International Journal of Endocrinology and Metabolism最新文献

Background: Polycystic ovary syndrome (PCOS) and Alzheimer's disease (AD) are two prevalent and complex conditions characterized by overlapping features such as metabolic dysfunction, hormonal imbalance, and chronic inflammation. These commonalities raise the possibility of a shared causal pathway. However, observational studies often face limitations due to confounding factors, complicating causal inference.

Objectives: The present study aimed to explore the causal link between PCOS and AD through Mendelian randomization (MR) analysis.

Methods: We conducted a two-sample MR analysis using summary-level data from two large genome-wide association studies (GWAS). For the exposure, genetic variants strongly associated with PCOS were obtained from a GWAS meta-analysis involving 10,074 cases and 103,164 controls of European ancestry. For the outcome, AD data were sourced from a separate GWAS comprising 1,036,225 cases and 90,338 controls, also of European descent. Multiple MR approaches were employed, with inverse variance weighted (IVW) as the primary method, supported by MR-Egger, weighted median, and weighted mode methods. Sensitivity analyses were performed to assess the robustness of the findings.

Results: The two-sample MR analysis did not provide evidence for a significant causal effect of genetically predicted PCOS on AD risk. The initial IVW analysis using all instrumental variables (IVs) yielded an odds ratio (OR) of 0.967 [95% confidence interval (CI): 0.905 - 1.03; P = 0.311]. After removing outlier single nucleotide polymorphisms (SNPs) based on sensitivity analyses, the refined IVW model showed an OR of 0.93 (95% CI: 0.866 - 1.002; P = 0.057), indicating no statistically significant association. The results were consistent across various MR methods, and sensitivity tests confirmed the robustness of the findings.

Conclusions: This MR study found no evidence of a significant causal relationship between genetically predicted PCOS and AD. These findings suggest that genetic predisposition to PCOS does not increase the risk of AD, indicating that previously observed associations in epidemiological studies may not reflect a causal link. Further studies are needed to explore alternative explanations beyond genetic causality.

Background: Previous studies have established that coronary artery calcification (CAC) is a robust predictor of adverse cardiovascular events.

Objectives: To examine the association between levels of glycated hemoglobin (HbA1c), an indicator of long-term blood glucose levels, and CAC in middle-aged and elderly Chinese populations undergoing routine health screenings.

Methods: A cross-sectional study was conducted on 8,955 Chinese adults over 40 years of age who underwent physical examinations in the Department of Health Medicine at our hospital from January 2022 to July 2023. The odds ratios (ORs) of CAC in relation to HbA1c were determined using multiple logistic regression analysis, both as a continuous and categorical variable. Furthermore, dose-response relationships between HbA1c levels and CAC were visualized using restricted cubic spline models.

Results: Compared to the group with HbA1c lower than 5.7%, individuals in the groups with HbA1c of 5.7% to 6.4% and ≥ 6.5% exhibited an elevated prevalence of CAC (P for trend < 0.0001). Multivariable logistic regression showed that each 1% increase in HbA1c was associated with a 24% increased risk of CAC (OR = 1.24, 95% CI: 1.03-1.48, P = 0.02). Compared with the group with HbA1c lower than 5.7%, the groups with HbA1c at 5.7% - 6.4% and HbA1c ≥ 6.5% were associated with a 28% (OR = 1.28, 95% CI: 1.07 - 1.52) and 116% (OR = 2.16, 95% CI: 1.48 - 3.16) (P for trend < 0.0001) increased risk of CAC, respectively. Restricted cubic spline analyses showed a non-linear association between HbA1c and CAC (P for nonlinearity < 0.0001). At higher levels of HbA1c exposure (> 5.7%), the exposure dose-response curves appeared upward-sloping. Subgroup analyses showed that the association between HbA1c and CAC was more pronounced in those aged less than 60 years, with normal weight and blood pressure less than 135/85 mmHg, although none of the interactions between HbA1c and subgroups were statistically significant.

Conclusions: This study indicated that higher HbA1c levels are associated with a greater likelihood of CAC in the middle-aged and elderly Chinese checkup population.

Introduction: Cushing syndrome is an endocrine disorder characterized by prolonged exposure to high levels of glucocorticoids, either from endogenous overproduction or exogenous sources. It presents with symptoms such as rapid weight gain, central obesity, muscle weakness, and hypertension. The diagnosis requires a combination of clinical, biochemical, and imaging tests. Dexamethasone suppression testing is pivotal in diagnosing hypercortisolism, but its accuracy may be affected by pharmacokinetic factors, such as drug interactions. This case report discusses a false-positive diagnosis of Cushing syndrome in a 16-year-old male, caused by the pharmacokinetic interference of carbamazepine, an enzyme-inducing medication.

