Endocrine journal最新文献

Managing thyroid nodules diagnosed cytologically as follicular neoplasms (FN) is challenging for patients and clinicians. Gene panel testing was recently introduced to determine the management strategy for FN; however, it is unavailable in Japan. In this study, we assessed FN management. This study included 2,144 FNs from 2,067 patients diagnosed between 2012 and 2018. Of these, 952 (44.5%) tumors underwent active surveillance, and 1,188 (55.6%) underwent immediate surgery (IS). Tumors of young patients (<55 years), male patients, and patients with serum thyroglobulin (Tg) ≥500 ng/mL, ultrasound diagnoses as FN or malignancy, large tumors (>4 cm), non-oxyphilic cytology, and cytological findings favoring malignancy and multiplicity underwent IS more frequently. Of the 1,412 tumors that underwent surgery, 279 (19.8%) and 1,133 (80.2%) were pathologically diagnosed as malignant and benign tumors or low-risk neoplasms, respectively. High Tg levels, non-benign ultrasound findings, cytological findings favoring malignancy, non-oncocytic cytology, and large tumor size were related to malignant pathology; however, tumor enlargement was not. The former three were independent predictors of malignancy in the multivariate logistic analysis. After assigning scores of 2 and 1 for cytological findings favoring malignancy and others, respectively, a receiver operating characteristic curve analysis indicated a score of 3 as the optimal cutoff for predicting malignant diagnosis; however, the area under the curve remained low, at 0.642. Accurately predicting the malignant pathology of FNs is challenging, and inducing gene panel testing will be helpful for managing FN tumors. Our scoring system would also be useful in estimating the risk of malignancy.

There are differences in the responsiveness to differential diagnostic tests for Cushing's disease (CD), corticotroph tumor size, and the somatostatin receptor (SSTR) 5 expression in corticotroph tumors between CD patients. The differences in SSTR5 expression are particularly significant for identifying therapeutic targets for CD. However, prospective predictors of SSTR5 expression remain unclear. Thus, our objective was to elucidate the relationships among these clinical characteristics of CD, including SSTR5 expression. In 27 hospitalized patients with CD at Osaka University Hospital, Osaka, Japan, associations between corticotroph tumor diameter, the response of ACTH and cortisol to differential diagnostic tests for CD (CRH, desmopressin [DDAVP], and high-dose dexamethasone suppression test [HDDST]), the ACTH/cortisol index, and the SSTR5 immunoreactive score were retrospectively investigated. The response to differential diagnostic tests, ACTH/cortisol index, tumor diameter, and SSTR5 expression were significantly related (vs. tumor diameter [CRH: r = -0.54; DDAVP: r = -0.54; HDDST r = -0.67; ACTH/cortisol index: r = 0.76; SSTR5: r = -0.61], vs. CRH [DDAVP: r = 0.63, HDDST: r = 0.72, ACTH/cortisol index: r = -0.45; SSTR5: r = 0.56], vs. DDAVP [HDDST: r = 0.66; ACTH/cortisol index: r = -0.46; SSTR5: r = 0.76], vs. HDDST [ACTH/cortisol index: r = -0.62; SSTR5: r = 0.77], ACTH/cortisol index vs. SSTR5: r = -0.67). The areas under the receiver operating characteristic curve for the prediction of high SSTR5 expression via the CRH test, DDAVP test, HDDST, ACTH/cortisol index, and tumor diameter were 0.79, 0.87, 0.80, 0.71, and 0.71, respectively. Tests for differential diagnosis of CD, the ACTH/cortisol index, and the corticotroph tumor diameter have the potential for identifying SSTR5 expression in corticotroph tumors. These parameters may reflect the biological characteristics of corticotroph tumors.

