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BACKGROUND: Primary hyperparathyroidism is a common endocrine disorder characterised by excessive parathormone secretion that results in hypercalcemia, primarily caused by parathyroid adenoma. Accurate localisation of hyperfunctioning tissue is essential for curative surgical treatment. Although conventional imaging modalities like ultrasonography and 99mTc-MIBI scintigraphy (SPECT) along with 18F-fluorocholine PET/CT are commonly employed, there are cases with false-negative imaging results. CASE PRESENTATION: This case report presents a patient with primary hyperparathyroidism and a parathyroid adenoma detected solely through 68Ga-PSMA-11 PET/CT, typically used for prostate cancer diagnosis. The lesion observed in the PET/CT was confirmed as a parathyroid adenoma through laboratory evaluation, while other imaging techniques failed to detect it. CONCLUSIONS: This finding suggests that the PSMA ligands' particular affinity for neovascularisation in focal changes may facilitate the visualisation of parathyroid adenomas. The utilisation of 68Ga-PSMA-11 PET/CT in primary hyperparathyroidism could potentially improve the preoperative localization of parathyroid adenomas when conventional imaging methods are inconclusive.
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Introduction: Normosmic isolated hypogonadotropic hypogonadism (nIHH) is a clinically and genetically heterogeneous disorder. Deleterious variants in over 50 genes have been implicated in the etiology of IHH, which also indicates a possible role of digenicity and oligogenicity. Both classes of genes controlling GnRH neuron migration/development and hypothalamic/pituitary signaling and development are strongly implicated in nIHH pathogenesis. The study aimed to investigate the genetic background of nIHH and further expand the genotype-phenotype correlation. Methods: A total of 67 patients with nIHH were enrolled in the study. NGS technology and a 38-gene panel were applied. Results: Causative defects regarded as at least one pathogenic/likely pathogenic (P/LP) variant were found in 23 patients (34%). For another 30 individuals, variants of unknown significance (VUS) or benign (B) were evidenced (45%). The most frequently mutated genes presenting P/LP alterations were GNRHR (n = 5), TACR3 (n = 3), and CHD7, FGFR1, NSMF, BMP4, and NROB1 (n = 2 each). Monogenic variants with solid clinical significance (P/LP) were observed in 15% of subjects, whereas oligogenic defects were detected in 19% of patients. Regarding recurrence, 17 novel pathogenic variants affecting 10 genes were identified for 17 patients. The most recurrent pathogenic change was GNRHR:p.Arg139His, detected in four unrelated subjects. Another interesting observation is that P/LP defects were found more often in genes related to hypothalamic-pituitary pathways than those related to GnRH. Conclusions: The growing importance of the neuroendocrine pathway and related genes is drawing increasing attention to nIHH. However, the underestimated potential of VUS variants in IHH etiology, particularly those presenting recurrence, should be further elucidated.
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Hormônio Liberador de Gonadotropina , Hipogonadismo , Humanos , Hormônio Liberador de Gonadotropina/genética , Masculino , Feminino , Hipogonadismo/genética , Adulto , Adulto Jovem , Adolescente , Transdução de Sinais/genética , Sistema Hipotálamo-Hipofisário/metabolismo , Mutação , Pessoa de Meia-Idade , Receptores LHRH/genética , Estudos de Associação Genética , CriançaRESUMO
Elevated immunoglobulin G4 (IgG4) serum antibodies are an important feature of IgG4-related disease. However, IgG4 antibodies can play a role in autoimmune thyroid disorders. In this study, we aimed to evaluate the impact of serum IgG4 levels on clinical features of Graves' disease (GD). We recruited 60 patients with GD (48 patients without thyroid eye disease, 12 patients with moderate-to-severe Graves' orbitopathy [GO], and 25 healthy control subjects). The prevalence of high IgG4 serum concentration was 4.2% among GD patients without GO and 33.33% in patients with moderate-to-severe GO. The group with GO had significantly higher median IgG4 levels (87.9 mg/dL) than the control group (41.2 mg/dL, P = 0.034) and the GD without GO group (30.75 mg/dL, P < 0.001). Patients with thyroid nodules had lower IgG4 levels than patients without thyroid nodules, but the difference was not statistically significant (35.7 [24.8; 41.53] mg/dL vs. 43 [30.1; 92.7] mg/dL, P = 0.064). IgG4 as a diagnostic tool for moderate-to-severe GO had the following parameters: area under the curve (AUC): 0.851 (P < 0.001), at the cut-off value of 49 mg/dL, negative predictive value: 100%, positive predictive value: 48%, sensitivity: 100%, specificity: 73%. There were no significant differences between the high and normal IgG4 groups in thyroid hormones, antithyroid antibodies, and ultrasound features. Serum IgG4 levels are associated with some of the clinical features of GD and can help in the diagnostic process of the disease. More research is needed to better understand the pathophysiology of IgG4 involvement in GD.
