Exercise interventions can improve parameters in offspring predisposed to metabolic issues. In this study, we investigate whether acute aerobic exercise in offspring can improve metabolism via miRNA modulation in mice programmed by maternal obesity. Female Swiss mice fed either a standard chow (C) or a high-fat diet (HF) during gestation and lactation were mated with C male mice. Offspring fed the C diet underwent swimming exercise protocols, consisting of water adaptation (14 days), a lactate minimum test, and an aerobic intensity exercise session or no exercise at 84 days of age. Offspring of obese dams (OHF) exhibited increased hepatic glycogen and triglyceride compared to offspring of control dams (OC). However, in offspring of obese dams subjected to an individualized aerobic session (OHF-E), these parameters did not differed from the other groups. Hepatic gene expression analysis showed that miR-122 was upregulated in OHF-E, inversely to Agpat levels. Additionally, OHF exhibited higher miR-370 and lower Cpt1a levels; exercise restored miR-370 and elevated Cpt1a levels in OHF-E. Regarding muscle tissue, exercise reduced Ptp1b expression in OHF-E and increased Hif1a and Pparg, despite no changes observed in miR-206 levels. A single session of exercise significantly affected miRNA and transcript levels related to hepatic lipid and muscle glucose metabolism, suggesting that even one bout of exercise can benefit offspring in the context of maternal metabolic programming. This highlights tissue responsiveness and adaptive capacity, warranting further investigation into its potential as a long-term, non-pharmacological intervention.
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). 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. 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). 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.
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. 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. 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. 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.
This study aimed to compare body composition measurements between patients with nonfunctional adrenal incidentalomas (NFAI) and mild autonomous cortisol secretion (MACS) using bioelectrical impedance analysis (BIA) and anthropometric methods. This cross-sectional study included patients diagnosed with MACS or NFAI. Body composition was assessed using BIA, anthropometric measurements, and the Durnin and Womersley (DW) method. Correlation and Bland-Altman analyses were performed to assess the relationship and agreement between the DW method and BIA. Fifty-seven patients (32 with MACS and 25 with NFAI) were included; those with MACS were older (p = 0.004). Post-dexamethasone suppression test cortisol levels (p < 0.001) and the incidence of bilateral tumors (p = 0.017) were higher in MACS patients. No significant differences in body composition parameters were observed between the MACS and NFAI groups. A strong correlation was observed between BIA- and DW-derived fat mass in MACS patients (r = 0.890, p < 0.001). Bland-Altman analysis revealed a slight mean bias for body fat mass of -0.4 kg (limits of agreement: -9.14-8.34 kg) and for body fat percentage of -0.83% (limits of agreement: -11.32-9.66%) between methods. A robust correlation and acceptable agreement was demonstrated between the DW method and BIA for estimating body fat. The DW equation may provide a practical and low-cost alternative for assessing body composition in MACS and NFAI cohorts. Limitations include the lack of a healthy control group and the inability to validate BIA and anthropometric estimates against gold-standard imaging techniques, potentially introducing accuracy bias.
This study aims to evaluate ultra-processed food consumption and eating behavior in adults with obesity. 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). 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). 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.
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.
This study aimed to analyze preoperative, intraoperative, and postoperative factors that affect the surgical prognosis of non-functioning pituitary adenomas (NFPA) and to determine postoperative complication rates. We conducted a retrospective cohort study of patients with NFPA who underwent surgery between 1995 and 2024 at a tertiary public hospital in Brazil. Variables analyzed included tumor size, cavernous sinus invasion (Knosp classification), endocrinological status, preoperative clinical features, surgical complications, and outcomes. Statistical significance was set at p ≤ 0.05. Seventy-three patients were included, with a mean age of 53 years and a slight predominance of females. Tumors were classified as macroadenomas (59%) and giant adenomas (41%). The transsphenoidal approach was used in 81% of cases. Partial resection was achieved in 56%, subtotal in 16%, and total in 27%. Immediate postoperative complications included diabetes insipidus (30%), bleeding (11%), hydrocephalus (10%), ischemia (10%), meningitis (6%), and cerebrospinal fluid fistula (11%). Mortality was 9.6%, significantly associated with postoperative hydrocephalus, ischemia, and larger tumor size. Giant tumors were correlated with higher rates of preoperative neurological deficits and postoperative complications. Transcranial surgery was more frequently performed in cases of giant adenomas and was associated with increased rates of ischemia and neurological deficits. Tumor recurrence was observed in 33% of patients over a mean follow-up of 48 months. Tumor size and postoperative complications such as hydrocephalus and ischemia were associated with increased morbidity and mortality. Postoperative hydrocephalus, ischemia, and tumor size are key determinants of mortality in NFPA surgical treatment. Implementing preventive and management strategies targeting these complications could improve patient outcomes, albeit rigorous long-term follow-up is essential due to the high rates of recurrence and reoperation.
