistical approaches consistently identified optimal cut-offs below 70 µg/L, in line with recent studies. Thresholds around 63-64 µg/L improved the balance between sensitivity and specificity. In contrast, the historical cut-off of 70 µg/L showed high sensitivity but reduced specificity, increasing the risk of false-positive results and unnecessary glucocorticoid substitution. The currently recommended cut-off for the OMT may be too high when using liquid chromatography-tandem mass spectrometry. Lower thresholds around 63-64 µg/L may improve diagnostic accuracy. Re-evaluation of current recommendations appears warranted.</p>","PeriodicalId":12999,"journal":{"name":"Hormone and Metabolic Research","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2026-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149244215","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Athyreosis and Thyroid Hormone Signaling: A System-Based Framework for Long-Term Endocrine Health.","authors":"Angela D Mazza","doi":"10.1055/a-2969-5828","DOIUrl":"https://doi.org/10.1055/a-2969-5828","url":null,"abstract":"<p><strong>Abstract: </strong>Thyroidectomy and radioactive iodine therapy are definitive treatments for Graves' disease, toxic nodular disease, and differentiated thyroid cancer. With improving survival rates and expanding indications for definitive therapy, a growing population is living for decades in a state of athyreosis requiring lifelong thyroid hormone replacement. Current management strategies largely emphasize serum thyroid-stimulating hormone targets and oncological surveillance, yet the long-term metabolic and physiological implications of chronic athyreosis remain incompletely explored. The potential longevity implications of long-term athyreosis are examined through a system-based framework integrating hormonal balance, mitochondrial regulation, metabolic adaptation, skeletal and cardiovascular health, and inflammatory signaling. This narrative review synthesizes evidence from endocrinology, metabolism, oncology, and aging research to evaluate physiological differences between endogenous thyroid hormone secretion and pharmacological replacement in athyreotic patients. Particular attention is given to tissue-level triiodothyronine availability, deiodinase activity, and downstream bioenergetic effects. Athyreotic patients lack intrinsic thyroidal triiodothyronine secretion and depend entirely on the peripheral conversion of levothyroxine to generate circulating and intracellular triiodothyronine. Emerging evidence suggests that levothyroxine monotherapy may not fully replicate physiological thyroid hormone dynamics in all individuals, potentially influencing mitochondrial biogenesis, resting energy expenditure, body composition, bone turnover, and cardiovascular remodeling. In thyroid cancer survivors, chronic thyroid-stimulating hormone suppression introduces additional considerations for skeletal and cardiac outcomes. Patients treated for autoimmune thyroid disease may also exhibit persistent immune dysregulation despite gland ablation. Athyreosis represents a distinct and permanent endocrine state with implications extending beyond biochemical euthyroidism. A system-based perspective that considers mitochondrial resilience, cardiometabolic integrity, skeletal preservation, and inflammatory tone may enhance long-term management strategies for this expanding survivorship population. Prospective studies are needed to clarify the impact of various thyroid hormone replacement paradigms on functional aging and longevity outcomes.</p>","PeriodicalId":12999,"journal":{"name":"Hormone and Metabolic Research","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149206760","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinicopathological Profile of Disordered Proliferative Endometrium in Anovulatory Abnormal Uterine Bleeding and Determinants of Response to Levonorgestrel-Releasing Intrauterine System Therapy.","authors":"Seetu Palo, Mishu Mangla, Raja Shekhar PRaja, Poojitha Kalyani Kanikaram, Naina Kumar, Akansha Mahaptra","doi":"10.1055/a-2966-0186","DOIUrl":"https://doi.org/10.1055/a-2966-0186","url":null,"abstract":"<p><strong>Abstract: </strong>Disordered proliferative endometrium is an under-recognized endometrial lesion, with limited evidence regarding its clinicopathological characteristics and predictors of treatment response. The present study aimed to characterize the clinical and histomorphological features of disordered proliferative endometrium, evaluate the response to treatment with a levonorgestrel-releasing