Endocrine最新文献

Purpose: Carney complex (CNC) is a rare, autosomal dominant syndrome, most commonly caused by PRKAR1A gene mutations and characterized by pigmented skin and mucosal changes with multiple endocrine and non-endocrine tumours. This case report highlights the diagnostic challenges associated with CNC in a patient with multiple neoplasms and a complex medical history, including cortisol-producing adrenal adenoma, breast cancer, melanoma, and atrial myxoma.

Methods: We report the case of a 41-year-old woman with a medical history of left adrenalectomy for cortisol producing adenoma (2005) with no sign of adrenal insufficiency at follow-up, right mastectomy for BRCA1/2 negative carcinoma (2013) and left parotid BRAF-V600E wild-type melanoma (2019), treated with nivolumab adjuvant therapy. In August 2019, following the fifth nivolumab administration, the patient developed central hypocortisolism due to iatrogenic hypophysitis, confirmed by brain MRI and properly treated with oral hydrocortisone. Nivolumab was discontinued due to the patient's decision. In October 2020 and April 2021, the patient had ischaemic strokes, requiring systemic thrombolysis. Echocardiographic examination then revealed a left atrial mass, with histological finding of myxoma.

Results: Given the rarity of this neoplasm and the suspicion of a syndromic disorder, a genetic evaluation was conducted, which confirmed a PRKAR1A gene mutation and the diagnosis of Carney complex.

Conclusion: This case illustrates the diagnostic challenges in CNC, especially in patients with multiple tumourous manifestations and a wide spectrum of life-threatening clinical presentations. It underscores the importance of a multidisciplinary approach to diagnose and manage rare diseases, improving patient outcomes through timely genetic testing and coordinated care.

Background: Severe symptomatic hyponatraemia is potentially life-threatening and hypertonic saline (HTS) is effective at rapidly correcting serum sodium. Several clinical guidelines have aimed to standardise the administration of HTS. However, evidence supporting the guidelines is limited, and concerns have been raised regarding the potential for overcorrection.

Objective: To assess the practices and perceptions surrounding HTS use in severe symptomatic hyponatraemia among United Kingdom (UK) endocrinologists and trainees.

Methods: An anonymous online survey was disseminated to Society for Endocrinology (UK) clinical members between 24/10/2023 and 30/11/2023 using a web-based multiple-choice questionnaire.

Results: We received 133 responses with a survey response rate of 8.3% (60.1% consultants, 33.1% trainees, 6.8% others). 85% of respondents employed bolus treatment with HTS only, with 9.8% using both bolus and continuous infusions. Most (53.2%) preferred 150 mL boluses, followed by 100 mL boluses (19.8%), while 5.5% of respondents used weight-based dosage. Commonly used HTS strengths were 2.7% (45.1%), followed by 1.8% (31.6%), while the 3% HTS strength recommended in guidelines was used by 21.8%. Contrary to guidelines, 78.6% did not administer a second bolus without waiting for the sodium result after the first bolus. Moreover, 86% have experience using venous blood gas sodium readings for monitoring. Overcorrection targets defined by 10 and 8 mmol/24 h cut-offs were used by 48.9% and 39.9%, respectively. For definite or anticipated overcorrection, 75.9% preferred 5% dextrose, while 40.6% had experience with desmopressin.

Conclusion: Significant variation exists in HTS use for severe symptomatic hyponatraemia in the UK. Most clinicians prefer a more cautious approach in administering HTS. These data offer insight into real-life care and call for future research.

Background: The severity of thyroid cancer is judged on the basis of histologic and clinical features. A limited number of studies have considered urinary metabolite signatures for its diagnosis, and no reliable urinary metabolite biomarkers have been proposed. This diagnostic method would be particularly valuable because of its non-invasive nature.

