Expert Review of Endocrinology & Metabolism最新文献

Introduction: Many patients struggle to control glucose without side effects. Due to their immunomodulatory and regenerative properties, mesenchymal stem cells (MSCs) might treat Diabetes Mellitus (DM). The authors employed this meta-analysis to evaluate the efficacy and safety of umbilical cord MSCs (UCMSCs) for DM management.

Methods: The PubMed, Cochrane, WOS, Embase, and Scopus databases were searched for randomized controlled trials (RCTs) investigating the effects of UCMSCs on DM (Types 1, 2) till January 2024. Patient demographics, interventions, and outcomes, including glycated hemoglobin (HbA1c%), C-peptide levels, and insulin requirements, were extracted. A comprehensive meta-analysis software was used.

Results: Eight CTs of 334 patients (172 experimental and 162 controls) were included. UMSCs treatment substantially lowered HbA1c levels (MD = -1.06, 95% CI [-1.27, -0.85], p < 0.00001) with consistent outcomes (i² = 0%, p = 0.43). Fasting C-peptide levels were heterogeneous but favored placebo (MD = 0.35, 95% CI [0.15, 0.56], p = 0.0007). In T1D patients, daily insulin requirements decreased considerably (MD = -0.24, 95% CI [-0.29, -0.18], p < 0.00001), with heterogeneity addressed by sensitivity analysis.

Conclusion: UMSCs therapy reduced HbA1c and insulin requirements, and increased C-peptide levels. Multicenter clinical trials are required to confirm the long-term efficacy and safety of UMSC therapy.

Background: Hypothyroidism (HT) is associated with different comorbidities comprising increased arterial stiffness and decreased flow-mediated dilatation. The exact pathological mechanism of endothelial activation and dysfunction (ED) in HT remains unknown. We conducted a systematic review and meta-analyses to provide an overview of the pathogenesis of ED in HT.

Methods: The literature search was done in February 2024 for studies analyzing traditional and novel circulating biomarkers of ED in patients with HT, including cytokines and chemokines. Random-effect models were used except when no heterogeneity was found. Protocol was registered under the number PROSPERO CRD42024540560.

Results: 25 macromolecules and 66 studies were entered into analyses. HT was associated with increased levels of E-selectin, soluble intercellular adhesion molecule-1, osteoprotegerin, and oxidized-LDL (p < 0.02). Results were not conclusive for endothelin-1. Interleukin (IL)-6, IL-12 and CXCL10 were higher in HT (p < 0.05). Subjects with overt HT may display a proinflammatory tendency with increased levels of IL-6 and interferon-γ, and decreased levels of TGF-β (p < 0.05).

Conclusions: The data presented and discussed here highlights the association between HT and soluble biomarkers of ED. Inflammatory mediators released by activated T-cells and macrophages may aggravate local and systemic inflammation, which arouses more inflammation, forming a vicious circle leading to ED.

Background: Sodium-glucose cotransporter-2 inhibitors (SGLT2is) are known for their cardiovascular benefits, but their impact on serum uric acid levels is not well understood. This study evaluates the hypouricemic effects of SGLT2is and their potential cardiovascular implications.

Methods: A network meta-analysis was performed, including 56 studies (16,788 participants) contributing data to the meta-analysis. The effects of SGLT2is on serum uric acid levels were analyzed with weighted mean difference (WMD) as the effect estimate. Bootstrapped meta-analysis, trial sequential analysis, and meta-regression were utilized to validate the findings and assess the influence of covariates. The certainty of the evidence was evaluated.

Results: The analysis revealed that SGLT2is significantly reduced serum uric acid levels (WMD: -40.01 μmol/L). Specific reductions were noted for ertugliflozin (-42.17 μmol/L), dapagliflozin (-40.28 μmol/L), empagliflozin (-46.75 μmol/L), canagliflozin (-35.55 μmol/L), and ipragliflozin (-10.48 μmol/L). Both low and high doses were effective, with empagliflozin showing the highest efficacy. No significant associations were found with covariates. The evidence was of moderate certainty.

Conclusion: SGLT2is significantly lower serum uric acid levels, with empagliflozin being the most effective. These findings suggest a potential role in reducing cardiovascular risk. Further research is needed to explore their effects on hyperuricemic patients, and monitoring serum uric acid levels is recommended.

