VALTER ANGELO SPERLING CESCATO

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Instituto Central, Hospital das Clínicas, Faculdade de Medicina - Médico
LIM/45 - Laboratório de Fisiopatologia Neurocirúrgica, Hospital das Clínicas, Faculdade de Medicina

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  • bookPart
    Tumores da Região Selar
    (2015) CESCATO, Valter A. S.; SILVA, Gilberto Ochman da; CUNHA NETO, Malebranche B. C.; MUSOLINO, Nina R. C.
  • article 10 Citação(ões) na Scopus
    PROP1 overexpression in corticotrophinomas: evidence for the role of PROP1 in the maintenance of cells committed to corticotrophic differentiation
    (2013) ARAUJO, Ricardo V.; CHANG, Claudia V.; CESCATO, Valter A. S.; FRAGOSO, Maria Candida B. V.; BRONSTEIN, Marcello D.; MENDONCA, Berenice B.; ARNHOLD, Ivo J. P.; CARVALHO, Luciani R. S.
    OBJECTIVE: The expression of transcription factors involved in early pituitary development, such as PROP1 and POU1F1, has been detected in pituitary adenoma tissues. In this study, we sought to characterize the transcriptional profiles of PROP1, POU1F1, and TBX19 in functioning and nonfunctioning pituitary adenomas in an attempt to identify their roles in tumorigenesis and hormone hypersecretion. METHODS: RT-qPCR analyses were performed to assess the transcriptional pattern of PROP1, POU1F1, TBX19, and hormone-producing genes in tissue samples of corticotrophinomas (n = 10), somatotrophinomas (n = 8), and nonfunctioning adenomas (n = 6). RESULTS: Compared with normal pituitary tissue, POU1F1 was overexpressed in somatotrophinomas by 3-fold. PROP1 expression was 18-fold higher in corticotrophinomas, 10-fold higher in somatotrophinomas, and 3-fold higher in nonfunctioning adenomas. TBX19 expression was 27-fold higher in corticotrophinomas. Additionally, the level of TBX19 mRNA positively correlated with that of pro-opiomelanocortin (r = 0.49, p = 0.014). CONCLUSIONS: Our data demonstrate that PROP1 is overexpressed in pituitary adenomas, mainly in corticotrophinomas. Together with previously published data showing that patients who harbor PROP1 loss-of-function mutations present a progressive decline in corticotrope function, our results support a role for PROP1 in pituitary tumor development and in the maintenance of cell lineages committed to corticotrophic differentiation.
  • article
    The effects of cabergoline in the presurgical and recurrence periods of Cushing's disease patients
    (2021) PEREIRA, Ana Julia Garcia; ANDRADE, Natalia Xavier Sant' Anna; MUSOLINO, Nina Rosa Castro; CESCATO, Valter Angelo Sperling; SILVA, Gilberto Ochman; FRAGOSO, Maria Candida; BRONSTEIN, Marcello D.; MACHADO, Marcio C.
