Therapeutic Advances in Endocrinology and Metabolism最新文献

Background: β-Thalassemia major patients are frequently vulnerable to endocrine dysfunction due to iron overload from chronic transfusions. This impairs growth, thyroid function, glucose metabolism, and bone health, ultimately compromising quality of life and long-term outcomes.

Objectives: This study investigates the prevalence and pattern of endocrine dysfunction in β-thalassemia major patients receiving iron-chelation therapy and explores associations with iron overload markers.

Methods: This case-control study involved 60 β-thalassemia major patients and 20 age- and sex-matched controls. Hormonal and biochemical parameters were measured and linked to iron status.

Results: Among β-thalassemia major patients (7-35 years), 73.3% (n = 44/60) were splenectomized; 36 received deferiprone, 19 deferasirox, and 5 deferoxamine. Concerning iron status, both splenectomized and non-splenectomized patients had significantly higher iron and ferritin and lower haptoglobin levels compared to controls. No significant differences were found in hepcidin or hemopexin levels. Regarding thyroid function, about 15% (n = 9/60) of β-thalassemia major patients had subclinical primary hypothyroidism. Ferritin negatively correlated with free thyroxine (r = -0.330, p = 0.010). As for glycemic status, 51.7% (n = 31/60) of β-thalassemia patients had glycated hemoglobin (HbA1c) ⩾6.5% and 38.3% (n = 23/60) showed impaired fasting blood sugar. With respect to metabolic markers, splenectomized patients had higher fibroblast growth factor 21 (FGF21) than the control (p = 0.042), while no significant group differences were found in galectin-1 or sortilin. Ferritin correlated significantly and positively with FGF21 levels (r = 0.353, p = 0.006). With respect to calcium-parathyroid-vitamin D axis, hypoparathyroidism and hyperparathyroidism were each found in 11.7% (n = 7/60) of β-thalassemia patients. Vitamin D levels were significantly lower in the β-thalassemia groups compared to controls (p = 0.0001) with 71.7% (n = 43/60) deficient despite 43.3% (n = 26/60) receiving supplements. Non-splenectomized patients had higher Procollagen Type I C-Peptide, a bone formation marker, compared to controls.

Conclusion: Endocrine disturbances are common in β-thalassemia major despite chelation therapy. Incorporating endocrine assessment into routine practice is essential for early detection and management.

Background: Polycystic ovary syndrome (PCOS) is a chronic, heterogeneous and prevalent endocrine-metabolic condition.

Objectives: This study aims to synthesize the available evidence on the comparison of lipid accumulation product (LAP) and visceral adiposity index (VAI) in women with and without PCOS.

Design: Systematic review and meta-analysis.

Data sources and methods: A systematic search was executed across five electronic databases. Continuous variables were assessed using the standardized mean difference (SMD) and its 95% confidence interval (CI).

Results: A total of 46 studies were included (n = 12,442). PCOS patients have higher values of LAP (n = 10,658; SMD: 0.65; 95% CI: 0.47-0.83, p < 0.05; I ² = 93.65%) and VAI (n = 7930; SMD: 0.53; 95% CI: 0.21-0.85; p < 0.05; I ² = 97.24%) compared to those without the syndrome.

Conclusion: Women with PCOS show significantly higher VAI and LAP values than those without this syndrome.

