Endocrine journal最新文献

To-and-fro puncture and to-and-fro whirling puncture are two common specimen acquisition methods of thyroid fine-needle capillary (FNC) biopsy. While both techniques are widely used, a direct comparison of their outcomes has been lacking. This prospective study enrolled 110 patients with 138 thyroid nodules. Each nodule underwent four punctures: two using the to-and-fro technique and two using the to-and-fro whirling technique. The primary outcome was specimen adequacy, while secondary outcomes included malignancy diagnosis rate, sensitivity, diagnostic accuracy, and procedure time. No significant difference was found in specimen adequacy between the two techniques (90.58% vs. 89.86%, p = 0.839). However, the to-and-fro technique demonstrated superior performance in terms of malignancy diagnosis rate (31.88% vs. 20.29%, p = 0.028), sensitivity (100.00% vs. 81.82%, p = 0.006), and diagnostic accuracy (97.78% vs. 83.33%, p = 0.041). Additionally, the to-and-fro technique required less procedure time (18.38 ± 8.34 seconds vs. 20.84 ± 10.54 seconds, p < 0.001). In conclusion, both the to-and-fro puncture technique FNC and the to-and-fro whirling puncture technique FNC demonstrated comparable specimen adequacy, and both can achieve good specimen adequacy. The to-and-fro puncture technique shows potential advantages in terms of operation time, reduction of the risk of missed diagnosis of malignant tumors, sensitivity, and diagnostic accuracy. Trial registration: Chinese Clinical Trial Registry, ChiCTR2400080882. Registered 14 February 2024.

Thyroid hormone (TH) prescribing practices, particularly on hypothyroid and euthyroid patients, were compared between Japan Thyroid Association (JTA)-certified thyroid specialists and non-certified members. A nationwide questionnaire survey (Treatment of Hypothyroidism in Europe by Specialists: An International Survey) was conducted among all 2,938 JTA members, including 874 certified specialists and 2,064 non-certified members, to assess self-reported TH prescription choices in various clinical scenarios. Responses from certified specialists and non-certified members were statistically compared. A total of 207 certified specialists (23.7%) and 129 non-certified members (6.3%) responded and completed the questionnaire. Although all certified specialists and non-certified members selected levothyroxine (LT4) as first-line therapy for hypothyroidism, certified specialists more often used liothyronine (LT3) plus LT4 combination therapy than non-certified members (28% vs. 12%, p < 0.001), particularly for LT4-treated patients with persistent hypothyroid-like symptoms (9% vs. 2%, p = 0.02). For euthyroid individuals, 71% of certified specialists and 60% of non-certified members considered TH treatment (p = 0.043). Non-certified members who see >100 hypothyroid patients per year were more inclined to use combination therapy for hypothyroid patients and TH for euthyroid patients than those of ≤100 patients (p < 0.049 and 0.001, respectively). In conclusion, JTA-certified thyroid specialists and non-certified members exhibit distinct TH prescribing patterns. Certified specialists are more open to combination therapy and treating selected euthyroid patients, whereas non-certified members favor guideline-based LT4 monotherapy. These differences underscore the impact of specialization on clinical practice and suggest a need for updated guidelines and targeted education to rationalize thyroid care.

Despite extensive research on miR-642a-5p, its specific function in pancreatic β-cells and its contribution to the pathogenesis of type 2 diabetes mellitus (T2DM) remain unclear. This study aimed to investigate the regulatory role of miR-642a-5p in pancreatic β-cells (EndoC-βH1) and its association with the transcription factor Mef2d. Differentially expressed miRNAs related to T2DM were identified through analysis of the GSE70318 dataset. Based on predictions from the TargetScan, miRDB, miWalk, and miRTarBase databases, the interaction between miR-642a-5p and Mef2d was validated using dual-luciferase reporter assays and gene interference experiments. In EndoC-βH1 cells treated with high glucose and palmitic acid, cell apoptosis, insulin secretion, and the expression of related genes were evaluated. The functional impact of co-transfection with miR-642a-5p and Mef2d on EndoC-βH1 cells was also analyzed. Results indicated that miR-642a-5p was abnormally expressed in the GSE70318 dataset, and Mef2d was confirmed as its target gene. Overexpression of miR-642a-5p promoted insulin secretion, upregulated insulin secretion-related genes, enhanced cell viability, inhibited cell apoptosis, reduced malondialdehyde (MDA) levels, suppressed Bax and Nox4 expression, and upregulated Bcl-2 and Sod2. These effects were reversed by Mef2d overexpression. Conversely, inhibition of miR-642a-5p impaired insulin secretion, downregulated Ins1 and Pdx1, reduced cell viability, promoted cell apoptosis, increased MDA levels, promoted Bax and Nox4 expression, and suppressed Bcl-2 and Sod2. These effects were reversed upon Mef2d silencing. In summary, miR-642a-5p protects EndoC-βH1 cells from apoptosis by targeting Mef2d and regulating cellular function and oxidative stress levels.

