MARCELLO DELANO BRONSTEIN
Projetos de Pesquisa
Unidades Organizacionais
LIM/25 - Laboratório de Endocrinologia Celular e Molecular, Hospital das Clínicas, Faculdade de Medicina
26 resultados
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Agora exibindo 1 - 10 de 26
- Pregnancy in Patients with Cushing's Syndrome(2018) MACHADO, Marcio Carlos; FRAGOSO, Maria Candida Barisson Vilares; BRONSTEIN, Marcello DelanoProgress in diagnosis and treatment of endocrine diseases has made pregnancy possible for women with endocrinopathies, including Cushing's syndrome (CS). The risk of maternal-fetal complications in patients who are not biochemically controlled, however, is substantial. Therefore, the surgical and/or medical control of hypercortisolism is mandatory before conceiving. A diagnosis of de novo CS during gestation is difficult because of changes in the hypothalamic-pituitary-adrenal axis during pregnancy, which may lead to some clinical features suggestive of CS along with abnormal laboratory test results. This article presents the diagnosis and management of CS during pregnancy.
- Pregnancy after pituitary surgery does not influence the recurrence of Cushing's disease(2022) LOUSADA, Lia Mesquita; TAPIA, Mariuxi Jacqueline Borja; CESCATO, Valter Angelo Sperling; SILVA, Gilberto Ochman da; MUSOLINO, Nina Rosa Castro; FRAGOSO, Maria Candida Barisson Villares; BRONSTEIN, Marcello Delano; MACHADO, Marcio CarlosPurpose Pregnancy is associated with the activation of the hypothalamus-pituitary-adrenal axis, which can cause a misdiagnosis of Cushing's syndrome. The aim of this study is to evaluate the impact of pregnancy after pituitary surgery on the recurrence rate in Cushing's disease (CD) patients. Methods This was a retrospective study in a tertiary center. Between 1990 and 2020, 355 CD patients underwent pituitary surgery. Of those, we included 113 female patients who were <= 45 years old (median age of 32 years, 14-45), PS remission, a follow-up of >= 6 months (median of 122 months, 6-402) and an available obstetric history. Recurrence was defined as the diagnosis of Cushing's syndrome via at least two altered first-line methods. The patients were divided into two subgroups according to pregnancy: no pregnancy or pregnancy prior to CD diagnosis (NP/PP) and pregnancy after CD pituitary surgery (PA). Results Overall, recurrence occurred in 43 out of 113 patients (38%). A higher recurrence rate was seen in the PA subgroup (11/22, 50%), but there was no significant difference between the NP/PP subgroup (32/91, 35%). No difference in survival-free recurrence (SFR) was found between NP/PP and PA subgroups. The lower SFR was related to a higher PS plasma ACTH and normal pituitary at pathological analyses. Conclusions There was no difference in the recurrence rate in patients according to pregnancy history. Other studies with higher numbers of patients are needed to confirm these data.
- Transcriptome analysis showed a Differential signature between invasive and non-invasive corticotrophinomas(2017) ARAUJO, Leonardo Jose Tadeu de; LERARIO, Antonio Marcondes; CASTRO, Margaret de; MARTINS, Clarissa Silva; BRONSTEIN, Marcello Delano; MACHADO, Marcio Carlos; TRARBACH, Ericka Barbosa; FRAGOSO, Maria Candida Barisson VillaresACTH-dependent hypercortisolism caused by a pituitary adenoma [Cushing's disease (CD)] is the most common cause of endogenous Cushing's syndrome. CD is often associated with several morbidities, including hypertension, diabetes, osteoporosis/bone fractures, secondary infections, and increased cardiovascular mortality. While the majority (approximate to 80%) of the corticotrophinomas visible on pituitary magnetic resonance imaging are microadenomas (MICs, <10 mm of diameter), some tumors are macroadenomas (MACs, >= 10 mm) with increased growth potential and invasiveness, exceptionally exhibiting malignant demeanor. In addition, larger and invasive MACs are associated with a significant increased risk of local complications, such as hypopituitarism and visual defects. Given the clinical and molecular heterogeneity of corticotrophinomas, the aim of this study was to investigate the pattern of genetic differential expression between MIC and MAC, including the invasiveness grade as a criterion for categorizing these tumors. In this study, were included tumor samples from patients with clinical, laboratorial, radiological, and histopathological diagnosis of hypercortisolism due to an ACTH-producing pituitary adenoma. Differential gene expression was studied using an Affymetrix microarray platform in 12 corticotrophinomas, classified as non-invasive MIC (n = 4) and MAC (n = 5), and invasive MAC (n = 3), according to modified Hardy criteria. Somatic mutations in USP8 were also investigated, but none of the patients exhibited USP8 variants. Differential expression analysis demonstrated that non-invasive MIC and MAC have a similar genetic signature, while invasive MACs exhibited a differential expression profile. Among the genes differentially expressed, we highlighted CCND2, ZNF676, DAPK1, and TIMP2, and their differential expression was validated through quantitative real-time PCR in another cohort of 15 non-invasive and 3 invasive cortocotrophinomas. We also identified potential biological pathways associated with growth and invasiveness, TGF-beta and G protein signaling pathways, DNA damage response pathway, and pathways associated with focal adhesion. Our study revealed a differential pattern of genetic signature in a subgroup of MAC, supporting a genetic influence on corticotrophinomas in patients with CD.
