Resumo em Inglês:

Abstract 11β-hydroxylasedeficiency (11β-OHD) is a rare form of congenital adrenal hyperplasia caused by biallelic pathogenic variants in the CYP11B1 gene. It leads to impaired cortisol synthesis, resulting in increased adrenocorticotropic hormone stimulation and consequent accumulation of steroid precursors, which are diverted to androgen synthesis. In addition, the accumulation of 11-deoxycorticosterone, which is a potent mineralocorticoid, causes hyporeninemic hypokalemic hypertension. We report the clinical, hormonal, and genetic profiles of five children with 11β-OHD, emphasising phenotypic variability, a median 2-year diagnostic delay, the crucial role of hormonal profile in diagnosis, and management challenges, including post-treatment central precocious puberty. Two novel CYP11B1 variants were identified in two unrelated patients. Hydrocortisone replacement resolved hypertension in only one of the three hypertensive patients; others required spironolactone. Early differentiation of 11β-OHD from 21-hydroxylase deficiency is critical to prevent hypertension-related morbidity.

Resumo em Inglês:

Abstract Neonatalsevere hyperparathyroidism (NSHPT) is a rare, life-threatening disorder caused by biallelic inactivation of the CASR gene, resulting in severe hypercalcemia and markedly elevated parathyroid hormone (PTH) levels in early life. Although total parathyroidectomy is often curative, long-term calcium balance and treatment requirements remain poorly understood. We describe the 25-year follow-up of a woman with NSHPT due to a homozygous CASR p.Arg680His variant who underwent total parathyroidectomy with autotransplantation at 32 days of age. Despite initial normalization of calcium levels, graft failure led to permanent hypoparathyroidism requiring long-term calcium and active vitamin D supplementation. Over time, calcium and calcitriol requirements progressively decreased despite persistently undetectable PTH, with recurrent episodes of hypercalcemia requiring careful dose adjustments. This case represents one of the longest documented follow-ups of genetically confirmed homozygous CASR-related NSHPT. The progressive decline in calcium requirements reflects impaired renal calcium excretion and an altered calcium-PTH set point characteristic of CASR inactivation. These physiological adaptations challenge the conventional supplementation strategies and suggest that standard hypoparathyroidism guidelines - largely derived from acquired or autoimmune forms - may require cautious individualization in patients with homozygous CASR variants, given their distinct renal calcium handling and the possibility of lower urinary calcium excretion. Our findings reinforce the complexity of long-term management in NSHPT patients and illustrates how calcium requirements may change over time. Long-term follow-up cases such as this may contribute to a better understanding of the physiological mechanisms and inform future guideline development for this rare condition.

Resumo em Inglês:

Abstract Objective: To assess the efficacy and safety of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in kidney transplant recipients (KTRs) with post-transplant diabetes mellitus (PTDM). Subjects and methods: This retrospective, single-center cohort study included 24 KTRs with PTDM who initiated GLP-1 RA therapy as an add-on to existing treatments between August 2013 and April 2024. Outcomes assessed included fasting plasma glucose (FPG), glycated hemoglobin (HbA1c), body weight, body mass index (BMI), blood pressure, lipid profile, renal function, and adverse events, with data collected at baseline and last follow-up. Results: Over a mean follow-up of 3.2 ± 2.1 years, GLP-1 RA therapy was associated with trends toward weight loss (-3.6 ± 8.5 kg; p = 0.051) and BMI reduction (-1.4 ± 3.3 kg/m2; p = 0.056). HbA1c decreased by -0.2% (p = 0.362), while FPG increased by +12.1 mg/dL (p = 0.232). Significant improvements were observed in total cholesterol (-41.5 mg/dL; p < 0.001) and systolic blood pressure (-8.5 mmHg; p = 0.041). Serum creatinine and estimated glomerular filtration rate remained stable (-0.09 mg/dL, p = 0.305; +3.2 mL/min/1.73 m2, p = 0.206, respectively). Nausea occurred in 21% (n = 5), and no other severe adverse events were reported. Conclusion: In KTRs with PTDM, GLP-1 RA therapy was associated with improvements in lipid profile and blood pressure, accompanied by non-significant trends toward weight reduction and stable renal function, and demonstrated an acceptable safety profile. Prospective studies are warranted to confirm long-term cardiorenal benefits.

