Abstract in English:

ABSTRACT Resistance to thyroid hormone syndrome (RTHS) is a rare disorder caused by mutations in the thyroid hormone receptor beta (THRB) gene, resulting in impaired action of thyroid hormones on target tissues and organs. We report a case of a 57-year-old Chinese male who presented with palpitations and hand tremors. Laboratory tests revealed elevated serum thyroid hormone levels, while serum thyroid-stimulating hormone (TSH) levels remained within the normal range. Enhanced magnetic resonance imaging of the pituitary gland showed no abnormalities. Through genetic testing, we identified a rare heterozygous point mutation in the THRB gene, specifically c.938T>C: p.M313T. To the best of our knowledge, this mutation site has not been previously reported in the literature. Clinically, RTHS is often misdiagnosed as hyperthyroidism, leading to inappropriate treatment and potential exacerbation of thyroid hormone resistance. Therefore, accurate diagnosis of this condition is crucial. Given the rarity of RTHS, we hope that this case report will enhance the understanding of its clinical manifestations and management, particularly in patients with THRB gene mutations.

Abstract in English:

ABSTRACT The Female Athlete Triad (Triad) and Relative Energy Deficiency in Sport (RED-S) are conditions associated with low energy availability (EA) that can lead to menstrual dysfunction, impaired bone health, and metabolic disturbances. This case report describes the remission of Triad in a professional triathlete during the COVID-19 pandemic. A 24-year-old female triathlete was evaluated in 2018. She reported bulimia nervosa from 12–15 years old and hypothalamic amenorrhea since she was 21 years old. Her training volume was approximately 20 hours per week (swimming, cycling, and running), and the amount of EA was critically low (< 10 kcal/fat free mass/day). The athlete had lower than expected BMD at DXA scan (lumbar spine Z-score -2.3 SD) and lower cortical and trabecular vBMD and trabecular number by comparison with HR-pQCT normative data for young Brazilian women. During the 2020 pandemic, training centers were closed, leading to a decrease in exercise volume and a more balanced energy intake. Menstrual cycles resumed and she conceived spontaneously in the same year. Pregnancy and postpartum recovery were uneventful. She returned to competitions post pandemic, but no longer as a professional athlete. Chronic energy deficiency significantly affects the hypothalamic-pituitary-gonadal axis and bone health. A forced reduction in training intensity and improved dietary intake were key factors in the restoration of menstrual function and reproductive health. This case highlights the potential reversibility of the Female Athlete Triad when energy balance is restored. Awareness and early intervention are essential for preventing long-term consequences in female athletes.

Abstract in English:

ABSTRACT Poorly differentiated thyroid carcinoma (PDTC) is a rare and aggressive malignancy with a poor prognosis. Immunotherapy is typically guided by agnostic biomarkers such as microsatellite instability-high or high tumor mutational burden (TMB); however, these biomarkers are uncommon in PDTC. Therefore, identifying alternative predictive biomarkers remains an urgent necessity. We report the case of a 71-year-old woman who presented with life-threatening locoregional disease and was ineligible for radioiodine or tyrosine kinase inhibitors due to a prior subarachnoid hemorrhage. Molecular profiling of the resected tumor revealed a high TMB (10 mut/Mb), somatic mutations in MSH2 and ATM, and microsatellite stability (MSS). Immunohistochemistry demonstrated complete loss of MSH2/MSH6 expression, while PD-L1 expression was 20% (tumor proportion score). Based on these findings, pembrolizumab was initiated as first-line therapy. The patient experienced clinical improvement and maintained a sustained partial response for seven months, with excellent tolerability. This case represents one of the few documented reports of PDTC with MSS exhibiting marked responsiveness to immunotherapy. Our findings underscore that alternative biomarkers, such as somatic mutations in DNA repair genes including MSH2 and ATM, may predict unexpected responses to immune checkpoint blockade and inform therapeutic decisions, even in the context of MSS and borderline TMB. Broader implementation of molecular profiling is warranted to identify such patients.

