Endocrine最新文献

Objective: The potential association between Hashimoto's thyroiditis (HT) and papillary thyroid carcinoma (PTC) has been studied from different perspectives for many years. This study was aimed to evaluate the impact of HT on the clinical outcomes of PTC patients after radioactive iodine (RAI) therapy.

Material and methods: We conducted a retrospective study on consecutive patients with PTC who underwent RAI therapy from April 2017 to May 2020. The diagnosis of HT was based on pathological examination, and patients were divided into the HT and non-HT group. Distributions of age, gender, ultrasound features, papillary variants, extrathyroidal extension, and other histopathological characteristics were observed. Propensity score matching (PSM) was used to compare the clinical features and outcomes between the two groups at 1 and 3-year follow-up.

Results: In total, 782 patients with PTC were enrolled (570 women, 212 men). HT was presented in 130 (16.6%) patients, and was associated with younger age, smaller primary tumors, less extrathyroidal extension, and less lymph node metastasis at presentation. On review of the images, only calcification and blood flow distribution were significantly different among the US features (P < 0.05). At the end of follow-up (three years), the responses to RAI therapy were significantly different between the two groups (ER: 76.9% vs 64.9%; IDR:11.5% vs 17.2%; BIR: 4.6% vs 10.7%; SIR: 6.9% vs 7.2%, P = 0.03). Patients with HT had less frequently evidence of disease (11.6% vs 17.9%). When compared with the matched groups, 123 pairs of patients were successfully matched, PTC patients with HT were found to have a better response to RAI therapy.

Conclusions: PTC patients with HT had less aggressive characteristics at presentation. Importantly, the presence of HT not only had a significant association with the outcome, but was also protective from the risk of recurrence.

Objective: To elucidate the fluctuations in glucose levels measured using CGM-metrics during the four distinct seasons of the year in individuals with type 1 diabetes mellitus (T1DM) using an intermittently scanned CGM (isCGM) device or sensor augmented pump (SAP).

Research design and methods: This retrospective, single-center study enrolled 93 individuals with T1DM who were equipped with an isCGM device or SAP at Kobe University Hospital. The subjects had a median age of 47.0 years [interquartile range, 37.0-62.0 years], 25 individuals (26.9%) were male, median body mass index was 22.0 kg/m² [20.8-23.8 kg/m²], and median hemoglobin A_1c level was 7.4% [6.9-8.0%]. CGM data were reviewed from January to December 2019, and the mean sensor glucose (SG) value, time above range (TAR), time in range (TIR), time below range (TBR), and standard deviation (SD) of SG were calculated for each season (spring, March-May; summer, June-August; autumn, September-November; winter, December-February).

Results: Seasonal fluctuations were detected for mean SG, TAR, TIR, and SD, with TIR being lower and mean SG, TAR, and SD being higher in cold seasons (spring or winter) than in warm seasons (summer or autumn).

Conclusion: Seasonal fluctuations in CGM metrics should be taken into account in future studies performed to evaluate the favorable impact of CGM on glycemic management in individuals with T1DM.

Background: Limited data indicated the performance of large language model (LLM) taking on the role of doctors. We aimed to investigate the potential for ChatGPT-3.5 and New Bing Chat acting as doctors using thyroid nodules as an example.

Methods: A total of 145 patients with thyroid nodules were included for generating questions. Each question was entered into chatbot of ChatGPT-3.5 and New Bing Chat five times and five responses were acquired respectively. These responses were compared with answers given by five junior doctors. Responses from five senior doctors were regarded as gold standard. Accuracy and reproducibility of responses from ChatGPT-3.5 and New Bing Chat were evaluated.

Results: The accuracy of ChatGPT-3.5 and New Bing Chat in answering Q2, Q3, Q5 were lower than that of junior doctors (all P < 0.05), while both LLMs were comparable to junior doctors when answering Q4 and Q6. In terms of "high reproducibility and accuracy", ChatGPT-3.5 outperformed New Bing Chat in Q1 and Q5 (P < 0.001 and P = 0.008, respectively), but showed no significant difference in Q2, Q3, Q4, and Q6 (P > 0.05 for all). New Bing Chat generated higher accuracy than ChatGPT-3.5 (72.41% vs 58.62%) (P = 0.003) in decision making of thyroid nodules, and both were less accurate than junior doctors (89.66%, P < 0.001 for both).

