Frontiers in Endocrinology最新文献

Background: The risk of malignancy in thyroid nodules is higher in children than in adults, often necessitating a more aggressive endocrine and surgical approach. However, given that not all solid thyroid nodules are malignant, a more conservative approach may also be appropriate in certain cases.

Objective: This study aims to present an illustrative analysis of the pathological foundations underlying the sonographic appearance of benign, borderline, and malignant thyroid nodules in the pediatric population at a single tertiary thyroid center.

Methods: A total of 47 well-documented pediatric patients referred for thyroid surgery between 2010 and 2023 were analyzed. This retrospective assessment included an examination of demographic data, hormonal profiles, ultrasound findings, and histopathology reports.

Results: Ultrasound and histopathology of thyroid nodules provided insights into subgroup differentiation. Benign nodules like dyshormonogenetic goiter showed solid hypoechoic features on ultrasound and dense fibrosis on histopathology, while thyroid follicular nodular disease exhibited isoechoic nodules with halos, histologically revealing dilated follicles. In borderline tumors, well-differentiated tumor of uncertain malignant potential (WDT-UMP) nodules were hypo/hyperechoic with occasional capsular invasion, resembling papillary thyroid carcinoma (PTC) features histologically. Non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) appeared as well-defined hypoechoic nodules with a hypoechoic rim, with histology showing follicular architecture and PTC nuclear features, but no invasion. Follicular tumor of uncertain malignant potential (FT-UMP) displayed hypo/hyperechoic patterns and indistinct borders, with uncertain capsular invasion and no PTC nuclear features. Malignant lesions showed distinct patterns: PTC as hypoechoic, irregular nodules with mixed vascularization, follicular thyroid carcinoma as large, hyperechoic nodules with invasive features, and poorly differentiated thyroid carcinoma (PDTC) as heterogeneous hypoechoic masses.

Conclusion: Because of the significant overlap in sonographic features among benign, borderline, and certain malignant thyroid lesions in pediatric patients, ultrasonography alone is insufficient for accurate risk stratification. This overlap necessitates referrals for fine-needle aspiration biopsy (FNAB) in children more frequently than in adults. Future studies utilizing artificial intelligence (AI) to predict clinical outcomes in thyroid nodule diagnostics may offer new advancements, particularly given the increasing number of pediatric patients with solid thyroid lesions.

Introduction: Chronic Chagasic Cardiomyopathy (CCC) has an infectious and inflammatory nature. Recent data also suggest an association with altered regulation of glucocorticoid (GC)-mediated circuits failing to control systemic inflammation. However, the involvement of glucocorticoid receptors (GR) and their isoforms have been unexplored.

Materials and methods: The expression of GR-α/β isoforms, 11β-hydroxysteroid dehydrogenase type-1 (11β-HSD1), inflammatory cytokines, and the GC-regulated gene tristetraprolin (TTP) in peripheral blood mononuclear cells (PBMCs) as well as GR immunoreactivity in the myocardium from CCC individuals were evaluated by qPCR and immunohistochemistry respectively. Heart control samples with no evidence of structural heart disease and from ischemic cardiomyopathy patients were included. The presence of inflammatory infiltrates and fibrosis were also recorded.

Results: GR-α was expressed similarly in the PBMCs from Co and CCC individuals, but 11β-HSD1 expression was increased only in CCC, conjointly with enhanced ratios of IL-6/TTP and IFN-γ/TTP. In the inflamed myocardium from CCC patients, positive GR expression correlated with the intensity of the inflammatory infiltrate and cardiac hypertrophy.

Conclusion: The infectious and inflammatory nature of CCC pathology seems strongly connected with the expression of GR in cardiac tissue samples, providing a stimulating background for further studies addressed to elucidate the influence of GR expression and function on CCC pathophysiology and cardiomyocyte hypertrophy.

This article aims to evaluate the effects of growth hormone (GH) therapy in a case with congenital tufting enteropathy (CTE). CTE is a rare autosomal recessive enteropathy that typically presents with persistent diarrhea. In this case, a 13-year-old girl presented with a diagnosis of CTE. Due to short stature, GH therapy was considered. Pre- and post-treatment evaluations were conducted for height, growth rate, and motor skills. As a result, an increase in growth rate and improvement in motor skills were observed with GH therapy. These findings suggest that the potential of GH therapy is to increase growth and improve the quality of life in patients with CTE. Further studies are needed to evaluate the long-term effects of GH therapy and its efficacy in broader patient groups.