Key takeaways Children living with growth hormone deficiency (GHD) are usually treated with daily injections of a growth hormone called somatropin to help them grow normally.Somatrogon is a growth hormone treatment that only needs to be injected once a week.A worldwide clinical study involving 224 children living with GHD found that weekly somatrogon injections were as effective (efficacy) and as safe as daily somatropin injections. Efficacy refers to how well a medicine works in a clinical study.This analysis focused specifically on the 45 children of Asian ethnicity from this worldwide study.Asian children who received somatrogon grew as fast as those who received somatropin.Both treatment groups had IGF-I levels that were in the normal range over 12 months of treatment. IGF-I is a hormone that works together with growth hormone to make children grow taller.Both treatments were just as safe. Most of the side effects children had during treatment were mild or moderate, and none of the children had to stop their treatment because of side effects. A side effect is a medical problem (expected or unexpected) that occurs during the study that may or may not be caused by the treatment being taken.The results from this analysis of 45 Asian children agreed with the results for the whole study group, which had 224 children.Asian children living with GHD may have better growth with weekly somatrogon than with daily somatropin because they may be less likely to miss injections if they only need to inject the treatment once a week instead of every day. The purpose of this plain language summary is to help you to understand the findings from recent research. Somatrogon and somatropin are approved to treat growth hormone deficiency (the condition under study that is discussed in this summary). Approval varies by country; please check with your local healthcare provider for more details.This summary reports the results of a single study. The results of this study may differ from those of other studies. Health professionals should make treatment decisions based on all available evidence and not on the results of a single study.

Thyroid eye disease (TED) is an autoimmune disorder that can threaten vision loss. In 90% cases, it is related to Graves' disease, and in 10% cases, it occurs with euthyroidism or with chronic autoimmune thyroiditis. It is the leading cause of orbital pathology in adults. The TED treatment remains challenging for clinicians, particularly in moderate-to-severe or sight-threatening forms of the disease. One-third of TED patients experience a relapse despite the corticosteroids as a first-line treatment. Some patients show poor response or even no response to the treatment. There are many adverse effects associated with chronic use of intravenous methylprednisolone (IVMP). There is a need for new, efficient therapeutic methods, such as immunomodulating drugs like mycophenolate mofetil (MMF). This paper describes the role and potential efficiency of MMF application in TED by its direct action on TED pathogenic mechanisms. The introduction of MMF in the second-line treatment helps decrease the level of clinical symptoms and the risk of chronic complications, while causing only a small number of adverse events. Nevertheless, it should be noted that there are no unified guidelines available for consolidating treatment focused on maintaining remission after the first dose of IVMP. Moreover, clinical knowledge on the use of MMF application in TED is still limited, and further research is needed. Nonetheless, the available evidence is promising and MMF may play a vital role in future therapeutic strategies.

Background: The proteome is vital for discovering therapeutic targets. We conducted a proteome-wide Mendelian randomization (MR) analysis to identify potential Type 2 Diabetes (T2D) biomarkers and therapeutic targets.

Methods: Data from deCODE Genetics (4907 proteins in 35,559 individuals) and the FinnGen study (65,085 T2D cases, 335,112 controls) were analyzed using inverse-variance weighted MR. Robustness was ensured through reverse MR and external cohort validation. Bayesian weighted MR further corroborated results. Additional analyses included protein-protein interaction (PPI) networks, pathway enrichment, druggability evaluation, and single-cell expression analysis.

Results: Proteome-wide MR analysis identified 233 proteins associated with T2D risk. After adjusting for false discovery rate at 0.05, 15 proteins remained significant. Further reverse MR and validation using external cohorts confirmed that TPST2 and CHRDL1 (Chordin-like 1) were identified as the most promising potential therapeutic targets. For the 233 proteins associated with T2D risk, we conducted Gene Ontology enrichment and KEGG pathway enrichment analyses. These causal proteins were found to be involved in regulating inflammation and oxidative stress, atherosclerosis progression, and intracellular signaling mechanisms. A PPI network identified the top 10 hub genes: IGF1R, PPARGC1A, PDGFRB, ADIPOQ, IL15, BDNF, MET, SCARB2, KDR, and VWF. Drug enrichment analysis revealed that IGF1R, PPARGC1A, ADIPOQ, MET, and von Willebrand Factor (VWF) are targeted by metformin. Notably, sunitinib targets IGF1R, PDGFRB, MET, KDR, and VWF. Single-cell RNA sequencing confirmed these proteins' expression.

Conclusion: This study identifies novel T2D therapeutic targets and highlights sunitinib as a promising candidate. Future work should validate these findings and assess sunitinib's efficacy in clinical trials.

Background: Ketoconazole is effective for treating Cushing's syndrome (CS) but its use is limited by the risk of hepatotoxicity. Fluconazole, with similar antifungal properties, is being investigated as a potentially safer alternative for managing CS. This study aims to evaluate the efficacy and safety of fluconazole in patients with CS.