Case presentation: A 16-year-old male with psychiatric comorbidities (bipolar disorder and epilepsy) presented with rapid weight gain, a hallmark symptom of Cushing syndrome. Initial laboratory testing revealed elevated cortisol and adrenocorticotropic hormone (ACTH) levels, with partial cortisol suppression during the low-dose dexamethasone suppression test, suggesting an ACTH-dependent cause of hypercortisolism. Imaging studies of the pituitary and adrenal glands were negative for abnormalities. High-dose dexamethasone suppression and 24-hour urinary free cortisol (UFC) levels further supported the diagnosis of hypercortisolism. A detailed medication review revealed the patient was taking carbamazepine, a CYP3A4 enzyme inducer, which could have accelerated the metabolism of dexamethasone and led to inadequate suppression of cortisol, producing falsely elevated levels.

Conclusions: Carbamazepine, through its enzyme-inducing effect on CYP3A4, likely interfered with the dexamethasone suppression test, leading to false-positive results for Cushing syndrome. Following the discontinuation of carbamazepine, the patient's cortisol levels normalized, weight stabilized, and the signs of Cushing syndrome resolved. Alternative psychiatric medications were initiated without further endocrine abnormalities. This case emphasizes the importance of considering pharmacokinetic interactions, such as those with enzyme-inducing drugs, when diagnosing Cushing syndrome. Clinicians should carefully review medications in patients with suspected hypercortisolism and consider these interactions when interpreting biochemical test results. A comprehensive medication review and interdisciplinary collaboration are crucial for accurate diagnosis, avoiding unnecessary interventions, and improving patient outcomes. The case advocates for tailored diagnostic protocols in similar clinical scenarios.

Background: Graves' disease (GD) is a leading cause of hyperthyroidism, characterized by excessive thyroid hormone production. Although the thyroid stimulating hormone receptor autoantibodies (TRAb) test is specific for GD, its limited accessibility often delays diagnosis and treatment, leading to potential complications. Thus, exploring alternative diagnostic markers, such as thyroid hormone ratios, may offer a feasible solution.

Objectives: This study aims to assess the diagnostic accuracy of the free thyroxine-to-thyroid stimulating hormone (FT4/TSH) ratio in distinguishing GD from other non-Graves' disease (NGD) hyperthyroidism.

Methods: A retrospective study was conducted at Hospital Raja Perempuan Zainab II in Kelantan, Malaysia, from 2021 to 2023. A total of 351 hyperthyroid patients who underwent initial TRAb testing during this period were included. These patients were categorized into two groups: Graves' disease and NGD hyperthyroidism, based on definitive diagnoses made by endocrinologists, as documented in the electronic medical records. Data on patients' TSH, FT4, and FT4/TSH ratios and TRAb results were retrieved from the laboratory information system (LIS) for analysis. The diagnostic accuracy of these parameters was assessed using receiver operating characteristic (ROC) curve analysis to determine optimal cut-off values, sensitivity, specificity, positive predictive values (PPVs), and negative predictive values (NPVs).

Results: Patients with GD had significantly higher FT4 and FT4/TSH ratios and lower TSH levels than NGD hyperthyroid patients (P < 0.001). Receiver operating characteristic analysis identified an FT4/TSH ratio cut-off of 13948.98 pmol/mIU, yielding a specificity of 99.4%, PPV of 92.31%, and an area under the curve (AUC) of 0.740.

Conclusions: The FT4/TSH ratio shows promise as an accessible diagnostic marker for GD, particularly where TRAb testing is limited. Its high specificity and PPV could facilitate timely diagnosis, improving patient management and outcomes. Further studies are needed to validate this approach in larger populations.

Introduction: Neonatal diabetes mellitus (NDM) is a rare disorder characterized by impaired blood glucose regulation that manifests before six months of age. Unlike autoimmune diabetes, NDM is caused by genetic mutations. One of the rarest causes of NDM is pancreatic agenesis, which results from mutations affecting the pancreas transcription factor 1A (PTF1A) gene and its enhancer. The following case report presents a rare instance of this condition.

Case presentation: This report describes a 2-year-old male child born to consanguineous Iranian parents, diagnosed with NDM due to pancreatic agenesis caused by a rare mutation in the PTF1A enhancer. Hyperglycemia was detected from the first day of life, and ultrasonography confirmed the absence of pancreatic tissue. Molecular analysis revealed homozygosity for the g.23508437A > G variant within the enhancer region of the PTF1A gene. At two years of age, with pancreatic enzyme replacement and insulin therapy, the patient exhibits normal neurological development, and his physical growth is at the 38th percentile.