intrauterine system, and identify the clinicopathological determinants of progesterone responsiveness. A 3-year cross-sectional study was conducted involving 124 women with histopathologically confirmed disordered proliferative endometrium. Clinical, demographic, radiological, and histopathological parameters were analysed, and the treatment response to the levonorgestrel-releasing intrauterine system was assessed after 3 months using pictorial blood assessment chart scores and symptom improvement. The median age at presentation was 42 years, with 59.7% of patients belonging to the perimenopausal age group (40-49 y). Heavy menstrual bleeding was the predominant presenting complaint (68.5%). Most patients were overweight or obese (64.5%), and 85.5% had anaemia. Hypertension (22.6%), hypothyroidism (13.7%), and diabetes mellitus (12.1%) were the most common associated comorbidities, while coexisting gynaecological pathologies were identified in 23.4% of cases. Histopathological examination consistently demonstrated focal glandular crowding and cystic glandular dilatation, with gland-to-stroma ratios ranging from 30:70 to 60:40; an irregular glandular architecture was observed in 93.5% of cases. Following levonorgestrel-releasing intrauterine system insertion, 69.4% of patients experienced significant clinical improvement. A higher body mass index was the only independent predictor of reduced treatment response. Disordered proliferative endometrium predominantly affects perimenopausal women with heavy menstrual bleeding and metabolic risk factors, exhibits characteristic histomorphological features, and responds well to progesterone therapy in most cases. Recognition of factors influencing the treatment response may facilitate individualized management and improve clinical outcomes.</p>","PeriodicalId":12999,"journal":{"name":"Hormone and Metabolic Research","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149136533","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diagnostic Performance of Routine Biochemical Markers and Internally Validated Multivariable Models in Primary and Normocalcemic Primary Hyperparathyroidism: A Multicenter Retrospective Study.","authors":"Berçem Ayçiçek, Musab Ahmed Khan Umair, Şenol Pişkin, J S Femilda Josephin, Umit Çavdar, Beyza Zeynep Kocabiçak, Özlem Eren, Kadir Alper Küçüker, Tevhid Turan, Mazhar Muslum Tuna, Ersen Karakiliç, Rumeysa Sahinbaş, Remziye Çetin, Denizcan Demir, Ümran Keskin, Melda Çelik, Çağri Canbolat, Gözde Nizamoğlu, Beyza Nur Yazici, Ceren Tufan, Sedat Çetin, Seval Erhamamci, Bülent Turgut","doi":"10.1055/a-2961-7052","DOIUrl":"https://doi.org/10.1055/a-2961-7052","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Abstract: &lt;/strong&gt;The aims of this study were to compare the biochemical characteristics of primary hyperparathyroidism and normocalcemic primary hyperparathyroidism and to evaluate the diagnostic performance of routinely available biochemical markers using validated patient-level multivariable statistical modeling. This retrospective multicenter study screened 1,832 individuals between January 2018 and December 2023. Baseline descriptive characteristics were obtained from an initial retrospective clinical cohort comprising 1,575 patients. Following the verification of the original database, duplicate encounters were consolidated, and all inferential statistical analyses were reconstructed at the patient level using the first eligible encounter for each patient. The final analytical cohort consisted of 375 patients (177 primary hyperparathyroidism and 198 normocalcemic primary hyperparathyroidism). Multivariable logistic regression with patient-level stratified cross-validation, bootstrap resampling and permutation testing, along with Spearman's correlation analyses, was performed. The effect of the synthetic minority over-sampling technique was evaluated using in-fold resampling. In the verified patient-level cohort, the multivariable logistic regression model demonstrated modest discrimination between primary hyperparathyroidism and normocalcemic primary hyperparathyroidism area under the curve: 0.578; 95% confidence interval: 0.516-0.639). Permutation testing indicated a statistically significant but limited diagnostic signal (&lt;i&gt;p&lt;/i&gt;=0.02). Application of the synthetic minority over-sampling technique did not materially improve model performance (area under the curve: 0.577). No significant association was observed between the parathyroid hormone and 25-hydroxyvitamin D in the overall cohort (Spearman's &lt;i&gt;ρ&lt;/i&gt;=- 