Measurement of serum prolactin levels is a common practice in clinical settings, particularly among women of reproductive age. In cases of hyperprolactinemia, identifying macroprolactinemia can help prevent unnecessary investigation and inappropriate treatments. This Position Statement, jointly prepared by the Brazilian Society of Endocrinology and Metabolism (SBEM) and the Brazilian Society of Clinical Pathology/Laboratory Medicine (SBPC/ML), addresses several aspects of macroprolactinemia relevant to clinical practice - including concepts, definitions, epidemiological aspects, measurement techniques, and the role of screening - and discusses some clinical dilemmas.
Oxytocin (OXT) is a neuropeptide hormone that plays a central role in numerous physiological and socio-emotional processes. Similar to arginine vasopressin (AVP), it is synthesized in the supraoptic and paraventricular hypothalamic nuclei and released both centrally and peripherally. Peripherally, OXT regulates uterine contractions during childbirth and milk ejection during lactation, metabolism, bone health, and cardiovascular functions. Centrally, it modulates social behavior, influencing trust, empathy, stress regulation, and emotional processing. Despite its close connection to AVP, the clinical significance of OXTDeficiency has only recently gained attention, particularly in patients with hypothalamic or pituitary damage with concomitant AVP-Deficiency. OXT-Deficiency may contribute to various neuropsychological symptoms seen in these patients, including social dysfunction, anxiety disorders, and reduced quality of life. However, a major challenge lies in accurately measuring OXT and thereby diagnosing a potential OXT-Deficiency. Basal plasma levels are unreliable, and most studied provocation tests only stimulate to a limited degree; hence, stronger provocation tests (e.g., using MDMA) and new surrogate parameters such as neurophysin I (NP-I) are gaining traction. Preliminary evidence from case reports and one small study suggests that intranasal OXT administration in patients with hypothalamic disorders may have beneficial effects on social behavior and emotion recognition. However, there is a clear need for larger, well-designed clinical trials, and several trials are currently underway to investigate the therapeutic potential of OXT in patients with AVP-Deficiency. OXT is also being explored as a possible treatment option in psychiatric conditions such as autism spectrum disorder, borderline personality disorder, and social anxiety disorder, with controversial results so far.
Thermal ablation (TA) encompasses various options such as radiofrequency ablation (RFA), microwave ablation (MWA), laser ablation (LA), and high-intensity focused ultrasound (HIFU). The fundamental principle of these techniques involves generating heat to induce coagulative necrosis of the nodules. The rising incidence of thyroid nodules, most of which are benign, has highlighted the importance of minimally invasive methods that effectively control symptoms, address cosmetic concerns, and achieve volume reduction. The potential complications associated with surgical interventions have driven the widespread adoption of TA modalities, now used not only for symptomatic benign thyroid nodules (BTN), including autonomously functioning thyroid nodules (AFTN), but also for low-risk papillary thyroid microcarcinoma (PTMC). The evidence presented in this consensus has demonstrated the comparable effectiveness of TA to surgery for BTN in terms of volume reduction percentage (VRP), resolution of symptoms, and cosmetic concerns. Similarly, TA could be considered a suitable option for treating AFTN when surgery or radioactive iodine (RAI) is contraindicated, or when patients decline either of these options, offering a comparable effectiveness profile to RAI in terms of normalizing thyroid-stimulating hormone levels. For PTMC, TA may serve as an alternative for patients at high surgical risk or those who decline surgery, showing comparable outcomes to surgery in terms of local recurrence and lymph node metastasis. Additionally, TA exhibits a superior safety profile compared to surgery or RAI, characterized by reduced complications, preservation of thyroid function, and shorter hospitalization durations. While evidence on cost-effectiveness in Latin America remains limited, studies conducted in other countries support the implementation of TA as a first-line treatment option for BTN. The lack of economic assessment specific to AFTN complicates its consideration as a primary treatment choice; however, the effectiveness and safety profile suggest that the widespread adoption of TA as a first-line therapy could be considered for carefully selected patients diagnosed with AFTN or PTMC. The Surgical Affairs Committee of the Latin American Thyroid Society conducted a comprehensive review of TA as a primary treatment modality for benign, autonomously functioning, and malignant thyroid nodules to ensure its appropriate utilization in the field.