Method: A nuclear magnetic resonance (NMR)-based metabolomics approach was used as the analytical platform to study the urine samples of patients with PTMC. Urine samples collected from 41 PTMC patients, 52 healthy subjects, and 13 patients with benign tumors were analyzed using 1H-NMR spectroscopy to identify metabolic changes. PLS-DA, or partial least squares discriminant analysis, was used to analyze the NMR spectra. A double cross-validation method and randomization tests were used to validate PLS-DA models.

Results: Clear discriminations between PTMC patients and healthy controls, as well as between PTMC patients and patients with benign tumors were obtained. Collectively, pi-methyhistidine, trimethylamine, myo-inositol, acetate, suberate, azelate, mannitol, tau-methylhistine, ascorbate, 3-aminoisobutyric acid, 2-oxoglutarate, and methanol contributed to the discrimination. Apart from myo-inositol and methanol, all of these metabolites exhibited increased levels in the urine samples of PTMC patients as compared to that of patients with benign tumors.

Conclusions: The application of this NMR-based metabolomics approach allowed the detection of anomalous metabolic traits directly connected PTMC, potentially yielding a more sensitive and comprehensive diagnostic results for PTMC.

Purpose: Previous investigations have assessed the connection between vitamin D deficiency and an increased risk of gestational diabetes mellitus (GDM); however, the findings remain inconsistent. The purpose of this study was to investigate the causal relationship between 25-hydroxyvitamin D (25OHD) levels and GDM.

Methods: Summary statistics data from genome-wide association studies (GWASs) were used to perform a bidirectional two-sample Mendelian randomization (MR) study. A total of 417,580 Europeans from the UK Biobank provided summary statistics data for 25OHD. The tenth data release of the FinnGen study provided the data for GDM, comprising 14,718 cases and 215,592 controls. For the univariate MR (uvMR) investigations, we employed the inverse variance weighted (IVW) method as our major analytical approach. Multiple sensitivity analyses were performed to evaluate the robustness of the results. Moreover, multivariate MR (mvMR) studies were conducted to account for potential confounding variables, including obesity, insulin resistance, and lipid traits.

Results: In the forward MR study, uvMR analysis did not provide evidence supporting a causal effect of 25OHD levels on the risk of GDM [IVW odds ratio (OR): 1.07, 95% confidence interval (CI): 0.95 to 1.19, p = 0.273]. After adjusting for obesity, fasting insulin levels, and lipid traits, the findings from the mvMR analysis aligned with those of the uvMR analysis. In the reverse MR study, uvMR analysis indicated that GDM had no causal effect on serum 25OHD levels (IVW β = -0.003, p = 0.804), and the robustness of this finding was confirmed in the mvMR study.

Conclusion: Our MR research revealed no causal effect of serum 25OHD levels on GDM, suggesting that 25OHD deficiency does not correlate with an increased risk of GDM. Furthermore, our reverse analysis revealed no causal effect of GDM on 25OHD levels.

Objective: To investigate the association between glucagon-like peptide 1 receptor agonists (GLP-1 RAs) and ophthalmic adverse drug reactions (OADRs) using data from the FDA Adverse Event Reporting System (FAERS).

Methods: This retrospective pharmacovigilance study analyzed post-marketing FAERS data from 2018 to 2023 to identify GLP-1 RA-related OADRs. This study employed the Weibull model for time-to-onset (TTO) analysis, Bayesian Information Component analysis for disproportionality comparing GLP-1 RAs with other drugs, and the Ω shrinkage method for co-medication analysis.

Results: FAERS reported 5003 OADRs associated with GLP-1 RAs, including retinopathy and visual impairment. Disproportionality analysis identified significant signals for semaglutide, liraglutide, and exenatide, suggesting potential associations with OADRs. Co-medication analysis indicated that OADRs primarily resulted from GLP-1 RA use. TTO analysis categorized most OADRs as early failures, emphasizing the need for early monitoring.