Circular RNAs (circRNAs) play an important role in regulating inflammation and oxidative stress during the pathogenesis of metabolic dysfunction-associated steatotic liver disease (MASLD); however, the underlying mechanism is unclear. This study aimed to determine the role of mmu_circ_0009303 in MASLD. We used a bioinformatics approach to identify potential targets and established an in vitro model of MASLD. Oil red O staining, cell transfection and dual-luciferase reporter assay were used to determine the role of mmu_circ_0009303. The results indicated that the mmu_circ_0009303 expression was significantly increased in the MASLD model both in vitro and in vivo and was associated with oxidative stress levels and inflammation. Moreover, bioinformatics analyses revealed that miRNA-182-5p and Foxo3 are targets of mmu_circ_0009303 and miRNA-182-5p, respectively. In the in vitro MASLD model, mmu_circ_0009303 promoted fat deposition in NCTC1469 cells, which was induced by free fatty acid (FFA) through the regulation of miRNA-182-5p/Foxo3. The expression of miRNA-182-5p and Forkhead box O3 (Foxo3) was associated with mmu_circ_0009303 expression in the liver of mice with MASLD, which was induced by a high-fat diet. Furthermore, mmu_circ_0009303 may be involved in regulating the expression of lipid metabolism-related regulatory proteins, such as CPT1A, SLC27A4, ACBD3, SREBP1, FAS, PPARα, and PPARγ. Taken together, mmu_circ_0009303 promotes oxidative stress, inflammation, and excessive fat accumulation in NCTC1469 cells induced by FFA through the regulation of miRNA-182-5p/Foxo3 and lipid metabolism-related regulatory proteins. These findings provide a potential target for the treatment of MASLD.

We and other investigators reported that mild TSH suppression with levothyroxine (LT₄) was needed to achieve normal free triiodothyronine (FT₃) levels and metabolic euthyroid state in athyreotic patients. Consequently, management methods based on thyroid tissue volume have been implemented for patients receiving LT₄ at the Kuma Hospital. This retrospective study examined the composition of the thyroid hormone measurement items (serum-free thyroxine [FT₄], FT₃, and FT₄ + FT₃) in patients receiving LT₄ monotherapy. According to the etiology of hypothyroidism, 36% of the 25,523 patients included in this study underwent total thyroidectomy (TT). Thirteen percent and 14% had undergone ¹³¹I treatment for hyperthyroidism (RIT) and partial thyroidectomy (PT), respectively. Moreover, 37% of patients had received non-invasive treatment (NIT). The proportion of patients who underwent only FT₃ measurements was higher (TT, 93%; RIT, 61%) in the first two groups, whereas the proportion of patients who underwent only FT₄ measurements was higher (PT, 50%; NIT, 65%) in the remaining two groups. Only FT₃ measurements were performed in 58% of patients. Only FT₄ measurements were performed in 34% of patients. The serum TSH levels were suppressed in nearly half of the patients (46%). Thus, FT₃ was the major thyroid hormone measured in patients receiving LT₄ treatment, and the serum TSH levels were suppressed in nearly half of the patients. This may be attributed to the management guidelines at our hospital, a specialized facility for thyroid disease, wherein half of the patients present are athyreotic or have atrophic thyroid glands after TT or RIT.

It has been reported that Graves' disease (GD) sometimes improves spontaneously during pregnancy, although exacerbation of GD during postpartum period or relapse of hyperthyroidism caused by GD might occur. This study aimed to investigate the incidence of postpartum diagnosis of thyroid eye disease (TED) in relation to thyroid dysfunction. This retrospective cross-sectional study enrolled 11,104 deliveries from the patients with GD between January 2004 and August 2022. Within the 12-month postpartum period, 72 patients (0.65%) were diagnosed with TED. The thyroid function of the 72 patients comprised 9 remission, 13 continued antithyroid medicine, and 50 thyroid dysfunction; 30 newly diagnosed GD, 1 hypothyroidism, and 19 relapse/recurrence of GD. In the 49 patients with thyroid dysfunction, no difference was observed in the median values of thyroid-stimulating hormone (TSH) receptor antibody (TRAb) and TSH receptor stimulating antibody between the TED diagnosis and the development of hyperthyroidism. However, when the patients were classified into the newly developed GD and relapse/recurrence of GD groups, the difference became significant and the TRAb level was high in the newly developed GD (16.1 vs. 5.0 IU/L, p < 0.0001, and 15.0 vs. 6.0 IU/L, p = 0.0003). Thyroid dysfunction preceded TED diagnosis in more than half of the patients and the median time for each event was 6.5 vs. 8.1 months. The active phase TED was observed in 8 of the 72 patients. Of the 72 patients newly diagnosed with TED in postpartum, two-thirds were accompanied by thyroid dysfunction and 8 of them were in active phase.