Cushing's syndrome, characterized by chronic hypercortisolism, is associated with various health risks, including psychiatric symptoms and cognitive impairments. This systematic review of case studies aimed to map and categorize these symptoms. We hypothesized that a broader range of psychiatric and cognitive manifestations would be observed beyond anxiety, depression, and memory impairment. The review followed PRISMA guidelines and was preregistered in PROSPERO (CRD42024433186). We conducted searches in PsycINFO, Embase, PubMed, and Scopus, identifying 273 potentially relevant studies. After screening, 66 studies were included, comprising 74 cases (81% female; mean age 35.7 years, range 13-81). revealed that 93% of cases presented psychiatric complaints, including depression (39.2%), psychosis/schizophrenic symptoms (35.1%), suicidal ideation/attempts (20.3%), anxiety (17.5%), panic attacks (2.7%), and post-traumatic stress disorder (1.4%). Cognitive complaints were reported in 32% of cases, primarily as general cognitive complaints (18.9%), memory impairment (9.5%), and attentional deficits (5.4%). An overlap of psychiatric and cognitive symptoms was observed in 26% of cases. This review underscores the clinical relevance of symptoms such as mania, psychosis, and suicidal behavior in Cushing's syndrome, which are often underreported. Individualized clinical assessment informed by these case studies is crucial for comprehensive management that extends beyond the typical focus on depression and memory. Moreover, greater awareness of the full spectrum of neuropsychiatric manifestations in hypercortisolism is needed.
This study aimed to evaluate body composition, quality of life, and depression risk in women with polycystic ovary syndrome (PCOS) compared to women without PCOS. This prospective, cross-sectional study assessed quality of life (QoL) and depressive symptoms in women with polycystic ovary syndrome (PCOS) compared with controls with and without overweight or obesity. Assessments included body composition, QoL, health-related quality of life (HRQoL), and depressive symptoms. Participants without PCOS were divided into two groups according to BMI: < 25 kg/m2 [median age 30 years (27-33)] and ≥ 25 kg/m2 [median age 32 years (29-35)]. The study included 47 women with polycystic ovary syndrome (PCOS) phenotypes A and B. The median age was 29 years (25-35), and the median body mass index (BMI) was 32.08 kg/m2 (28.48-36.40). Women with PCOS showed a higher risk of depression (24% with moderate to severe risk) compared with women without PCOS, both with and without overweight or obesity (5% and 3%, respectively). Additionally, women with PCOS consistently reported lower QoL and HRQoL scores, particularly in the physical, environmental, and overall QoL domains, as well as in functional capacity, pain, general health status, vitality, emotional well-being, and mental health domains of HRQoL. Based on these findings, we concluded that body composition does not appear to be a determining factor for increased risk of depressive symptoms or poorer perceptions of QoL and HRQoL in women with PCOS.
The separation of the interior from the exterior environment through the skin was fundamental for the evolutionary progression from prevertebrates into vertebrates. The development of the skin also established an internal environment controlled by hormones. The skin is influenced by different hormones; it is also the largest endocrine organ, producing several hormones. Skin inspections often save lives from skin cancer but can also diagnose potentially deadly endocrine diseases. The objectives of this review were to describe the emergence and definition of dermatoendocrinology and to focus on the clinical diagnosis of cutaneous manifestations of endocrine disorders, some of which are potentially fatal. This narrative review was based on a comprehensive search using the term "dermatoendocrinology" since its creation in 2001 in the PubMed® database. Subsequently, a complementary search was performed with combinations of the keywords "skin", "insulin", "diabetes", "thyroid", "adrenal", "sex hormones", "parathyroid hormone", and "growth hormone." A total of 111 articles were included. The cutaneous manifestations of Itabaianinha syndrome (isolated growth hormone deficiency) and five anecdotal cases that enabled life-saving therapeutic measures are reported. The dermatoendocrine conditions described include acanthosis nigricans and androgenetic alopecia (insulin resistance), necrobiosis lipoidica diabeticorum and granuloma annulare (diabetes), pretibial myxedema (hyperthyroidism), xerosis cutis (hypothyroidism), purple striae and facial plethora (hypercortisolism), hyperpigmentation (primary adrenal insufficiency), dryness and urogenital atrophy (hypoestrogenism), hirsutism and virilization (hyperandrogenism), pruritus and calcium deposition (hyperparathyroidism), thinness, wrinkling, and reduced sweating (growth hormone deficiency), and thick oily skin with excessive sweating (acromegaly). Skin inspection allows the diagnosis of serious endocrinopathies.