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Doença de Graves , Oftalmopatia de Graves , Imunoglobulina G , Humanos , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Masculino , Feminino , Doença de Graves/sangue , Doença de Graves/diagnóstico , Doença de Graves/imunologia , Pessoa de Meia-Idade , Adulto , Oftalmopatia de Graves/sangue , Oftalmopatia de Graves/diagnóstico , Oftalmopatia de Graves/imunologia , Biomarcadores/sangue , Índice de Gravidade de Doença , Idoso , Sensibilidade e Especificidade , Estudos de Casos e Controles , Nódulo da Glândula Tireoide/sangue , Nódulo da Glândula Tireoide/diagnóstico , Nódulo da Glândula Tireoide/imunologia , Relevância ClínicaRESUMO
PURPOSE: The imbalance of thyroid hormones affects the metabolic activity of various tissues, including periodontium. Also, autoimmune diseases present an increased tendency to suffer from periodontal disease. Therefore, our systematic review was designed to answer the question "Is there a relationship between thyroid diseases and periodontal disease?". MATERIALS AND METHODS: Following the inclusion and exclusion criteria, 10 studies were included in this systematic review using the databases PubMed, Scopus and Web of Science (according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement guidelines). RESULTS: Based on the meta-analysis, patients with thyroid diseases (especially with hypothyroidism) demonstrated significantly worse periodontal status than systemically healthy controls. Moreover, according to the cross-sectional studies, 5.74 â% of periodontitis patients reported the concomitance of thyroid diseases. CONCLUSIONS: In summary, the included studies suggest a potential relationship between thyroid diseases and periodontal disease. However, further research is necessary to reliably assess the oral health in patients with hypothyroidism and hyperthyroidism.
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OBJECTIVES: The use of levothyroxine (LT4) treatment aiming to improve fertility in euthyroid women with positive thyroid peroxidase antibodies (TPOAb) is not supported by the available evidence. The aim of the study was to document the use of LT4 by European thyroid specialists in such patients. DESIGN: The data presented derive from Treatment of Hypothyroidism in Europe by Specialists, an International Survey (THESIS), a questionnaire conducted between 2019 and 2021 to document the management of hypothyroidism by European thyroid specialists. Here, we report the aggregate results on the use of LT4 in infertile, euthyroid women with positive TPOAb. RESULTS: A total of 2316/5406 (42.8%) respondents stated that LT4 may be indicated in TPOAb positive euthyroid women with infertility. The proportion of those replying positively to this question varied widely across different countries (median 39.4, range 22.9%-83.7%). In multivariate analyses males (OR: 0.8; CI: 0.7-0.9) and respondents >60 years (OR: 0.7; 0.6-0.8) were the least inclined to consider LT4 for this indication. Conversely, respondents managing many thyroid patients ("weekly" [OR: 1.4; CI: 1.0-1.9], "daily" [OR: 1.8; CI: 1.3-2.4]) and practicing in Eastern Europe (OR: 1.5; CI: 1.3-1.9) were most likely to consider LT4. CONCLUSIONS: A remarkably high number of respondents surveyed between 2019 and 2021, would consider LT4 treatment in TPOAb positive euthyroid women with infertility. This view varied widely across countries and correlated with sex, age and workload, potentially influencing patient management. These results raise concerns about potential risks of overtreatment.