The physical and/or electrical properties of the peptide-binding pockets of Human Leukocyte Antigen (HLA) class II molecules vary depending on their amino acid sequence, influencing peptide-binding affinity. Previous studies have reported associations between HLA-DRB1 amino acid polymorphisms and susceptibility to Graves' disease (GD) and Hashimoto's disease (HD). We hypothesized that polymorphisms in the peptide-binding region of HLA-DRB1 contribute to disease development and prognosis. This study investigated associations between HLA-DRB1 amino acid polymorphisms and both the development and prognosis of autoimmune thyroid diseases. We analyzed HLA-DRB1 sequences in 136 GD patients, 132 HD patients, and 109 healthy Japanese controls. HLA-DRB1 typing was performed using polymerase chain reaction (PCR) with sequence-specific primers (PCR-SSP) and PCR with sequence-based typing (PCR-SBT). Glu9, His13, and Leu67 were more frequent in intractable GD than in GD remission or controls. Lys9, Phe13, Tyr26, and Val57 were associated with susceptibility to HD, whereas Trp9, Ser37, Phe47, and Asp57 were associated with resistance to HD. Structural modeling revealed that GD-susceptible pockets showed a positive electrostatic potential in pocket 7, while GD-resistant pockets showed a negative electrostatic potential. In pockets 4, 7, and 9, HD-susceptible pockets showed a positive electrostatic potential, whereas HD-resistant pockets showed neutral or negative electrostatic potential. Therefore, specific amino acids in pockets 4, 7, and 9 of HLA-DRB1 are associated with the development and prognosis of GD and HD in the Japanese population.

Pancreatic α-cells secrete glucagon, a hormone that elevates blood glucose levels. In type 2 diabetes, high plasma glucagon levels are associated with hyperglycemia. However, the underlying mechanisms of increasing glucagon secretion remain unclear. We focused on the intrinsic regulatory mechanisms of glucagon secretion in α-cells, in particular sodium-glucose cotransporter 1 (SGLT1), which is involved in the early steps of glucose sensing. We previously demonstrated that SGLT1 is expressed in α-cells and is significantly upregulated in diabetic mice compared with non-diabetic mice. In isolated islets from diabetic mice, SGLT1 knockdown attenuated glucagon hypersecretion, and in αTC1 cells, SGLT-specific substrates promoted glucagon secretion by raising intracellular calcium. On the basis of these findings, we hypothesized that SGLT1 upregulation in α-cells under diabetic conditions impairs the suppression of glucagon secretion, thereby contributing to hyperglycemia. However, a previous study showed that systemic SGLT1 knockout (KO) mice exhibit a higher proportion of α-cells in the islets and atypically high plasma glucagon levels. To clarify the roles of SGLT1 specifically in α-cells, we generated α-cell-specific SGLT1 KO mice using a tamoxifen-inducible Cre-loxP system and analyzed these mice fed a high-fat, high-sucrose diet. The results clearly showed that, inconsistent with the results from the systemic SGLT1 KO mice, SGLT1 deficiency specifically in α-cells did not affect glucagon secretion, glucose tolerance, or α-cell proportion in the islets under diabetic conditions. Thus, though SGLT1 is upregulated in diabetic α-cells, this does not appear to contribute to hyperglucagonemia and impaired glucose tolerance in diabetic mice.

