Archives of Endocrinology Metabolism最新文献

Immune checkpoint inhibitors have become transformative therapies, significantly enhancing survival outcomes for various neoplasms. However, they often trigger immune-related adverse events, including endocrinopathies. Cushing's syndrome, characterized by exposure to elevated levels of circulating cortisol, presents a wide range of clinical features and is closely associated with increased morbidity and mortality. This article reports on a case of a patient under checkpoint inhibitor therapy, who developed cyclic adrenocorticotropic hormone-dependent hypercortisolism. The patient exhibited a Cushingoid phenotype, and testing revealed increased cortisol levels following the administration of 1 mg of dexamethasone, indicating endogenous hypercortisolism. Notably, the cortisol levels followed a cyclic pattern, decreasing as the next dose of pembrolizumab neared, thereby linking the hypercortisolism to fluctuations in the medication's serum concentration. Given the significant morbidity linked to hypercortisolism, it is crucial for physicians prescribing immune checkpoint inhibitors to recognize the potential onset of endocrinopathies with unconventional presentations, such as cyclic hypercortisolism. Such conditions may present diagnostic and therapeutic challenges, ultimately impacting patient survival.

Objective: Metabolic dysfunction-associated steatotic liver disease (MASLD), a worldwide public health challenge with a prevalence of around 25%, is strongly related to obesity and insulin resistance. The present study investigated the possible association between MASLD and the leptin gene (LEP) -2548G>A (rs7799039) polymorphism.

Subjects and methods: A total of 250 subjects (125 biopsy-proven MASLD patients and 125 controls) were genotyped for the -2548G>A promoter variant using the PCR-RFLP technique.

Results: There was no deviation from Hardy-Weinberg equilibrium for LEP -2548G>A polymorphism in both groups (P > 0.05). A significant association between this gene variant and MASLD was found. The LEP -2548G>A "GG" genotype compared with ''AA+AG'' genotype was underrepresented in the MASLD patients than controls, even after adjustment for confounding factors (P = 0.016; OR = 0.42, 95% CI = 0.40-0.83).

Conclusion: For the first time, our findings demonstrated that the "GG" genotype of LEP -2548G>A gene variant can be a potential protective factor for MASLD. Further studies in other populations, however, are required to support this finding.

Objective: Obesity prevalence is increasing in Brazil. Real-world observational data were used to understand clinical weight management practice, and the economic and health-related quality-of-life (HRQoL) impact of obesity.

Materials and methods: Data were derived from the Adelphi Real World Obesity Disease Specific Programme (DSP)™, a cross-sectional survey of people with obesity (PwO) and treating physicians, conducted in Brazil May-October 2022. Physicians reported demographic/clinical characteristics and current/previous weight management. PwO reported emotional/financial impact of obesity, and completed patient-reported outcomes on HRQoL, and activity/work impairment.

Results: In total, 99 physicians reported on 895 PwO. Mean ± SD PwO age was 43.1 ± 13.7, majority were female (60.9%) and white (71.7%). Mean ± SD BMI at survey was 33.8 ± 9.4 with 40.5%, 23.2% and 11.1% of PwO having class 1, 2 or 3 obesity. Weight management was most commonly at PwO request (43.4%), and consisted of prescription weight loss drug (53.6%), and dietician or physician-supervised diets (79.9% and 55.1%). Most PwO reported financial impact due to obesity treatment and reported being bothered/embarrassed by their weight. SF-36v2 physical summary scores ranged from 52.4 ± 9.3 to 45.6 ± 8.6 and mental summary scores from 45.5 ± 9.3 to 42.2 ± 12.3 (BMI < 30 to class 3 obesity). Overall work and activity impairment ranged from 20.0 ± 22.7 to 42.4 ± 28.4 (BMI < 30 and class 2 obesity) and from 24.7 ± 25.2 to 43.2 ± 32.5 (BMI < 30 to class 3 obesity), and 3.2% did not work due to obesity.

Conclusion: PwO have a substantial impact on work, and financial, emotional and quality-of-life burden. Our data highlight the need for more efficacious obesity management, to help reduce work and activity impairment, improve quality of life.

Objective: Transgender and gender-diverse (TGD) refers to people whose gender identity does not correspond to the sex assigned to them at birth. This study evaluated the knowledge of medical residents at a tertiary hospital in northeastern Brazil regarding healthcare for the TGD population.

Materials and methods: This cross-sectional, single-center observational study surveyed medical residents at a tertiary hospital in northeastern Brazil in 2023. It utilized a self-developed online questionnaire, which residents completed voluntarily and anonymously. Descriptive statistics, chi-square analyses, and multivariate logistic regression were applied to the data.

Results: A total of 107 residents completed the questionnaire (40.83% of the eligible cohort); most were clinicians (69.15%). All participants identified as cisgender. Nearly all participants considered it important to understand healthcare for TGD patients. About half reported prior education on the topic; gynecology, obstetrics, and endocrinology residents (specialists) demonstrated the highest rates (p = 0.0009). Approximately 40% of the participants were unaware of where to refer TGD people for specialized care in hormone therapy and gender-affirming surgeries (p = 0.007). Lack of experience (p = 0.002) was the primary reason among the 30 residents who felt insecure about providing healthcare to TGD patients.

Conclusion: Residents acknowledge the importance of this field in their practice but demonstrate a lack of specific knowledge and prior education.