Conclusions: Based on previous studies, the g.23508437A > G variant in the PTF1A gene enhancer region should be considered in cases of pancreatic agenesis. While whole-exome sequencing (WES) remains the gold standard for genetic diagnosis, it may fail to detect certain mutations. Therefore, targeted evaluation of PTF1A is essential when a genetic etiology is suspected.

Background: Studies have reported that the activity of alanine aminotransferase (ALT) is a key biomarker for screening liver cell damage, such as non-alcoholic fatty liver disease (NAFLD).

Objectives: Since individuals with metabolic syndrome (MetS) are at high risk for NAFLD, we aimed to determine gender-specific ALT thresholds for screening MetS in the Tehranian population.

Methods: We conducted a cross-sectional study from 2018 to 2022, involving 4,968 adults aged 20 - 70 years (2,732 females). Multivariable logistic regression analysis was performed to assess the association between ALT levels and the prevalence of MetS, as well as its individual components. Additionally, gender-specific ALT cut-off points were determined using the maximum Youden's Index. The area under the receiver operating characteristic curve (AUC) was calculated to derive thresholds and compare them with the previously introduced cut-off points for liver-related mortality in the U.S. population (US-LRM) (ALT > 19 U/L for females, > 29 U/L for males). We also examined the diagnostic performance of the derived cut-off points in 11 147 individuals (7,154 women) from the atherosclerosis risk in communities (ARIC) study as an external validation.

Results: The odds ratio (OR) from the logistic regression analysis showed that each 5 U/L increase in ALT level was associated with an increased prevalence of MetS [19% for females and 8% for males] and its components (ranging from 7 - 19% in females and 3-10% in males; all P-values < 0.05). The suggested cut-off point for ALT in males was 21 U/L, with a sensitivity of 72.1% and specificity of 47.1%. For females, with a threshold of 18 U/L, the corresponding values were 57.9% sensitivity and 66.5% specificity. Compared to the US-LRM suggested cut-off points in the US population, the AUC of our suggested threshold increased in males (60% vs. 56%, respectively), while for females, it remained the same as in the pretest (≈ 62%). Using ARIC data, our suggested threshold showed nearly identical AUC values to the US-LRM threshold in females (58% vs. 57%, respectively), whereas for males, the highest AUC was observed for our suggested cut-off points (56%), followed by the mortality-related threshold (53%).

Conclusions: The cut-off point for screening MetS among Iranian women was almost identical to the lower suggested threshold in American guidelines but was notably lower for defining abnormal ALT levels in males.

Background: Hyperglycemia in pregnancy (HIP) comprises gestational diabetes mellitus (GDM) and pre-existing diabetes; type 1 diabetes (T1DM), type 2 diabetes (T2DM), and undetermined diabetes. Hyperglycemia in pregnancy leads to fetal and maternal complications.

Objectives: To observe and compare glycemic profiles (GP) and hypoglycemia awareness (HA) in women with GDM and pre-existing diabetes.

Methods: This prospective observational comparative study enrolled women with HIP registered at Sulaimani Maternity Teaching Hospital from January to April 2024. Self-monitoring blood glucose (SMBG) was used to document GP through mean blood glucose (MBG) analysis and the proportions of hyperglycemic, euglycemic, and hypoglycemic records. The Gold score was used to assess HA. Statistical analysis was conducted using SPSS version 27.0, employing chi-square, Mann-Whitney, Fisher's exact test, Kruskal-Wallis test, ANOVA, and independent t-tests. A P-value of ≤ 0.05 was considered significant.

Results: One hundred patients were included in the final analysis. Half of the women were over 35 years old, 53% had GDM, and 47% had pre-existing diabetes. The MBG levels at fasting, 1-hour post-breakfast, and post-dinner were significantly highest in T1DM and lowest in GDM, while the levels were similar after lunch. Compared with pre-existing diabetes, women with GDM had a significantly greater proportion of euglycemic records and a lesser proportion of hyperglycemic and hypoglycemic records. Daily insulin requirements were significantly higher in women with pre-existing diabetes than in those with GDM (0.52 ± 0.35 vs 0.24 ± 0.12 units/kg, respectively, P < 0.001). Hypoglycemia episodes (HE) were 5.7 vs 1.83 events/patient/month in pre-existing diabetes vs GDM, respectively (P = 0.002). Using the Gold score to determine HA, 40% of T1DM patients had reduced HA, 40% had borderline HA, while 20% of T1DM and patients with other types of diabetes had normal HA (P < 0.001).

Conclusions: Women with GDM had a significantly more stable GP, fewer HE, and lower insulin requirements than those with pre-existing diabetes. Type 1 diabetes patients had the most unstable GP, with significantly higher proportions of hyperglycemic and hypoglycemic records and reduced HA.

Background: Metabolic Syndrome (MetS) is a prevalent condition associated with an increased risk of cardiovascular disease (CVD) and CVD mortality. Due to the limited clinical applicability of MetS, the standardized continuous metabolic syndrome severity score (cMetS-S) has the potential to provide continuous assessment of metabolic risk.

