International Journal of Endocrinology and Metabolism最新文献

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.

Introduction: Sertoli cell tumors are rare sex cord-stromal tumors, accounting for less than 1% of primary testicular tumors. They typically arise in the testes and ovaries, with other localizations being uncommon. We present the case of a Sertoli cell tumor in the adrenal gland, which, to our knowledge, is the first reported in the literature.

Case presentation: A 44-year-old male patient was admitted to the clinic for endocrine surgery for laparoscopic surgery of a right adrenal gland incidentaloma measuring 57 × 47 × 59 mm, discovered during a routine abdominal ultrasonography. The patient had a history of hypertension but no other comorbidities. Biochemical and physical examinations revealed no signs of hypercortisolism. Urinary metanephrine and normetanephrine levels were within normal limits. A right laparoscopic adrenalectomy was performed, and a 5 cm tumor was identified without evidence of locoregional invasion. Pathological examination confirmed a Sertoli cell tumor of the adrenal gland. Immunohistochemical analysis revealed positive staining for vimentin, steroidogenic factor 1 (SF1), and beta-catenin, while chromogranin A, hCG, PSA, and TTF1 were negative. The Ki-67 index was 3%. The patient was subsequently referred to a urologist, where testicular ultrasonography showed no abnormalities. There were no signs of recurrence during a 15-month follow-up period. Additionally, the patient's biannual antihypertensive treatment was discontinued by a cardiologist 1.5 months post-surgery.

Conclusions: Sertoli cell tumors are an exceptionally rare entity. To our knowledge, this is the first reported case of a primary Sertoli cell tumor originating in the adrenal gland. Given their potential for malignancy, regular follow-up and additional diagnostic evaluations may be necessary. Laparoscopic adrenalectomy appears to be a suitable definitive treatment for this condition.

Background: Obesity is a complex disease that has become increasingly prevalent. While obesity itself is not new, its widespread occurrence is a more recent concern. Stimulating brown adipose tissue (BAT) and promoting the browning of white adipose tissue (bWAT) have shown promise as therapeutic targets to increase energy expenditure and counteract weight gain.

Objectives: This study aimed to investigate two main aspects. First, we examined how obesity affects the expression of the fibronectin type-III domain containing 5 (FNDC5) and uncoupling protein 1 (UCP1) genes in male Wistar rats. Second, we assessed the effects of six weeks of aerobic exercise, exposure to cold water, and the combination of both on the expression of the FNDC5 and UCP1 genes in obese male Wistar rats.

Methods: In this experiment, 25 male Wistar rats were randomly assigned to five groups (5 rats per group) after inducing obesity. The groups included: A control group (C), an obesity group (O), an obesity group exposed to cold water (OC), an obesity group engaged in aerobic exercise (OE), and an obesity group exposed to both cold water and aerobic exercise (OCE). The aerobic exercise sessions lasted 30 - 60 minutes, with a speed of 15 - 25 meters per minute. The cold water exposure protocol involved shallow water (2 - 4 cm) with a temperature of 14 - 18°C. The OCE group performed both aerobic and cold water exercises in each session. The expression of the FNDC5 gene in the soleus muscle and the FNDC5 and UCP1 genes in subcutaneous fat was evaluated using Real-Time PCR. All statistical analyses were performed using SPSS software version 16, with a significance level set at P ≤ 0.05.

Results: Obesity significantly increased the expression of the FNDC5 gene (P = 0.008). After six weeks of aerobic exercise (P = 0.016) or cold water exposure (P = 0.016), there was a significant decrease in FNDC5 gene expression. Surprisingly, the combination of both interventions did not result in a significant effect (P = 0.75). On the other hand, none of the interventions-whether aerobic exercise, cold water exposure, or their combination-had a significant effect on the expression of the UCP1 gene (P > 0.05).

Conclusions: The increase in FNDC5 gene expression caused by obesity may serve as a compensatory mechanism to cope with the condition. However, both cold water exposure and aerobic exercise appear to mitigate this increase in FNDC5 gene expression through enhanced thermogenesis.

Context: This paper aims to review the findings of the Tehran Obesity Treatment Study (TOTS) on obesity and bariatric surgery (BS).

Evidence acquisition: The objective of this review is to assess all aspects of BS in individuals with severe obesity, focusing on research conducted within the TOTS framework.

Results and conclusions: The TOTS studies have produced significant national-level findings, highlighting critical issues related to the effectiveness and outcomes of bariatric procedures, the importance of comprehensive nutritional management, and the complications associated with these interventions in this population.

Background: Growth hormone replacement is indicated in adults with severe growth hormone (GH) deficiency, adult growth hormone deficiency assessment (AGHDA) score of at least 11 and are receiving treatment for other pituitary hormone deficiencies. There are no data looking at the cessation of GH replacement in adult patients with severe GH deficiency and the factors that predict the likelihood of patients continuing or stopping growth hormone replacement.

Methods: We audited patients on the GH register between January 2006 and January 2023 in Hull University Teaching Hospitals NHS foundation Trust, a UK tertiary hospital. Baseline characteristics, the cause of GH deficiency, AGHDA score at diagnosis and the reason for stopping GH were collected. Proportions were compared between patients adhering to GH replacement and those who had ceased it. Logistic regression analysis was used to identify factors independently associated with cessation of GH.

Results: The study comprised 141 adult patients with a mean age of 52 years, of which 75 (53%) were female. 54 (38%) individuals had discontinued GH replacement therapy. Predominant reasons for discontinuation were lack of therapeutic benefit (46%) and a change in clinical indication (26%). Among patients who discontinued GH therapy, the most frequent cause of GH deficiency was idiopathic (57%), while for those on GH replacement, pituitary surgery was the leading cause of GH deficiency (53%). Logistic regression analysis showed no baseline factor was statistically significantly associated with GH cessation, except female gender which had a borderline significance (P = 0.05).

Conclusions: In this real-world investigation of patients with severe GH deficiency, over two in five individuals who discontinued GH therapy cited the absence of perceived benefits. We show a borderline association of female gender with GH cessation and large population-based studies will be needed to investigate this and other causes of GH cessation.