Resumo em Inglês:

Abstract Objective: To evaluate pregnancy outcomes in women with early gestational diabetes mellitus (eGDM) diagnosed by mild elevation of fasting plasma glucose (FPG) in the first trimester. Subjects and methods: This prospective cohort study included 114 pregnant women with first trimester FPG <100 mg/dL (5.6 mmol/L). Women with FPG ≥92 mg/dL (5.1 mmol/L) and <100 mg/dL (5.6 mmol/L) were classified as having eGDM, and FPG was reassessed after approximately 3-4 weeks. Women whose repeated FPG was <92 mg/dL (5.1 mmol/L) were assigned to Group 1 (G1; n = 33) and did not receive eGDM treatment. These participants underwent an oral glucose tolerance test (OGTT) between 24-28 weeks of gestation and, depending on the results, initiated treatment as indicated. Women with eGDM and a second FPG 92-125 mg/dL (5.1-6.9 mmol/L) were assigned to Group 2 (G2; n = 31) and immediately started eGDM treatment. The control group (G3; n = 50) was composed by pregnant women with FPG <92 mg/dL (5.1 mmol/L) in the first trimester. Results: G1 and G3 had lower pre-pregnancy body mass index, less chronic hypertension, lower rates of GDM history, and lower multiparity compared to G2. There was no significant difference in GDM diagnosis by OGTT between G1 and G3 (27.3% vs. 20.0%, p = 0.594). G3 gained more weight (10.2 ± 7.6 kg, 7.5 ± 6.4 kg, and 13.5 ± 6.1 kg for G1, G2, and G3, respectively; p = 0.001). Other outcomes between G1 and G3 were similar. Conclusion: Women with eGDM diagnosed by mild, non-persistent FPG elevation in the first trimester had similar outcomes to those with normal early FPG.

Resumo em Inglês:

Abstract Objective: To evaluate the effect of taurine supplementation on the lipid profile of male hypothyroid Wistar rats. Materials and methods: Adult male Wistar rats were induced to hypothyroidism by treatment with 0.03% methimazole in drinking water. After 21 days, half of the hypothyroid animals received daily taurine supplementation by gavage (520 mg/kg b.w.), while the other half received water. Control animals received taurine at the same dose or water by gavage for an additional 21 days, totaling 42 days of treatment. The groups were: Control (C), Taurine (T), Hypothyroid (H), and Hypothyroid + Taurine (H+T) (n = 5-20/group). Data were expressed as mean ± SEM, and statistical analysis was performed using two-way ANOVA followed by Tukey’s post-test. Results: Hypothyroidism increased serum total cholesterol (TC) and LDL levels, which were reduced by taurine supplementation. Hepatic diacylglycerol concentration increased with taurine supplementation, but this effect was not observed in hypothyroid animals. Taurine increased AMPK and ACC phosphorylation in the liver independently of thyroid hormone levels. Conclusion: Hypothyroidism induces changes in the lipid profile, particularly increasing TC and LDL cholesterol levels. Taurine supplementation in hypothyroid rats partially reversed lipid alterations and increased AMPK and ACC phosphorylation in the liver, suggesting metabolic benefits.