Conclusions: The exploration of ChatGPT-3.5 and New Bing Chat in the diagnosis and management of thyroid nodules illustrates that LLMs currently demonstrate the potential for medical applications, but do not yet reach the clinical decision-making capacity of doctors.

Purpose: To assess the prevalence of osteosarcopenia (OS) in elderly patients with type 2 diabetes mellitus (T2DM) and explore the related risk factors for developing this condition.

Methods: This cross-sectional study enrolled hospitalized T2DM patients aged 60 years and older. Patients underwent assessments of total hip bone mineral density (BMD), grip strength, the Short Physical Performance Battery (SPPB), and body composition. Based on the 2019 Asian Working Group for Sarcopenia (AWGS) criteria, appendicular skeletal muscle mass (ASM), grip strength, and SPPB were measured to diagnose sarcopenia. BMD and T values of the lumbar spine and hip were measured using dual-energy X-ray absorptiometry (DXA). Osteosarcopenia was defined when both sarcopenia and osteoporosis criteria were met. Statistical analysis included binary logistic regression to identify significant risk factors.

Results: A total of 254 hospitalized T2DM patients (80 males and 174 females) were included. They were divided into T2DM-OS (n = 58) and T2DM-NOS (n = 196) groups based on the presence of osteosarcopenia. The average ages were 72.724 ± 6.463 and 69.265 ± 6.035 years, respectively. The prevalence of osteosarcopenia in T2DM patients was 22.8%, with 20.7% (12 males) and 79.3% (46 females) in the T2DM-OS group. After adjusting for confounding factors, it was found that male gender (OR: 5.738, 95% CI: 1.602-20.551, P = 0.007), fasting plasma glucose (OR: 0.904, 95% CI: 0.821-0.995, P = 0.038), and ASMI (OR: 0.049, 95% CI: 0.013-0.184, P < 0.001) were major influencing factors for the development of osteosarcopenia in elderly T2DM patients.

Conclusions: The prevalence of T2DM-OS is relatively high, with male gender, low fasting plasma glucose, and low ASMI identified as risk factors.

Purpose: Preculturing isolated islets with Mesenchymal Stromal Cells (MSCs) improves their functional survival in vitro and subsequent transplantation outcomes in vivo. The MSC secretory product Annexin A1 (ANXA1) is a key modulator of MSC-mediated improvements in islet function. The current study aims to determine the influence of MSCs and defined MSC secretory products, including ANXA1, on the inflammatory crosstalk between isolated islets and Endothelial Cells (ECs), using in vitro models of the clinically-preferred intraportal islet transplantation niche.

Methods: Islets were cultured alone, with MSCs, or with MSC secretory products and exposed to pro-inflammatory cytokines. Islet gene expression of C-C Motif Chemokine Ligand 2 (CCL2), C-X-C Motif Chemokine Ligand (CXCL)-10 (CXCL10) and CXCL1 were assessed by RT-qPCR. EC activation was induced with 100 U/ml TNF for 24 h. Islet-EC co-cultures were used to determine the influence of MSCs, or MSC secretory products on the inflammatory crosstalk between isolated islets and ECs. VCAM-1 and ICAM-1 expression were assessed at the mRNA and protein level in ECs, using RT-qPCR and immunofluorescence.

Results: MSCs reduce pro-inflammatory cytokine-induced islet CCL2, CXCL10, and CXCL1 gene expression, which is partially mimicked by ANXA1. MSCs and ANXA1 have a similar capacity to reduce TNF-induced EC activation. Isolated islets exacerbate TNF-induced EC activation. Preculturing islets with MSCs reduces islet-exacerbated EC activation. ANXA1 reduces islet-exacerbated EC activation, when present during the islet preculture and islet-EC co-culture period.

Conclusion: MSC-derived secretory factors, including ANXA1, may be used in islet transplantation protocols to target donor islet and host EC inflammation at the intraportal niche.

