Endocrine最新文献

Purpose: Agranulocytosis is a rare but serious adverse effect associated with antithyroid drug (ATD) therapy for hyperthyroidism. The relative risk between methimazole (MMI) and propylthiouracil (PTU), and the potential dose-dependent effect of MMI remain unclear. To evaluate the incidence and relative risk of agranulocytosis associated with MMI and PTU, and to determine whether higher MMI doses are linked to increased risk.

Methods: We conducted a systematic review and meta-analysis of clinical studies reporting agranulocytosis in patients treated with MMI or PTU. A comprehensive search was performed in MEDLINE, Cochrane Library, and LILACS up to March 2025. Studies were selected based on predefined inclusion criteria. Risk of bias was assessed using RoB 2.0 and ROBINS-I tools. Meta-analyses were performed using random-effects models. Publication bias was evaluated using funnel plots, Egger's test, and the trim-and-fill method. The protocol was registered in PROSPERO (CRD42024548791).

Results: Thirteen studies were included in the meta-analysis, comprising 313 cases of agranulocytosis. No significant difference in risk was found between MMI and PTU (OR = 0.87; 95% CI: 0.40-1.88; I² = 74.1%). In the dose-comparison analysis, patients receiving <30 mg/day of MMI had a significantly lower risk of agranulocytosis compared to those receiving ≥30 mg/day (OR = 0.34; 95% CI: 0.22-0.54; I² = 0%). No publication bias was detected. Sixteen additional studies were included in the qualitative synthesis but excluded from quantitative analysis due to methodological limitations. A lower incidence of agranulocytosis was observed in randomized controlled trials compared to retrospective studies.

Conclusion: This meta-analysis found no significant difference in agranulocytosis risk between MMI and PTU. However, higher MMI doses (≥30 mg/day) were associated with an increased risk. These findings support the use of the lowest effective MMI dose and emphasize the importance of standardized reporting and methodological rigor in studies assessing the safety of ATD.

Purpose: Klinefelter syndrome (XXY) has a wide range of presentations and health consequences. The aim of this systematic review was to identify potential core outcomes reported in males with XXY.

Methods: Systematic searches of PubMed, Science Direct, and Cochrane were performed to source studies. The inclusion criteria were studies involving males with KS with any intervention, comparison, or outcome, with separate searches for studies reporting on children <16 years of age and for adults ≥16 years of age.

Results: For children <16 years old, 56 studies met the eligibility criteria. Thirty-seven (66%) studies reported anthropometric measurements and physical characteristics. Behavioural, cognitive developmental and psychiatric outcomes were also commonly reported (27, 48%) as were biochemical results in 27 (48%) studies. Other outcomes included presence of co-morbidities (16, 29%) and fertility outcomes (10, 18%). In the studies focusing on individuals ≥16 years of age, 183 studies met the eligibility criteria. Outcomes relating to biochemistry, physical characteristics, fertility and occurrence of co-morbidities were reported in 118 (64%), 89 (49%) 65 (36%) and 62 (34%) studies respectively. Quality of life was reported least frequently in only 2 (4%) paediatric studies and 5 (3%) of adult studies.

Conclusion: The present study highlights the variety of outcomes studied in boys and men with KS. These results can support the development of age-specific core outcome sets for clinical research to promote homogeneity and to aid standardised data collection.

Background: Continuous glucose monitoring (CGM) has improved diabetes management, yet not all patients benefit equally. We previously developed a predictive calculator using clinical and socioeconomic variables to estimate the likelihood of achieving optimal control after CGM initiation. This study prospectively validated the calculator in a real-world cohort.

Methods: A single-center prospective study included 102 adults with type 1 or pancreatic diabetes using multiple daily insulin injections, followed for three months. Optimal control was defined as time in range (TIR, 70-180 mg/dL) > 70% and time below range (TBR, <70 mg/dL) < 4%. Model performance was assessed using ROC analysis and correlation tests.

Results: Of 102 participants, 85 completed follow-up (median age: 53.6 years; 48% women; median diabetes duration: 12.9 years; baseline HbA1c: 7.6%). Thirty-three (38.8%) achieved optimal control. The calculator showed moderate discrimination (AUC = 0.639) and significant correlations with TIR (p = 0.230, p = 0.023) and time in tight range (TITR, 70-140 mg/dL) (p = 0.271, p = 0.019). Overall accuracy was 61.9%, lower than in the original cohort. Smoking predicted non-completion (p = 0.038).