- Differential Expression of Stem Cell Markers in Human Adamantinomatous Craniopharyngioma and Pituitary Adenoma(2017) CHANG, Claudia Veiga; ARAUJO, Ricardo Vieira; CIRQUEIRA, Cinthya Santos; CANI, Carolina Maria Gomes; MATUSHITA, Hamilton; CESCATO, Valter Angelo Sperling; FRAGOSO, Maria Candida Barisson Villares; BRONSTEIN, Marcello Delano; ZERBINI, Maria Claudia Nogueira; MENDONCA, Berenice Bilharinho; CARVALHO, Luciani RenataBackground/Aims: Although craniopharyngioma (CP) is histologically benign, it is a pituitary tumour that grows rapidly and often recurs. Adamantinomatous CP (ACP) was associated with an activating mutation in beta-catenin, and it has been postulated that pituitary stem cells might play a role in oncogenesis in human ACP. Stem cells have also been identified in pituitary adenoma. Our aim was to characterize the expression pattern of ABCG2, CD44, DLL4, NANOG, NOTCH2, POU5F1/OCT4, SOX2, and SOX9 stem cell markers in human ACP and pituitary adenoma. Methods and Results: We studied 33 patients (9 ACP and 24 adenoma) using real- time quantitative PCR (RT-qPCR) and immunohistochemistry. SOX9 was up-regulated in ACP, exhibiting positive immunostaining in the epithelium and stroma, with the highest expression in patients with recurrence. CD44 was overexpressed in ACP as confirmed by immunohistochemistry. SOX2 did not significantly differ among the tumour types. The RT-qPCR array showed an increased expression of MKI67, OCT4/POU5F1, and DLL4 in all tumours. NANOG was decreased in ACP. ABCG2 was down-regulated in most of the tumours. NOTCH2 was significantly decreased in the adenomas. Conclusion: Our results confirm the presence of stem cell markers in human pituitary tumours as well as the different expression patterns of ACP and adenoma. These findings suggest that ACP may originate from a more undifferentiated cell cluster. Additionally, SOX9 immunodetection in the stroma and the highest expression levels related to the relapse of patients suggest a contribution to the aggressive behaviour and high recurrence of this tumour type. (C) 2016 S. Karger AG, Basel.
- A review of Cushing's disease treatment by the Department of Neuroendocrinology of the Brazilian Society of Endocrinology and Metabolism(2018) MACHADO, Marcio Carlos; FRAGOSO, Maria Candida Barisson Vilares; MOREIRA, Ayrton Custodio; BOGUSZEWSKI, Cesar Luiz; NETO, Leonardo Vieira; NAVES, Luciana A.; VILAR, Lucio; ARAUJO, Luiz Antonio de; MUSOLINO, Nina Rosa Castro; MIRANDA, Paulo Augusto C.; CZEPIELEWSKI, Mauro A.; GADELHA, Monica R.; BRONSTEIN, Marcello Delano; RIBEIRO-OLIVEIRA JR., AntonioThe treatment objectives for a patient with Cushing's disease (CD) are remission of hypercortisolism, adequate management of co-morbidities, restoration of the hypothalamic-pituitary-adrenal axis, preservation of fertility and pituitary function, and improvement of visual defects in cases of macroadenomas with suprasellar extension. Transsphenoidal pituitary surgery is the main treatment option for the majority of cases, even in macroadenomas with low probability of remission. In cases of surgical failure, another subsequent pituitary surgery might be indicated in cases with persistent tumor imaging at post surgical magnetic resonance imaging (MRI) and/or pathology analysis of adrenocorticotropic hormone-positive (ACTH+) positive pituitary adenoma in the first procedure. Medical treatment, radiotherapy and adrenalectomy are the other options when transsphenoidal pituitary surgery fails. There are several options of medical treatment, although cabergoline and ketoconazole are the most commonly used alone or in combination. Novel treatments are also addressed in this review. Different therapeutic approaches are frequently needed on an individual basis, both before and, particularly, after surgery, and they should be individualized. The objective of the present review is to provide the necessary information to achieve a more effective treatment for CD. It is recommended that patients with CD be followed at tertiary care centers with experience in treating this condition.