This study aimed to focus on the role of radiologists in the diagnosis and management of adrenal lesions, particularly primary aldosteronism (PA) and secondary hypertension. As hypertension affects more than one-third of the population in Japan, identifying secondary causes such as PA and adrenal lesions is crucial. Establishing a radiological differential diagnosis of adrenal lesions using advanced imaging techniques, such as computed tomography and magnetic resonance imaging, is crucial. Knowledge of the imaging findings of various benign and malignant adrenal lesions, such as adrenocortical adenomas, cortisol-producing lesions, pheochromocytomas, adrenocortical carcinoma, malignant lymphoma, and metastatic tumors, is necessary. Adrenal venous sampling (AVS) plays a crucial role in accurately localizing aldosterone hypersecretion in PA, especially when imaging fails to provide a clear diagnosis. This paper details the technical aspects of AVS, emphasizing catheterization techniques, anatomical considerations, and the importance of preprocedural imaging for successful sampling. Furthermore, we explore segmental adrenal venous sampling (SAVS), a more refined technique that samples specific adrenal tributary veins, offering enhanced diagnostic accuracy, particularly for microadenomas or challenging cases that may be missed with conventional AVS. The methodology for performing SAVS, along with the interpretation criteria for successful sampling and lateralization, is also outlined. Furthermore, radiologists have initiated treatments for unilateral PA, such as radiofrequency ablation, and play an integral role in the management of adrenal lesions. Collaborative approaches across clinical departments are required to enhance patient management in medical care involving the adrenal gland.

Cushing's syndrome, a clinical condition characterized by hypercortisolemia, exhibits distinct clinical signs and is associated with cyclic cortisol secretion in some patients. The clinical presentation of cyclic Cushing's syndrome can be ambiguous and its diagnosis is often challenging. We experienced a 72-year-old woman with cyclic ACTH-dependent Cushing's syndrome caused by a pulmonary carcinoid tumor. Diagnosis was challenging because of the extended trough periods, and the responsible lesion was initially unidentified. A subsequent follow-up computed tomography revealed a pulmonary lesion, and ectopic ACTH secretion from this lesion was confirmed by pulmonary artery sampling. Despite the short peak secretion period of ACTH (approximately one week), immunostaining of the surgically removed tumor confirmed ACTH positivity. Interestingly, stored plasma chromogranin A levels were elevated during both peak and trough periods. The experience in evaluating this patient prompted us to investigate the potential use of plasma chromogranin A as a diagnostic marker of ACTH-dependent Cushing's syndrome. A retrospective study was conducted to determine the efficacy of plasma chromogranin A in three patients with ectopic ACTH syndrome (EAS), including the present case, and six patients with Cushing's disease (CD) who visited our hospital between 2018 and 2021. Notably, plasma chromogranin A levels were higher in patients with EAS than in those with CD. Additionally, a chromogranin A level in the present case during the trough phase was lower than that in the peak phase, and was similar to those in CD patients. The measurement of plasma chromogranin A levels could aid in differentiating EAS from CD.