    Background: The dopaminergic agonist cabergoline (CAB) has been used in the pharmacological treatment of Cushing's disease (CD). The effect is attributed to the frequent expression of the dopamine receptor subtype 2 in corticotroph tumors. However, in vivo studies have demonstrated the normalization of 24-h urinary cortisol (24-h UC) in approximately 30-40% of patients over the long term, mainly after surgical failure. Objective: To evaluate the effect of CAB as monotherapy in the early preoperative period and on the recurrence of CD. Methods: A single-center retrospective study was conducted in a tertiary referral center. Twenty-one patients with confirmed CD were included. The median age was 32 years (13-70), 86% were female, 10 had microadenomas, and 11 had macroadenomas. They were diagnosed from 1986 to 2016 and used CAB as monotherapy either in the preoperative period (n=7, CABi) or upon recurrence before any other treatment (n=14, CABr). A 'complete response' was considered 24-h UC normalization and a 'partial response' was considered a 24-h UC reduction of >50%. UC was obtained at the last follow-up evaluation. The normalization of late-night salivary cortisol (LNSC) after CAB use was evaluated in most patients, as well as the tumor diameter by pituitary MRI, before and after CAB treatment. Results: Complete response was achieved in 29% (6/21) of subjects after 14.9 +/- 16.4 months of treatment, with an average dose of 2.2 +/- 1.0 mg/week. Partial response occurred in 9.5% (2/21). LNSC normalized in 35% (6/17) of patients, and no variation in tumor diameter before and after CAB use was observed (n=13): 6.8 +/- 6.8 vs. 7.2 +/- 7.1 mm. There was no normalization of 24-h-UC in the CABi subgroup at the end of the treatment, whereas 43% (6/14) of patients in the CABr subgroup reached complete response. The CABi subgroup was treated for 4.7 +/- 1.9 months, and the CABr subgroup was treated for 20.1 +/- 18.1 months. Both groups were administered similar doses of CAB (CABi 2.1 +/- 0.9 and CABr 2.3 +/- 1.1 mg/week). Interestingly, the difference between the subgroups' complete response was evident early on in the three months of treatment: no patients in the CABi subgroup vs. 6/10 (60%) in the CABr subgroup (p=0.035), despite a lower dose in the CABr subgroup (1.1 vs. 1.6; p=0.008). The normalization of LNSC occurred in 20% of the CABi subgroup and in 42% of the CABr subgroup. Conclusions: The normalization of 24-h UC and LNSC occurred in approximately 30% of all patients, mainly in those who used CAB for the recurrence of CD. Despite the small number of subjects in the CABi subgroup, the absence of hormone control in this subgroup discourages the use of this medication as primary therapy or as a preoperative treatment option. PubMed Disclaimer
  • article 0 Citação(ões) na Scopus
    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 Carlos
    Purpose 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.
  • conferenceObject
    Comparative Study of Silent Corticotrophic Adenomas and Null CELL Pituitary Adenomas
    (2014) BATISTA, Rafael Loch; NETO, Malebranche Cunha; BORBA, Clarissa Groberio; CESCATO, Valter Angelo Sperling; SILVA, Gilberto Ochman; MUSOLINO, Nina de Castro
  • conferenceObject
    Initial results of stereotactic linear accelerator based irradiation for pituitary adenoma
    (2013) CAMPOS, A. De; MUSOLINO, N. R. C.; CUNHA NETO, M. B. C.; SOUZA, E. C.; LEAL, S. C.; CESCATO, V. A. S.; CARVALHO, I. T.; VILLAR, R. C.; NADALIN, W.; WELTMAN, E.
  • article 42 Citação(ões) na Scopus
    Cabergoline in the Management of Residual Nonfunctioning Pituitary Adenoma A Single-Center, Open-Label, 2-Year Randomized Clinical Trial
    (2019) BATISTA, Rafael L.; MUSOLINO, Nina R. C.; CESCATO, Valter A. S.; SILVA, Gilberto O. da; MEDEIROS, Raphael S. S.; HERKENHOFF, Clarissa G. B.; TRARBACH, Ericka B.; CUNHA-NETO, Malebranche B.
    Background: Complete tumor removal by transsphenoidal surgery is usually difficult for large nonfunctioning pituitary adenomas (NFPAs). A validated medical treatment may be useful for their management. This study evaluates the clinical efficacy of the dopaminergic agonist cabergoline for residual NFPA. Design, Setting, and Participants: We conducted a randomized, parallel, open-label clinical trial that compared cabergoline with nonintervention in patients with residual NFPA after transsphenoidal surgery over 2 years. The primary outcome was clinical efficacy (tumor reduction). The secondary outcome was the relationship between tumor dopamine D2 receptor (D2R) expression and clinical responsiveness. Tumor measurements and clinical evaluations were performed every 6 months. Results: In total, 59 and 57 individuals were randomly assigned to the study and control groups, respectively. At the end of the study, residual tumor shrinkage, stabilization, and enlargement were observed in 28.8%, 66.1%, and 5.1% of patients, respectively, in the medical-therapy group and in 10.5%, 73.7%, and 15.8% of patients, respectively, in the control group (P=0.01). The progression-free survival rate was 23.2 and 20.8 months for the study and control groups, respectively (P=0.01). D2R was not associated with cabergoline responsiveness. No major side effects were related to cabergoline use. Conclusions: Cabergoline was an effective drug for treating residual NFPA, and its use was associated with a high rate of tumor shrinkage ( NCT03271918).