VitaminD deficiency is a global concern, and calcifediol serves as an alternative to cholecalciferol for achieving and maintaining optimal vitamin D levels, despite the lack of international guidelines for calcifediol supplementation regimens. We present a case involving a 58-year-old patient with osteoporosis and a medical history of type 2 diabetes, obesity, and cirrhosis. Standard treatment with calcium, cholecalciferol, and bisphosphonate was initiated; however, supplementation failed to achieve the target vitamin D levels during follow-up. Subsequently, calcifediol was introduced at a dose of 10 mcg daily, which was increased to 20 mcg daily after one month. Nonetheless, the vitamin D serum concentration rose to 80 ng/mL by the third month, prompting discontinuation of the drug and levels gradually decreased to 28 ng/mL over 2.5 months. Upon the administration of calcifediol at 10 mcg three times a week, serum levels stabilized at 35 ng/mL. Calcifediol offers several advantages over cholecalciferol, including better intestinal absorption, bypassing the need for hepatic hydroxylation, and a more rapid increase in 25-hydroxyvitamin D (25[OH]D) levels. Current guidelines recommend considering calcifediol in cases of obesity, malabsorption syndromes, and chronic hepatic diseases, although optimal dosages remain uncertain. Based on the commercially available tablet in Brazil, we suggest initiating calcifediol at 10 mcg per day and adjusting the dose according to 25(OH)D levels.

Objective: Long non-coding RNAs (lncRNAs) do not encode proteins and are transcripts longer than 200 nucleotides. The precise involvement of lncRNAs in type 1 diabetes mellitus (T1DM) pathogenesis remains unclear. Therefore, this study aimed to analyze the expressions of five lncRNAs in peripheral blood mononuclear cells of individuals with T1DM and without DM.

Materials and methods: This study comprised 27 patients with T1DM (cases) and 13 individuals without DM (controls). The case group was divided into two subgroups based on T1DM duration: < 5 years of diagnosis group and long-term diabetes group (≥5 years). LncRNA expression was evaluated by qPCR.

Results: MALAT1 and TUG1 were upregulated in patients within the first five years of diagnosis of T1DM compared to the other groups. MEG3 was upregulated in the case group of < 5 years of diagnosis compared to controls. TUG1 and MALAT1 levels were negatively correlated with the duration of T1DM, while TUG1 and MEG3 were positively correlated with glycated hemoglobin levels. Bioinformatics analysis revealed that MALAT1, MEG3, and TUG1 regulate and interact with protein-codifying genes and microRNAs involved in T1DM-related pathways.

Conclusion: Our study revealed MALAT1, MEG3, and TUG1 upregulation in patients within the first five years of diagnosis of T1DM.

Objective: Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as nonalcoholic fatty liver disease, affects approximately 38% of the global population. MASLD's strong association with obesity and type 2 diabetes positions it as an increasingly prevalent indication for liver transplantation. Hence, this study sought to assess the prevalence of MASLD as an indication for liver transplantation, to characterize the clinical and epidemiological profile of the affected population, and to investigate the rates of post-transplant recurrence and de novo occurrence. We also compared survival outcomes between recipients with MASLD and other etiologies. Materials and methods: We conducted a retrospective analysis of 610 patients listed for liver transplantation at Hospital das Clínicas (University of São Paulo) between 2005 and 2015. Data regarding demographics, comorbidities, and post-transplant outcomes were collected from medical records. The statistical analysis encompassed both descriptive and inferential methods. Results: Out of 610 patients, 61 (10%) were diagnosed with MASLD-related cirrhosis, presenting a waitlist mortality rate of 42.6%. Among the 264 who received transplants, 36 (13.6%) had MASLD as the primary diagnosis. Post-transplantation, 58 recipients developed steatosis, with 82.8% of these cases being de novo allograft steatosis. Pre-transplant obesity and hypertension were identified as significant risk factors. Importantly, patients undergoing transplantation for MASLD showed lower survival rates compared to those with other etiologies. Conclusion: MASLD patients who undergo liver transplantation exhibit distinctive clinical outcomes and reduced survival rates. These findings underscore the critical need for targeted risk assessments and developing long-term strategies to enhance the prognosis for this increasingly common patient demographic.

Objective: To evaluate muscle functionality, physical performance and body composition in young people living with human immunodeficiency virus (PLWH).

Subjects and methods: Eighty-one HIV-infected and 54 uninfected (20 to 50 years) male and female subjects were enrolled to participate. Patient evaluation included body composition by DXA (dual energy X-rays), SARC-F questionnaire, hand grip and timed up & go (TUG) tests.

Results: Fifty PLWH and 50 age-gender matched controls completed the study. The median age was 40 (25-49) vs. 36.5 (22-50) for the HIV and control groups, respectively (p 0.120). Race, gender, body mass index, phosphorus and 25-hydroxyvitamin D were similar between groups. HDL-c was significantly lower in HIV-infected (p 0.006). Groups had similar body composition parameters, although more PLWH presented appendicular lean mass (ALM) and ALM adjusted to height (ALM/h2) below reference values (18% vs 4%). SARC-F questionnaire and TUG were significantly compromised in HIV-infected when compared to controls (p 0.001 and 0.005, respectively). Hand grip test was slightly lower in PLWH than in control group (29.0 kg (9.3-56.0) vs. 32.8 kg (13.3-57.3); p 0.052).

Conclusion: Our results suggest that there is loss of functionality, physical performance and muscle strength in young PLWH. Therefore, screening using SARC-F, hand grip and TUG test might be interesting in HIV-infected which are considered at high-risk for sarcopenia. With early diagnosis there is the possibility of decreasing muscle dysfunction, morbimortality, providing an increase in quality of life and working hours.