Thyroidectomy is the primary treatment for papillary thyroid carcinoma (PTC) and the type of incision has a significant impact on the short- and long-term recovery of patients. This retrospective study included data from 280 patients with PTC who underwent thyroidectomy. Patients were divided into 2 groups according to incision type: traditional low-collar incision thyroidectomy (TLCIT); and supraclavicular oblique incision thyroidectomy (SOIT). Demographic characteristics, clinical features, and postoperative complications were compared between the 2 groups. Generalized estimating equations were used to analyze the effects of the 2 incision types on short-term (postoperative pain, wound swelling, heat sensation, and neck discomfort) and long-term (quality of life, scar score, anxiety, and depression scores) indicators. In terms of short-term recovery, SOIT significantly reduced postoperative pain, wound swelling, sensation of heat, and neck discomfort. Interaction analysis revealed that SOIT had a significant effect on reducing postoperative pain 1 week after surgery and on reducing heat sensation and neck discomfort 1 month after surgery. In terms of long-term effects, SOIT significantly improved Short-Form-36 and EQ-5D quality of life scores, reduced scar scores, and decreased anxiety and depression scores. Interaction analysis further indicated that SOIT significantly reduced scar scores at 3 and 6 months postoperatively, and significantly reduced anxiety scores at 6 months postoperatively. Compared with the traditional low-collar incision, the supraclavicular oblique incision yielded better short- and long-term prognoses in thyroidectomies for patients diagnosed with PTC.

Unilateral primary aldosteronism (UPA) is characterized by a severe clinical phenotype and can be cured by adrenalectomy. Establishing accurate cutoff values that indicate the need for adrenal venous sampling (AVS) is crucial. Therefore, we aimed to identify appropriate cutoff values for screening and confirmatory testing to predict UPA by LC-MS/MS-equivalent plasma aldosterone concentration (PAC) using chemiluminescent enzyme immunoassay (CLEIA). A retrospective cohort analysis was conducted as part of the JPAS-II study of 443 patients diagnosed with PA using CLEIA-measured PAC, of whom 179 were confirmed by AVS as having UPA. The screening aldosterone-to-renin ratio (sARR), screening PAC, post-captopril challenge test (CCT) aldosterone-to-renin ratio (ARR), post-CCT PAC, and post-saline infusion test (SIT) PAC were significantly higher in patients with UPA than in those with bilateral PA (p < 0.05). Receiver operator characteristic curve analysis yielded an sARR cutoff value of >183 pg/mL/ng/mL/h (sensitivity of 0.95). The post-CCT ARR (AUC: 0.824 ± 0.022) and post-CCT PAC (AUC: 0.845 ± 0.021) were superior predictors of UPA to post-SIT PAC (AUC: 0.782 ± 0.037). When the cutoff values were designed to maximize sensitivity without a significant reduction in specificity, cutoff values for post-CCT ARR of >153 pg/mL/ng/mL/h (sensitivity: 0.85, specificity: 0.55) and for post-SIT PAC of >48 pg/mL (sensitivity: 0.80, specificity: 0.61) were obtained. Importantly, these cutoff values contributed to a diagnosis of UPA when the presence of hypokalemia or adrenal tumor was also considered. In conclusion, LC-MS/MS-equivalent CLEIA-measured cutoff values for post-CCT ARR of >153 pg/mL/ng/mL/h and for post-SIT PAC of >48 pg/mL are considered to indicate AVS. Study registration number: UMIN ID: 000046631.

This report describes the case of a 44-year-old woman without structural heart disease who developed ventricular fibrillation (VF) during preoperative management of multiple pancreatic neuroendocrine tumors (NETs) associated with multiple endocrine neoplasia type 1. She had an insulinoma in the uncinate process and a non-functioning NET in the pancreatic tail. Immediately after intravenous glucose administration for recurrent hypoglycemia, VF occurred. An electrocardiogram obtained immediately before VF onset showed repolarization abnormalities with marked QTc prolongation, terminal T-wave bulging, and U waves. Laboratory testing revealed concomitant mild hypokalemia. No coronary artery disease was detected. The severe repolarization abnormalities improved after resection of the insulinoma. The presumed mechanism was that mild hypokalemia and recurrent hypoglycemia, together with hypoglycemia-induced epinephrine surge and extracellular-to-intracellular potassium shift, synergistically prolonged the action potential duration and induced early afterdepolarizations, which progressed from torsades de pointes to VF. This case highlights that unstable glycemic control in insulinoma can precipitate life-threatening arrhythmias, even in the absence of structural heart disease. Particularly when surgery is delayed, maintaining serum potassium as 4.5-5.0 mmol/L and preventing recurrent hypoglycemia are crucially important. Early recognition and intervention might help reduce arrhythmic risk in such patients.