0.079, &lt;i&gt;p&lt;/i&gt;=0.185) or within the primary hyperparathyroidism and normocalcemic primary hyperparathyroidism subgroups. An exploratory visit-level screening model based solely on laboratory test-ordering patterns achieved higher discrimination (area under the curve: 0.733), suggesting that laboratory test-ordering patterns contributed to the observed classification signal. Primary hyperparathyroidism and normocalcemic primary hyperparathyroidism exhibit overlapping biochemical characteristics that provide only modest patient-level discrimination when evaluated using routinely available laboratory variables. Multivariable predictive modeling demonstrated limited diagnostic performance after rigorous patient-level validation, and the synthetic minority over-sampling technique did not improve model performance. These findings underscore the importance of patient-level validation and standardized analytical pipelines when developing predictive models using retrospective clinical data sets. Prospective studies with standardized biochemical assessment and external validation are required before such predictive models can be","PeriodicalId":12999,"journal":{"name":"Hormone and Metabolic Research","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149127111","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Renal Function, Appendicular Lean Mass, and Bone Stiffness: Indirect Associations Through Fibroblast Growth Factor 21.","authors":"Masahiro Matsui, Chie Saito, Seiji Maeda, Makoto Kuro-O, Kunihiro Yamagata, Keisei Kosaki","doi":"10.1055/a-2961-7220","DOIUrl":"https://doi.org/10.1055/a-2961-7220","url":null,"abstract":"<p><strong>Abstract: </strong>Reduced renal function has been associated with lower skeletal muscle mass and bone stiffness; however, the mechanisms linking renal function to skeletal muscle and bone health remain unclear. Fibroblast growth factor-21, whose circulating levels increase with impaired renal function, may be involved in these associations. This study examined whether renal function indices showed indirect associations with an appendicular lean mass index and bone stiffness through serum fibroblast growth factor-21 levels in middle-aged and older adults. This cross-sectional study included 301 middle-aged and older adults. Estimated glomerular filtration rate, urinary albumin-to-creatinine ratio, serum fibroblast growth factor-21 levels, appendicular lean mass index, and bone stiffness index were measured. Partial correlation, multivariable linear regression, and indirect-effect analyses were performed after adjustment for potential covariates. After adjustment for potential covariates, serum fibroblast growth factor-21 levels were inversely associated with the estimated glomerular filtration rate, appendicular lean mass index, and bone stiffness index and positively associated with the urinary albumin-to-creatinine ratio. In multivariable linear regression analyses, higher serum fibroblast growth factor-21 levels were independently associated with lower appendicular lean mass index and bone stiffness index, whereas neither the estimated glomerular filtration rate nor the urinary albumin-to-creatinine ratio was significantly associated with either outcome. Indirect-effect analyses showed significant indirect associations through serum fibroblast growth factor-21 levels for the associations of the estimated glomerular filtration rate and urinary albumin-to-creatinine ratio with an appendicular lean mass index and for the association of the estimated glomerular filtration rate with the bone stiffness index. The indirect association between the urinary albumin-to-creatinine ratio and the bone stiffness index was not statistically significant. Higher serum fibroblast growth factor-21 levels were independently associated with the lower appendicular lean mass index and bone stiffness index. Cross-sectional indirect-effect analyses suggested indirect associations of the estimated glomerular filtration rate and urinary albumin-to-creatinine ratio with the appendicular lean mass index and of the estimated glomerular filtration rate with the bone stiffness index through serum fibroblast growth factor-21 levels.