Objectives: Chronic kidney disease has a global morbidity burden of >10%, with diabetes being a major cause.  Nutrition therapy is vital in managing both chronic conditions, yet CKD dietary guidelines contradict healthy eating advice, and can result in major psychological and social burdens. Few studies investigate the patient's experience of being placed on such a restrictive diet. This auto/biographical review provides a unique perspective and aims to assist practitioners as they guide patients on 'what is left to eat.'

Method: An auto/biographical approach, supported by a comprehensive literature review using data from MEDLINE, Embase, and PsychoINFO, was used to answer the question: 'What are the diet and lifestyle challenges of following a restrictive Type 1 Diabetes/CKD dialysis diet?'

Results: Restrictive dietary and fluid regimes have a major effect on patients' illness beliefs, anxieties, and independence. This is discussed through five themes: Food is belonging; Normal is a Fallacy; Your numbers define you; A disease disguised as a virtue and Meeting the Elephant: ESKD diagnosis and the burden of dialysis.

Conclusion: Dietary intervention is crucial in the management of T1D and ESKD, but equally important is to consider the implications of strict dietary regimes without sufficient evidence, guidance, and support.

Introduction: Endocrine paraneoplastic syndromes (ePNS) are caused by malignant cells that induce hormonal alterations unrelated to the tissue of origin of the neoplasm. The aim of this manuscript is to review the pathophysiology, diagnosis, and treatment of endocrine paraneoplastic syndromes (ePNS).

Areas covered: We searched the PubMed/Medline, Embase, and Scielo databases, including 96 articles. The pathogenesis of ePNS involves mutations that activate hormonal genes. Hypercalcemia, the most common ePNS, is marker of poor prognosis in most cases. The syndrome of inappropriate antidiuresis causes euvolemic hyponatremia. Ectopic Cushing's syndrome is commonly associated with lung cancer. Paraneoplastic acromegaly is very rare and is associated with pancreatic and lung tumors. Paraneoplastic hypoglycemia usually requires surgical treatment. Other endocrine paraneoplastic syndromes include ectopic secretion of hormones such as calcitonin, renin, vasoactive intestinal polypeptide, fibroblast growth factor 23, paraneoplastic autoimmune hypophysitis, and others.

Expert opinion: In addition to the local manifestations and metastasis of neoplasms, some secrete bioactive substances causing PNS. Recognizing and treating PNS early improves clinical outcomes. Larger-scale studies and clinical trials are needed to enhance their management and prognosis.

Introduction: Classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency (CAH) is a rare genetic condition characterized by cortisol deficiency and excess adrenal androgens. CAH treatment is a lifelong balancing act between the need to reduce excess androgens, typically with supraphysiologic glucocorticoid (GC) doses, and concerns about potentially serious GC-related adverse events. Tradeoffs between the consequences of excess androgens versus GCs must be constantly reassessed throughout each patient's lifetime, based on current clinical needs and treatment goals. Adding to this burden are limited treatment options and the need for new CAH medications.

Areas covered: This narrative review describes the current challenges of CAH treatment, the potential of new non-GC therapies to reduce excess androgens and thereby allow for lower GC doses, and the potential implications of decreasing GC doses to a more physiologic range (i.e. sufficient to replace missing cortisol, but without the need to reduce androgens).

Expert opinion: Even with non-GC therapies, patients' needs will continue to shift throughout their lifetimes. Treatment will therefore always require joint decision-making between physicians and patients. However, over the lifetimes of patients with CAH, any reduction in GC daily dose may have a large cumulative impact in decreasing the GC-related burden of this disease.

Introduction: Incidence rates for cancer among adolescent and young adults (AYA) have increased 30% since 1970. Declines in mortality underscore the importance of discussing fertility preservation (FP) options prior to receiving gonadotoxic treatments. National guidelines outline FP options including oocyte (OC), embryo (EC), and ovarian tissue cryopreservation (OTC) for female AYA patients. Significant progress has led to changes in FP practices, initially limited to EC. Subsequently, OC was deemed non-experimental in 2013, followed by OTC in 2020. Despite these advancements and guideline recommendations, the availability and utilization of FP services vary.