Vitamin D (VD) status is assessed by measuring serum 25-hydroxyvitamin D (25(OH)D) levels using immunoassays. In December 2024, a Japanese diagnostic laboratory transitioned from chemiluminescent immunoassay (CLIA: LIAISON^® 25 OH Vitamin D Total Assay) to an electrochemiluminescent immunoassay (ECLIA: Elecsys^® Vitamin D Total III assay). Although these methods yield comparable results in adults, it remains unclear whether this applies to children, particularly newborns and infants. This study aims to clarify the impact of transition from CLIA to ECLIA on 25(OH)D levels during early infancy. Serum 25(OH)D levels were measured in 84 infants under three months old (67 under four days old) using both CLIA and ECLIA. Correlation and agreement were assessed using Passing-Bablok regression and Bland-Altman analyses, respectively. The obtained regression equation was applied to 252 age- and sex-matched cases from 2,253 historical controls in the registry to evaluate changes in VD classification. The regression equation was Y_ECLIA = 0.846X_CLIA - 2.281 (τ = 0.53, p < 0.001). Bland-Altman analysis revealed a constant negative bias of -4.89 ± 3.53 ng/mL [-5.66, -4.12] (mean ± standard deviation [95% confidence interval]) for ECLIA versus CLIA. Reclassification revealed an increase in VD deficiency (25(OH)D < 12 ng/mL) from 27.8% to 61.9%, and VD insufficiency (25(OH)D < 20 ng/mL) from 75.4% to 91.7%. The transition from CLIA to ECLIA led to lower measured 25(OH)D levels in newborns and infants and increased VD deficiency and insufficiency diagnoses. Method-specific differences should be considered when evaluating VD status during early infancy, particularly in infants under four days.

Osteoporosis (OP) is a metabolic bone disease characterized by impaired bone formation and excessive resorption. Ferroptosis has been implicated in osteoblast dysfunction. Adipose-derived stem cell exosomes (ADSC-exos) have emerged as promising regenerative therapies. This study investigated whether ADSC-exos alleviate ferroptosis and promote osteogenic differentiation by modulating the miR-215-5p/USP1/PTEN/AKT/GSK3β/NRF2 pathway. Human ADSC-exos were evaluated using transmission electron microscopy, nanoparticle tracking analysis, and western blot. Ferroptosis was induced in MG63 cells using ferric ammonium citrate (FAC). Cell viability, lipid peroxidation, and osteogenic differentiation were evaluated using the CCK-8 assay, C11-BODIPY staining, malondialdehyde quantification, ALP staining, and Alizarin Red S staining. The effects of ADSC-exos on PTEN ubiquitination and AKT/GSK3β/NRF2 pathway activation were assessed using western blot, RT-qPCR, and immunoprecipitation. ADSC-exos significantly improved osteoblast viability, reduced lipid peroxidation, and enhanced osteogenic differentiation in FAC-treated MG63 cells. Dual-luciferase reporter assay identified miR-215-5p as a key exosomal cargo that targets USP1. Mechanistically, ADSC-exos downregulated USP1, leading to PTEN ubiquitination and degradation, thereby activating the AKT/GSK3β/NRF2 signaling pathway. USP1 overexpression reversed the protective effects of ADSC-exos, confirming that miR-215-5p-mediated USP1 inhibition plays a crucial role in regulating ferroptosis and osteogenic differentiation. In conclusion, ADSC-exos diminish ferroptosis and enhance osteogenic differentiation by delivering miR-215-5p, which inhibits USP1, promotes PTEN ubiquitination, and activates the AKT/GSK3β/NRF2 pathway. These findings provide new insights into the mechanisms by which ADSC-exos promote bone repair and highlight their potential as an innovative treatment for OP.