International Journal of Endocrinology最新文献

The increasing global prevalence of obesity, exacerbated by factors such as high-fat diets and reduced physical activity, poses a substantial risk for lifestyle-related diseases, particularly in postmenopausal women. Premenopausal women initially have a lower incidence of cardiovascular disease than men, but this risk increases after menopause, highlighting menopause as a critical risk factor. Our previous study showed that the extract of Cordyceps militaris (CM) modulates androgen metabolism partially by inhibiting the gene expression of catabolizing enzyme 5α-reductase. In this study, we investigated the effect of CM on estrogen deficiency-induced obesity in ovariectomized (OVX) mice fed a 0.1% CM diet (estimated human equivalent dose: 7.5 g/day) for 52 days. OVX mice had increased body weight, which subsequently decreased with CM, without altering daily food intake. Regarding visceral fat, CM suppressed OVX-induced adipogenic markers (Pparg, Cebpa, Cebpb, Fabp4, and Adipoq) and protein levels of C/EBPβ, PPARγ, and p-AKT. CM effectively reversed the OVX-induced reduction in the levels of adipose Cyp17a1 and Hsd17b1, key enzymes involved in steroid hormone biosynthesis, increased the cellular senescence markers p21 and p53, and decreased Lmnb1 expression. CM reduced the expression of oxidative stress markers HO-1, NRF2, and 4-HNE. Moreover, CM increased uterine weight and serum superoxide dismutase in 17β-estradiol-treated OVX rats. These findings suggested that CM, particularly its component cordycepin, holds promise as a natural agent for mitigating weight gain, particularly in the context of postmenopausal obesity.

Background: This study aimed to evaluate the medium-term outcomes of radiofrequency ablation (RFA) for thyroid nodules with cytology of follicular neoplasm and low standard uptake value (SUV) in a positron emission tomography (PET/CT) study.

Methods: Between January 2018 and January 2021, 40 patients diagnosed with follicular neoplasm underwent ultrasound, fine needle aspiration (FNA), or core needle biopsy (CNB) before RFA. PET/CT scans were performed in 34 patients before treatment. RFA, conducted under local anesthesia with an 18-gauge internally cooled electrode and RF generator, was followed by evaluations of nodule volume modifications via ultrasonography, changes in symptomatic and cosmetic scores, and assessment of complications during and after the procedure. Six to twelve months post-RFA, 33 patients received FNA for reassessment.

Results: Significant volume reductions were observed during follow-up, comparing values before RFA and at 6 months post-RFA (7.31 ± 12.83 cm³, p < 0.001). The mean volume reduction ratios at 6 months and final follow-up were 71.5% and 81.45%, respectively. The mean follow-up time was 2.38 ± 0.9 years. Complications included vocal cord palsy and ptosis in one patient each, both recovering after RFA. No post-RFA hypothyroidism was reported. Positive correlation was found between pre-RFA thyroglobulin levels and PET/CT SUVmax values (p = 0.001).

Conclusions: RFA is a safe and effective treatment for patients with low-risk follicular neoplasm (SUVmax value < 5) in medium-term follow-up. For patients who are either ineligible for or prefer to avoid surgery, RFA presents a feasible alternative treatment option.

Although the World Health Organization has clearly defined silent pituitary adenomas (SPAs) and functional adenomas (non-SPAs), the detailed biological mechanisms remain unclear. This study conducted a comprehensive analysis of clinical, genomic, transcriptomic, and proteomic differences between SPA and non-SPA. The results revealed significant differences in mutational profiles, with a notably higher mutation rate of the TCHH gene in non-SPA samples. Transcriptomic and proteomic analyses identified distinct expression patterns, highlighting the enrichment of the oxidative phosphorylation pathway and other related Gene Ontology terms in SPA samples. To validate these findings, 11 additional pituitary adenoma samples were analyzed, confirming the critical role of oxidative phosphorylation in SPA. Activation of oxidative phosphorylation altered the hormone secretion, and the electron transfer chain inhibitor restored this in both human and rat pituitary adenoma cell lines. Furthermore, a protein-protein interaction network was constructed, revealing key regulatory differences between SPA and non-SPA, and identifying MAPK1, MAPK3, IDH1, and PKM as key hubs in the network. MAPK1 and PKM knockdown significantly reduced the hormone secretion and apoptosis of both cell lines. These findings suggest that the oxidative phosphorylation pathway plays a pivotal role in the secretory functions of pituitary adenomas. This study offers new insights into the biological mechanisms underlying pituitary adenomas and provides valuable directions for future research, emphasizing the importance of oxidative phosphorylation in tumor behavior and potential therapeutic targets.

Introduction: Observational studies have established the connection between a decrease in bone mineral density (BMD) and an increased susceptibility to age-related macular degeneration (AMD). However, the cause-and-effect link of this correlation remains uncertain. This study employed Mendelian randomization (MR) methods to examine the causality between BMDs and AMD.

