Endocrinology and Metabolism最新文献

Background: Active surveillance (AS) has emerged as a viable management strategy for low-risk papillary thyroid microcarcinoma (PTMC), following pioneering trials at Kuma Hospital and the Cancer Institute Hospital in Japan. Numerous prospective cohort studies have since validated AS as a management option for low-risk PTMC, leading to its inclusion in thyroid cancer guidelines across various countries. From 2016 to 2020, the Multicenter Prospective Cohort Study of Active Surveillance on Papillary Thyroid Microcarcinoma (MAeSTro) enrolled 1,177 patients, providing comprehensive data on PTMC progression, sonographic predictors of progression, quality of life, surgical outcomes, and cost-effectiveness when comparing AS to immediate surgery. The second phase of MAeSTro (MAeSTro-EXP) expands AS to low-risk papillary thyroid carcinoma (PTC) tumors larger than 1 cm, driven by the hypothesis that overall risk assessment outweighs absolute tumor size in surgical decision-making.

Methods: This protocol aims to address whether limiting AS to tumors smaller than 1 cm may result in unnecessary surgeries for low-risk PTCs detected during their rapid initial growth phase. By expanding the AS criteria to include tumors up to 1.5 cm, while simultaneously refining and standardizing the criteria for risk assessment and disease progression, we aim to minimize overtreatment and maintain rigorous monitoring to improve patient outcomes.

Conclusion: This study will contribute to optimizing AS guidelines and enhance our understanding of the natural course and appropriate management of low-risk PTCs. Additionally, MAeSTro-EXP involves a multinational collaboration between South Korea and Australia. This cross-country study aims to identify cultural and racial differences in the management of low-risk PTC, thereby enriching the global understanding of AS practices and their applicability across diverse populations.

Backgruound: We aimed to investigate the predictive values of plasma C-peptide levels and the continuous glucose monitoring (CGM)-defined coefficient of variation (CV) in risk prediction for hypoglycemia in Korean people with diabetes with normal and impaired kidney function.

Methods: We analyzed data from 1,185 participants diagnosed with type 1 and type 2 diabetes who underwent blinded professional CGM between January 2009 and May 2021 at outpatient clinics. We explored correlations among CGM-defined CV, plasma C-peptide levels, and time below range at <70 and 54 mg/dL across different kidney function categories.

Results: In patients with chronic kidney disease (CKD) stages 1-2 (n=934), 89.3% who had a random plasma C-peptide level higher than 600 pmol/L exhibited a CV of ≤36%. Among those in CKD stage 3 (n=161) with a random plasma C-peptide level exceeding 600 pmol/L, 66.7% showed a CV of ≤36%. In stages 4-5 of CKD (n=90), the correlation between random C-peptide levels and CV was not significant (r=-0.05, P=0.640), including cases with a CV greater than 36% despite very high random plasma C-peptide levels. Random plasma C-peptide levels and CGM-assessed CV significantly predicted hypoglycemia in CKD stages 1-2 and 1-5, respectively.

Conclusion: The established C-peptide criteria in Western populations are applicable to Korean people with diabetes for hypoglycemic risk prediction, unless kidney function is impaired equivalent to CKD stage 3-5. The CGM-defined CV is informative for hypoglycemic risk prediction regardless of kidney function.

Backgruound: Gestational diabetes mellitus (GDM) affects women with diverse pathological phenotypes, but little is known about the effects of this variation on perinatal outcomes. We explored the metabolic phenotypes of GDM and their impact on adverse pregnancy outcomes.

Methods: Women diagnosed with gestational glucose intolerance or GDM were categorized into subgroups according to their prepregnancy body mass index (BMI) and the median values of the gestational Matsuda and Stumvoll indices. Logistic regression analysis was employed to assess the odds of adverse pregnancy outcomes, such as large-for-gestational age (LGA), small-for-gestational age, preterm birth, low Apgar score, and cesarean section.

Results: A total of 309 women were included, with a median age of 31 years and a median BMI of 22.3 kg/m2. Women with a higher pre-pregnancy BMI had a higher risk of LGA newborns (adjusted odds ratio [aOR] for pre-pregnancy BMI ≥25 kg/m2 compared to 20-23 kg/m2, 4.26; 95% confidence interval [CI], 1.99 to 9.12; P<0.001; P for trend=0.001), but the risk of other adverse pregnancy outcomes did not differ according to pre-pregnancy BMI. Women with insulin resistance had a higher risk of LGA (aOR, 1.88; 95% CI, 1.02 to 3.47; P=0.043) and cesarean section (aOR, 2.12; 95% CI, 1.29 to 3.50; P=0.003) than women in the insulin-sensitive group. In contrast, defective β-cell function did not affect adverse pregnancy outcomes.

Conclusion: Different metabolic phenotypes of GDM were associated with heterogeneous pregnancy outcomes. Women with obesity and those with insulin resistance are at greater risk of adverse outcomes and might need strict glycemic management during pregnancy.

Backgruound: Hypercalcemia of malignancy (HCM), a major metabolic complication of cancer, is often managed with bisphosphonates (BP) and, increasingly, with denosumab. We aimed to compare the effectiveness and safety of denosumab with that of BP, with or without calcitonin, in treating HCM.

Methods: This retrospective cohort study was conducted at a tertiary hospital from 2017 to 2022 and included 317 patients treated for HCM. Participants were divided into three treatment groups: denosumab, intravenous (IV) BP only, and IV BP combined with calcitonin. The primary outcomes measured were changes in calcium levels and the incidence of hypocalcemia. Analysis of covariance was used to adjust for age, sex, body mass index, creatinine level, type of malignancy, and the use of furosemide and steroids.

Results: The mean participant age was 65 years, and 37.5% were female. After adjustment, both denosumab and IV BPs were found to effectively lower calcium levels. Denosumab led to a decrease of 2.0 mg/dL (-15.9%), while IV BP alone resulted in a reduction of 1.8 mg/dL (-13.9%). The largest reduction, of 2.7 mg/dL (-20.9%), occurred with IV BP and calcitonin. Both denosumab and IV BP+calcitonin yielded their lowest calcium levels within 48 hours, whereas the IV BP only group reached a nadir within 72 hours. Despite these differences in treatment effectiveness, hypocalcemia occurred significantly less frequently in the denosumab group compared to the other groups.

Conclusion: Denosumab and IV BP were similarly effective in reducing calcium levels. However, IV BP combined with calcitonin yielded a more rapid and pronounced decrease.

Backgruound: 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.

Backgruound: 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.

Backgruound: 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.

Backgruound: 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.