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  • The Endocrine Society  (11)
  • 2020-2024  (11)
  • Medicine  (11)
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  • The Endocrine Society  (11)
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  • 2020-2024  (11)
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  • Medicine  (11)
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  • 1
    Online Resource
    Online Resource
    The Endocrine Society ; 2023
    In:  The Journal of Clinical Endocrinology & Metabolism Vol. 108, No. 8 ( 2023-07-14), p. 2078-2086
    In: The Journal of Clinical Endocrinology & Metabolism, The Endocrine Society, Vol. 108, No. 8 ( 2023-07-14), p. 2078-2086
    Abstract: The evidence of long-term polyethylene glycol recombinant human GH (PEG-rhGH) in pediatric GH deficiency (GHD) is limited. Objective This study aimed to examine the effectiveness and safety of long-term PEG-rhGH in children with GHD in the real world, as well as to examine the effects of dose on patient outcomes. Design A prospective, observational, posttrial study (NCT03290235). Setting, participants and intervention Children with GHD were enrolled from 81 centers in China in 4 individual clinical trials and received weekly 0.2 mg/kg/wk (high-dose) or 0.1 to & lt;0.2 mg/kg/wk (low-dose) PEG-rhGH for 30 months. Main outcomes measures Height SD score (Ht SDS) at 12, 24, and 36 months. Results A total of 1170 children were enrolled in this posttrial study, with 642 patients in the high-dose subgroup and 528 in the low-dose subgroup. The Ht SDS improved significantly after treatment in the total population (P & lt; 0.0001), with a mean change of 0.53 ± 0.30, 0.89 ± 0.48, 1.35 ± 0.63, 1.63 ± 0.75 at 6 months, 12 months, 24 months, and 36 months, respectively. In addition, the changes in Ht SDS from baseline were significantly improved in the high-dose subgroup compared with the low-dose subgroup at 6, 12, 24, and 36 months after treatment (all P & lt; 0.05). A total of 12 (1.03%) patients developed serious adverse events. There was no serious adverse event related to the treatment, and no AEs leading to treatment discontinuation or death occurred. Conclusions PEG-rhGH showed long-term effectiveness and safety in treating children with GHD. Both dose subgroups showed promising outcomes, whereas PEG-rhGH 0.2 mg/kg/wk might show additional benefit.
    Type of Medium: Online Resource
    ISSN: 0021-972X , 1945-7197
    RVK:
    Language: English
    Publisher: The Endocrine Society
    Publication Date: 2023
    detail.hit.zdb_id: 2026217-6
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  • 2
    In: The Journal of Clinical Endocrinology & Metabolism, The Endocrine Society, Vol. 106, No. 1 ( 2021-01-01), p. e217-e231
    Abstract: Postoperative hypercortisolemia mandates further therapy in patients with Cushing’s disease (CD). Delayed remission (DR) is defined as not achieving postoperative immediate remission (IR), but having spontaneous remission during long-term follow-up. Objective We aimed to develop and validate machine learning (ML) models for predicting DR in non-IR patients with CD. Methods We enrolled 201 CD patients, and randomly divided them into training and test datasets. We then used the recursive feature elimination (RFE) algorithm to select features and applied 5 ML algorithms to construct DR prediction models. We used permutation importance and local interpretable model–agnostic explanation (LIME) algorithms to determine the importance of the selected features and interpret the ML models. Results Eighty-eight (43.8%) of the 201 CD patients met the criteria for DR. Overall, patients who were younger, had a low body mass index, a Knosp grade of III–IV, and a tumor not found by pathological examination tended to achieve a lower rate of DR. After RFE feature selection, the Adaboost model, which comprised 18 features, had the greatest discriminatory ability, and its predictive ability was significantly better than using Knosp grading and postoperative immediate morning serum cortisol (PoC). The results obtained from permutation importance and LIME algorithms showed that preoperative 24-hour urine free cortisol, PoC, and age were the most important features, and showed the reliability and clinical practicability of the Adaboost model in DC prediction. Conclusions Machine learning–based models could serve as an effective noninvasive approach to predicting DR, and could aid in determining individual treatment and follow-up strategies for CD patients.