Conclusion: This study emphasizes the importance of ophthalmic surveillance in patients using GLP-1 RAs, particularly semaglutide, dulaglutide, and exenatide. Enhanced monitoring and patient education are essential for timely detection and management of potential OADRs. Regulatory agencies should consider updating drug labels to include comprehensive warnings about OADRs associated with GLP-1 RA therapies.

Background: Cervical lymph node metastasis (CLNM) is the most common form of thyroid cancer metastasis. Accurate preoperative CLNM diagnosis is of more importance in patients with papillary thyroid cancer (PTC). However, there is currently no unified methods to objectively predict CLNM risk from ultrasonography in PTC patients.This study aimed to develop a deep learning (DL) model to help clinicians more accurately determine the existence of CLNM risk in patients with PTC and then assist them with treatment decisions.

Methods: Ultrasound dynamic videos of 388 patients with 717 thyroid nodules were retrospectively collected from Zhejiang Cancer Hospital between January 2020 and June 2022. Five deep learning (DL) models were investigated to examine its efficacy for predicting CLNM risks and their performances were also compared with those predicted using two-dimensional ultrasound static images.

Results: In the testing dataset (n = 78), the DenseNet121 model trained on ultrasound dynamic videos outperformed the other four DL models as well as the DL model trained using the two-dimensional (2D) static images across all metrics. Specifically, using DenseNet121, the comparison between the 3D model and 2D model for all metrics are shown as below: AUROC: 0.903 versus 0.828, sensitivity: 0.877 versus 0.871, specificity: 0.865 versus 0.659.

Conclusions: This study demonstrated that the DenseNet121 model has the greatest potential in distinguishing CLNM from non-CLNM in patients with PTC. Dynamic videos also offered more information about the disease states which have proven to be more efficient and robust in identifying CLNM compared to statis images.

Purpose: In absence of nodal metastases or aggressive features, thyroid lobectomy (TL) should be preferred over total thyroidectomy (TT) for 1-4 cm unifocal, papillary thyroid carcinoma (PTC). However, occult, despite non-microscopic (≥2 mm), nodal metastases may be present in clinically node-negative (cN0) PTC.

Methods: Among 4216 thyroidectomies for malignancy (2014-2023), 110 TL plus ipsilateral central neck dissection (I-CND) were scheduled for unifocal cT1b/small cT2 (≤3 cm) cN0 PTCs. Frozen section examination (FSE) of removed nodes was performed: when positive, completion thyroidectomy (CT) was accomplished during the same procedure. In presence of aggressive pathologic features, CT was suggested within 6 months from index operation.

Results: FSE was positive for occult not-microscopic nodal metastases in 33 cases (30%), underwent synchronous CT. Among the remaining 77 patients, 24 (31.2%) were scheduled for CT, after multidisciplinary tumor board discussion, due to at least 2 high-risk factors. The median number of removed and metastatic nodes was 8 (5-11) and 2 (1-5), respectively, at definitive histopathology. Furthermore, multifocality was present in 53 (48.2%) cases, lymphovascular invasion in 66 (60%) cases, aggressive subtypes in 20 (18.2%) cases and extracapsular invasion in 5 (4.5%) cases. Overall, 57 (51.8%) patients underwent immediate or delayed CT.

Conclusion: More than 50% of patients with unifocal cT1b/small cT2 cN0 PTC scheduled for TL may be eligible for CT because of aggressive tumor features. An intraoperative decision-making approach based on I-CND and nodes FSE may ensure accurate staging and risk stratification, thus reducing the risk of recurrence and the need for reoperation.

Purpose: Hypoparathyroidism, sensorineural deafness, and renal dysplasia (HDR) syndrome is a rare autosomal dominant genetic disease associated with mutations in the GATA3 gene, which encodes GATA3 that plays essential roles in vertebrate development. This study aimed to identify and report the pathogenic mutation in GATA3 in a Chinese family diagnosed with HDR syndrome and determine its functional impacts in vivo.