</p>","PeriodicalId":12999,"journal":{"name":"Hormone and Metabolic Research","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2026-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149108727","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of Progesterone and Prolactin with Hepatic Steatosis in Premenopausal Women: A Prospective Cross-Sectional Study.","authors":"Muhammed Aziz Ulusoy, Mustafa Comoglu, Oguzhan Zengin, Huseyin Camli, Esma Andac Uzdogan, Emra Asfuroglu Kalkan, Ihsan Ates","doi":"10.1055/a-2949-7994","DOIUrl":"10.1055/a-2949-7994","url":null,"abstract":"<p><strong>Abstract: </strong>This study aimed to investigate the association between hepatic steatosis and serum levels of reproductive hormones in premenopausal women, with particular focus on progesterone and prolactin. A total of 87 premenopausal women aged 18-45 years were included in this prospective study. Participants were classified by ultrasonographic steatosis status and grade. Blood samples obtained on day 3 of the menstrual cycle were used to measure follicle-stimulating hormone, luteinizing hormone, estradiol, progesterone, and prolactin levels. Women with overt metabolic and endocrine disorders were excluded. Multivariable logistic regression and receiver operating characteristic analyses were performed. Hepatic steatosis was present in 53 participants (60.9%), whereas 34 participants had no steatosis. Progesterone and prolactin levels were significantly lower in participants with hepatic steatosis than in those without steatosis (0.6 vs. 1.1 ng/mL and 7.9 vs. 11.0 ng/mL, respectively; both <i>p</i><0.001). In multivariable analysis, older age (odds ratio: 1.32, 95% confidence interval: 1.12-1.56; <i>p</i>=0.001), higher body mass index (odds ratio: 1.57, 95% confidence interval: 1.19-2.08; <i>p</i>=0.002), lower progesterone levels (odds ratio: 0.75, 95% confidence interval: 0.58-0.98; <i>p</i>=0.037), and lower prolactin levels (odds ratio: 0.51, 95% confidence interval: 0.34-0.79; <i>p</i>=0.002) were independently associated with hepatic steatosis. Estradiol, follicle-stimulating hormone, and luteinizing hormone were not associated with steatosis. Receiver operating characteristic analysis showed a discriminative value for progesterone (area under the curve: 0.751) and prolactin (area under the curve: 0.790). Lower serum progesterone and prolactin levels were associated with hepatic steatosis after adjustment for age and body mass index. These findings support a possible relationship between reproductive hormonal milieu and hepatic steatosis in a selected premenopausal population, while the progesterone finding should be interpreted in the context of early follicular-phase measurement.</p>","PeriodicalId":12999,"journal":{"name":"Hormone and Metabolic Research","volume":" ","pages":"413-418"},"PeriodicalIF":2.3,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148955840","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Early Hormonal Responses of Irisin and Nesfatin-1 Following Sleeve Gastrectomy in Women with Obesity: A Preliminary Study.","authors":"Ibrahim Ozalp, Remzi Kiziltan, Sermin Algul, Oguz Ozcelik","doi":"10.1055/a-2941-6895","DOIUrl":"10.1055/a-2941-6895","url":null,"abstract":"<p><strong>Abstract: </strong>Laparoscopic sleeve gastrectomy (LSG) is an effective surgical intervention for morbid obesity, yet early hormonal changes contributing to metabolic adaptation remain underexplored. The objective of this study was to evaluate the early postoperative changes in the energy-regulating hormones irisin and nesfatin-1 following LSG in obese female patients. These hormones were selected due to their established roles in metabolic regulation and appetite control. This preliminary study included 27 women with obesity (body mass index, BMI>40 kg/m² or>35 kg/m² with comorbidities) undergoing LSG. Serum irisin and nesfatin-1 levels, body composition, and standard metabolic parameters were assessed preoperatively and at 1 month postoperatively. ELISA assays were used for hormone quantification. Repeated measures ANOVA and Spearman's correlation analyses were applied. One month postoperatively, serum irisin levels showed a significant increase (<i>p</i><0.001), whereas nesfatin-1 levels demonstrated a significant decrease (<i>p</i><0.001). Interestingly, nesfatin-1 exhibited a significant positive correlation with fat mass in the preoperative period; however, this relationship shifted to a negative correlation following the surgery, suggesting a potential alteration in regulatory mechanisms post-intervention. Reductions in BMI, fat mass, and muscle mass and improvements in glycemic and lipid profiles were also observed. The findings of this study reveal significant early postoperative shifts in irisin and nesfatin-1 levels following LSG, underscoring the potential regulatory role of these hormones in the body's initial metabolic adaptation to surgical weight loss.