Abstract in English:

ABSTRACT Objective: This study aims to evaluate ultra-processed food consumption and eating behavior in adults with obesity. Subjects and methods: A cross-sectional study with 77 volunteers from São Paulo, Brazil. Food consumption was assessed using three 24-hour dietary recalls, classified by using the NOVA classification system, and the Diet Quality Index was also evaluated. Eating behavior and symptoms of binge eating and bulimia were assessed using the Bulimic Investigatory Test Edinburgh (BITE), the Dutch Eating Behaviour Questionnaire (DEBQ), and the Three Factor Eating Questionnaire (TFEQ-21). Results: The average BMI of the sample was 39.14 kg/m² ± 5.57, and the median caloric intake was 1661 kcal (756.07–4774.40), with a macronutrient distribution of 48% carbohydrates, 32% fat, and 20% protein. Volunteers were divided into tertiles of calories ingested from ultra-processed foods (%): 1st < 24.10% (n = 25); 2nd between 24.10%–35.40% (n = 26); and the 3rd > 35.40% (n = 26). The sample showed intermediate diet quality (43.08 ± 10.17), while the 3rd tertile presented a low-quality diet (37 ± 10), differing from other groups (p = 0.001; p = 0.003). All groups showed intermediate BITE scores (19,6 ± 9,8), an indicator of unusual eating behavior. The third tertile had a higher symptom score than the first tertile (p = 0.008). In the association analysis, the consumption of ultra-processed foods was positively associated with the presence of binge eating and bulimia symptoms (p = 0.018), emotional (p = 0.001) and external eating (p = 0.001) as assessed by the DEBQ, and emotional (p = 0.008) and uncontrolled eating (p = 0.006) as assessed by the TFEQ-21. In contrast, diet quality was negatively associated with the consumption of ultra-processed foods (p < 0.001). Conclusion: Our findings suggest that higher consumption of ultra-processed foods by volunteers with obesity may be associated with higher scores for unusual eating behavior, symptoms of binge eating, and bulimia, in addition to augmented emotional, external and uncontrolled eating, and lower diet quality scores.

Abstract in English:

ABSTRACT Objective: To measure serum insulin-regulated aminopeptidase levels in women diagnosed with polycystic ovary syndrome and to investigate their potential contribution of these levels to the development of insulin resistance, which plays a central role in the pathophysiology of polycystic ovary syndrome. Methods: The study group, recruited between May and December 2021, consisted of 40 patients diagnosed with polycystic ovary syndrome and 40 age-matched healthy controls. Serum insulin-regulated aminopeptidase levels were compared between the groups using the ELISA method. Results: Serum insulin-regulated aminopeptidase levels were significantly lower in the polycystic ovary syndrome group compared with the control group (p < 0.001). Subparameter assessments revealed that insulin-regulated aminopeptidase levels were even lower in insulin-resistant polycystic ovary syndrome patients (p = 0.001). Moreover, insulin-regulated aminopeptidase levels demonstrated a statistically significant negative correlation with fasting blood glucose, insulin, glycated hemoglobin, and HOMA-IR values. Conclusion: Serum insulin-regulated aminopeptidase levels were found to be lower in women with polycystic ovary syndrome than those in healthy controls. Furthermore, these levels appear to reflect insulin resistance, a key factor in the pathogenesis of polycystic ovary syndrome. Overall, these findings suggest that insulin-regulated aminopeptidase may serve as a potential biomarker for the identifification of insulin resistance in women with polycystic ovary syndrome.

Abstract in English:

ABSTRACT Objective: To evaluate and describe the changes in the therapeutic approach to Graves’ disease at a tertiary hospital center over a 20-year period, with an emphasis on the frequency of prescription and the timing of radioactive iodine indication. Subjects and methods: We conducted a retrospective analysis of data from medical records of patients recently diagnosed with Graves’ disease (GD) and followed up at a single institution during two consecutive periods: Group A diagnosed between 2002 and 2010, and Group B between 2011 and 2022. We analyzed the percentage of patients who underwent iodine therapy and were considered to have failed therapy if they did not achieve hypothyroidism or euthyroidism, comparing the results between both groups. Results: A total of 597 GD patients were included, of which 223 underwent radioactive iodine (RAI) therapy (37.35%). In Group A, 176 patients (64%) received RAI treatment, whereas, in Group B, only 47 patients were given this therapeutic indication (14.6%) (p < 0.001). The reduction in RAI prescriptions between both periods was independent of the therapeutic indication. Interestingly, RAI prescription due to relapse after clinical treatment was uncommon in both study groups. There was a significant increase in the duration of antithyroid drug (ATD) therapy before RAI prescription in Group B compared to Group A. Conclusion: Significant changes were observed in GD treatment, with a decline in the use of RAI as a first-line or salvage therapy. Nonetheless, radioiodine therapy remained an effective and safe treatment modality with successful cure rates.