  • article 6 Citação(ões) na Scopus
    Differential gene expression of sirtuins between somatotropinomas and nonfunctioning pituitary adenomas
    (2018) GRANDE, Isabella P. P.; AMORIM, Paulo V. G. H.; FREIRE, Ane Caroline The B.; JALLAD, Raquel S.; MUSOLINO, Nina R.; CESCATO, Valter A.; SILVA, Gilberto O. da; BRONSTEIN, Marcello D.; TRARBACH, Ericka B.
    Sirtuins 1-7 (SIRT) are a highly conserved family of histone deacetylases involved in the regulation of longevity that have a considerable impact in transcription, DNA repair regulation, telomeric stability, cell senescence and apoptosis. In the present study, SIRT1-7 mRNA levels were evaluated in 37 somatotropinomas and 31 nonfunctioning pituitary adenomas (NFPAs) using qPCR and relation to tumor size, invasiveness and Ki-67 proliferative index was made. Overexpression of SIRT1 was observed in 86.5% of somatotropinomas versus 41.9% of NFPAs (P < 0.01). SIRT3 was more underexpressed in NFPAs than somatotropinomas (77.4 and 40.5%, respectively, P < 0.01) as well as SIRT4 and SIRT7. Despite the lack of association between sirtuins and invasiveness or Ki-67 index, SIRT1 and SIRT3 expressions were related to tumor size. Mean of the largest diameter was smaller in adenomas with SIRT1 overexpression than with normal expression (P < 0.01) and SIRT3 underexpression was associated with larger tumors (P < 0.01). In conclusion, a pronounced difference in sirtuins expression was identified between pituitary adenomas, suggesting that these genes are potential markers of pituitary adenomas and could be employed in the characterization of somatotropinomas and NFPAs. The role of sirtuins in pathogenesis of pituitary tumors merits further investigation and possibly will provide new molecular insight about their progression.
  • article 1 Citação(ões) na Scopus
    Resolution of Cyclicity After Pasireotide LAR in a Patient With Cushing Disease
    (2021) MACHADO, M. C.; CESCATO, V. A. S.; FRAGOSO, M. C. B. V.; BRONSTEIN, M. D.
    Objective: The cyclicity (CIC) of cortisol spontaneously occurs in a minority of patients with Cushing syndrome (CS). When it arises, diagnostic and therapeutic approaches become more challenging. This study aimed to report a patient with Cushing disease (CD) who achieved normalization of cortisol and CIC pattern with pasireotide long-acting release (pasi/LAR). Methods: A 43-year-old female patient related an 8-month history of CS. An 8-mm pituitary nodule depicted by magnetic resonance imaging, serum cortisol suppression of >50% after 8 mg of dexamethasone therapy, and the absence of other lesions were compatible with a CD diagnosis. The patient presented with a CIC pattern with 1 episode before and 17 episodes after an unsuccessful pituitary surgery. Results: Medical treatment with cabergoline alone up to 3.5 mg/wk and a combined treatment with ketoconazole 400 mg/d did not improve CIC CS. Pasi/LAR was initiated at a dose of 20 mg/mo. A few days after the first dose, the patient experienced symptoms suggestive of adrenal insufficiency. The medication and dose were maintained for 24 months. During this period, there was a normalization of UFC levels and progressive clinical improvement. Additionally, new episodes of CIC were not observed. Conclusion: A CD patient with a challenging issue of CIC was reported. The condition was not controlled after pituitary surgery and by the combined treatment with cabergoline and ketoconazole, although hypercortisolism was abated by the continuous use of pasi/LAR. To our knowledge, this is the first report as regards the use of this medication to control CIC in a patient with CD. © 2021 AACE
  • article 18 Citação(ões) na Scopus
    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 Renata
    Background/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.