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Autoanticorpos , Hipotireoidismo , Infertilidade Feminina , Tiroxina , Humanos , Tiroxina/uso terapêutico , Feminino , Hipotireoidismo/tratamento farmacológico , Hipotireoidismo/sangue , Europa (Continente) , Adulto , Autoanticorpos/sangue , Infertilidade Feminina/tratamento farmacológico , Pessoa de Meia-Idade , Masculino , Inquéritos e Questionários , Iodeto Peroxidase/imunologiaRESUMO
Breast cancer, known for its diverse subtypes, ranks as one of the leading causes of cancer-related deaths. Prostate-specific membrane antigen (PSMA), primarily associated with prostate cancer, has also been identified in breast cancer, though its role remains unclear. This study aimed to evaluate PSMA expression across different subtypes of early-stage breast cancer and investigate its correlation with clinicopathological factors. This retrospective study included 98 breast cancer cases. PSMA expression was examined in both tumor cells and tumor-associated blood vessels. The analysis revealed PSMA expression in tumor-associated blood vessels in 88 cases and in tumor cells in 75 cases. Ki67 expression correlated positively with PSMA expression in blood vessels (p < 0.0001, RSpearman 0.42) and tumor cells (p = 0.010, RSpearman 0.26). The estrogen and progesterone receptor expression correlated negatively with PSMA levels in blood vessels (p = 0.0053, R Spearman -0.26 and p = 0.00026, R Spearman -0.347, respectively). Human epidermal growth factor receptor 2 (HER2) status did not significantly impact PSMA expression. We did not detect any statistically significant differences between breast cancer subtypes. These findings provide evidence for a heterogenous PSMA expression in breast cancer tissue and suggest its correlation with tumor aggressiveness. Despite the limited sample size, the study provides valuable insights into the potential of PSMA as a prognostic, diagnostic, and therapeutic target in the management of breast cancer.
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Antígenos de Superfície , Biomarcadores Tumorais , Neoplasias da Mama , Glutamato Carboxipeptidase II , Imuno-Histoquímica , Humanos , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Feminino , Glutamato Carboxipeptidase II/metabolismo , Pessoa de Meia-Idade , Antígenos de Superfície/metabolismo , Idoso , Biomarcadores Tumorais/metabolismo , Estudos Retrospectivos , Estadiamento de Neoplasias , Adulto , Receptor ErbB-2/metabolismo , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo , Idoso de 80 Anos ou maisRESUMO
Hashimoto's thyroiditis (HT) is the leading cause of hypothyroidism, affecting mainly the female population. Many patients with HT have metabolic disorders and nutritional deficiencies. The aim of this study was to evaluate vitamin D, A, E, B2, and B6 concentrations, thyroid function, metabolic profile, and anthropometric parameters of patients with Hashimoto's thyroiditis. In 81 female patients with HT (study group), vitamin A and B2 concentrations were significantly lower than in 34 healthy women (control group). No differences were noted in vitamin D, E, and B6 concentrations between groups. Moreover, HT patients had similar anthropometric parameters, lipid profiles, and glucose and insulin concentrations compared to controls. This study showed some relationships between vitamin concentrations and anthropometric or biochemical profiles in HT patients. Among others, in the HT group, the concentration of vitamin D was positively correlated with the level of HDL and negatively correlated with BMI, total fat mass, and insulin level, which influence cardiovascular risk. The results indicate that patients with HT should be routinely tested for vitamin concentrations to prevent nutritional deficiencies. Further studies are also needed on the role of vitamins in the development and progression of HT and the presence of metabolic complications in this population.
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Doença de Hashimoto , Glândula Tireoide , Vitaminas , Humanos , Feminino , Doença de Hashimoto/sangue , Adulto , Glândula Tireoide/fisiopatologia , Glândula Tireoide/metabolismo , Pessoa de Meia-Idade , Vitaminas/sangue , Antropometria , Testes de Função Tireóidea , Estudos de Casos e Controles , Estado Nutricional , Vitamina D/sangue , Vitamina D/análogos & derivados , Índice de Massa Corporal , Glicemia/metabolismoRESUMO
Despite recent advances, neuroendocrine tumors (NETs) remain a challenging topic, due to their diversity and the lack of suitable biomarkers. Multianalyte assays and the shift to an omics-based approach improve on the conventional single-analyte strategy, albeit with their own drawbacks. We explored the potential of serum ß-hCG as a biomarker for NETs and discussed its role in disease monitoring. We recruited 40 patients with non-functioning pancreatic NETs, all with liver metastases. Serum ß-hCG concentrations were measured at 3-month intervals over 48 months. We performed a comparative and a repeated measures analysis of ß-hCG depending on WHO grade (G1, G2), liver tumor burden (LTB; below 10%, 10-25%), and RECIST 1.1. (stable disease, progressive disease). Patients with progressive disease (p < 0.001), 10-25% LTB (p < 0.001) and WHO Grade 2 (p < 0.001) displayed higher ß-hCG concentrations. Throughout the study, ß-hCG concentrations consistently increased across the entire cohort. Delta ß-hCG during the study period was greater in patients with 10-25% LTB (p < 0.001), progressive disease (p < 0.001), and G2 (p = 0.003). Serum ß-hCG correlates with established indicators of malignancy and disease progression in metastatic NETs, supporting further studies as a monitoring and prognostic biomarker. Despite promising results from novel biomarkers, there is still a place for single-analyte assays in NETs.