    Type of Medium: Online Resource
    ISSN: 0021-972X , 1945-7197
    RVK:
    Language: English
    Publisher: The Endocrine Society
    Publication Date: 2021
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  • 3
    Online Resource
    Online Resource
    The Endocrine Society ; 2021
    In:  The Journal of Clinical Endocrinology & Metabolism Vol. 106, No. 1 ( 2021-01-01), p. e273-e287
    In: The Journal of Clinical Endocrinology & Metabolism, The Endocrine Society, Vol. 106, No. 1 ( 2021-01-01), p. e273-e287
    Abstract: The accumulation of aberrant lipids and abnormal lipid metabolism in silent corticotroph adenomas (SCAs) could contribute to changes in clinical phenotypes, especially sphenoid sinus invasion. Objective To systematically investigate lipidomic and transcriptomic alterations associated with invasiveness and their potential molecular mechanisms in SCAs and to provide candidate biomarkers for predicting invasiveness and novel treatment options for invasive SCAs by targeting lipids. Methods Fifty-four SCAs (34 invasive/20 noninvasive) were subjected to lipidomic analysis based on ultraperformance liquid chromatography mass spectrometry, and 42 clinically nonfunctioning pituitary adenomas (23 invasive/19 noninvasive) were subjected to transcriptomic analysis. Differential analysis was performed to determine differential lipids and genes between invasive and noninvasive tumors. A functionally connected network was constructed with the molecular pathways as cores. Multiple machine learning methods were applied to identify the most critical lipids, which were further used to construct a lipidomic signature to predict invasive SCAs by multivariate logistic regression, and its performance was evaluated by receiver operating characteristic analysis. Results Twenty-eight differential lipids were identified, and a functionally connected network was constructed with 2 lipids, 17 genes, and 4 molecular pathways. Connectivity Map (CMap) analysis further revealed 32 potential drugs targeting 4 genes and related pathways. The 4 most critical lipids were identified as risk factors contributing to the invasive phenotype. A lipidomic signature was constructed and showed excellent performance in discriminating invasive and noninvasive SCAs. Conclusions The lipidomic signature could serve as a promising predictor for the invasive SCA phenotype and provide potential therapeutic targets for SCAs.
    Type of Medium: Online Resource
    ISSN: 0021-972X , 1945-7197
    RVK:
    Language: English
    Publisher: The Endocrine Society
    Publication Date: 2021
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  • 4
    In: The Journal of Clinical Endocrinology & Metabolism, The Endocrine Society, Vol. 106, No. 2 ( 2021-01-23), p. e573-e581
    Abstract: Ultrasound-guided thermal ablation plays an important role in the management of thyroid disease. The objective of this study was to evaluate the feasibility, efficacy, and safety of thermal ablation for patients with solitary T1bN0M0 papillary thyroid carcinoma (PTC) who are ineligible for or unwilling to undergo surgery. Materials and Methods Data pertaining to 172 patients (38 males and 134 females) who received thermal ablation therapy at 12 hospitals between April 2015 and March 2020 were retrospectively analyzed. The mean duration of follow-up was 24.9 ± 14.1 months (range, 12–60). The technical feasibility, technical success, efficacy, and safety of treatment were analyzed. Postablation tumor size at various time points was compared with preablation measurement. Results All patients selected for thermal ablation received enlarged ablation, according to contrast-enhanced ultrasound postablation. The maximum diameter and volume of ablation zone at 6, 12, 18, 24, 36, and 48 months postablation were significantly smaller than those recorded preablation (P  & lt; 0.05 for all). At the most recent follow-up, 106 (61.6%) tumors had completely disappeared. The rate of lymph node metastasis was 0.6% (1/172) and the incidence of new tumors was 1.2% (2/172). The overall complication rate was 5.2% (9/172) (major complications: 4.6% [8/172]; minor complications: 0.6% [1/172] ). All major complications were relieved within 4 months postablation. Conclusion Thermal ablation may be a feasible, effective, and safe treatment option for patients with solitary T1bN0M0 PTC who are ineligible for or unwilling to undergo surgery. It may provide a novel treatment option for selected patients.