Abstract in English:

ABSTRACT Objective: Differentiated thyroid carcinoma (DTC) is the most common endocrine malignancy and usually has a favorable prognosis. However, both diagnostic and prognostic evaluations currently rely mainly on postoperative histopathological results. Systemic inflammation-based indices — such as the Systemic Immune-Inflammation Index (SII), Systemic Inflammation Response Index (SIRI), and Pan-Immune Inflammation Value (PIV) — have recently emerged as potential biomarkers in various cancers. This study aimed to evaluate the diagnostic and prognostic utility of these indices in patients undergoing thyroid surgery. Subjects and methods: This retrospective study included 554 patients who underwent total thyroidectomy between 2014 and 2021. Tumors were categorized as benign or malignant according to final histopathology. SII, SIRI, and PIV were calculated from preoperative complete blood counts. Multivariate logistic regression was performed and included age, sex, thyroid-stimulating hormone (TSH) level, glycated hemoglobin (HbA1c) level, and diabetes status. Receiver operating characteristic (ROC) analysis was used to determine diagnostic performance. Results: Among 554 patients, 366 had benign and 188 had malignant tumors. Among the systemic inflammatory markers, only the SII differed significantly between groups (p = 0.002) and remained an independent predictor of malignancy in multivariate analysis (OR = 0.85 per 100-unit increase, p = 0.007). ROC analysis revealed an AUC of 0.597, with 65.8% sensitivity and 58.2% specificity. None of the indices demonstrated prognostic value in the subgroup analyses. Conclusion: The SII demonstrated independent but clinically limited diagnostic value in differentiating malignant from benign thyroid lesions. Although its accuracy was poor (AUC <0.6), the SII may serve as a low-cost adjunct within multivariable preoperative models, particularly in indeterminate cytology cases.

Abstract in English:

ABSTRACT Objective: To determine the frequency and types of breast calcif ication, the distribution of breast imaging-reporting and data system (BI-RADS) scores, and the association between calcif ication and biochemical/clinical findings in patients with primary hyperparathyroidism (PHPT). Subjects and methods: We recruited ≥ 40-year-old female patients with PHPT (n = 104) and age-matched healthy women (n = 107) as controls. Mammography was performed on all participants. Calcif ication, calcif ication type, and BI-RADS scores were recorded, and patients were divided into two groups based on PHPT duration and presence/absence of calcification. Results: BI-RADS score distribution was indifferent between groups. The frequency of calcification and distribution of calcification types showed no difference between groups. Likewise, mammography findings were consistent among PHPT patients regardless of disease duration. There was no cutoff for disease duration that could predict the presence of calcification. Breast calcification was negatively correlated with parathyroid hormone (r = -0.220, p = 0.025) and 24-hour urine calcium levels (r = -0.195, p = 0.048), and positively correlated with age (r = 0.219, p = 0.025) in PHPT patients. Of the six patients who underwent cytological examination, one was found to be malignant (PHPT group). Conclusion: Female patients with PHPT do not have an increased incidence of breast calcification or higher BI-RADS scores compared to healthy women, and the calcification rates were unaffected by the duration of the disease. The presence of calcification does not appear to be associated with an increased risk of breast cancer in PHPT patients. Nonetheless, given the frequency of breast cancer and that the only patient with breast cancer was part of the PHPT group, it would be appropriate to screen these patients for breast cancer carefully.