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Dyslipidemia is one of the most common disorders worldwide, which, if left untreated, results in a multitude of complications. Thus proper diagnostics, which includes identifying of secondary causes of dyslipidemia is crucial. Endocrine disorders are an important cause of secondary dyslipidemia. This paper aims to review the publications on lipoprotein alterations in endocrine disorders from the past two years and provide an overview of the recent discoveries in this dynamically developing and large field. Significant changes in lipoprotein serum concentrations are present in most endocrinological diseases and can be modified with proper treatment. Some lipoproteins have also been proposed as markers in some endocrine diseases, e.g., thyroid carcinoma. From the scope of endocrine disorders, the largest number of studies explored the lipoprotein changes in polycystic ovary syndrome and in women during the menopausal and peri-menopausal period. Even though the association of thyroid disorders with dyslipidemia is already well studied, new research has delivered some exciting findings about lipoprotein alterations in euthyroid patients with either positive antithyroid peroxidase antibodies or reduced sensitivity to thyroid hormones. The problem of the adverse metabolic profile, including dyslipidemia in hypoprolactinemia has been recognized. Moreover, this review describes other significant discoveries encompassing lipoprotein alterations in disorders of the adrenals, thyroid, parathyroid glands, pituitary, and gonads. The up-to-date knowledge of the influence of endocrine disorders and hormonal changes on serum lipoproteins is prudent as it can significantly impact therapeutic decisions.
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Dislipidemias , Síndrome do Ovário Policístico , Humanos , Feminino , Triglicerídeos , Lipoproteínas , Hormônios Tireóideos/uso terapêuticoRESUMO
Glioblastoma multiforme (GBM) is the most aggressive malignant brain tumour. The average survival time for a patient diagnosed with GBM, using standard treatment methods, is several months. Authors of the article pose a direct question: Is it possible to treat GBM solely with radioactive iodine (¹³¹I) therapy without employing the sodium iodide symporter (NIS) gene? After all, NIS has been detected not only in the thyroid but also in various tumours. The main author of this article (A.C.), with the assistance of her colleagues (physicians and pharmacologists), underwent ¹³¹I therapy after prior iodine inhibition, resulting in approximately 30% reduction in tumour size as revealed by magnetic resonance imaging (MRI). Classical therapy for GBM encompasses neurosurgery, conventional radiotherapy, and chemotherapy (e.g. temozolomide). Currently, tyrosine kinase inhibitors (imatinib, sunitinib, and sorafenib) are being used. Additionally, novel drugs such as crizotinib, entrectinib, or larotrectinib are being applied. Recently, personalised multimodal immunotherapy (IMI) based on anti-tumour vaccines derived from oncolytic viruses has been developed, concomitant with the advancement of cellular and molecular immunology. Thus, ¹³¹I therapy has been successfully employed for the first time in the case of GBM recurrence.