Purpose: Pituitary neuroendocrine tumors (PitNETs) with invasion of the cavernous sinus (CS) are particularly challenging to treat. Tumor associated fibroblasts (TAFs) are recognized for their pivotal role in reprogramming extracellular matrix (ECM). Herein, we aimed to explore the potential involvement of TAFs in ECM reprogramming and elucidate the underlying mechanism involved.

Methods: We applied dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) to measure tumor vessel permeability and applied atomic force microscopy (AFM) to measure the matrix stiffness of PitNETs located in both CS and sella turcica (ST). Western blotting, immunofluorescence, immunohistochemistry, and quantitative RT-PCR were utilized to analyze the ECM components. Proteomic biochemical analysis was utilized to uncover potential mechanisms governing ECM dynamics.

Results: We found that PitNETs in the CS were stiffer than those in the ST. Increased ECM stiffness within the CS facilitated the acquisition of stem-like properties, enhanced proliferation, and induced epithelial-to-mesenchymal transition (EMT) of GH3 cells. Furthermore, the expression levels of lysyl oxidase (LOX), matrix metallopeptidase 2 (MMP2) and MMP9 in pituitary adenoma cells increased in the stiffer matrix. Proteomic analysis suggested TAFs were activated in the CS area and contributed enhanced matrix stiffness by secreting Col-1 and Col-3. Furthermore, mTOR pathway was activated under higher matrix stiffness and the migration and invasion of GH3 cells be repressed by mTOR inhibitor.

Conclusion: These findings demonstrated that activated TAFs contributed to stiffer matrix and increased ECM stiffness stimulating mTOR pathway in pituitary tumor cells. Our study indicated that mTOR inhibitor was a promising treatment strategy from the standpoint of PitNET biomechanical properties.

Purpose: This study aimed to assess subclinical peripheral diabetic neuropathy (PDN) in adolescents with type 1 diabetes mellitus (T1DM).

Methods: Subjects included 53 T1DM patients (age (mean ± SE): 15.8 ± 0.54 years, disease duration: 6.0 ± 0.51 years and HbA1c: 7.9 ± 0.19%), and 37 healthy gender matched controls (age: 15.6 ± 0.52 years). PDN was assessed by vibration perception threshold (VPT) and by quantitative sensory testing (QST). In controls, 95% confidence intervals were calculated.

Results: Among patients, VPT prevalence of abnormality ranged from 60-73.4% on different sites. Higher VPT was found in patients on all examined sites (p < 0.01). In controls, VPT correlated with height (r = 0.48, p = 0.05). Regarding QST prevalence of abnormality, cold detection threshold (CDT) ranged 7.3-39.0%, cold pain threshold (CPT) ranged 22.22-29.63%, hot detection threshold (HDT) ranged 34.14-63.41%, and hot pain threshold (HPT) ranged 15.79-36.84%. In patients, CPT correlated with BMI (r = 0.42, p = 0.05) and diabetes duration, (r = 0.40, p = 0.05), HPT correlated with age (r = 0.36, p = 0.05) and height (r = 0.35, p = 0.05), while in controls with BMI (r = 0.51, p = 0.05). No correlation of VPT or QST with HbA1c was observed.

Conclusion: Adolescents with T1DM in this study, although asymptomatic, showed a high prevalence of impaired indices of PDN, highlighting potential clinical implications of early identification of PDN.

Purpose: The evaluation of the effect of dulaglutide on glycated hemoglobin (HbA1c) and non-invasive indices of hepatic steatosis among different genotypes of the PNPLA3 I148M (rs738409) and CETP Taq1B (rs708272) polymorphisms in patients with type 2 diabetes mellitus (T2DM) and non-alcoholic fatty liver disease (NAFLD).

Methods: Relevant data from patients with inadequately controlled T2DM, also displaying NAFLD, administered 1.5 mg dulaglutide weekly for 6 months were retrospectively retrieved. The non-invasive indices, fatty liver index (FLI) and hepatic steatosis index (HSI), were calculated. Genotyping for rs738409 and rs708272 were performed with polymerase chain reaction.

