Journal of Clinical Endocrinology & Metabolism最新文献

Context: Percutaneous laser ablation (LA) is today regarded as a valuable therapy for symptomatic, benign solid (non-cystic) thyroid nodules.

Objective: We assessed the prevalence of complications from laser ablation (LA) for benign and solid thyroid nodules (STNs) and their management.

Methods: We conducted a systematic review with meta-analysis of data from published studies on LA of STNs, in addiction to author's institution. A random effects meta-analysis was performed on the prevalence rates.

Results: The literature search yielded 1351 studies, of which 38 studies were included, in addition to our institutional experience (4745 STNs in total). The overall quality of each included study was judged as fair. The prevalence of "Overall" complications of LA was 23% ([CI 17-30%], I2 93.7%, 1208 of 4702 thyroid nodules [TNs]). The prevalence of "Minor" complications of LA was 21% ([CI 15-27%], I2 93.7%, 1159 of 4702 TNs). The prevalence of "Major" complications of LA was 2% ([CI 1-3%], I2 54.0%, 49 of 4745 TNs). Sensitivity analyses did not modify the results, except for dysphonia whose pooled prevalence was higher when using local anesthesia (2%, CI [1-3], I2 25.2, p-value 0.010) or conscious sedation (2%, CI [1-4], I2 27.2, p-value 0.014). The pooled prevalence rate of local pain was 15% (CI [12-20], I2 89.3). Local pain was transient and typically mild to moderate, sometimes severe requiring analgesics for 1-5 days up to one month. The pooled prevalence rate of dysphonia was 2% (CI [1-2], I2 30.3). All cases of dysphonia were transient except for one permanent case.

Conclusion: LA for benign and solid (non-cystic) thyroid nodules could be considered a generally safe technique. Major complications were rare.

Context: Dyslipidemia adversely affects reproduction outcomes; however, its relation with repeated implantation failure (RIF) remains unclear.

Objective: This study aims to analyze the impact of dyslipidemia on assisted reproductive technology (ART) outcomes, endometrial transcriptome, and microbiome of RIF women.

Design: A retrospective real-world analysis and a prospective study.

Setting: University Clinic.

Patients: 6,499 infertile women, including 5,618 non-RIF, and 881 RIF.

Interventions: Dyslipidemia.

Main outcome measures: Implantation rate (IR), clinical pregnancy rate (CPR), and live birth rate (LBR) were compared in RIF women with or without dyslipidemia. Results of endometrial studies, including RNA-seq-based endometrial receptivity test (ERT), 16S rRNA-based microbiome study, next-generation-sequencing (NGS)-based gene comparison, and bulk RNA-seq deconvolution analysis were analyzed.

Results: The prevalence of dyslipidemia in RIF women was significantly higher. In dyslipidemia women, IR, CPR, and LBR were significantly lower, and the prevalence of non-receptive ERT and the presence of endometrial pathogenic bacteria were higher than those of controls. After the personalized treatment, CPR 73.3% and LBR 60.0% were achieved in dyslipidemia women. NGS revealed that 176 differentially expressed genes in the endometrium of RIF women with dyslipidemia compared to those without, suggesting highly enriched in cholesterol and steroid biosynthesis and monocyte differentiation processes. An increased endometrial CD56dim NK cells and macrophage (M)1/M2 ratio with dysregulated immune factors, were found by bulk RNA-seq deconvolution analysis.

Conclusion: RIF women with dyslipidemia have significantly poorer ART outcomes. In women with dyslipidemia, immune homeostasis was breached in the luteal phase endometrium, implicating a possible immune mechanism for dyslipidemia-related implantation failure.

Several reasons led to the change in the nomenclature from non alcoholic fatty liver disease (NAFLD) to metabolic dysfunction associated steatotic liver disease (MASLD); the most important being limitations due to the reliance on exclusionary confounder terms and the use of potentially stigmatising language (the terms "nonalcoholic" and "fatty"). The new name was decided through a Delphi process and now includes in the name, and definition, the metabolic origin (the presence of at least 1 of 5 cardiometabolic risk factors) without the stigmatising terms. The recognition of a new category termed "metabolic and alcohol related/associated liver disease" (Met-ALD) opens up a new area for exploration although the relative contribution of alcohol and metabolic risk factors requires further evaluation as does the evidencing at a patient rather than population level.