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Neoplasias Encefálicas , Glioblastoma , Radioisótopos do Iodo , Humanos , Glioblastoma/radioterapia , Glioblastoma/terapia , Glioblastoma/tratamento farmacológico , Radioisótopos do Iodo/uso terapêutico , Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/terapia , Recidiva Local de Neoplasia/prevenção & controle , Terapia CombinadaRESUMO
Background: Tumour-induced osteomalacia (TIO) is a rare paraneoplastic syndrome. Detecting the primary tumour in TIO is challenging using conventional imaging methods. This study assesses the efficacy of [68Ga]Ga-DOTATATE PET/CT in identifying the primary tumour. Methods: Six patients with suspected TIO underwent [68Ga]Ga-DOTATATE PET/CT. The patients' clinical history and biochemical parameters were analysed. Results: [68Ga]Ga-DOTATATE PET/CT successfully identified primary tumours in four patients (femoral bones for two, iliac bone for one, subcutaneous tissue of pubic region for one). Tumour removal led to clinical and laboratory improvement. In one patient, PET/CT showed rib uptake, but the biopsy was negative. One patient showed no tumour lesions on PET/CT despite clinical evidence. Two patients had focal recurrence at the primary tumour site, detected by follow-up PET/CT. Conclusions: [68Ga]Ga-DOTATATE PET/CT is a valuable tool for detecting primary tumours in TIO, aiding in accurate diagnosis and guiding surgery, leading to improved outcomes. Further research is needed to validate these findings and explore [68Ga]Ga-DOTATATE PET/CT in other paraneoplastic syndromes.
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Immunoglobulin G4-related disease (IgG4-RD) is a multi-organ disorder characterized by a highly variable clinical presentation depending on the affected organ/s, extent of tumefactive fibroinflammatory lesions, and associated functional impairment. The disease pursues a chronic, relapsing, often asymptomatic course and hence may pose a significant diagnostic challenge. Diagnostic delay can lead to progressive fibrosis and irreversible organ damage resulting into significant morbidity and even mortality. Given its broad clinical spectrum, physicians of all specialties may be the first clinicians facing this diagnostic challenge. Outside the pancreatobiliary system, the head and neck represents the major site of IgG4-RD with variable organ-specific diffuse or mass-forming lesions. In up to 75% of cases, elevated serum IgG4 levels are observed, but this figure possibly underestimates the fraction of seronegative cases, as the disease manifestations may present metachronously with significant intervals. Together with negative serology, this can lead to misdiagnosis of seronegative cases. A standardized nomenclature and diagnostic criteria for IgG4-RD were established in 2012 and revised in 2020 facilitating scientific research and expanding the range of diseases associated with IgG4 abnormalities. In addition to orbital pseudotumor, dacryoadenitis, Riedel thyroiditis, sinonasal manifestations, and rare miscellaneous conditions, IgG4-related sialadenitis is one of the most frequent presentations in the head and neck region. However, controversy still exists regarding the relationship between sialadenitis and IgG4-RD. This review focuses on the clinicopathological features of IgG4-related sialadenitis and its contemporary diagnostic criteria.
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Doenças Autoimunes , Doença Relacionada a Imunoglobulina G4 , Sialadenite , Humanos , Doença Relacionada a Imunoglobulina G4/diagnóstico , Doença Relacionada a Imunoglobulina G4/patologia , Doenças Autoimunes/patologia , Diagnóstico Tardio , Glândulas Salivares/patologia , Sialadenite/diagnóstico , Imunoglobulina GRESUMO
Background: Hypothyroidism is common, however, aspects of its treatment remain controversial. Our survey aimed at documenting treatment choices of European thyroid specialists and exploring how patients' persistent symptoms, clinician demographics, and geo-economic factors relate to treatment choices. Methods: Seventeen thousand two hundred forty-seven thyroid specialists from 28 countries were invited to participate in an online questionnaire survey. The survey included respondent demographic data and treatment choices for hypothyroid patients with persistent symptoms. Geo-economic data for each country were included in the analyses. Results: The response rate was 32.9% (6058 respondents out of 17,247 invitees). Levothyroxine (LT4) was the initial treatment preferred by the majority (98.3%). Persistent symptoms despite normal serum thyrotropin (TSH) while receiving LT4 treatment were reported to affect up to 10.0% of patients by 75.4% of respondents, while 28.4% reported an increasing such trend in the past 5 years. The principal explanations offered for patients' persistent symptoms were psychosocial factors (77.1%), comorbidities (69.2%), and unrealistic patient expectations (61.0%). Combination treatment with LT4+liothyronine (LT3) was chosen by 40.0% of respondents for patients who complained of persistent symptoms despite a normal TSH. This option was selected more frequently by female thyroid specialists, with high-volume practice, working in countries with high gross national income per capita. Conclusions: The perception of patients' dissatisfaction reported by physicians seems lower than that described by hypothyroid patients in previous surveys. LT4+LT3 treatment is used frequently by thyroid specialists in Europe for persistent hypothyroid-like symptoms even if they generally attribute such symptoms to nonendocrine causes and despite the evidence of nonsuperiority of the combined over the LT4 therapy. Pressure by dissatisfied patients on their physicians for LT3-containing treatments is a likely explanation. The association of the therapeutic choices with the clinician demographic characteristics and geo-economic factors in Europe is a novel information and requires further investigation.