    Type of Medium: Online Resource
    ISSN: 0021-972X , 1945-7197
    RVK:
    Language: English
    Publisher: The Endocrine Society
    Publication Date: 2021
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  • 5
    In: The Journal of Clinical Endocrinology & Metabolism, The Endocrine Society, Vol. 107, No. 1 ( 2022-01-01), p. e84-e94
    Abstract: Diabetes, hypertension and dyslipidemia accelerates the incidence of cardiovascular disease (CVD) events. However, data regarding the association between main cardiometabolic morbidities such as diabetes, hypertension, and dyslipidemia and the subsequent risk of CVD events in Chinese adults are still limited. Objective To investigate the associations between individual and combined cardiometabolic morbidities and incident cardiovascular events in Chinese adults. Methods Baseline data were obtained from a prospective, nationwide, and population-based cohort study in China during 2011–2012. A total of 133 572 participants aged ≥40 years were included in the study. The main outcome measures were CVD events. Results Compared with participants without diabetes, hypertension and dyslipidemia, participants with only diabetes (hazard ratio [HR], 1.58; 95% CI, 1.32-1.90) or only hypertension (2.04; 1.82-2.28) exhibited significantly higher risk for CVD events, while participants with only dyslipidemia (0.97; 0.84-1.12) exhibited no significantly higher risk for CVD events. When analyzed collectively, participants with diabetes plus hypertension (HR, 2.67; 95% CI, 2.33-3.06), diabetes plus dyslipidemia (1.57; 1.32-1.87), and hypertension plus dyslipidemia (2.12; 1.88-2.39) exhibited significantly higher risk for CVD. Moreover, participants with the combination of diabetes, hypertension, and dyslipidemia exhibited the highest risk for CVD events (HR, 3.06; 95% CI, 2.71-3.46). Multivariable-adjusted HRs (95% CIs) for CVD associated with diabetes based on fasting glucose ≥7.0 mmol/L, oral glucose tolerance test 2-hour glucose ≥11.1 mmol/L, and hemoglobin A1c ≥6.5% were 1.64 (1.51-1.78), 1.57 (1.45-1.69), and 1.54 (1.42-1.66), respectively; associated with hypertension based on systolic blood pressure ≥140 mmHg and diastolic blood pressure ≥90 mmHg were 1.89 (1.76-2.03) and 1.74 (1.60-1.88), respectively; associated with dyslipidemia based on total cholesterol ≥6.22 mmol/L, low-density lipoprotein cholesterol ≥4.14 mmol/L, high-density lipoprotein cholesterol & lt;1.04 mmol/L, and triglycerides ≥2.26 mmol/L were 1.18 (1.08-1.30), 1.30 (1.17-1.44), 1.00 (0.92-1.09), and 1.10 (1.01-1.20), respectively. Conclusion Diabetes, hypertension and dyslipidemia showed additive associations with the risk of CVD events in middle-aged and elderly Chinese adults.