Conclusions: The calculator shows moderate accuracy in predicting glycemic control and TITR after CGM initiation. CGM adherence remains a challenge, warranting further study in publicly funded healthcare settings.

Purpose: To evaluate the potential role of pre-treatment clinical activity score (CAS) and extraocular muscle (EOM) signal intensity ratio (SIR) values on orbital MRI in predicting the steroid response in patients with moderate-to-severe active Graves' orbitopathy (GO).

Methods: The data of 51 patients with moderate to severe GO (CAS ≥ 3) were retrospectively evaluated. The patients were categorized into two groups: steroid-resistant (n = 25) and steroid-responsive (n = 26). Demographic and clinical characteristics, CAS, VISA (vision, inflammation, strabismus, appearance), laboratory data and orbital MRI measurements were compared. Two standardized MRI sequences were utilized for analysis: T2-weighted short-tau inversion-recovery (T2w-STIR) and contrast-enhanced T1-weighted fat-suppressed (T1w-CE) imaging. Predictors of steroid resistance were identified through multivariate logistic regression analysis, and ROC curve was performed to determine predictive performance and optimal cut-off values.

Results: Pre-treatment CAS (5.05 ± 1.07 vs 4.00 ± 0.93, p = 0.002) and T2w-STIR SIR (4.77 ± 0.93 vs 3.95 ± 1.32, p = 0.031) were both significantly higher in the steroid-resistant group. Higher pretreatment CAS (OR 2.380, p = 0.001) and T2w-STIR SIR (OR 1.862, p = 0.040) predicted steroid resistance. ROC analysis demonstrated good discriminative performance for CAS (AUC = 0.786); with a cut-off value > 4 yielding 71.4% sensitivity and 68.2% specificity. T2w-STIR SIR with a threshold value > 3.6 provided high sensitivity (94.4%) but limited specificity (37.5%), indicating moderate overall accuracy (AUC = 0.673).

Conclusion: Pre-treatment CAS and T2w-STIR SIR values may serve as potential predictors of steroid resistance in moderate-to-severe active GO. Early identification of high-risk patients may facilitate consideration of alternative treatments such as immunosuppressive agents or radiotherapy. Larger scale prospective studies are required to validate optimal T2w-STIR SIR cut-off values and the role of imaging biomarkers in risk stratification.

Aims: To compare the effect on maternal and neonatal outcomes of 75-g oral glucose tolerance test (75-g OGTT) versus 50-g glucose challenge test (GCT) plus 75-g OGTT for diagnosis of gestational diabetes mellitus (GDM).

Materials and methods: A non-randomized trial was conducted in a tertiary hospital between January and December 2020. Participants were assigned into the one-step (i.e., 75-g OGTT) and two-step screening (50-g GCT plus 75-g OGTT) groups. Primary outcomes were GDM, hypertensive disorder in pregnancy (HDP), macrosomia, and Cesarean section.

Results: 2265 eligible participants were enrolled in the trial, including 1130 in the one-step group and 1135 in the two-step group. GDM was diagnosed in 197 (17.4%) participants in the one-step group and 123 (10.8%) in the two-step group (OR, 1.94; 95% CI, 1.49, 2.54). There was only borderline statistical significance in the difference of HDP between two groups (OR, 0.64; 95% CI, 0.40, 1.01), while all other outcomes showed no statistically significant differences. In pregnant women with high risk factors for GDM (maternal age ≥ 35 years, pre-pregnancy BMI ≥ 24 kg/m², multipara, history of GDM, or family history of diabetes), the incidence of GDM was higher (OR, 1.74; 95% CI, 1.19, 2.56) for the one-step versus two step-step screening, while the incidences of HDP (OR, 0.51; 95% CI, 0.29, 0.90) and macrosomia (OR, 0.62; 95% CI, 0.39, 0.97) were lower.

Conclusions: The one-step screening at least performs as well as the two-step screening, potentially more suitable for Chinese pregnant women with high risk factors for GDM. The study was registered at the Chinese Clinical Trial Registry (ChiCTR2100054505) on Dec 18^th, 2021.

Purpose: To evaluate the efficacy and cost-effectiveness of recombinant human growth hormone (rhGH) therapy in adolescents with idiopathic short stature during mid-to-late puberty, using knee MRI to predict therapeutic response.