Results: Data from 80 patients (39 females), aged 64.4 ± 9.5 years and displaying a baseline BMI of 34.5 ± 5.8 kg/m², were retrieved at baseline and after 6 months (endpoint) of dulaglutide treatment. Glycated hemoglobin (HbA1c; -0.72 ± 1.10%; p < 0.001), FLI (-5.8 ± 9.8; p < 0.001) and HSI (-1.18 ± 3.51; p = 0.004) significantly decreased after treatment. Lipid profile and liver function tests also improved after treatment. Overall, homozygotes for the reference rs738409 allele (CC) displayed a 2.4-fold decrease (p = 0.002) and heterozygotes (CG) an 1.6-fold decrease (p = 0.013) compared to GG homozygotes after treatment, but the effect was largely limited to female patients. No similar effect was observed in FLI, HSI and other relevant parameters. No association was observed between rs708272 and any of the parameters studied.

Conclusions: rs738409, but not rs708272, was associated with the effect of dulaglutide on HbA1c, but not on presumed hepatic steatosis or other relevant parameters. Sex-specific effects were also noticed.

Purpose: Aims of this study were to investigate the prevalence of TP53 and TERT mutations in Medullary Thyroid carcinoma (MTC) and their role in inducing aggressiveness in positive cases.

Methods: We performed a literature search in PubMed to identify studies investigating the prevalence of TERT and TP53 mutations in MTC. We also included data on MTC cases (n = 193) obtained at our center and unpublished. The in-silico pathogenicity of the TP53 mutations has been evaluated by predictor tools.

Results: We identified a total of 25 and 11 published papers: all together 1280 cases have been investigated for the presence of TP53 mutations and 974 for TERT promoter mutation. Twenty-five out of 1280 (2%) cases had a TP53 mutation while only 3/974 MTC cases (0.3%) have been found to be positive for TERT promoter mutations. Among all, we identified 19 different TP53 mutations that in 12 cases were demonstrated to have an in silico predicted high pathogenic role and a high impact on protein function. Three non-sense and 4 probably not damaging mutations were also reported. The pathogenic role of the TERT promoter mutations has been previously in vitro determined. No correlation between TP53 and/or TERT mutations and aggressiveness of MTC has been demonstrated.

Conclusion: The prevalence of TP53 and TERT promoter mutations is very low in MTC. The reported mutations are pathogenic in the majority of cases. Because of their rarity it is not possible to clarify if they play or not a role in the pathogenesis and/or aggressiveness of this specific thyroid tumor.

Purpose: Thyroidectomy is the treatment of choice for malignant thyroid diseases as well as for benign conditions who cannot be treated medically. The most common complication following thyroidectomy is hypocalcaemia and hypoparathyroidism that usually results from accidental damage or removal of one or more parathyroid glands. Parathyroid gland autotransplantation has been one of the most common intraoperative strategies applied to tackle this problem. The aim of this study is to assess whether parathyroid auto trasnplantation is associated with a decrease in postoperative hypoparathyroidism following thyroidectomy.

Methods: We conducted a thorough systematic review and meta-analysis of relevant studies published up to February 2024 in MEDLINE, Scopus, Embase and Cochrane Library databases. We compared the incidence of postoperative hypoparathyroidism between the group of patients who underwent autotransplantation and the patients were the parathyroid glands were preserved in situ. A trial sequential analysis was performed subsequently to confirm the findings.

Results: Eighteen studies fulfilled all the inclusion criteria and were ultimately included in our study. The total number of patients was 8,182 with 4,029 receiving parathyroid gland autotransplantation. Autotransplantation was associated with a higher incidence of immediate (within 24 h) and transient hypoparathyroidism (RR 1.58, 1.45-1.73, CI 95%, p < 0.00 and RR 1.60, 1.47-1.76, CI 95%, p < 0.001, respectively). However, it did not affect the rate of permanent postoperative hypoparathyroidism (RR 0.85, 0.51-1.41, CI 95%, p = 0.54). The subsequent trial sequential analysis confirmed these findings.

Conclusion: Parathyroid autotransplantation does not lead to a decrease in the rate of permanent post-thyroidectomy hypoparathyroidism. The most important factor to decrease its incidence remains the accurate identification and preservation of the parathyroid glands intraoperatively.