Papillary thyroid carcinoma (PTC) is the most common malignancy of the thyroid gland, typically associated with an indolent course and favourable prognosis. However, although rare, PTC can demonstrate aggressive behaviour, including vascular invasion with extension into major vessels. Intraluminal tumor thrombus involving the great veins, such as the internal jugular vein (IJV), is an uncommon but significant complication. We present the case of a 56-year-old male who was referred to our clinic for evaluation of a right-sided anterior neck mass. Neck ultrasonography revealed a 5.5 x 6.5 cm heterogeneous mass within the right thyroid lobe and a suspected intraluminal thrombus in the right internal jugular vein. Fine-needle aspiration biopsy under ultrasound guidance confirmed the diagnosis of papillary thyroid carcinoma. Subsequent preoperative contrast-enhanced computed tomography (CT) of the neck confirmed the presence of an intraluminal tumours thrombus extending into the right IJV. The patient underwent total thyroidectomy, right modified radical neck dissection, and resection of the involved segment of the IJV. Postoperatively, the patient received radioactive iodine (I-131) ablation therapy. At the one-year follow-up, imaging studies indicated a recurrence of the disease. A review of the literature focusing on vascular involvement in PTC and diagnostic methods for tumours thrombus reveals that, while rare, intraluminal tumor thrombus should be considered in patients with PTC, especially when there is evidence of vascular invasion. Early and accurate preoperative diagnosis using Doppler ultrasonography and/or contrast-enhanced CT is critical for optimal surgical planning and improved prognosis. Given the potential for recurrence, vigilant long-term follow-up is recommended.

Objective: The aim of this study was to investigate the bidirectional causal relationship between sex hormones and IBD through a two-sample bidirectional Mendelian randomization (MR) study.

Methods: Based on Genome-Wide Association Study (GWAS) pooled data on SHBG, total testosterone, bioavailable testosterone, estradiol, and IBD in a European population, we performed two-sample bidirectional MR analyses using single nucleotide polymorphisms (SNPs) as instrumental variables. We used inverse variance weighting (IVW), weighted median, weighted mode, and MR-Egger to assess bidirectional causality between sex hormones and IBD.

Results: There was no causal relationship between sex hormones and IBD in women (P > 0.05), and there was a causal and positive correlation between SHBG and testosterone and IBD in men.The OR for SHBG was 1.22 (95% CI: 1.09-1.37, P = 0.0004), and for testosterone was 1.20 (95% CI: 1.04-1.39, P = 0.0145).IBD did not significantly interact with female sex hormones but resulted in a decrease in SHBG (OR = 1.02, 95% CI: 1.00-1.04, P = 0.0195) and testosterone (OR = 1.01, 95% CI: 1.00 -1.02, P = 0.0200) in men.

Conclusion: There is no causal relationship between female sex hormones and IBD, but male SHBG and testosterone are positively correlated with the risk of IBD and IBD promotes elevated levels of SHBG and testosterone in males, suggesting that sex hormones play different roles in IBD patients of different sexes.

Objective: To detect primary factors influencing pregnancy loss(PL) following the transfer of euploid blastocysts?

Design: Retrospective cohort study.

Methods: To identify potential factors influencing PL, we analyzed multiple variables in both the PL group and the live birth group. In order to minimize the impact of confounding factors, various variables were included in a binary logistic regression analysis.

Results: The PL rate after the transfer of euploid embryos is 13.3% (36 cases of PL out of 270 cases of single embryo transfer). Compared to the live birth group, the PL group had lower E2 levels (2376.03 ± 1553.25 vs 3412.88 ± 2116.47, P=0.007), higher LH levels (2.66 ± 2.47 vs 1.96 ± 1.52, P=0.023) on trigger day of fresh cycle, fewer retrieved oocytes (10.08 ± 5.01 vs 12.77 ± 7.20, P=0.044), higher female BMI (23.26 ± 3.27 vs 22.05 ± 2.69, P=0.016), higher proportion of maternal smokers (50% vs 20.51%, P<0.001), and more day 6 blastocyst transfers ((38.89% vs14.53, P=0.001). Logistic regression analysis revealed that higher LH levels(OR=1.304, 95%CI=1.054-1.613, P=0.015), low E2 levels (OR=0.438, 95%CI=0.242-0.794, P=0.007) on trigger day of fresh cycle, maternal smoking(OR=4.574, 95%CI=1.974-10.601, P<0.001), and day 6 blastocyst transfer(OR=4.610, 95%CI=1.907-11.141, P=0.001) appeared to be associated with increased risk of PL following the transfer of euploid embryos.