Abstract in English:

ABSTRACT Objective: To evaluate the diagnostic performance and determine the optimal cutoff values of the triglyceride-to-high-density lipoprotein cholesterol ratio and lipid accumulation product index as predictors of metabolic syndrome among adults with obesity in Indonesia. Materials and methods: This cross-sectional study analyzed secondary data from the 2023 Indonesia Health Survey, which included 3,988 samples (2,958 women). Descriptive statistics were used to characterize the sample. Receiver Operating Characteristic curve analysis and the Youden index were employed to assess diagnostic performance and determine the optimal cutoff values of the triglyceride-to-high-density lipoprotein cholesterol ratio and lipid accumulation product index. The associations between both predictors and the presence of metabolic syndrome were examined using multivariable logistic regression. Results: The lipid accumulation product index exhibited greater predictive accuracy than the triglyceride-to-high-density lipoprotein cholesterol ratio, particularly among men. This result indicated the superior utility of the lipid accumulation product index as a clinical screening tool for metabolic syndrome, with area under the curve values of 0.842 (95% CI 0.817-0.866) for men and 0.737 (95% CI 0.720-0.755) for women, compared to that of the triglyceride-to-high-density lipoprotein cholesterol ratio, with area under the curve values of 0.810 (95% CI 0.784–0.837) for men and 0.728 (95% CI 0.710-0.746) for women. The optimal cutoff values of the triglyceride-to-high-density lipoprotein cholesterol ratio and lipid accumulation product index were 4.456 (sensitivity 64.8%, specificity 81.4%) and 45.752 (sensitivity 75.5%, specificity 81.2%) for men and 2.792 (sensitivity 59.2%, specificity 76.8%) and 41.285 (sensitivity 58.6%, specificity 75.8%) for women, respectively. Conclusion: The lipid accumulation product index demonstrated superior accuracy in predicting metabolic syndrome among adults with obesity, particularly among men. Sex-specific cutoff values enhance its reliability and practicality for early screening and intervention to prevent metabolic complications.

Abstract in English:

ABSTRACT Objective: Accurate assessment of metastatic status is crucial for determining radioactive iodine (RAI) dosing in postoperative papillary thyroid carcinoma (PTC) patients. This study aimed to identify unbiased biomarkers in metastatic PTC patients after surgery by applying a metabolomics workflow in saliva samples. Materials and methods: Saliva samples from 70 postoperative PTC patients (35 metastatic PTC patients in metastasis group and 35 non-metastatic PTC patients in control group) were analyzed using liquid chromatography – mass spectrometry. Orthogonal partial least-squares-discriminant analysis was applied to identify differential metabolites and significant pathways were examined within these metabolites. Receiver operating characteristic curve (ROC) analysis was utilized to further evaluate the diagnostic performance of candidate metabolites. Results: A total of 119 differential metabolites were identified, with 108 upregulated and 11 downregulated. Pathway analysis revealed 13 significantly dysregulated metabolic pathways in metastatic PTC, including necroptosis, choline metabolism in cancer, sphingolipid signaling, valine, leucine and isoleucine biosynthesis, linoleic acid metabolism and pantothenate and CoA biosynthesis. ROC analysis demonstrated six discriminating biomarkers (5 lipids, 1 amine) that effectively distinguished metastatic from non-metastatic PTC, with all area under the curve values exceeding 0.8. Notably, these metabolites maintained diagnostic performance even in the thyroglobulin antibody-positive subgroup (≥ 4.11 IU/mL) for metastatic screening. Conclusion: This study demonstrates the potential of salivary biomarkers as a non-invasive diagnostic approach for metastatic PTC to aid the appropriate dosing for RAI therapy. It also offers new insights into the mechanisms of PTC metastasis and potential targets for adjuvant therapy.

