Endocrine journal最新文献

Children with Down syndrome (DS) have a high prevalence of thyroid dysfunction; however, age-related changes in thyroid hormone profiles remain unclear. We investigated the age-related changes in thyroid function in children with DS. We retrospectively analyzed the thyroid function test results of 762 patients with DS aged 3-14 years without known thyroid disease, and compared them with those of 764 age-matched controls with idiopathic short stature. Serum thyroid-stimulating hormone (TSH), free triiodothyronine (FT3), and free thyroxine (FT4) levels and the FT3/FT4 ratio were compared between patients with DS with/without congenital heart disease (CHD) and gastrointestinal malformations. In each age group, the log-transformed TSH distribution exhibited similar standard deviation and kurtosis, but showed consistently higher mean values in patients with DS than in controls. Mean FT3 levels were slightly lower in the DS group, except at ages 11-12 years. Mean FT4 levels were slightly lower in the DS group after 9 years of age. The mean FT3/FT4 ratio was lower in the DS group at ages 3-8 years but normalized after 9 years of age. Patients with DS and CHD had higher TSH levels than those without CHD after 11 years of age, whereas FT3, FT4, and the FT3/FT4 ratio showed no significant differences. A rightward shift in serum TSH distribution was observed in patients with DS without thyroid disease, suggesting that TSH levels are generally high in patients with DS. These variations highlight the need for personalized management of thyroid function in patients with DS.

Proptosis, a key clinical manifestation of thyroid eye disease (TED), serves as an objective indicator of this disease's severity. Although body compositions and the prevalences of myopia and tobacco smoking have changed in Japan, no updated reference exophthalmometry values have been reported since the 1980s. To determine normal values for exophthalmometry in a contemporary Japanese general population and identify factors associated with exophthalmos in people with/without Graves' disease (GD), we conducted a cross-sectional study using a general population cohort and a GD cohort, from October 2023 to October 2024. We used a Hertel exophthalmometer to measure the exophthalmometry values in both cohorts, and we obtained clinical data from medical records and/or questionnaires. Eighty-six patients with GD and 502 general population controls were included. The GD cohort's mean exophthalmometry value (17.0 ± 3.3 mm) was significantly higher than the general population (15.6 ± 2.8 mm), which was larger than the upper limit of the normal references (15.0 mm) defined by the Japan Thyroid Association based on a 1970s' report. Multiple regression analyses revealed that age, BMI, myopia, and dyslipidemia remained independently associated with exophthalmometry values in the general population cohort, whereas height, smoking, and anti-thyroglobulin autoantibody negativity were associated with the GD cohort's exophthalmometry values. Our findings suggest a possible increase in mean exophthalmometry values in the contemporary Japanese general population. They highlight the need to update normative exophthalmometry values, accounting for body-composition including metabolic profiles and myopia, which could lead to accurate assessments of proptosis severity and appropriate therapeutic strategies for patients with TED. Clinical Trials Registry (CTR) registration: UMIN-CTR no. 000051753.

The biological clock enables organisms to align their intrinsic rhythms with daily environmental cycles thereby maintaining homeostasis and imparting resilience against metabolic derangements. Endocrine hormones and neural networks are key mediators of temporal coordination across remote tissues. The potential impact of maternal-fetal synchronization during pregnancy has been extensively studied, as alterations in maternal circadian rhythms because of mistimed food intake, sleep disturbances, and jet-lagged conditions appear to influence organ development, maturation, and behavior, leading to enduring metabolic consequences in offspring. In support, the in utero environment and maternal nutritional state influence long-term health outcomes, as proposed in the developmental origins of health and disease. While the molecular mechanisms connecting maternal circadian disruption to sustained alterations in progeny are still under investigation, endocrine hormones and metabolites may engage in temporal communication between the mother and fetus and induce epigenetic changes. This review outlines recent discoveries on maternal circadian rhythms as an external input for the fetus and discusses future strategies to strengthen metabolic fitness in subsequent generations.

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.

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.

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.

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.