Previous studies suggest a bidirectional relationship between thyroid dysfunction and sleep disorders. However, prospective evidence regarding the impact of sleep characteristics on subclinical hypothyroidism remains limited. This study aimed to evaluate the association between insomnia symptoms, sleep duration, and sleep debt and the incidence of subclinical hypothyroidism. We conducted a prospective cohort analysis of 7,983 euthyroid participants from the second wave (2012-2014) of the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) who were not taking thyroid-related or psychiatric medications. Insomnia symptoms (initial, middle, and terminal), sleep duration, sleep debt, sociodemographic characteristics, and health behaviors were assessed via questionnaires. Subclinical hypothyroidism was defined as thyrotropin >4.0 μIU/mL and normal free thyroxine in the third wave (2016-2018). Crude and adjusted log-binomial regression models estimated relative risks (RR) and 95% confidence intervals (95% CI). The incidence of subclinical hypothyroidism was 6.6% for both sexes. In women, middle insomnia was associated with a 35% reduced risk of subclinical hypothyroidism (RR: 0.65; 95% CI: 0.44-0.92). Among men, sleep debt was linked to a 30% increased incidence (RR: 1.30; 95% CI: 1.01-1.66), and in the continuous model, each additional hour of sleep debt raised the risk by 9% (RR: 1.09; 95% CI: 1.02-1.14). Of the sleep characteristics assessed, middle insomnia due to nocturnal awakenings appeared to be protective against subclinical hypothyroidism among women, while sleep debt increased the risk among men.
The thyroid-gut axis represents a dynamic interaction between the intestinal microbiota and thyroid function, with growing evidence linking gut dysbiosis to thyroid diseases. The gut microbiome, comprising over 100 trillion microorganisms, influences immune modulation, iodine metabolism, and thyroid hormone regulation. Short-chain fatty acids, produced by beneficial gut bacteria, support immune homeostasis and thyroid function, while pathogenic bacteria and lipopolysaccharides trigger inflammatory pathways that impair thyroid activity. Alterations in gut microbiota composition have been associated with autoimmune thyroid diseases, including Hashimoto's thyroiditis and Graves' disease. Dysbiosis increases intestinal permeability, antigen exposure, and immune activation, exacerbating thyroid autoimmunity. A reduction in short-chain fatty acids-producing bacteria weakens immune tolerance, promoting inflammatory cytokine release and autoantibody production. Recent studies highlight microbial metabolites such as tryptophan derivatives and their role in immune regulation. Gut dysbiosis is also implicated in thyroid nodules and cancer. Decreased butyrate-producing bacteria and increased inflammatory bacterial taxa have been observed in thyroid malignancies. Microbiota influence iodine and selenium bioavailability, essential for thyroid hormone synthesis, and modulate sodium-iodide symporter expression, affecting thyroid cancer response to radioactive iodine therapy. Microbiome-targeted interventions, including probiotics, prebiotics, dietary modifications, and fecal microbiota transplantation, may restore microbial balance, enhance immune regulation, and improve thyroid treatments. This review synthesizes our current understanding of the thyroid-gut axis, indicating that the intestinal microbiota and its metabolites may act directly or indirectly on the thyroid gland, highlighting potential clinical implications and paving the way for therapeutic strategies targeting the intestinal microbiota.
