Endocrinology and Metabolism最新文献

Gestational diabetes mellitus (GDM) affects over 10% of all pregnancies, both in Korea and worldwide. GDM not only increases the risk of adverse pregnancy outcomes such as preeclampsia, preterm birth, macrosomia, neonatal hypoglycemia, and shoulder dystocia, but it also significantly increases the risk of developing postpartum type 2 diabetes mellitus and cardiovascular disease in the mother. Additionally, GDM is linked to a higher risk of childhood obesity and diabetes in offspring, as well as neurodevelopmental disorders, including autistic spectrum disorder. This review offers a comprehensive summary of clinical epidemiological studies concerning maternal and fetal complications and explores mechanistic investigations that reveal the underlying pathophysiology.

Background: Laryngotracheal invasion occurs in a subset of patients with well-differentiated thyroid cancer (WDTC) and is associated with a poor prognosis. We aimed to analyze patterns and predictors/outcomes related to this high-risk manifestation.

Methods: This population-based analysis utilized the Surveillance, Epidemiology, and End Results (SEER) registry (2000 to 2015) to identify WDTC patients. Temporal trends and geographic variation in invasion rates were assessed. Logistic regression and propensity score matching were employed to identify predictors of secondary malignancy, mortality, and treatment impact on overall and thyroid cancer (TC)-specific survival.

Results: Of 131,721 WDTC patients, 1,662 (1.3%) had tracheal invasion and 976 (0.7%) had laryngeal invasion at diagnosis. Tracheal and laryngeal invasion rates declined from 3.7%-0.7% and 1.5%-0.6%, respectively, from 2000 to 2015. Compared to 98,835 noninvasive cases, patients with laryngotracheal invasion were older and more often male, Asian, and Hispanic (all P<0.001). This group had larger tumors with higher rates of nodal (N1: 61.8% vs. 15.1%) and distant metastases (M1: 9.3% vs. 0.4%). Age ≥55 years (hazard ratio [HR], 1.19; P=0.004) and metastases (HR, 1.75; P<0.001) increased TC-specific mortality, whereas the converse pattern was found for Asian race (HR, 0.63; P=0.002) and surgery (HR, 0.35; P<0.001). In rigorously matched groups to control confounding, adding radioactive iodine to surgery reduced mortality by 30% (P<0.001). However, external beam radiation and systemic therapy did not improve survival over surgery alone.

Conclusion: Laryngotracheal invasion is present in 0.7% to 1.3% of cases, conferring over double the mortality risk. Radioactive iodine with surgery improves outcomes in this aggressive WDTC subset.

Background: Data on the carcinogenic potential of tirzepatide from randomized controlled trials (RCTs) are limited. Furthermore, no meta-analysis has included all relevant RCTs to assess the cancer risk associated with tirzepatide.

Methods: RCTs involving patients receiving tirzepatide in the intervention arm and either a placebo or any active comparator in the control arm were searched through electronic databases. The primary outcome was the overall risk of any cancer, and secondary outcomes were the risks of specific types of cancer in the tirzepatide versus the control groups.

Results: Thirteen RCTs with 13,761 participants were analyzed. Over 26 to 72 weeks, the tirzepatide and pooled control groups had identical risks of any cancer (risk ratio, 0.78; 95% confidence interval, 0.53 to 1.16; P=0.22). The two groups had comparable cancer risks in patients with and without diabetes. In subgroup analyses, the risks were also similar in the tirzepatide versus placebo, insulin, and glucagon-like peptide-1 receptor agonist groups. The overall cancer risk was also comparable for different doses of tirzepatide compared to the control groups; only a 10-mg tirzepatide dose had a lower risk of any cancer than placebo. Furthermore, compared to the control groups (pooled or separately), tirzepatide did not increase the risk of any specific cancer types. Despite greater increments in serum calcitonin with 10- and 15-mg tirzepatide doses than with placebo, the included RCTs reported no cases of papillary thyroid carcinoma.

Conclusion: Tirzepatide use in RCTs over 26 to 72 weeks did not increase overall or specific cancer risk.

Background: The associations between thyroid cancer and skeletal outcomes have not been thoroughly investigated. We aimed to investigate the risk of osteoporotic fractures in patients with thyroid cancer compared to that in a matched control group.

