Expert Review of Endocrinology & Metabolism最新文献

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.

Background: The rapid rise of non-communicable diseases, particularly type 2 diabetes mellitus (T2DM), poses a significant global public health challenge, with South Asia experiencing an increasingly severe burden. This study aimed to analyse historical trends of T2DM across South Asia from 1990 to 2021 and forecast incidence through 2031.

Research design and methods: We carried out analysis based on the data from the 2021 Global burden of disease study. Joinpoint regression was used to identify significant changes in trends over time, and ARIMA models were applied to forecast incidence rates.

Results: Between 1990 and 2021, the average annual percentage change (AAPC) of age-standardized prevalence rates and incidence rates increased by 2.15 and 1.72 respectively. The age-standardized mortality rate rose more slowly, at 1.05 AAPC, with females experiencing a slightly higher AAPC than males. ARIMA forecasts suggest that by 2031, T2DM incidence rates will continue to rise significantly across all South Asian countries.

Conclusions: This study highlights the need for public health policies focused on preventing obesity, promoting physical activity, and improving healthcare access. It also calls for addressing regional disparities in T2DM prevalence and mortality to better allocate resources and prioritize policies to combat the diabetes epidemic inSouth Asia.

Introduction: The global incidence of thyroid cancer (TC) has increased in the last decades. While improvements in diagnosis may contribute, overdiagnosis is also a possibility. This review focuses on the epidemiology, risk factors, and immune microenvironment associated with differentiated TC (DTC).

Areas covered: A search was conducted in Scielo, Scopus, and EMBASE databases, involving 72 articles. TC is the most common endocrine neoplasm, with DTC form being predominant. Its incidence has globally risen, particularly among women aged over 45. Endogenous risk factors for DTC include genetic disorders, race, age, female gender, obesity, and type 2 diabetes mellitus. Environmental risks involve ionizing radiation, whether through therapeutic treatment or environmental contamination from nuclear accidents, iodine deficiency, endocrine disruptors, residence in volcanic areas, environmental pollution, and stress. The use of anti-obesity medications remains controversial. The tumor's immune microenvironment is the histological space where tumor cells interact with host cells, crucial for understanding aggressiveness. Immunotherapy emerges as a promising intervention.

Expert opinion: Recent advances in DTC management offer transformative potential, requiring collaborative efforts for implementation. Emerging areas like precision medicine, molecular profiling, and immunotherapy present exciting prospects for future exploration, shaping the next era of diagnostic and therapeutic strategies in thyroid cancer research.

Introduction: Achondroplasia is a heritable disorder of the skeleton that affects approximately 300,000 individuals worldwide. Until recently, treatment for this condition has been purely symptomatic. Efficacious treatment options for children are now approved or are in clinical trials.

Areas covered: This review discusses key advances in the therapeutic management of children with achondroplasia, including vosoritide, the first approved drug, and other emerging precision therapies. These include navepegritide, a long-acting form of C-type natriuretic peptide, and infigratinib, a tyrosine kinase receptor inhibitor, summarizing trial outcomes to date.

Expert opinion: The advent of the first approved precision therapy for achondroplasia in vosoritide has been a paradigm shifting advance for children affected by this condition. In addition to changing their natural growth history, it is hoped that it will decrease their medical complications and enhance functionality. These new treatment options highlight the importance of prompt prenatal identification and subsequent testing of a suspected fetus with achondroplasia and counseling of families. It is hoped that, in the near future, families will have the option to consider a range of effective targeted therapies that best suit their child with achondroplasia, starting from birth should they choose.

Objective: Time in Tight Range (TITR), defined as the percentage of time within the glucose range of 70 to 140 mg/dL, is anticipated to be challenging to maintain without causing hypoglycemia, especially in individuals with type 1 diabetes (T1D). This study aimed to investigate the TITR target value in individuals with T1D on multiple daily injections (MDI).

Methods: The study included 101 individuals with T1D on MDI aged 15 to 75 who were hospitalized at Jikei University School of Medicine from September 2006 to November 2013 to conduct Continuous Glucose Monitoring (CGM). The cutoff values of TITR for predicting the attainment of GMI < 7.0%, and TBR < 4% were determined using Receiver Operating Characteristic (ROC) curves.

Results: The TITR cutoff value was calculated to be 41% (sensitivity 81%, specificity 88%) and 40% (54%,72%) for predicting GMI < 7.0% and TBR < 4%.

Conclusions: In individuals with T1D on MDI without devices capable of preventing hypoglycemia, it is recommended to target TITR at 40% to address the risk of increased hypoglycemia sufficiently.

Introduction: Incretin-based therapies have emerged as effective treatments for type 2 diabetes (T2D) and obesity. However, not all patients achieve optimal outcomes with existing treatments, highlighting the need for more effective solutions.

Areas covered: We present a comprehensive evaluation of Tirzepatide (TZP), a novel dual glucose-dependent insulinotropic polypeptide/glucagon-like peptide-1 (GIP/GLP-1) receptor agonist, for managing obesity and T2D. We conducted a systematic search of Cochrane, PubMed, Scopus, and Web of Science databases from inception to April 2024. The focus of the review is on the development and therapeutic potential of TZP, with detailed exploration on pharmacodynamics, pharmacokinetics, clinical efficacy, and safety. Furthermore, it reviews TZP's impacts on glycemic control, weight management, and its potential cardiovascular (CV) benefits.

Expert opinion: TZP represents a significant advancement in the dual-targeted approach to treating T2D and obesity. Its unique mechanism of action offers superior efficacy in reducing glycemic levels and body weight compared to existing therapies. New data suggesting improvements in CV outcomes indicate that TZP could set a new standard in the treatment paradigm. While long-term data on efficacy and safety are still forthcoming, current evidence positions TZP as a promising option for patients who have not reached their therapeutic goals with existing treatments.

Background: According to previous reports, very high percentages of individuals in Saudi Arabia are undiagnosed for type 2 diabetes mellitus (T2DM). Despite conducting several screening and awareness campaigns, these efforts lacked full accessibility and consumed extensive human and material resources. Thus, developing machine learning (ML) models could enhance the population-based screening process. The study aims to compare a newly developed ML model's outcomes with the validated American Diabetes Association's (ADA) risk assessment regarding predicting people with high risk for T2DM.

Research design and methods: Patients' age, gender, and risk factors that were obtained from the National Health Information Center's dataset were used to build and train the ML model. To evaluate the developed ML model, an external validation study was conducted in three primary health care centers. A random sample (N = 3400) was selected from the non-diabetic individuals.

Results: The results showed the plotted data of sensitivity/100-specificity represented in the Receiver Operating Characteristic (ROC) curve with an AROC value of 0.803, 95% CI: 0.779-0.826.

Conclusions: The current study reveals a new ML model proposed for population-level classification that can be an adequate tool for identifying those at high risk of T2DM or who already have T2DM but have not been diagnosed.