The effectiveness of a hybrid closed-loop (HCL) system in improving glycemic control is unclear in Japanese individuals. Therefore, we assessed the effect impact of the MiniMed 770G HCL system on glycemic control in this population. This prospective, single-center, 24-week observational study (registration number: UMIN000047394) enrolled 23 individuals with type 1 diabetes mellitus using the Medtronic MiniMed 640G system. The primary endpoint was the improvement in time in the range of 70-180 mg/dL after transitioning to the MiniMed 770G HCL system. We observed an increase in time in range (from 64.1 [55.8-69.5] to 70.9 [67.1-74.4] %, interquartile range 25-75%, p < 0.001) and a decrease in glycated hemoglobin level (from 7.4 [7.0-7.9] to 7.1 [6.8-7.4] %, p = 0.003). There was a significant reduction in time above the range (181-250 mg/dL: 25.8 [20.9-28.6] to 19.5 [17.1-22.1] %, p < 0.001; >251 mg/dL: 8.7 [4.0-13.0] to 4.7 [3.6-9.1] %, p < 0.001). Time below the range remained unchanged (54-69 mg/dL: 1.8 [0.4-2.4] to 2.1 [0.4-3.9] %, p = 0.24; <54 mg/dL: 0.2 [0.0-1.0] to 0.5 [0.1-1.3] %, p = 0.14). In a subgroup of 12 patients with a high HCL implementation rate, the basal insulin infusion decreased immediately after mealtime insulin administration and increased after approximately 120 minutes. The ratings from questionnaires assessing treatment burden, satisfaction, and quality of life remained unchanged. The MiniMed 770G HCL system improved glycemic control and optimized insulin delivery, particularly in patients with high implementation rates.

Significant overlap in the epidemiology and coinfection of chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) has been identified, which accelerates the development of severe liver cirrhosis and hepatocellular carcinoma worldwide. Interferon-α (IFN-α), a cytokine with antiviral properties, exerts profound physiological effects on innate immunity by regulating interferon-stimulated genes (ISGs) within cells. However, the underlying mechanism of IFN-α in hepatic inflammation remains to be fully elucidated. Here, we utilized LO2 cells treated with the recombinant IFN-α protein and conducted microRNA (miR) sequencing. MiR-122-3p and miR-122-5p_R+1 were the most enriched miRNAs involved in the pathogenesis of IFN-α-induced inflammatory responses and were significantly downregulated by IFN-α treatment. Furthermore, we identified interferon induced protein with tetratricopeptide repeats 1 (IFIT1) as a potential target gene of miR-122. IFN-α markedly increased the expression of proinflammatory cytokines and fibrogenic genes but decreased the mRNA expression of ISGs. Additionally, IFN-α significantly activated the NF-κB p-p65, MAPK p-p38, and Jak/STAT pathways to trigger inflammation. Importantly, supplementation with a miR-122 mimic significantly alleviated IFN-α-induced inflammation and induced IFIT1 expression in LO2 cells. Conversely, the suppression of miR-122 markedly exacerbated the inflammatory response triggered by IFN-α. Furthermore, silencing IFIT1 via an siRNA elicited an inflammatory response, whereas IFIT1 overexpression ameliorated hepatic inflammation and fibrosis in a manner comparable to that induced by IFN-α treatment. Taken together, our findings suggest that miR-122 and its target, IFIT1, reciprocally regulate the inflammatory response associated with IFN through the Jak/STAT pathway.

We previously reported that a high HbA1c level 3 months before vitrectomy for vitreous hemorrhage or a large preoperative decrease in the HbA1c level over 3 months tended to increase the risk of rebleeding in diabetic retinopathy patients evaluated between 2010 and 2014. Here, we aimed to confirm these results with an extended study period and an increased number of operated eyes. This study included 121 diabetic patients who were admitted to Osaka University Hospital between 2010 and 2019 and who underwent vitrectomy for vitreous hemorrhage. Binomial logistic regression analysis was performed with the presence of postoperative bleeding as the outcome. The present study showed that the duration of the operation was associated with rebleeding (odds ratio = 1.02, p = 0.0016). A high HbA1c level just before vitrectomy tended to be associated with the bleeding (odds ratio = 1.27, p = 0.05), while preoperative HbA1c changes were not associated with rebleeding. The results of this study suggest that a high preoperative HbA1c level just before vitrectomy, not a decrease in HbA1c levels, in addition to the duration of the operation may increase the risk of postoperative bleeding after vitrectomy in diabetic retinopathy patients.