Areas covered: Rapid review methodologies were employed to classify trends in female AYAs utilization of FP cryopreservation options following guideline updates. FP options reviewed include OC, EC, and OTC. Additionally, the review examined if aspects of the decision-making process relevant to FP were present.

Expert opinion: Ten articles met inclusion criteria. Results suggest that the declassification of OTC has not necessarily increased its use and OC and EC appear to be most frequently used. The factors associated with decision making appear to have remained consistent with financial constraints having the most impact, followed by partner status and concerns about recurrence.

Introduction: Adrenocortical tumors (ACTs) are frequently encountered in clinical practice. They vary in clinical and biological characteristics from nonfunctional to life threatening hormone excess, from benign to highly aggressive malignant tumors. Most ACTs appear to be benign and nonfunctioning. It has been controversial how these apparently benign and nonfunctioning tumors should be monitored. Over the past few decades, significant advances have been made in understanding the regulation of growth and tumorigenesis in adrenocortical cells. Defining the molecular pathomechanisms in inherited tumor syndromes led to the expansion of research to sporadic ACTs. Distinct molecular signatures have been identified in sporadic ACTs and a potential genomic classification of ACT has been proposed.

Areas covered: In this review, we discuss the various adrenocortical pathologies associated with hereditary syndromes with special focus on their molecular pathomechanisms, the understanding of which is important in the era of precision medicine.

Expert opinion: Identifying the molecular pathomechanisms of the adrenocortical tumorigenesis in inherited syndromes has led to the understanding of the alterations in different signaling pathways that help explain the wide variations in the biology and behavior of ACTs.

Introduction: Acromegaly is due in almost all cases to a GH-secreting pituitary tumor. GH and IGF-1 excesses lead to its multi-system clinical manifestations and comorbidities. Acromegaly is under-diagnosed and typically presents with advanced disease. When early or mild, clinical recognition and biochemical confirmation are especially challenging. Individualized treatment may optimize patient outcome.

Areas covered: This review covers challenges to diagnosing acromegaly and reviews therapies for acromegaly with a focus on those aspects that can be individualized.

Expert opinion: The first step in diagnosing acromegaly is recognizing it clinically. To improve this, increase awareness and education of the general population and healthcare professionals about the acromegaly phenotype is needed. Once suspected clinically, IGF-1 measurement is the initial step in making the biochemical diagnosis. GH may be < 1.0 µg/L after oral glucose suppression in early/mild cases. GH and IGF-1 should be considered in concert. Providers should be aware of conditions that can alter GH and IGF-1 levels and each assay's performance. An individualized treatment approach is best employed. Surgery is preferred as initial treatment and medical therapy as initial adjuvant therapy. In individualizing therapy, the advantages and disadvantages of each option and predictors of response to them should be considered.

Background: Hypothyroidism (HT) is associated with numerous well-characterized comorbidities and established biomarkers for subclinical atherosclerosis which may lead to an elevated risk of cardiovascular disease; however, the precise molecular mechanism underlying these pathological features remains elusive. Increased levels of adipokines may have adverse effects on multiple atherosclerotic risk factors in HT. Different studies have evaluated the association between HT and adipokines with conflicting results.

Methods: A systematic review and meta-analyses were conducted to provide an overview of adipokine levels in HT. The last literature search was done in February 2024 for studies analyzing traditional and novel circulating adipokines levels (excluding resistin and irisin) in patients with HT. The standard mean differences and 95% confidence intervals (CI) were calculated using random-effect models except if no heterogeneity was found.

Results: HT was not associated with leptin, adiponectin, omentin-1, visfatin, or apelin levels; however, increased retinol-binding protein 4 (RPB4) levels were found in both overall and subclinical HT (p-values = 0.0002 and 0.004 respectively).

Conclusion: While pooled analysis suggested a role for RBP4 in hypothyroid patients, associations do not imply cause-effect relationships, and therefore the potential clinical implications of these findings should await further mechanistic studies.

Registration: The protocol has been registered in the Prospective Register of Systematic Reviews (PROSPERO) under the identification number CRD42024537717.