Materials and methods: The GEnetic Factors for OSteoporosis (GEFOS) Consortium, UK Biobank, and FinnGen Biobank offered summary statistics for BMD and AMD. We adopted an array of quality control procedures to screen for eligible instrumental single nucleotide polymorphisms (SNPs). The inverse variance weighting (IVW) algorithm was the most trustworthy approach in MR analyses. Furthermore, we employed additional analytical methods such as MR-Egger and weighted median (WM) for confirming the soundness of the present MR outcomes.

Results: The findings indicated that genetically predicted total body BMD (TB-BMD, IVW: OR = 0.772, 95% CI = 0.642-0.928, p = 0.006), lumbar spine BMD (LS-BMD, IVW: OR = 0.739, 95% CI = 0.583-0.937, p = 0.013), femoral neck (FN-BMD, WM: OR = 0.626, 95% CI = 0.432-0.906, p = 0.013), and TB-BMD (age over 60, MR-Egger, OR = 0.383, 95% CI = 0.163-0.902, p = 0.041) were associated with lower odds of wet AMD. No significant causal relationship can be found between other BMDs and Wet-AMD, or between BMDs and Dry-AMD.

Conclusion: Our MR analysis supported the causal correlation between genetically predicted BMD and Wet-AMD. As to Dry-AMD, it was not causally related to BMD. Our study complemented the evidence from previous observational surveys and emphasized the extraordinary importance of monitoring BMD for preventing and treating AMD.

Background: Growth hormone deficiency (GHD) and idiopathic short stature (ISS) are common causes of short stature in children. In China, PEGylated recombinant human GH (PEG-rhGH, Jintrolong) has been approved for the treatment of both conditions. This study aimed to evaluate the efficacy and safety of PEG-rhGH in children diagnosed with GHD or ISS and to compare clinical outcomes between the two groups.

Methods: This real-world study included 91 treatment-naïve children with short stature at Kunming Children's Hospital between 2020 and 2021. Participants were categorized into the GHD group (n = 39) and the ISS group (n = 52) based on etiological diagnosis. All subjects received weekly subcutaneous PEG-rhGH injections at an initial dose of 0.20 mg/kg/wk and were followed for 18 months. Growth-related parameters were assessed throughout the study.

Results: PEG-rhGH treatment significantly improved height standard deviation score (Ht SDS) in both groups. In the GHD group, Ht SDS increased from -3.14 (-4.06, -2.02) at baseline to -1.53 (-1.98, -1.08) at Month 18 (p < 0.001), with a mean ΔHt SDS of 1.69 ± 0.98. The ISS group demonstrated an improvement from -3.33 ± 1.23 at baseline to -1.33 (-2.03, -0.92) at 18 months (p < 0.001), with a mean ΔHt SDS of 1.77 ± 1.06. No significant differences were identified between the groups regarding Ht SDS, ΔHt SDS, Insulin-Like Growth Factor 1 SDS (IGF-1 SDS), ΔIGF-1 SDS, or height velocity (all p > 0.05). Thyroid function markers (T3, T4, FT3, FT4) and fasting plasma glucose levels remained within normal ranges throughout treatment, with no significant intergroup differences (all p > 0.05). No serious adverse events were observed.

Conclusion: PEG-rhGH effectively promoted height gain in children with GHD and ISS, with similar therapeutic efficacy in both groups. However, children with ISS required a longer duration to achieve catch-up growth to normal height, potentially due to reduced GH sensitivity and a need for higher dosing. PEG-rhGH was well tolerated, with a favorable safety profile in both cohorts.

Background: Thyroid eye disease (TED) is an autoimmune inflammatory condition linked to thyroid dysfunction, which can result in disfigurement and potential vision loss. Recently, immunomodulatory therapies such as rituximab have demonstrated potential benefit in managing TED. However, the optimal dosing and timing of rituximab administration remain uncertain.

Objective: This study aimed to assess the efficacy and safety of early, low-dose rituximab therapy in patients with mild to moderate TED.

Methods: Eight untreated patients with mild to moderate TED were enrolled in the study. Weekly rituximab infusions at a low dose (100 mg weekly for 4 weeks) were administered, followed by a 16-week follow-up period. Thyroid function, thyrotropin receptor antibody (TRAb) levels, ophthalmic examinations, and adverse effects were evaluated at each visit. Additionally, orbital MRI, radionuclide orbital imaging, and clinical activity score (CAS) were performed before treatment and at the final follow-up.

Results: The mean follow-up duration was 16 weeks for the eight patients. Detailed baseline patient characteristics were recorded. CD3-CD20 levels decreased significantly after rituximab treatment, compared to baseline levels. TRAb levels also showed a statistically significant decline during the treatment period compared to the baseline levels (p = 0.012). The CAS showed a significant decrease from baseline to 16 weeks post-treatment (p = 0.027). There were no significant differences in orbital MRI imaging before and after treatment yet. Nuclear medicine orbital imaging assessment indicated an improvement trend in orbital inflammatory activity among patients. Few adverse effects were observed during the therapy.

Conclusions: The preliminary exploratory study suggested that the early low-dose rituximab treatment (100 mg weekly for 4 weeks) may be associated with immunological changes (TRAb reduction, B-cell depletion) in patients with early progressive, mild-to-moderate TED. These hypothesis-generating findings require validation in randomized, placebo-controlled trials with adequate sample sizes and longer follow-up.