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Hipotireoidismo , Tireotropina , Humanos , Feminino , Hipotireoidismo/tratamento farmacológico , Hipotireoidismo/epidemiologia , Tiroxina , Tri-Iodotironina , DemografiaRESUMO
PURPOSE: Patients receiving long-term glucocorticoid (GC) treatment are at risk of osteoporosis, while bone effects of substitution doses in Addison's disease (AD) remain equivocal. The project was aimed to evaluate serum bone turnover markers (BTMs): osteocalcin, type I procollagen N-terminal propeptide (PINP), collagen C-terminal telopeptide (CTX), sclerostin, DKK-1 protein, and alkaline phosphatase (ALP) in relation to bone mineral density (BMD) during GC replacement. METHODS: Serum BTMs and hormones were assessed in 80 patients with AD (22 males, 25 pre- and 33 postmenopausal females) on hydrocortisone (HC) substitution for ≥3 years. Densitometry with dual-energy X-ray absorptiometry covered the lumbar spine (LS) and femoral neck (FN). RESULTS: Among BTMs, only PINP levels were altered in AD. BMD Z-scores remained negative except for FN in males. Considering T-scores, osteopenia was found in LS in 45.5% males, 24% young and 42.4% postmenopausal females, while osteoporosis in 9.0%, 4.0% and 21.1%, respectively. Lumbar BMD correlated positively with body mass (p = 0.0001) and serum DHEA-S (p = 9.899 × 10-6). Negative correlation was detected with HC dose/day/kg (p = 0.0320), cumulative HC dose (p = 0.0030), patient's age (p = 1.038 × 10-5), disease duration (p = 0.0004), ALP activity (p = 0.0041) and CTX level (p = 0.0105). However, only age, body mass, ALP, serum CTX, and sclerostin remained independent predictors of LS BMD. CONCLUSION: Standard HC substitution does not considerably accelerate BMD loss in AD patients and their serum BTMs: CTX, osteocalcin, sclerostin, DKK-1, and ALP activity remain within the reference ranges. Independent predictors of low lumbar spine BMD, especially ALP activity, serum CTX and sclerostin, might be monitored during GC substitution.
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Doença de Addison , Biomarcadores , Densidade Óssea , Glucocorticoides , Osteoporose , Humanos , Densidade Óssea/efeitos dos fármacos , Feminino , Doença de Addison/tratamento farmacológico , Doença de Addison/sangue , Masculino , Pessoa de Meia-Idade , Glucocorticoides/efeitos adversos , Glucocorticoides/administração & dosagem , Adulto , Idoso , Osteoporose/sangue , Biomarcadores/sangue , Terapia de Reposição Hormonal , Peptídeos/sangue , Osteocalcina/sangue , Proteínas Adaptadoras de Transdução de Sinal , Fragmentos de Peptídeos/sangue , Pró-Colágeno/sangue , Fosfatase Alcalina/sangue , Remodelação Óssea/efeitos dos fármacos , Colágeno Tipo I/sangue , Marcadores Genéticos , Absorciometria de Fóton , Hidrocortisona/sangue , Peptídeos e Proteínas de Sinalização Intercelular/sangue , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/efeitos dos fármacos , Adulto JovemRESUMO
BACKGROUND: Triple-negative breast cancer (TNBC) exhibits high aggressiveness and a notably poorer prognosis at advanced stages. Nuclear medicine offers new possibilities, not only for diagnosis but also potentially promising therapeutic strategies. This prospective study explores the potential of prostate-specific membrane antigen (PSMA) as a diagnostic and therapeutic target in TNBC. METHODS: the research investigates PSMA expression in vivo among TNBC patients using [18F]PSMA-1007 PET/CT and compares it head-to-head with the standard-of-care [18F]FDG PET/CT. RESULTS: The study involves 10 TNBC patients, revealing comparable uptake of [18F]PSMA-1007 and [18F]FDG in primary and metastatic lesions. Nodal metastases were found in eight patients, showing similar SUVmax values in both modalities. Two patients had uncountable lung metastases positive in both [18F]FDG and [18F]PSMA-1007 scans. PET-positive bone metastases were identified by 18F-PSMA in four patients, while elevated [18F]FDG uptake was found only in three of them. Distant metastases displayed higher SUVmax values in the [18F]PSMA-1007 PET/CT, as compared to [18F]FDG. Additionally, brain metastases were exclusively detected using [18F]PSMA-1007. CONCLUSIONS: the findings provide valuable insights into the expression of PSMA in TNBC and underscore the potential clinical significance of [18F]PSMA-1007 PET/CT in enhancing both diagnostic and therapeutic approaches for this aggressive breast cancer subtype.