    Type of Medium: Online Resource
    ISSN: 0021-972X , 1945-7197
    RVK:
    Language: English
    Publisher: The Endocrine Society
    Publication Date: 2022
    detail.hit.zdb_id: 2026217-6
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  • 6
    In: The Journal of Clinical Endocrinology & Metabolism, The Endocrine Society, Vol. 105, No. 10 ( 2020-10-01), p. e3840-e3841
    Type of Medium: Online Resource
    ISSN: 0021-972X , 1945-7197
    RVK:
    Language: English
    Publisher: The Endocrine Society
    Publication Date: 2020
    detail.hit.zdb_id: 2026217-6
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  • 7
    In: The Journal of Clinical Endocrinology & Metabolism, The Endocrine Society, Vol. 106, No. 8 ( 2021-07-13), p. e3159-e3177
    Abstract: Although metabolic profiles appear to play an important role in menopausal bone loss, the functional mechanisms by which metabolites influence bone mineral density (BMD) during menopause are largely unknown. Objective We aimed to systematically identify metabolites associated with BMD variation and their potential functional mechanisms in peri- and postmenopausal women. Design and Methods We performed serum metabolomic profiling and whole-genome sequencing for 517 perimenopausal (16%) and early postmenopausal (84%) women aged 41 to 64 years in this cross-sectional study. Partial least squares regression and general linear regression analysis were applied to identify BMD-associated metabolites, and weighted gene co-expression network analysis was performed to construct co-functional metabolite modules. Furthermore, we performed Mendelian randomization analysis to identify causal relationships between BMD-associated metabolites and BMD variation. Finally, we explored the effects of a novel prominent BMD-associated metabolite on bone metabolism through both in vivo/in vitro experiments. Results Twenty metabolites and a co-functional metabolite module (consisting of fatty acids) were significantly associated with BMD variation. We found dodecanoic acid (DA), within the identified module causally decreased total hip BMD. Subsequently, the in vivo experiments might support that dietary supplementation with DA could promote bone loss, as well as increase the osteoblast and osteoclast numbers in normal/ovariectomized mice. Dodecanoic acid treatment differentially promoted osteoblast and osteoclast differentiation, especially for osteoclast differentiation at higher concentrations in vitro (eg,10, 100 μM). Conclusions This study sheds light on metabolomic profiles associated with postmenopausal osteoporosis risk, highlighting the potential importance of fatty acids, as exemplified by DA, in regulating BMD.
    Type of Medium: Online Resource
    ISSN: 0021-972X , 1945-7197
    RVK:
    Language: English
    Publisher: The Endocrine Society
    Publication Date: 2021
    detail.hit.zdb_id: 2026217-6
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  • 8
    In: The Journal of Clinical Endocrinology & Metabolism, The Endocrine Society, ( 2023-04-21)
    Abstract: Longitudinal patterns of resting heart rate (RHR) in patients with diabetes mellitus and their association with health outcomes are not well-characterized. Objective We sought to explore the RHR trajectories in patients with diabetes mellitus and their association with cardiovascular disease (CVD) and all-cause mortality. Design The Kailuan Study is a prospective cohort study. Participants underwent health examinations biennially starting in 2006 and were followed until December 31, 2020. Setting General community. Participants A total of 8218 diabetic participants who attended at least 3 of the examinations conducted in 2006, 2008, 2010, and 2012 were included. Main outcome measures CVD and all-cause mortality. Results We identified 4 RHR trajectories in participants with diabetes mellitus between 2006 and 2012: low-stable (range, 66.83-64.91 beats/min; n = 1705), moderate-stable (range, 76.30-76.95 beats/min; n = 5437), high-decreasing (mean decreased from 92.14 to 85.60 beats/min; n = 862), and high-increasing (mean increased from 84.03 to 111.62 beats/min; n = 214). During an average follow-up of 7.25 years, 977 cases of CVD and 1162 deaths were identified. Compared with the low-stable trajectory, adjusted hazard ratios (HRs) for CVD were 1.48 (95% CI, 1.02-2.14; P = .04) for the high-increasing trajectory, adjusted HRs for all-cause mortality were 1.34 (95% CI, 1.14-1.58; P & lt; .01) for the moderate-stable trajectory, 1.68 (95% CI, 1.35-2.10; P & lt; .01) for the high-decreasing trajectory, and 2.47 (95% CI, 1.85-3.31; P & lt; .01) for the high-increasing trajectory. Conclusions RHR trajectories were associated with the subsequent risks of CVD and all-cause mortality in patients with diabetes mellitus.