Conclusions: Maternal smoking, day of blastocyst transferred, estradiol (E2) and Luteinizing hormone (LH) levels on trigger day of corresponding fresh cycle for transferred blastocysts are all associated with PL following transfer of euploid embryos.

Introduction: Sirtuin 1, a class III histone deacetylase, plays a critical role in the pathophysiology of both diabetes mellitus and bone metabolism by promoting osteoblast differentiation and inhibiting osteoclast maturation. However, its exact impact on bone mineral density (BMD) and bone metabolism in type 2 diabetes mellitus (T2DM) remains unclear. This study investigates the relationship between Sirtuin 1 levels, BMD, and bone metabolism in newly diagnosed T2DM patients, specifically examining alterations in Sirtuin 1 levels in those with concomitant osteoporosis or osteopenia.

Methods: A total of 69 newly diagnosed T2DM patients and 82 control subjects with normal glucose tolerance (NGT) were enrolled. Serum Sirtuin 1 levels and bone turnover markers, including osteocalcin (OC), procollagen type 1 N-terminal propeptide (P1NP), and β-C-terminal telopeptide of type I collagen (β-CTX), were measured using enzyme-linked immunosorbent assay (ELISA). BMD was assessed via dual-energy X-ray absorptiometry (DXA). Comparisons of these parameters were made between the T2DM and NGT groups.

Results: T2DM patients were further categorized into a normal BMD group (DMn) and an osteopenia or osteoporosis group (DMo), and differences in Sirtuin 1 levels between these subgroups were analyzed. Risk factors for osteoporosis/osteopenia in T2DM patients were also evaluated. Serum Sirtuin 1 levels were found to be significantly diminished in the T2DM group relative to the control group (P < 0.05), with no significant differences in lumbar spine BMD, OC, 25(OH)D, and β-CTX between groups (P > 0.05). Osteoporosis incidence was higher in T2DM subjects compared to controls (34.8% vs. 18.3%, P = 0.026). Subgroup analysis revealed that SIRT1 levels in T2DM patients with osteoporosis or osteopenia exhibited a significant reduction compared to those with normal BMD (P < 0.05). Logistic regression indicated that Sirtuin 1, age, HDL-C, P1NP, and β-CTX were independent risk factors for osteoporosis in T2DM patients.

Discussion: In conclusion, decreased serum Sirtuin 1 levels are associated with bone turnover markers in T2DM patients and may serve as an independent risk factor and potential biomarker for diagnosing bone metabolism disorders in newly diagnosed T2DM patients.

Molecular therapy uses nucleic acid-based therapeutics agents and becomes a promising alternative for disease conditions unresponsive to traditional pharmaceutical approaches. Antisense oligonucleotides (ASOs) and small interfering RNAs (siRNAs) are two well-known strategies used to modulate gene expression. RNA-targeted therapy can precisely modulate the function of target RNA with minimal off-target effects and can be rationally designed based on sequence data. ASOs and siRNA-based drugs have unique capabilities for using in target groups of patients or can be tailored as patient-customized N-of-1 therapeutic approach. Antisense therapy can be utilized not only for the treatment of monogenic diseases but also holds significant promise for addressing polygenic and complex diseases by targeting key genes and molecular pathways involved in disease pathogenesis. In the context of endocrine disorders, molecular therapy is particularly effective in modulating pathogenic mechanisms such as defective insulin signaling, beta-cell dysfunction and hormonal imbalances. Furthermore, siRNA and ASOs have the ability to downregulate overactive signaling pathways that contribute to complex, non-monogenic endocrine disorders, thereby addressing these conditions at their molecular origin. ASOs are also being studied worldwide as unique candidates for developing therapies for N-of-1 therapies. The sequence-specific ASOs binding provides exceptional accuracy in N-of-1 approaches, when the oligonucleotide can be targeted to a patient's exact mutant sequence. In this review we focus on diseases of the endocrine system and discuss potential RNA-targeted therapeutic opportunities in diabetes mellitus, including monogenic beta cell diabetes, and obesity, including syndrome obesity and monogenic obesity, as well as in non-monogenic or complex endocrine disorders. We also provide an overview of currently developed and available antisense molecules, and describe potentials of antisense-based therapeutics for the treatment of rare and «ultrarare» endocrine diseases.