Objective: Hereditary hypophosphatemic disorders such as X-linked hypophosphatemia (XLH) are rare phosphate wasting disorders that cause abnormal bone mineralization, which manifests as bone deformities and dental problems. Pain, stiffness, and fatigue are the main symptoms reported by adult patients with XLH, interfering with their quality of life and activities of daily living. Here, we provide a comprehensive evaluation of pain and health related quality of life in patients with XLH.

Design and methods: In this cross-sectional study, forty-nine adult patients with XLH and forty-two healthy sex- and age- matched control participants underwent pressure algometry to determine pain sensitivity. In addition, we collected patient reported outcome data on pain, quality of life and mental health through the following questionnaires: (i) brief pain inventory- short form, (ii) SF-36v2™ Health Survey, (iii) painDETECT, (iv) Functional Assessment of Cancer Therapy- Bone Pain, (iv) Pain Catastrophizing Scale, (v) Generalized Anxiety Disorder 7 and (vi) Patient Health Questionnaire 9.

Results: Patients with XLH present altered skin, but not bone mechanical pressure pain thresholds, which may suggest referred pain through sensitization mechanisms. Questionnaire data highlight significantly higher pain scores in patients with XLH, which correlate with depression scores. Additionally, patients with XLH report decreased quality of life and mental health, increased pain catastrophizing thinking and anxiety.

Conclusion: Our results suggest that using patient-reported outcomes is important to understand the pain phenotype and mental health in patients with XLH and can be helpful to dictate treatment aimed at improving their pain and quality of life.

Context: Lipodystrophy syndromes are rare disorders characterized by deficient adipose tissue, leading to insulin resistance, dyslipidemia, and organ system abnormalities.

Objective: Our goal was to develop a lipodystrophy severity score (LDS) to holistically capture the diverse manifestations of lipodystrophy into a numerical score to aid in prediction of clinical outcomes and/or treatment impact.

Design: An 8-domain LDS was developed by eight disease experts in consultation with patient organizations. The LDS was rated for feasibility and content validity by 28 additional clinicians and 9 patient representatives. LDS was compared to Clinical Global Impression (CGI) of severity for 20 putative patient profiles, each at two different time points, and by comparing change in LDS to global impression of change. For external validation, LDS was calculated in two cohorts of patients with lipodystrophy treated with metreleptin.

Results: LDS domains include Diabetes/Insulin Resistance, Microvascular Complications of Diabetes, Lipids, Cardiovascular, Liver, Kidney, Reproductive, and Other. Each domain is assessed by one or more questions assessing both lifetime and recent complications of lipodystrophy. The LDS had high content validity and feasibility, and high reliability by intraclass correlation coefficients (>0.95). Global and domain-specific LDS were strongly correlated with CGI, as were changes in scores across visits (R=0.79-0.99, P<0.001 for all). In generalized lipodystrophy, metreleptin significantly reduced LDS (from 46 to 26 at 12 months, P<0.001). The reductions were smaller in partial lipodystrophy (from 65 to 61 at 12 months, P=0.04).

Conclusions: The LDS can reflect the severity of diverse manifestations of lipodystrophy and monitor changes following interventions.

Context: The ability to differentiate sporadic primary hyperparathyroidism (sPHPT) caused by a single parathyroid adenoma (PTA) from multiglandular parathyroid disease (MGD) preoperatively, as well as definitely diagnose sPHPT in difficult patients, would enhance surgical decision-making.

Objective: This work aimed to identify miRNA (miR) signatures for MGD, single- and double-PTA, as well as cell-free miRNA (cfmiR) in plasma samples from patients with single-PTAs to use as biomarkers.

Methods: A total of 47 patients with sPHPT (single-PTA n = 32, double-PTA n = 12, MGD n = 9). Preoperative plasma samples from 16 single-PTA and 29 normal healthy donors (NHDs). All specimens were processed and analyzed for 2083 miRs using HTG EdgeSeq miR whole-transcriptome assay and normalized using DESeq2 to identify differentially expressed (DE) miRs. MiR classifiers were identified using Random Forest. Main outcome measures were receiver operating characteristic curves and areas under the curve.