    Type of Medium: Online Resource
    ISSN: 0021-972X , 1945-7197
    RVK:
    Language: English
    Publisher: The Endocrine Society
    Publication Date: 2023
    detail.hit.zdb_id: 2026217-6
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  • 9
    In: The Journal of Clinical Endocrinology & Metabolism, The Endocrine Society, Vol. 105, No. 7 ( 2020-07-01), p. e2600-e2608
    Abstract: Hashimoto’s thyroiditis (HT) and Graves’ disease (GD) are the 2 main autoimmune thyroid diseases that have both similarities and differences. Determining the genetic basis that distinguishes HT from GD is key for a better understanding of the differences between these closely related diseases. Objects To identify the susceptibility genes for HT in the Chinese cohort and compare susceptibility genes between GD and HT. Design In the current study, 18 SNPs from 18 established GD risk loci were selected and then genotyped in 2682 patients with HT, 4980 patients with GD, and 3892 controls. The association analysis between HT and controls and heterogeneity analysis between HT and GD were performed on SPSS, with the logistic regression analysis adjusted for sex and age. Results We identified 11 susceptibility loci for HT in the Chinese Han population, with 4 loci, including the rs1265883 in SLAMF6 locus, rs1024161 in CTLA4, rs1521 in HLA-B, and rs5912838 in GPR174/ ITM2A at X chromosome, reaching genome-wide significance of 5 × 10–8. Five loci were reported to be associated with HT for the first time. We also identified 6 susceptibility loci with heterogeneity between GD and HT. Out of them, 4 loci were associated with GD but not with HT, including HLA-DPB1, CD40, TSHR, and TG; the association of HLA-B with GD was stronger than that with HT, but the association of SLAMF6 was reversed. Conclusion Our findings suggested that the pathogenesis of HT and GD was different.
    Type of Medium: Online Resource
    ISSN: 0021-972X , 1945-7197
    RVK:
    Language: English
    Publisher: The Endocrine Society
    Publication Date: 2020
    detail.hit.zdb_id: 2026217-6
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  • 10
    Online Resource
    Online Resource
    The Endocrine Society ; 2020
    In:  The Journal of Clinical Endocrinology & Metabolism Vol. 105, No. 9 ( 2020-09-01), p. e3207-e3223
    In: The Journal of Clinical Endocrinology & Metabolism, The Endocrine Society, Vol. 105, No. 9 ( 2020-09-01), p. e3207-e3223
    Abstract: The tumor immune microenvironment is associated with clinical outcomes and immunotherapy responsiveness. Objective To investigate the intratumoral immune profile of pituitary adenomas (PAs) and its clinical relevance and to explore a novel immune classification for predicting immunotherapy responsiveness. Design, Patients, and Methods The transcriptomic data from 259 PAs and 20 normal pituitaries were included for analysis. The ImmuCellAI algorithm was used to estimate the abundance of 24 types of tumor-infiltrating immune cells (TIICs) and the expression of immune checkpoint molecules (ICMs). Results The distributions of TIICs differed between PAs and normal pituitaries and varied among PA subtypes. T cells dominated the immune microenvironment across all subtypes of PAs. The tumor size and patient age were correlated with the TIIC abundance, and the ubiquitin-specific protease 8 (USP8) mutation in corticotroph adenomas influenced the intratumoral TIIC distributions. Three immune clusters were identified across PAs based on the TIIC distributions. Each cluster of PAs showed unique features of ICM expression that were correlated with distinct pathways related to tumor development and progression. CTLA4/CD86 expression was upregulated in cluster 1, whereas programmed cell death protein 1/programmed cell death 1 ligand 2 (PD1/PD-L2) expression was upregulated in cluster 2. Clusters 1 and 2 exhibited a “hot” immune microenvironment and were predicted to exhibit higher immunotherapy responsiveness than cluster 3, which exhibited an overall “cold” immune microenvironment. Conclusions We summarized the immune profile of PAs and identified 3 novel immune clusters. These findings establish a foundation for further immune studies on PAs and provide new insights into immunotherapy strategies for PAs.
    Type of Medium: Online Resource
    ISSN: 0021-972X , 1945-7197
    RVK:
    Language: English
    Publisher: The Endocrine Society
    Publication Date: 2020
    detail.hit.zdb_id: 2026217-6
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