</p>","PeriodicalId":12999,"journal":{"name":"Hormone and Metabolic Research","volume":" ","pages":"406-412"},"PeriodicalIF":2.3,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148850484","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Glucocorticoid Receptor Expression in Whole Blood Cells of Professional Water Polo Athletes During the Competitive Season: A Pilot Study.","authors":"Rodrigo Marcondes Soares, Elisangela Oliveira Araújo, Fabiano Gomes Teixeira, Paula Baccarini Cunha, Flavio Richeti, Renato Alvarenga, Tiago Mestriner Costa, Tatiane Sousa Silva, Carlos Alberto Longui","doi":"10.1055/a-2948-4276","DOIUrl":"10.1055/a-2948-4276","url":null,"abstract":"<p><strong>Abstract: </strong>Regular physical exercise plays a role in modulating the hypothalamic-pituitary-adrenal axis in sedentary individuals, but its effects on athletes remain unclear. As athletes depend on inflammation and micronutrient metabolism to improve, glucocorticoids, which interfere with both, may have an impact on their performances. The objective was to describe the characteristics of the HPA axis in athletes during their training season, as well as determine how high-performance training affects this axis. The inclusion criterion for this prospective observational study was participation as a water polo professional athlete since 2017 and the exclusion criteria were the presence of any chronic disease or the use of any kind of drug that affects the HPA axis during the last 6 months or until the end of the study. Nineteen professional water polo athletes were selected for the analysis of glucocorticoid receptor (isoforms α and β) expression and of glucocorticoid receptor polymorphisms (Bcl-I and A3669G). These analyses were carried out at the beginning of the season (T0), when the athletes were less physically prepared, and again at mid-season (T1) during the peak of physical preparation. The results revealed a good adaptive response in athletes during the progressive stress of the season, characterized by lower expression levels of glucocorticoid receptor alpha and glucocorticoid receptor beta and a lower glucocorticoid receptor alpha/glucocorticoid receptor beta ratio, irrespective of the presence of protective polymorphisms. This adaptation decreases sensitivity to the glucocorticoid receptor, reducing hyper-response to stress, and potentially representing a protective mechanism in athletes. This study explores a plausible theory that relates physical fatigue with the HPA axis and its adaptations.</p>","PeriodicalId":12999,"journal":{"name":"Hormone and Metabolic Research","volume":" ","pages":"419-427"},"PeriodicalIF":2.3,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148955833","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy of Low Insulin-Like Growth Factor-1 Levels and a Single Insulin Tolerance Test in Diagnosing Growth Hormone Deficiency.","authors":"Chayanit Yuenyong, Worapimon Lerdrassameethad, Khomsak Srilanchakon","doi":"10.1055/a-2930-3751","DOIUrl":"10.1055/a-2930-3751","url":null,"abstract":"<p><strong>Abstract: </strong>Pediatric growth hormone deficiency requires dynamic testing for accurate diagnosis because of the pulsatile secretion of growth hormone. The insulin tolerance test (ITT) is regarded as one of the most robust individual provocative tests for growth hormone deficiency, although the broader pediatric diagnostic standard requires a composite of auxological, clinical, and biochemical criteria together with an inadequate response to two independent stimulation tests, except in specific high-probability contexts; insulin-like growth factor-1 (IGF-1) alone has limited diagnostic accuracy. This study evaluated whether combining low IGF-1 levels with a single failed ITT could improve diagnostic efficiency for pediatric growth hormone deficiency. We conducted a retrospective cohort study of 214 children with short stature (aged 2-16 y) evaluated at King Chulalongkorn Memorial Hospital between August 2019 and January 2025. Growth hormone deficiency was confirmed in 63 patients using two growth hormone stimulation tests (peak growth hormone level: < 7 ng/mL). IGF-1 levels were expressed as standard deviation scores and analyzed at cutoff values of ≤ -1, -1.5, -2, and -2.5 in combination with failed ITT results. Diagnostic performance indices were calculated at each predefined cutoff/test combination, including sensitivity, specificity, positive predictive values, negative predictive values, area under the receiver operating characteristic curve, odds ratios, and accuracy. An IGF-1 standard deviation score of ≤ -2.5 combined