International Journal of Endocrinology and Metabolism
Volume:23 Issue: 1, Jan 2025

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).

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.

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.

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%).

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.

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.

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.

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).

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.

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.

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

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.

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.

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.

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

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.

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.

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.

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.

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.

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.