Subjects and methods: The clinical features of a 25-year-old male patient with HDR syndrome and his parents were collected. GATA3 gene exome sequencing and Sanger sequencing were performed on the proband and his family, respectively. Functional analyses of GATA3 were performed using bioinformatics tools and zebrafish assays to determine pathogenicity and phenotype spectrum.

Results: A novel, heterozygous, missense mutation in exon 4 of the GATA3 gene, c.863 G > A, p.Cys288Tyr, in the proband and his mother who presented the complete HDR triad, was predicted to be deleterious by in silico tools. 3D structure modeling showed that the variant caused significant structural changes. In vivo studies using a zebrafish animal model revealed the deleterious impact of the variant on the gill buds, otoliths, and pronephros.

Conclusion: We identified a novel missense mutation, GATA3 p.Cys288Tyr, within a family with HDR syndrome and delineated it as a loss-of-function variant in vivo. This expands the spectrum of GATA3 mutations associated with HDR syndrome in the Chinese population and mimics HDR-related changes in vivo.

Purpose: Diabetic kidney disease (DKD) is the primary reason of chronic kidney disease. Our objective was to discover potential autophagy-related biomarkers of tubulointerstitial injury in DKD and assess their clinical value.

Methods: We retrieved four datasets (GSE104954, GSE30122, GSE30529, and GSE99340) of renal tubule samples from Gene Expression Omnibus (GEO) and used two algorithms (LASSO and SVM-RFE) to screen for autophagy-related differentially expressed genes (ARDEGs) in DKD. Tripartite motif containing 22 (TRIM22) was identified for subsequent validation. Validation of TRIM22 and autophagic indicators expression in clinical samples and HK-2 cells stimulated by high glucose using immunohistochemistry, immunofluorescence, and western blot.

Results: We identified four ARDEGs (TRIM22, PLK2, HTR2B, and FAS) using a diagnostic gene model. ROC curves further confirmed that TRIM22 had the best diagnostic efficacy for DKD. Both clinical samples and HK-2 cells stimulated by high glucose showed high protein expression of TRIM22. The correlation analysis revealed that TRIM22 correlates with SQSTM1, NGAL, and some clinical and pathological indicators in patients with DKD.

Conclusion: We identified TRIM22 as a potential diagnostic biomarker for DKD, revealing its high diagnostic value in patients with DKD with moderate-to-severe interstitial fibrosis and tubular atrophy (IFTA). TRIM22 is involved in tubulointerstitial injury and autophagy dysregulation in DKD.

Purpose: ChatGPT is a widely used artificial intelligence modeling tool. Healthcare is one potential area of use of ChatGPT. This study aimed to test the usability and reliability of ChatGPT in acromegaly, which is less known in society and should be evaluated by a group of specialized physicians.

Methods: The study is designed in two parts. For the first part, 35 questions regarding acromegaly that patients frequently ask were identified, and these questions were asked to ChatGPT. In the second part, four patient examples were presented to ChatGPT using medical terminology. Three experts evaluated ChatGPT's answers to the questions and approaches in case management using 7-point scales in terms of safety, reliability, correctness, and usability.

Results: When the ChatGPT answers to the patient's questions were evaluated, a mean score of 6.78 ± 0.55 was given for correctness and 6.69 ± 0.60 for reliability. The mean scores given by the raters for correctness, safety and usability in the evaluation of the cases were as follows: 6.33 ± 0.88, 6.16 ± 0. 71 and 6.08 ± 0.79 points for case 1; 5.35 ± 1.88, 5.29 ± 1.80 and 5.20 ± 1.86 points for case 2; 6.08 ± 0.97, 6.00 ± 0.93 and 5.91 ± 0.82 points for case 3; 6.10 ± 1.29, 6.13 ± 1.30 and 6.16 ± 1.14 points for case 4.

Conclusion: ChatGPT can actively answer the questions of acromegaly patients. Although it is not a reliable source alone in managing patients with acromegaly, it can be a supportive tool for physicians.