Methods: This one-year prospective cohort study included 50 idiopathic short stature adolescents and 100 healthy controls. Participants underwent knee MRI to classify growth plates into "continuous" and "discontinuous" subgroups. Growth response to growth hormone was measured through height and height standard deviation score changes, while cost-effectiveness was assessed using cumulative growth hormone dose and growth outcomes. Kaplan-Meier analysis was performed to evaluate therapy response, and linear mixed models analyzed height growth differences.

Results: After one year, the treatment group showed significant height gains (6.08 ± 2.73 cm) compared to controls (3.91 ± 2.70 cm; P < 0.001). Subgroup analysis revealed that adolescents with continuous growth plates at proximal tibia exhibited greater height improvements (ΔHtSDS = 0.92 ± 0.37) than those with discontinuous plates (ΔHtSDS = 0.73 ± 0.49; P = 0.016); subgroups categorized by distal femur achieved ΔHtSDS 0.91 ± 0.44 and 0.56 ± 0.29, respectively (P = 0.004). Cost-effectiveness was higher in the continuous growth plate subgroup, requiring lower rhGH doses per centimeter of growth.

Conclusions: Knee MRI classification of growth plate continuity is a reliable predictor of rhGH therapy response and cost-effectiveness in mid-to-late pubertal adolescents with idiopathic short stature. Continuous growth plates correlate with better treatment outcomes and more favorable cost-effectiveness, emphasizing the importance of early intervention for optimal results.

Objetive: To analyze the Time in Tight Range (TITR) (70-140 mg/dL) and the relationship between TITR-Time in Range (TIR) and assess their possible differences according to Coefficient of Variation (CV) in a cohort of patients with type 1 Diabetes Mellitus (DM) and Multiple Daily Injections in real life.

Patients and methods: 355 adult users of Continuous Glucose Monitoring (CGM) with at least one HbA1c (October 1, 2023-October 1, 2024) and glucose data in the 90 days prior were included.

Results: Age 46.9 years (SD 13.6); 57.2% male; time of evolution 21.6 years (SD 12.6). Mean TITR was 38.4% (SD 14.6) and 20.3% had a TITR ≥ 50%. The correlation TITR-TIR was strong (β = 0.83; CI 95% 0.8-0.87; R² Adjusted 0.89; p < 0.001) and varied according to CV [CV ≤ 36% (β = 0.88; CI 95% 0.83-0.93; R² Adjusted 0.89; p < 0.001); CV > 36% (β = 0.84; CI 95% 0.81-0.87; R² Adjusted 0.93; p < 0.001)]. The cutoff value for TIR to discriminate TITR ≥ 50% varied according to CV [(CV ≤ 36% 75.9% (sensitivity 98%, specificity 94%, AUC 0.99, p < 0.001); CV > 36% 70.5% (sensitivity 100%, specificity 98%, AUC 0.99, p < 0.001)]. The variables that were independently associated with TITR in CV ≤ 36% group were TIR (β = 0.74; CI 95% 0.57-0.9; p < 0.001) and mean glucose (β = -0.11; CI 95% -0.21 to -0.01; p = 0.045). However, in CV > 36% group were time of evolution (β = 0.04; CI 95% 0.01-0.07; p = 0.008), HbA1c (β = -0.63; CI 95% -1.22 to -0.4; p = 0.036; CV (β = 0.33; CI 95% 0.24-0.41; p < 0.001) and TIR (β = 0.84; CI 95% 0.74-0.93; p < 0.001).

Conclusions: The correlation between TITR-TIR was strong and higher in patients with CV > 36%. Cutoff value for TIR to discriminate TITR ≥ 50% and factors that were associated with TITR also differ depending on CV. It is essential to take glycemic variability into account when interpreting metabolic control data.

Objectives: The Captopril Challenge Test (CCT) is favored in the diagnosis of primary aldosteronism (PA) for its simplicity and high patient compliance, yet optimal diagnostic criteria for CCT remain controversial. This study compared the accuracy of different CCT criteria for the diagnosis of PA.

Methods: This study included retrospective and prospective cohorts. High-risk PA patients were enrolled to complete aldosterone-to-renin ratio (ARR) screening, CCT, and the saline infusion test (SIT). SIT was used as the reference standard, and receiver operating characteristic (ROC) curves were constructed to evaluate the diagnostic accuracy.