Objectives: This study evaluated the optimal cMetS-S cut-off points in the Tehran Lipid and Glucose Study (TLGS) for predicting CVD and CVD mortality.

Methods: The study included 7,776 participants over 30 years old at baseline, followed for 18 years. Sex-specific sensitivity (SS) and specificity (SP) of cMetS-S measures for predicting CVD and CVD mortality were evaluated using a receiver operating characteristic (ROC) curve, along with the area under the curve (AUC), employing a naive estimator and considering event failure status and MetS variables.

Results: The cut-off point of cMetS-S for CVD was 0.13 (SS: 65.5%, SP: 59.6%) for the total population, 0.44 (SS: 49.6%, SP: 68.1%) for men, and 0.27 (SS: 64.2%, SP: 69.2%) for women. The cut-off point of cMetS-S for CVD mortality was 0.53 (SS: 51.3%, SP: 71.9%) for the total population, 0.76 (SS: 35.1%, SP: 76.2%) for men, and 0.28 (SS: 78.8%, SP: 66.4%) for women. The AUC (95% CI) of MetS based on the International Diabetes Federation (IDF) and Joint Interim Statement (JIS) definitions were 60.0 (65.3 - 56.8) and 61.1 (59.6 - 56.8) for CVD, and 59.3 (56.0 - 62.5) and 59.4 (56.3 - 62.6) for CVD mortality.

Conclusions: The cut-off points of cMetS-S for CVD and CVD mortality differ between men and women. The cMetS-S could be a better predictive tool for CVD and CVD mortality than MetS.

Background: Reoperation for recurrent papillary thyroid cancer (PTC) is associated with a high risk of complications and limited success in achieving sustained remission. Percutaneous ethanol injection (PEI) presents a potential non-surgical alternative for managing locally recurrent PTC.

Objectives: This study aimed to evaluate the safety and effectiveness of PEI in treating recurrent PTC.

Methods: From October 2017 to September 2021, PEI was administered to 39 recurrent lesions (23 lateral and 16 central) in 17 patients with PTC. The median follow-up duration was 21.4 months (range, 4.1 - 37.9), with ethanol injections delivered every 3 months under ultrasound (US) guidance as needed.

Results: Most patients tolerated the treatment well, experiencing only mild local pain, though one patient reported Horner syndrome following the procedure. In terms of treatment frequency, 31 lesions required 3 or fewer injections, while the remaining lesions required more. The mean initial volume of the lesions decreased from 0.12 mm³ (range: 0.06 - 0.34 mm³) to 0.03 mm³ (range: 0.0 - 0.14 mm³), representing an average reduction of 72.6% (range: 20.0 - 100.0%). Of the 39 lymph nodes treated in 17 patients, 21 lymph nodes (54%) were completely resolved. Seven lymph nodes remain under ongoing ethanol treatment, while 11 lymph nodes in 4 patients were addressed with alternative treatments, including surgery.

Conclusions: Percutaneous ethanol injection appears to be a safe and effective treatment option for managing locally recurrent thyroid carcinomas in select patients. However, further comparative, prospective, long-term studies are needed to evaluate PEI's impact on patient survival and recurrence rates.

Background: The macronutrient composition of daily meals plays a crucial role in influencing the body's metabolic responses during the postprandial phase. However, existing research on the effects of macronutrients, particularly fats and carbohydrates, has produced inconsistent findings.

Objectives: This study aims to evaluate the postprandial effects of two high-protein meals-one low in fat and high in carbohydrates (HP-LF-HC) and the other high in fat and low in carbohydrates (HP-HF-LC)-on energy metabolism, appetite response, and blood markers in overweight and obese men and women without underlying health conditions.

Methods: This study was conducted as an acute randomized crossover clinical trial at the Health Monitoring Center of Mashhad University of Medical Sciences (MUMS) within Imam Reza Hospital, Mashhad, Iran. A total of 30 overweight and obese men and women, meeting the eligibility criteria and free of underlying diseases, were recruited through a public call. Participants were randomly assigned to receive both intervention meals, with a washout period of at least one week between each trial.

Results: The primary outcomes focused on the acute effects of the two dietary interventions on energy metabolism, particularly resting metabolic rate (RMR), and appetite response. Secondary outcomes included changes in lipid profiles, insulin, blood glucose levels, thyroid hormones, and epinephrine.

Conclusions: This study aims to identify which macronutrient composition most effectively enhances resting energy expenditure. The findings could provide valuable insights for dietitians in developing more efficient dietary plans, helping overweight and obese individuals maintain an ideal weight or achieve weight loss by modifying food composition without altering meal volume.