Methods: This retrospective cohort study included 2,514 patients with thyroid cancer and 75,420 matched controls from the Korean National Health Insurance Service-National Sample Cohort (NHIS-NSC, 2006-2019). The rates of osteoporotic fractures were analyzed, and associations with the levothyroxine dose were evaluated.

Results: Patients with thyroid cancer had a significantly lower risk of fracture than did the control group (hazard ratio [HR], 0.81; 95% confidence interval [CI], 0.69 to 0.94; P=0.006). Patients diagnosed with thyroid cancer after the age of 50 years (older cancer group) had a significantly lower risk of fracture than did those in the control group (HR, 0.72; 95% CI, 0.6 to 0.85; P<0.001), especially those diagnosed with spinal fractures (HR, 0.66; 95% CI, 0.51 to 0.85; P=0.001). Patients in the older cancer group started osteoporosis treatment earlier than did those in the control group (65.5±7.5 years vs. 67.3±7.6 years, P<0.001). Additionally, a lower dose of levothyroxine was associated with a reduced risk of fractures.

Conclusion: In the clinical setting, the risk of fracture in women diagnosed with thyroid cancer after the age of 50 years was lower than that in the control group, which was caused by more proactive osteoporosis treatment in postmenopausal women with thyroid cancer.

In East Asians, type 2 diabetes mellitus (T2DM) is primarily characterized by significant defects in insulin secretion and comparatively low insulin resistance. Recently, the prevalence of T2DM has rapidly increased in East Asian countries, including Korea, occurring concurrently with rising obesity rates. This trend has led to an increase in the average body mass index among East Asian T2DM patients, highlighting the influence of insulin resistance in the development of T2DM within this group. Currently, the incidence of T2DM in Korea is declining, which may indicate potential adaptive changes in insulin secretory capacity. This review focuses on the changing epidemiology of T2DM in East Asia, with a particular emphasis on the characteristics of peak functional β-cell mass.

Osteoporosis management in post-menopausal women focuses on fracture prevention, with denosumab as a key therapeutic option. Despite its proven efficacy in reducing fracture risk and increasing bone mineral density (BMD) over 10 years, its long-term impact remains uncertain. We evaluated the literature on its efficacy and safety beyond the initial decade. Clinical trials and real-world studies confirm denosumab's sustained efficacy, especially in lumbar spine BMD, with hip BMD stabilizing. Concerns about adverse events (AEs) like hypocalcemia and osteonecrosis of the jaw necessitate vigilant monitoring. Risks of atypical femoral fractures and malignancies also require attention, despite unclear links to treatment duration. Clinical guidelines for denosumab beyond 10 years are limited, emphasizing the need for careful monitoring. In certain scenarios, such as advanced chronic kidney disease, prolonged denosumab may be required to balance AE risks with fracture prevention benefits. Denosumab shows potential for long-term efficacy in augmenting BMD; however, monitoring for AEs is crucial to guide clinical decision-making effectively.

Background: Antithyroid drug (ATD) treatment is the preferred initial treatment for Graves' disease (GD) in South Korea, despite higher treatment failure rates than radioactive iodine (RAI) therapy or thyroidectomy. This study aimed to evaluate the incidence of treatment failure associated with the primary modalities for GD treatment in real-world practice.

Methods: We included 452,001 patients diagnosed with GD between 2004 and 2020 from the Korean National Health Insurance Service-National Health Information Database. Treatment failure was defined as switching from ATD, RAI, or thyroidectomy treatments, and for ATD specifically, inability to discontinue medication for over 2 years.

Results: Mean age was 46.2 years, with females constituting 70.8%. Initial treatments for GD included ATDs (98.0%), thyroidectomy (1.3%), and RAI (0.7%), with a noted increment in ATD application from 96.2% in 2004 to 98.8% in 2020. During a median follow- up of 8.5 years, the treatment failure rates were 58.5% for ATDs, 21.3% for RAI, and 2.1% for thyroidectomy. Multivariate analysis indicated that the hazard ratio for treatment failure with ATD was 2.81 times higher than RAI. RAI treatments ≥10 mCi had 37% lower failure rates than doses <10 mCi.