The pleiotropic role of vitamin D in human health has been implicated in modulating bone metabolism and other several extraskeletal areas, including muscle and adipose tissues regulation, and in influencing general and systemic outcomes. In the elderly, vitamin D deficiency is considered as an emerging public health issue affecting 40%-70% of older adults worldwide with higher rates occurring in institutionalized individuals or patients with multiple chronic comorbidities. The pathophysiology of vitamin D deficiency in the elderly is multifactorial and includes age-related reduced skin synthesis, limited sun exposure, declined renal and liver function, and long-term use of interfering medications. Given its pleiotropic effects, vitamin D deficiency in the elderly has been consistently associated with progressive bone deterioration and muscle and adipose dysfunctions, concurring to the occurrence of the osteosarcopenic obese phenotype. This multifaced deleterious scenario is strongly correlated with an increasing risk of fragility fractures, falls, functional and metabolic decline, all of which contribute to higher morbidity and mortality. Early diagnosis and screening with individualized criteria, targeted and personalized strategies for supplementation, and structured follow-up monitoring are required to reduce the clinically significant impact of vitamin D deficiency in this highly vulnerable population.
Postoperative weight regain remains a challenge after bariatric surgery and affects long-term outcomes. This study aimed to develop a clinical model to predict weight regain within 12 months, prior to surgery by using preoperative inflammatory, metabolic, and ferritin as biomarkers. This retrospective observational study included 394 patients with obesity who underwent bariatric surgery (2020-2023), including laparoscopic sleeve gastrectomy (LSG) and laparoscopic Roux-en-Y gastric bypass (LRYGB). Patients were divided into a training set (70%, n = 276) and a validation set (30%, n = 118) using a random number table. Weight regain was defined as a ≥ 10% increase from the postoperative nadir (median time to regain: 8.2 months). Key variables included peripheral blood inflammatory markers [systemic immune-inflammation index (SII, calculated as platelet count × neutrophil count/lymphocyte count), neutrophil-to-lymphocyte ratio (NLR)], glycolipid metabolism indicators [low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C)], and ferritin levels. Multivariate logistic regression was used to identify independent predictive variables, and the nomogram model was validated via calibration, area under the receiver operating characteristic curve (AUC), and decision curve analysis (DCA). The weight regain rate was 19.9% (55/276) in the training set. Independent predictive variables included elevated SII (OR=1.004; 95% CI = 1.000-1.007), LDL-C (OR = 1.873; 95% CI = 1.054-3.329), ferritin (OR = 1.005; 95% CI = 1.003-1.008), and reduced HDL-C (OR = 0.103; 95% CI = 0.013-0.844) (all P < 0.05). The model showed strong discrimination (training AUC = 0.852, 95% CI = 0.795-0.910; validation AUC = 0.812, 95% CI = 0.709-0.915) and good calibration (Hosmer-Lemeshow P > 0.05). DCA confirmed the model's clinical utility across threshold probabilities. Preoperative SII, LDL-C, ferritin, and HDL-C levels effectively predict postoperative weight regain. Early monitoring of these biomarkers may guide personalized interventions to improve long-term outcomes.
Pheochromocytomasand paragangliomas (collectively referred as PPGLs) are highly heritable neoplasms arise from chromaffin cells of neural crest tissues; 40% of patients with PPGLs harbour germline pathogenic variants (PV), which up to 45% of patients exhibit somatic mutations in similar susceptibility genes. Endothelial PAS domain-containing protein-1 [also known as hypoxia inducible factor-2α, HIF-2α] is encoded by EPAS1, and along with other hypoxia-inducible factors (HIFs) acts as a key mediator in the cellular response to hypoxia. Gain-of-function mutations in EPAS1 have been linked to the Pacak-Zhuang syndrome, congenital cyanotic heart disease and sickle cell anaemia. Hypoxia due to chronic anaemia and/or associated nephropathy in patients with sickle cell disease (SCD) may increase the expression of genes related to HIFs, thereby increasing susceptibility to the development of PPGLs. We describe a case of young female with a history of sickle cell anaemia and sickle cell nephropathy who was found to have a para-aortic mass. Histology confirmed the diagnosis of a paraganglioma. She did not exhibit somatic mutations of the common predisposition genes but demonstrated a likely pathogenic activating somatic EPAS1 variant mutation. This case illustrates the predisposition of patients with SCD to PPGLs due to somatic EPAS1 mutations, and should increase awareness of such tumours in these patients.
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. 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. 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. 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.
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.