Results: MiR signatures distinguished normal parathyroid from MGD and PTA as well as MGD from PTA in tissue samples. Common miRs were found in the single-PTA and double-PTAs. Data integration identified a 27-miR signature in single-PTA tissue samples compared to the rest of the tissue samples. In plasma samples analysis, significant cfmiRs were DE in single-PTA patients compared to NHD. Of those, only 9 miRNAs/cfmiRs were found DE both in tissue and plasma samples from patients diagnosed with a single PTA (AUC = 76%).

Conclusion: Twenty-seven miRs were consistently found DE in single-PTA tissue and plasma samples. Data integration showed a 9-cfmiR signature with potential clinical utility to preoperatively diagnose sPHPT caused by a single PTA, which could decrease more invasive parathyroid explorations.

Context: Insulin sensitivity (SI) varies with age in type 1 diabetes (T1D).

Objective: To compare postprandial glucose turnover and SI between adolescents and adults with T1D.

Design: This cross-sectional comparison at a clinical research unit included 21 early adolescents with T1D (T1D-adol) (12 F; age, 11.5 ± 0.5 years; BMI 19 ± 2 kg/m2), 13 adults with T1D (T1D-adult) (5 F; 37.8 ± 9.1 years; BMI 27 ± 2 kg/m2), and 14 anthropometrically matched adults without diabetes (ND) (7 F; 26.9 ± 7.0 years; BMI 25 ± 2.5 kg/m2). Using triple tracer mixed meal and oral glucose models, SI in T1D-adol and T1D-adult was compared.

Results: Postprandial glucose excursions were not different in T1D-adol vs T1D-adult (P = .111) but higher than in ND (P < .01). Insulin excursions were also similar in T1D-adol vs T1D-adult (P = .600) and they were both lower (P < .05) compared to ND, while glucagon excursions were lower (P < .01) in T1D-adol than in T1D-adult and ND. Integrated rates of endogenous glucose production and glucose disappearance were lower in T1D-adol than in T1D-adult and in ND vs T1D-adult but did not differ between T1D-adol and ND. Meal glucose appearance did not differ between groups. While SI in T1D-adol vs ND was similar (P = .299), it was higher in T1D-adol and ND vs T1D-adult (P < .01).

Conclusion: We report differences in parameters of postprandial glucose turnover and insulin sensitivity between adults and early adolescents with T1D that could, at least in part, be due to the shorter duration of diabetes among T1D-adol. These data support the concept that over time with T1D, endogenous glucose production increases and SI deteriorates.

Context: The putative association between pro-inflammatory and hyperinsulinemic dietary patterns and susceptibility to gestational diabetes mellitus (GDM) remains unclear.

Objective: We aimed to compare the risk associated with the Mediterranean diet, as well as insulinemic and pro-inflammatory dietary patterns, in relation to the occurrence of GDM, and evaluate their predictive value.

Methods: We prospectively followed 8495 women from the Maternal and Infant Health cohort in Hefei, China (2015-2021). Using a food frequency questionnaire, we calculated the empirical dietary inflammatory pattern (EDIP), the empirical dietary index for hyperinsulinemia (EDIH) score, and the Mediterranean diet (MD) score. GDM was diagnosed based on a 2-hour 75-gram oral glucose tolerance test conducted between 24 to 28 weeks of gestation. Logistic regression was used to estimate the risk of GDM, while receiver operating characteristic (ROC) curves were constructed to evaluate the predictive performance of the empirical dietary index for GDM.

Results: Participants who followed hyperinsulinemic or pro-inflammatory dietary patterns to the greatest extent had a higher risk of developing GDM. The odds ratio (OR) for the highest quartile compared to the lowest quartile were 1.39 (95% CI, 1.30-1.49) for EDIH and 2.40 (95% CI, 1.88-3.01) for EDIP. The OR for the lowest quartile compared to the highest quartile was 1.33 (95% CI, 1.14-1.55) for MD. The ROC curve analysis indicated that the combination of EDIP and EDIH (AUC = 0.81; 95% CI, 0.78-0.82; P = .003) can effectively predict the occurrence of GDM.

Conclusion: Utilizing both empirical dietary indexes, EDIP and EDIH, might offer a potentially more effective approach in preventing GDM when compared to solely focusing on adherence to the MD pattern.