Conclusion: ATDs are the most commonly used for GD in South Korea, followed by thyroidectomy and RAI. Although the risk of treatment failure for ATD is higher than that of RAI therapy, initial RAI treatment in South Korea is relatively limited compared to that in Western countries. Further studies are required to evaluate the cause of low initial RAI treatment rates in South Korea.

Background: Achieving optimal glucose control is essential in the management of type 2 diabetes (T2D). This study aimed to evaluate the effectiveness and safety of oral quadruple combination therapy for the treatment of T2D.

Methods: This meta-analysis reviewed original research on oral quadruple combination therapy for T2D, including both experimental and observational studies with a minimum duration of 12 weeks. The primary endpoint was the change in glycated hemoglobin (HbA1c) from baseline to follow-up. The secondary endpoint was the incidence rate of adverse events. Two investigators independently extracted data and assessed the risk of bias. Outcomes were pooled as the standardized mean difference (using Hedge's g) and the risk ratio for adverse events in random-effects meta-analyses.

Results: The meta-analysis included 17 studies. Oral quadruple combination therapy resulted in an additional mean reduction in HbA1c levels of 1.1% in patients who did not achieve glycemic control with oral triple combination therapy. Compared with switching to injectables, such as insulin or a glucagon-like peptide-1 receptor agonist-containing regimen, this therapy was non-inferior, even demonstrating a slightly superior glucose-lowering effect. Furthermore, it was determined to be safe, with an adverse event rate of 0.25, indicating no significant difference in safety compared with adding a placebo or switching to an injectable-containing regimen.

Conclusion: Oral quadruple combination therapy is a valid option for patients with T2D who are unable to achieve glycemic targets with oral triple combination therapy, offering both effective glycemic control and a favorable safety profile.

Background: This study aimed to evaluate the applicability of deep learning technology to thyroid ultrasound images for classification of thyroid nodules.

Methods: This retrospective analysis included ultrasound images of patients with thyroid nodules investigated by fine-needle aspiration at the thyroid clinic of a single center from April 2010 to September 2012. Thyroid nodules with cytopathologic results of Bethesda category V (suspicious for malignancy) or VI (malignant) were defined as thyroid cancer. Multiple deep learning algorithms based on convolutional neural networks (CNNs) -ResNet, DenseNet, and EfficientNet-were utilized, and Siamese neural networks facilitated multi-view analysis of paired transverse and longitudinal ultrasound images.

Results: Among 1,048 analyzed thyroid nodules from 943 patients, 306 (29%) were identified as thyroid cancer. In a subgroup analysis of transverse and longitudinal images, longitudinal images showed superior prediction ability. Multi-view modeling, based on paired transverse and longitudinal images, significantly improved the model performance; with an accuracy of 0.82 (95% confidence intervals [CI], 0.80 to 0.86) with ResNet50, 0.83 (95% CI, 0.83 to 0.88) with DenseNet201, and 0.81 (95% CI, 0.79 to 0.84) with EfficientNetv2_ s. Training with high-resolution images obtained using the latest equipment tended to improve model performance in association with increased sensitivity.

Conclusion: CNN algorithms applied to ultrasound images demonstrated substantial accuracy in thyroid nodule classification, indicating their potential as valuable tools for diagnosing thyroid cancer. However, in real-world clinical settings, it is important to aware that model performance may vary depending on the quality of images acquired by different physicians and imaging devices.

Endogenous Cushing's syndrome (CS) refers to the manifestations of chronic cortisol excess. This rare disease is associated with multiple comorbidities, impaired quality of life, and increased mortality. The management of CS remains challenging. Regardless of the underlying cause, surgical resection of the tumor is typically the first-line and preferred treatment. However, when surgery is not feasible or has been unsuccessful, medical therapies may be employed to control CS. The therapeutic strategy should be individualized based on the recommendations of a multidisciplinary team of experts and the patient's preferences, informed by detailed information on the available options. All medications require careful monitoring, along with adequate instructions for patients and caregivers. The aim of this mini-review is to provide an overview of the main medical therapies currently used to treat CS, including their efficacy, safety, and management. Despite the availability of new drugs in recent years, the need remains for more effective specific targeted pharmacological therapies.