Background: Diabetic nephropathy (DN), a severe complication of Type 2 diabetes mellitus (T2DM), is the primary reason of end-stage kidney disease (ESKD) and is closely associated with an elevated cardiovascular risk. While miR-484 has been implicated in diabetes, its specific role in DN remains to be elucidated.

Objective: To analyze miR-484 expression in DN and its association with clinicopathological parameters, as well as to elucidate its molecular regulation of Sodium-glucose cotransporter protein 2 (SGLT2), providing evidence for the early diagnosis of DN and miR-484/SGLT2-targeted therapies.

Method: Clinical data were collected from healthy controls and T2DM patients. Total RNA was extracted for real-time PCR analysis. ROC curves, Pearson correlation, and logistic regression evaluated their clinical value. High glucose (30 mM)-treated HK-2 cell models and transfections with miR-484 mimics/inhibitors assessed cell proliferation, oxidative stress (MDA/SOD), inflammation (TNF-α/IL-6/IL-1β) using cell counting kit-8 (CCK-8) and ELISA, and SGLT2 targeting via dual-luciferase assays.

Results: DN patients exhibited lower serum miR-484 levels compared to controls and T2DM, negatively correlating with HbA1c and ACR, and positively correlating with eGFR. miR-484 was an independent risk factor for DN demonstrating high diagnostic sensitivity. High glucose downregulated miR-484 in HK-2 cells, inducing proliferation inhibition, oxidative stress, and inflammation; all of which were reversed by miR-484 mimics. Dual-luciferase assays confirmed that miR-484 directly targets the 3'UTR of SGLT2 to suppress its expression.

Conclusion: The miR-484/SGLT2 axis is key to DN pathogenesis. miR-484 serum levels reflect DN severity and serve as a potential biomarker. Targeting SGLT2 via miR-484 offers new therapeutic strategies for DN by mitigating glucose reabsorption, oxidative stress, and inflammation.

Purposes: To treat large benign thyroid nodules (BTNs), radiofrequency ablation (RFA) and transarterial embolization (TAE) combined with RFA are both used. This study aimed to compare the effectiveness of both treatments.

Methods: Nineteen subjects with 20 BTNs received two sessions of RFA, while eight patients with 10 BTNs underwent TAE followed by RFA in a single medical center. Propensity score matching (PSM) was utilized to control for inherent potential biases by matching similar characteristics between the two groups.

Results: Prior to treatment, a larger median nodule volume was observed in the TAE with the RFA group (150.75 ± 202.61 mL) compared to that of the double-session RFA group (81.44 ± 58.00 mL). The volume reduction ratio (VRR) was found to be 74.60 ± 14.49% in the TAE/RFA group and 83.93 ± 12.70% in the double-session RFA group. To account for follow-up duration, we calculated the variation of VRR (ΔVRR, %) divided by the follow-up time in days. The TAE with the RFA group showed a median reduction of 0.17 ± 0.05%/day, while the double-session RFA group showed 0.13 ± 0.05%/day, with a p value of 0.040. The TAE with the RFA group exhibited a relatively higher daily VRR after treatment. Additionally, a higher nodular volume reduction was observed in the TAE with the RFA group due to the larger pretreatment nodular volume.

Conclusions: Our findings suggest that TAE combined with RFA may be a more effective treatment option for large BTNs compared to two sessions of RFA alone, thus providing an alternative treatment approach.

Background: Familial Mediterranean fever (FMF) is a hereditary autoinflammatory disease frequently observed in populations along the Eastern Mediterranean coast, characterized by recurrent fever, abdominal pain, and joint inflammation. The disease results from mutations in the MEFV gene, which plays a critical role in regulating IL-1β secretion. Mutations in pyrin lead to uncontrolled IL-1β release, driving FMF's inflammatory symptoms. IL-1 inhibitors, such as anakinra, rilonacept, and canakinumab, have been introduced as adjunctive treatments. This paper aims to investigate the effects of IL-1 inhibitors on pituitary functions in FMF patients.

Methods: The study was conducted at Sivas Cumhuriyet University Hospital and included patients who had been using IL-1 inhibitors for at least 6 months. The control group consisted of patients receiving colchicine treatment only. Blood samples were collected to measure various pituitary and endocrine hormones. Patients with conditions like corticosteroid use, cancer, or hemodialysis were excluded. Hormonal levels were analyzed, and cortisol-deficient patients underwent a Synacthen test.

Results: No significant differences were found in TSH, ACTH, cortisol, LH, estradiol, IGF-1, or PRL levels between the groups. However, differences were noted in FSH, total testosterone, and GH levels, with higher FSH and GH in the control group and higher testosterone in the experimental group.

Conclusions: Although IL-1 plays a role in hormone secretion pathways, further studies are needed to better understand the effect of IL-1 antagonists on pituitary function, as no significant adrenal or pituitary insufficiencies were observed.

[This corrects the article DOI: 10.1155/ije/5878361.].