Resumo em Inglês:

Abstract Objective: To examine the association between triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio and the onset of diabetes mellitus (DM) within an ongoing prospective cohort in China. Subjects and methods: Participants were categorized into four groups according to their TG/HDL-C ratio quartiles. Kaplan-Meier estimator determined the cumulative incidence during follow-up and generated time-to-event curves. Additionally, a Cox proportional hazards regression analysis assessed the hazard ratios (HRs) and their corresponding 95% confidence intervals (CIs) for new-onset DM. A sensitivity analysis was also performed to mitigate the possible effects of reverse causation. Results: During a median follow-up duration of 13.67 years, 38,210 individuals developed DM. Kaplan-Meier curves revealed that the cumulative DM incidence across quartiles 1 to 4 was 40.95%, 42.04%, 41.42%, and 44.38%, respectively. The risk of developing DM increased over time according to the baseline TG/HDL-C ratio quartiles. After adjusting for potential confounding variables, the HRs reached 1.045 (95% CI, 1.015-1.076), 1.026 (95% CI, 0.996-1.058), and 1.095 (95% CI, 1.058-1.133) for quartiles 2, 3, and 4, respectively (P for trend < 0.001). These findings were consistent in sensitivity analyses, with HRs of 1.045 (95% CI, 1.016-1.075), 1.026 (95% CI, 0.996-1.058), and 1.095 (95% CI, 1.058-1.133) for quartiles 2, 3, and 4, respectively (P for trend < 0.0001). Conclusion: TG/HDL-C ratio is significantly and positively associated with new-onset DM.

Resumo em Inglês:

Abstract Objective: This study aims to analyze the clinical characteristics and prognostic factors of patients with parathyroid carcinoma (PC) treated at a tertiary institution. Subjects and methods: This retrospective cohort included 30 patients with PC who were treated between 1970 and 2023 at a single reference center. Clinical, pathological, and survival data were reviewed and prognostic factors were evaluated. Results: Of the 30 cases, 16 (53.3%) were women. Mean age at diagnosis was 45.9 years, median follow-up was 60 months and mean tumor size was 33 mm. Median follow-up was 60 months. Disease recurrence occurred in 16 (53.3%) cases, with disease persistence in three (10.0%). Median disease-free survival was 80 months, with a 57% overall survival rate. Neither gender nor age showed significant impact on survival. Patients with lower-stage tumors (T1 by the AJCC/UICC and T1+T2 by the Shaha classification) had significantly better overall survival (p = 0.004 and p = 0.0018, respectively) and disease-free survival (p = 0.03 and p = 0.04, respectively) than those with more advanced stages (p = 0.03 and p = 0.04, respectively). Additionally, patients who experienced tumor recurrence after 36 months had significantly better survival outcomes than those with earlier recurrences (p = 0.02). Conclusion: Advanced tumor stage (T3 by the Shaha or T2 and above by the AJCC/UICC) is associated with higher mortality in patients with PC. Furthermore, a disease-free interval exceeding 36 months emerged as a relevant factor associated with improved overall survival.

Resumo em Inglês:

Abstract Objective: Obesity and diabetes are widely recognized risk factors for cardiovascular disease, and their increase among Indigenous populations has been documented in the medical literature. Given the regional differences in the prevalence of metabolic disorders, this study aimed to evaluate the prevalence of obesity, diabetes, and other metabolic conditions in the Bororo population of the Central-West region of Brazil. Subjects and methods: In this cross-sectional study, 152 Bororo individuals from the Meruri Reservation in Mato Grosso, Brazil, underwent clinical, anthropometric, and laboratory assessments. Results: Women presented a worse metabolic profile than men, demonstrating significantly higher body mass index, waist circumference, total cholesterol, LDL-c, and 2-hour glucose levels, whereas men exhibited higher systolic blood pressure. Obesity was observed in 30.2% of the participants, with a higher prevalence among women (40.0% vs. 21.9%, p = 0.02). Prediabetes affected 51.3% of the participants, showing a higher prevalence in older men than in younger men (70.6% vs. 43.7%, p = 0.02). Diabetes was diagnosed in 9.2% of the participants, exclusively among women (20.0%), and rose to 38.7% in women aged ≥40 years. Hypertension was present in 23.0% of the participants and was positively associated with age. Central obesity was highly prevalent in this study cohort (72.3%). Conclusion: Our findings revealed an unfavorable metabolic profile among the Bororo Indigenous population, particularly in older women. This underscores the critical need for sexand age-specific preventive measures and management strategies for metabolic diseases in this population.