Abstract in English:

ABSTRACT Objective: Familial non-medullary thyroid cancer (FNMTC) is defined as non-medullary thyroid cancer occurring in two or more first-degree relatives, without features of known hereditary syndromes. Although familial predisposition is well established, its clinical behavior remains debated. This study aimed at characterizing familial cases compared to sporadic non-medullary thyroid cancer (SNMTC). Subjects and methods: FNMTC and SNMTC patients were recruited from the Endocrine Division (SEMPR) of the Federal University of Paraná, Brazil, and private endocrine clinics in Curitiba, Paraná, Brazil (2000-2019). Baseline, histopathological, and clinical data were analyzed using SPSS Statistics 26.0. Statistical comparisons employed chi-square, Student’s t test, and Mann-Whitney U test, as appropriate. Post hoc power analysis was performed using G*Power 3.1.9.7, and R 2025.05.0. Results: We analyzed 39 FNMTC and 119 SNMTC patients. Papillary thyroid carcinoma was the predominant histological type in both groups. FNMTC patients were diagnosed at a younger age (38.5 ± 14.2 vs. 46.6 ± 13.8 years, p = 0.003) and more frequently presented with lymph node metastases at diagnosis (46.2% vs. 21.8%, p = 0.007), with a 4.57-fold increased risk. Despite these differences, long-term outcomes did not differ significantly between groups. An earlier disease onset in subsequent generation suggests a possible anticipation phenomenon. Conclusion: These findings suggest that FNMTC patients may present with earlier onset and higher rates of lymph node involvement, underscoring the need for thorough preoperative lateral neck evaluation. In view of a possible anticipation phenomenon, cervical ultrasound screening might be considered starting in adolescence.

Abstract in English:

Abstract Objective: This study aimed to evaluate the expression of miR-29a-3p and miR-192-5p in patients with type 1 diabetes mellitus (T1DM) with diabetic kidney disease (DKD) compared to those without DKD. Subjects and methods: This study included 29 patients with T1DM, comprising 13 without DKD (non-DKD group) and 16 with DKD, who were further subdivided into nine patients with moderate DKD and seven with severe DKD. MiR-29a-3p and miR-192-5p expression levels were measured in urine samples using qPCR and are presented as medians (25-75th percentiles). Results: miR-29a-3p levels were higher in patients with DKD compared to the non-DKD group [1.24 (0.97-1.74) versus 0.83 (0.72-0.99); P = 0.008]. Its expression showed a negative correlation with estimated glomerular filtration rate (eGFR) (P = 0.007) and a positive correlation with creatinine levels (P = 0.004). MiR-192-5p levels were higher in patients with moderate DKD compared to the non-DKD group [2.15 (1.45-4.21) versus vs. 1.42 (0.98-2.45); P = 0.015], showing a negative correlation with eGFR (P = 0.003) and a positive correlation with creatinine (P = 0.006). Conclusion: The differential expression of miR-29a-3p and miR-192-5p in DKD highlights their potential as promising biomarkers for this complication.

Abstract in English:

Abstract Objective: Screening and diagnosing gestational diabetes mellitus (GDM) usually requires a 2-hour, 75 g oral glucose tolerance test (OGTT), which can be challenging for both patients and healthcare systems. Alternative clinical risk factor-based models have been suggested but have not been extensively tested, particularly in low-resource countries. This study aimed to evaluate the accuracy of these risk factor-based models as screening tools. Subject and methods: This prospective cohort study involved 400 consenting pregnant women receiving antenatal care in Lagos, Nigeria. Participants were evaluated for GDM risk using three clinical models and underwent universal screening and diagnosis at 24 to 28 weeks with a single-step, 2-hour 75g OGTT, using IADPSG/WHO criteria. The Receiver Operating Characteristic (ROC) curve was used to assess the accuracy of the risk factor-based models. Results: The mean age of the subjects was 31.0 ± 5.3 years. The prevalence of GDM, according to the IADPSG/WHO 2013 criteria, was 19.0%. Using the clinical risk score models developed by Naylor and cols., Caliskan and cols., and Phaloprakarn and cols., positive risk scores for GDM were found in 85%, 67.3%, and 93.8% of subjects, respectively. The sensitivity, specificity, and accuracy of these models ranged from 71.1% to 96.1%, 6.7% to 33.6%, and 23.8% to 40.8%, respectively. However, the negative predictive values were relatively high, ranging from 83.2% to 88%. Conclusion: The clinical risk factor-based prediction models evaluated in this study may effectively identify women at low risk for GDM who can be exempted from the 2-hour OGTT.