bookPart Adenomas Hipofisários Clinicamente não funcionantes(2016) GUZZO, Mariana Furieri; BRONSTEIN, Marcello Delano- High accuracy of bilateral and simultaneous petrosal sinus sampling with desmopressin for the differential diagnosis of pediatric ACTH-dependent Cushing's syndrome(2020) CAVALCANTE, Lara Bessa Campelo Pinheiro; FREITAS, Thais Castanheira; MUSOLINO, Nina Rosa Castro; CESCATO, Valter Angelo Sperling; SILVA, Gilberto Ochman; FRAGOSO, Maria Candida Barisson Villares; JR, Paulo Puglia; BRONSTEIN, Marcello Delano; MACHADO, Marcio CarlosPurpose To analyze the bilateral and simultaneous petrosal sinus sampling (BIPSS) in a subgroup of children and adolescents with ACTH-dependent Cushing's syndrome (ADCS) Methods Retrospective study in a tertiary reference center. From 1993 and 2017, 19 children and adolescents (PED) were submitted to the BIPSS, median age of 14 years (range 9-19 years), 53% were males, 18 had Cushing's disease (CD) and one had ectopic ACTH syndrome (EAS). All procedures were performed with 10 mu g of intravenous desmopressin. Results The catheter positioning was successful in all cases. The central ACTH gradient was met in 17/19 cases. At baseline, central gradient occurred in 16/19 (84%) with gradient values of 7.2 +/- 6.0. After stimulation, there was an increase in the center-periphery gradient values (33.6 +/- 44.3). In one case, central gradient was defined only after stimulation. Two cases presented without a central gradient; one case of CD with a false-negative and one EAS case. Lateralization occurred in all cases with a central gradient. Confirmation of the tumor location presumed by the procedure with the surgical description occurred in 60% of the cases. The BIPSS in this PED subgroup of ADCS presented a sensitivity of 94.4% and specificity of 100%. There were no complications of the procedure. Conclusion In a series of children and adolescents with ADCS, BIPSS was safe and highly accurate in defining the central to peripheral ACTH gradient using desmopressin as secretagogue. Nevertheless, there was a limited value of the ACTH-gradient between the petrosal sinuses for the tumor location.
bookPart Acromegalia(2016) JALLAD, Raquel Soares; BRONSTEIN, Marcello DelanobookPart Tratamento dos prolactinomas(2017) GLEZER, Andrea; BRONSTEIN, Marcello Delano- Determination of nighttime salivary cortisol during pregnancy: comparison with values in non-pregnancy and Cushing's disease(2016) LOPES, Ludmilla Malveira Lima; FRANCISCO, Rossana Pulcineli Vieira; GALLETTA, Marco Aurelio Knippel; BRONSTEIN, Marcello DelanoPurpose Nighttime salivary cortisol (NSC) has been proposed for the diagnosis of Cushing's syndrome during pregnancy. However, reference values for NCS in pregnant women have not been adequately determined. The aim of this study was to determine the reference values of NSC in the three gestational trimesters in order to help distinguish physiological from pathological hypercortisolism during pregnancy. Methods This prospective and retrospective study evaluated 85 pregnant women in whom samples were collected in the first, second and/or third gestational trimester (pregnancy group), 33 non-pregnant women (control group), and 25 non-pregnant women with Cushing's disease (CD group). NSC was measured by enzyme-linked immunosorbent assay. Results NSC increased progressively during pregnancy, reaching maximum levels on the third trimester (median 2.1-fold increase compared with controls, p< 0.001). Reference values for NSC were determined and the upper limits on each gestational trimester were: first trimester 0.25 mu g/dL (6.9 nmol/L), second trimester 0.26 mu g/dL (7.2 nmol/L), and third trimester 0.33 mu g/dL (9.1 nmol/L). Cutoff values that separated the CD group from the three trimesters in the pregnancy groups were, respectively, 0.255 mu g/dL (7.0 nmol/L), 0.260 mu g/dL (7.2 nmol/L), and 0.285 mu g/dL (7.9 nmol/L). Comparison of NSC cutoff values in pregnant women with CD patients showed high sensitivity and specificity in all three trimesters. Conclusions We established cutoff values for determination of NSC which can be useful for pregnant women with a diagnostic suspicion of CD.
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