Methods: This retrospective study evaluated a total of 22 patients with CS, including 12 with Cushing's disease (CD), 3 with adrenal Cushing's syndrome (ACS), and 7 with ectopic Adrenocorticotropic hormone (ACTH) syndrome. Fluconazole was administered orally, ranging from 112.5 to 450 mg daily, with the duration varying from 2 weeks to over 5 years. The efficacy of fluconazole was assessed by changes in 24-hour urinary free cortisol (24-h UFC) levels. Additionally, hepatic safety was assessed by monitoring changes in alanine aminotransferase (ALT) levels.

Results: Following fluconazole treatment, 24-h UFC levels significantly decreased from 717.6 ± 1219.4 to 184.1 ± 171.8 µg/day (p = 0.035). ALT levels showed an increase from 38.5 ± 28.4 to 56.5 ± 47.8 U/L, though this change was not statistically significant (p = 0.090). ALT levels exceeding the upper limit of normal range (ULN) were observed in 12 patients (54.5%), with only 4 patients (18.2%) showing ALT levels more than three times the ULN. Out of 10 patients who received treatment for over 1 year, 5 patients (50.0%) experienced a recurrence, with 24-h UFC levels more than 1.5 times the ULN within 3 to 12 months after fluconazole treatment.

Conclusion: Fluconazole effectively reduces hypercortisolism in patients with CS without significant liver injury, suggesting it as a viable therapeutic option for CS. While some cases have shown treatment escape, more studies are required to confirm the long-term efficacy.

Combination therapy is commonly used to achieve better glycemic control, but Medication Regimen Complexity (MRC) can pose challenges for treatment adherence and outcomes. While some studies have explored the impact of MRC on patient outcomes, evidence remains inconclusive. Therefore, we aimed to explore the impact of MRC on diabetes management. This rapid review systematically identified studies on diabetes patients with complex medication regimens and their clinical and nonclinical outcomes. A comprehensive search was conducted across four databases (PubMed, Web of Science, Scopus, and Cochrane) from January 1967 to September 2023. Study quality was assessed using the Joanna Briggs Institute tool, while the overall evidence certainty was evaluated using the GRADE approach. Thirteen studies met the inclusion criteria, of which 11 focused on type 2 diabetes. The primary outcomes assessed were glycemic control and medication adherence. While findings on glycemic control conflicted among 12 studies, most indicated that higher MRC was associated with poor glycemic control. Four studies reported improved adherence with lower MRC. Additionally, high MRC was associated with greater medication burden and diabetes-related distress, though its impact on body weight remained inconclusive. Conversely, regimen simplification was linked to improved quality of life and increased treatment satisfaction. In conclusion, the findings suggest that MRC may contribute to various challenges in diabetes management. Simplifying regimens and standardizing outcome assessments are essential for optimizing treatment strategies in both practice and policy.

Polycystic ovary syndrome (PCOS) is a prevalent disorder in the modern world, affecting around 6%-20% of females of childbearing age. Hormonal and metabolic symptoms vary over time but often arise throughout puberty. Treatment includes lifestyle interventions as a first line of treatment. In certain cases, specific medications may be considered. However, there is a growing interest in using Glucagon-like Peptide-1 Receptor Agonists (GLP-1RAs) in PCOS due to their efficacy in weight loss, insulin resistance, and heart health. Aside from the metabolic role of GLP-1RAs, which aids in the relief of PCOS symptoms, there is also the possibility of direct involvement in reproductive health in PCOS, including its role in the hypothalamic-gonadal axis, menstrual irregularity, ovulation, ovarian morphology, anti-inflammatory properties, and fertility. This review discusses the latest data on GLP-1RAs' metabolic and reproductive health benefits in PCOS. Moreover, this article covers pharmaceutical interactions and synergistic effects of drugs, including metformin and other medications, with GLP-1RAs. It also conveys an overview of recent clinical trials utilizing GLP-1RAs to treat PCOS.