Results: The retrospective cohort included 871 patients with PA and 464 with EH. The AUC for PAC post-CCT in diagnosing PA was 0.90, significantly higher than that of ARR post-CCT (0.73) or PAC suppression percentage (0.72). The prospective cohort included 134 patients with PA and 162 with EH, showing an AUC for PAC post-CCT of 0.89, significantly higher than that of ARR post-CCT (0.71) or PAC suppression percentage (0.58). Using a PAC post-CCT cutoff of 11 ng/dL for diagnosing PA achieved a sensitivity of 0.89 and specificity of 0.66 in the retrospective cohort, and a sensitivity of 0.77 and specificity of 0.84 in the prospective cohort, respectively.

Conclusion: PAC post-CCT served as a superior indicator for the diagnosis of PA, with 11 ng/dL recommended as the optimal diagnostic cutoff.

Purpose: The consistency of pituitary adenomas (PAs) significantly influences the success of complete tumor resection, which is crucial for prognosis in patients. The aim of this study is to use preoperative diffusion-weighted imaging (DWI) to evaluate tumor consistency, thereby assisting surgeons in achieving optimal resection outcomes during neuroendoscopic procedures.

Methods: We collected clinical data (including age, sex, symptoms, and consistency), pathological data (including collagen content), and imaging data (including tumor size and ADC ratio) from 264 patients with pituitary macroadenomas. Patients were categorized based on intraoperative consistency assessments and postoperative resection rates to analyze the efficacy of DWI in predicting consistency and identifying determinants of the completeness of resection. Correlation analysis and multiple linear regression were used to explore the relationships among the ADC ratio, tumor consistency, and collagen content. Logistic regression was applied to analyze the factors influencing tumor resection.

Results: This study included 264 patients. There were 202 patients with a soft consistency and 62 patients with a hard consistency. A total of 212 patients achieved complete resection. The median ADC ratio for the soft consistency group was 1.27 [1.04, 1.59], and that for the hard consistency group was 0.89 [0.83, 0.94] (P < 0.05). The median collagen content in the soft group was 4.55 [2.13, 6.69], and that in the hard group was 13.91 [10.30, 19.20] (P < 0.05). The ADC ratio was significantly related to the collagen content (ρ = -0.965; 95% CI: -0.973 ~ -0.955; P < 0.05). The ADC ratio was a significant predictor for achieving gross-total tumor resection (OR: 5.714; 95% CI: 1.032-31.628; P < 0.05).

Conclusion: For most patients with pituitary macroadenomas, neuroendoscopic transsphenoidal surgery is the first-line treatment. Preoperative apparent diffusion coefficient (ADC) ratios obtained from diffusion-weighted imaging (DWI) can help to evaluate tumor consistency and collagen content, thus guiding neurosurgeons in predicting resection ability under neuroendoscopy and thereby improving preoperative assessments for these patients.

Objective: To clarify the possible mechanism of leptin and α-MSH on the onset of puberty in female offspring rats after prenatal androgen exposure.

Methods: Sixteen 8-week-old specific pathogen free (SPF) healthy Sprague Dawley (SD) pregnant rats were randomly divided into the testosterone-treated group (TG, female offspring termed PNA group) or the olive oil control group (OOG, female offspring termed VEH group). The female offspring rats of two groups were raised to 21 days (PND21) and weaned. Six female offspring rats at PND21 (VEH:PNA = 3:3) were randomly selected for transcriptome sequencing. Twenty-seven offspring female rats were randomly divided into three groups (VEHI:VEHII:PNA = 9:9:9). VEHI group was observed until the onset of puberty, VEHII and PNA groups were observed until the 8th week.

Results: Compared with VEH group, onset of puberty was not observed in PNA group, and hypothalamic Pomc gene expression at PND21 was lower. Compared with the VEHI group, the body weight, abdominal fat, serum testosterone (T), dehydroepiandrosterone (DHEA) and leptin (LEP) levels were upregulated in the PNA group, while serum gonadotropin-releasing hormone (GnRH), mRNA of hypothalamic estrogen receptor α (ERα), α-melanocyte stimulating hormone (α-MSH), melanocortin receptor-4 (MC4R), GnRH and adipose AR, and the protein of androgen receptor (AR) and leptin receptor (LEPR) in the hypothalamic arcuate nucleus (ARC) were decreased. In the PNA group, there were positive correlations between serum DHEA and mRNA of hypothalamic ERα, MC4R and AR, negative correlations between mRNA of adipose AR and serum T and free testosterone (FT).

Conclusion: Prenatal androgen exposure delayed the onset of puberty in female offspring, the possible mechanism of which is that prenatal androgen exposure may increase the levels of androgen and LEP, decreases their sensitivity and the expression of AR, LEPR, and MC4R, reducing GnRH secretion.