with a single failed ITT showed a sensitivity of 38.6% and a specificity of 92.6%, with a positive predictive value and a negative predictive value of 73.9% and 73.5%, respectively (<i>p</i><0.001). Because the reference standard for the growth hormone deficiency required failure of two stimulation tests, one of which was the ITT, we assessed this circularity directly: among 100 patients with both the ITT and clonidine results, findings were discordant in 37 (exact McNemar <i>p</i>=0.008), and IGF-1 standard deviation scores did not differ significantly across concordant and discordant subgroups (Kruskal-Wallis <i>p</i>=0.407). An IGF-1 standard deviation score cutoff of ≤ -2.5 combined with a single failed ITT identifies a subgroup of children at higher probability of growth hormone deficiency who may be prioritized for confirmatory evaluation. Given the modest sensitivity and positive predictive values of this criterion and the circularity inherent in a reference standard that itself incorporates the ITT, these findings should be regarded as hypothesis-generating rather than as a basis for changing current diagnostic practice, which continues to require two independent stimulation tests except in specific high-probability contexts; prospective, multicenter validation is required.</p>","PeriodicalId":12999,"journal":{"name":"Hormone and Metabolic Research","volume":" ","pages":"399-405"},"PeriodicalIF":2.3,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148760282","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Feasibility of Fast Turnaround Genetic Screening for Type 1 Diabetes Risk in Newborns - Recruiting Infants for the Global Platform for the Prevention of Autoimmune Diabetes Primary Prevention Study Supplementation with B ifidobacterium infantis for Mitigation of Type 1 Diabetes Autoimmunity.","authors":"Annika Fehn, Ezio Bonifacio, Elisa Bonnin, Kristina Casteels, Melanie Gündert, Martin Heigermoser, Ida Jönsson, Olga Kordonouri, Anja Loff, Markus Lundgren, Mariusz Ołtarzewski, Catherine Owen, Stephen Robson, Frank Roloff, Agnieszka Szypowska, Anne Rochtus, Andreas Weiss, Christiane Winkler, Anette-Gabriele Ziegler, Florian Haupt","doi":"10.1055/a-2960-5380","DOIUrl":"10.1055/a-2960-5380","url":null,"abstract":"<p><strong>Abstract: </strong>Screening using polygenic risk scores can identify infants at increased risk for islet autoimmunity and type 1 diabetes. The Supplementation with <i>B</i> <i>ifidobacterium</i> <i>infantis</i> (EVC001) for Mitigation of Type 1 Diabetes Autoimmunity study is a primary prevention study that enrolled infants aged between 7 and 42 days with an elevated genetic risk for type 1 diabetes identified through newborn screening. Here, we describe the screening process that enabled timely genetic risk assessment and enrolment into the Supplementation with <i>B.</i> <i>infantis</i> (EVC001) for Mitigation of Type 1 Diabetes Autoimmunity clinical intervention study within the required enrolment window. Screening was conducted in Belgium, Germany, Poland, Sweden, and the United Kingdom. Among 257,784 screened newborns included in the analysis, 3,309 newborns (1.3%) had an eligible genotype associated with a>10% risk of developing early-stage type 1 diabetes by 6 years of age. Samples were collected at a median age of 2 days (interquartile range, 0-3), registered at a median age of 9 days (interquartile range, 6-11), and genotyped at a median age of 21 days (interquartile range, 18-24). Study sites received validated genotyping results at a median age of 22 days (interquartile range, 19-25). Consultation visits occurred at a median age of 29 days (interquartile range, 25-34) and enrolment into the Supplementation with <i>B. infantis</i> (EVC001) for Mitigation of Type 1 Diabetes Autoimmunity study took place at a median age of 38 days (interquartile range, 35-41). Overall, 1,149 eligible infants were enrolled into the Supplementation with <i>B. infantis</i> (EVC001) for Mitigation of Type 1 Diabetes Autoimmunity study (34.7% of eligible infants). These findings demonstrate the feasibility of accelerated genetic screening programs and show that newborn screening workflows can be completed within the first 6 weeks of life to support timely enrolment into early intervention trials.</p>","PeriodicalId":12999,"journal":{"name":"Hormone and Metabolic Research","volume":" ","pages":"391-398"},"PeriodicalIF":2.3,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13686779/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149074509","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}