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Breast cancer is a major health concern, and its accurate diagnosis and management depend on identifying its histological type and biological subtype. Semaphorin-3A (SEMA3A) is a membrane protein with diverse roles in cellular processes, including cancer progression and angiogenesis regulation. However, its role in breast cancer remains poorly understood. This study aimed to evaluate SEMA3A expression in breast cancer and investigate its distribution across breast cancer subtypes: luminal A, luminal B, HER2-positive, and triple-negative breast cancer (TNBC). Immunohistochemical evaluation was performed on 98 breast cancer patients' tumor specimens, and SEMA3A expression was assessed in tumor cells and vessels. The study included the analysis of the Ki67 proliferation index, estrogen receptor (ER) expression, progesterone receptor (PR) expression, and HER2 status in conjunction with SEMA3A expression. Analysis indicated positive expression of SEMA3A in breast cancer cells in 60 out of 98 cases. SEMA3A expression correlated positively with Ki67 levels in tumor cells (p = 0.0005, R Spearman 0.338). Notably, a negative correlation was found between SEMA3A expression and ER and PR levels in tumor cells (p = 0.04, Spearman's R = - 0.21 and p = 0.016, Spearman's R = - 0.25 respectively). HER2 status did not significantly influence SEMA3A expression. The study demonstrated positive SEMA3A expression in tumor vessels across all subtypes in 91 out of 98 cases, suggesting its involvement in endothelial cell function. However, no significant differences in SEMA3A expression were observed between breast cancer subtypes either in vessels or tumor cells. These findings suggest that elevated SEMA3A expression may be associated with worse prognosis in breast cancer, especially in ER- and PR-negative tumors. Further investigations are warranted to fully comprehend the role of SEMA3A in breast cancer biology, which may lead to the identification of novel therapeutic targets and personalized treatment strategies for breast cancer patients.
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Semaforina-3A , Neoplasias de Mama Triplo Negativas , Humanos , Antígeno Ki-67 , Estrogênios , ProgesteronaRESUMO
BACKGROUND: Graves' orbitopathy (GO) is an autoimmune disorder of the orbit and retro-ocular tissues and the primary extrathyroidal manifestation of Graves' disease. In moderate-to-severe and active GO iv glucocorticoids (GCs) are recommended as first-line treatment. The aim was to assess the safety profile of methylprednisolone administered intravenously for three consecutive days at 1 g in patients with active, moderate-to-severe or sight-threatening Graves' orbitopathy. METHODS: We retrospectively evaluated 161 medical records of patients with GO treated with high-dose systemic GCs in the Department of Endocrinology, Metabolic Disorders, and Internal Medicine in Poznan between 2014 and 2021. Clinical data included age, gender, laboratory results, activity and severity of GO, smoking status, disease duration, and presented side effects. RESULTS: The presence of mild side effects was observed during 114 (71%) hospitalizations. The most common complications were hyperglycemia (n = 95) and elevated aminotransferases (n = 31). Increased levels of aminotransferases were more likely observed in smokers and GO duration above 12 months. Based on the multivariate logistic regression, higher TRAb and CAS values were significantly associated with lower odds of hyperglycemia. In turn, the increased odds of elevated aminotransferases were significantly correlated with higher initial ALT levels, female gender, and GO duration above 12 months. In addition, the multidimensional correspondence analysis (MPA) showed that GO patients who declared smoking and had not L-ornithine L-aspartate applied demonstrated a higher probability of elevated aminotransferases. CONCLUSIONS: Active GO treatment with high-dose systemic GCs is not associated with serious side effects. Hyperglycemia is the most common steroid-induced complication.