Abstract in English:

Abstract Objective: This study aims to evaluate the correlation between parathyroid hormone measured by a second-generation assay (PTHG2) and by a third-generation assay (PTHG3), and their association with mineral and bone disorder (MBD) biochemical parameters and radiographic vascular calcification score in kidney transplant recipients (KTRs). Materials and methods: We evaluated 87 KTRs and measured PTHG2, PTHG3, biochemical profile, urinary fractional excretion of calcium (FE Ca) and phosphate, 25(OH)D3, and Kauppila score for vascular calcification. Statistical analysis: Non-parametric tests and logistic regression analysis were performed. The significance level was set to 5%. Results: In our population, the mean age was 54 years, the mean time after transplantation was 9.4 years (± 7.6), and the mean estimated glomerular filtration rate (GFR, calculated using the Chronic Kidney Disease Epidemiology Collaboration equation - CKD-EPI) was 59.1 mL/min/1.73 m2. The correlation between PTHG2 and PTHG3 was almost perfect (r = 0.99; 95% CI = 0.98-0.99) and there was no significant difference between the PTHG2/PTHG3 ratio from different KTR-CKD stages. Investigating the association among PTH and the MBD biochemical profile, there was only correlation between PTH and FE Ca (p-value 0.01). Conclusion: We concluded that there is no advantage in PTHG3 dosage over PTHG2 measurement in this population.

Abstract in English:

Abstract Objective: This study aimed to evaluate extracellular vesicles (EVs) in a group of carriers of familial hypercholesterolemia (FH)-related genetic variants compared to those in family members without FH. Subjects and methods: Annexin V-positive EVs (PS+-EVs), cardiomyocyte-derived EVs (CardioEVs), endothelial cell-derived EVs (EEVs), platelet-derived EVs (PEVs) and tissue factor-expressing EVs (TFEVs) were evaluated to compare individuals with FH and genetic variants (n = 16) and non-FH patients without genetic variants (n = 16). Results: Increased numbers of PS+-EVs, CardioEVs, EEVs and TFEVs were observed in the group c arrying genetic variants. Furthermore, patients with FH who did not use statins had higher counts of these same EVs than non-FH patients who did not use statins. These EVs were significantly correlated with low-density lipoprotein cholesterol (LDL-c) levels. Conclusion: The data suggest that EVs are related to FH and that their cellular origins could be related to cardiovascular complications commonly observed in this disease.

Abstract in English:

ABSTRACT Mahvash disease is a rare autosomal recessive condition caused by biallelic inactivating variants in the GCGR gene, impairing glucagon signaling and leading to alpha-cell hyperplasia and pancreatic neuroendocrine tumors (PNETs). Fewer than 20 cases have been reported, and the clinical impact of heterozygous variants remains unclear. Case Presentation: We report a family with a novel GCGR splice-site variant (c.1176+1_1176+7delGTGCCCG). The index case, a 61-year-old woman, presented with extensive pancreatic cystic disease and was found to be homozygous for the variant. She developed well-differentiated PNETs and underwent total pancreatectomy. Her sister, also homozygous, had similar clinical features and surgical history. In contrast, the heterozygous brother and two sons showed mild biochemical changes, such as elevated glucagon levels and small pancreatic cysts, without overt disease. The two homozygous sisters required pancreatic surgery followed by insulin and enzyme replacement therapy, whereas heterozygous carriers are currently being managed with biochemical and imaging surveillance. This family’s phenotype suggests a broader spectrum of GCGR-related disease. While homozygous individuals displayed classic Mahvash disease, heterozygotes exhibited subtle biochemical and structural pancreatic changes, indicating possible semidominant expression. These findings are consistent with emerging evidence that monoallelic receptor pathway mutations may produce mild or subclinical phenotypes. This case challenges the classical recessive model of Mahvash disease and highlights the potential for disease expression in heterozygous carriers. These findings suggest that heterozygosity is not entirely silent and underline the need to reconsider surveillance recommendations for GCGR heterozygotes.