VALTER ANGELO SPERLING CESCATO
Índice h a partir de 2011
7
Projetos de Pesquisa
Unidades Organizacionais
Instituto Central, Hospital das Clínicas, Faculdade de Medicina - Médico
LIM/45 - Laboratório de Fisiopatologia Neurocirúrgica, Hospital das Clínicas, Faculdade de Medicina
LIM/45 - Laboratório de Fisiopatologia Neurocirúrgica, Hospital das Clínicas, Faculdade de Medicina
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- 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
- 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.
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- 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.
conferenceObject Evolution of Cushing's Disease By Pituitary Carcinoma: A Diagnostic Challenge(2014) BATISTA, Rafael Loch; ALCANTARA, Ana Elsa Evangelista; BORBA, Clarissa Groberio; MUSOLINO, Nina de Castro; CESCATO, Valter Angelo Sperling; MACHADO, Vanielle Carvalho; CUNHA NETO, Malebranche Beraldo Carneiro da- 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.
conferenceObject Immunohistochemistry Is NOT Predictive of Response to Cabergoline in Clinically Nonfunctioning Pituitary Adenomas(2014) BATISTA, Rafael Loch; MUSOLINO, Nina de Castro; BORBA, Clarissa Groberio; CESCATO, Valter Angelo Sperling; CUNHA NETO, MalebrancheconferenceObject Cabergoline Effectivenes in Patients with Clinically Nonfunctioning Pituitary Adenomas(2014) BATISTA, Rafael Loch; MUSOLINO, Nina de Castro; BORBA, Clarissa Groberio; CESCATO, Valter Angelo Sperling; SILVA, Gilberto Ochman; CUNHA NETO, Malebranche- Cushing's disease due to somatic USP8 mutations: a systematic review and meta-analysis(2019) WANICHI, Ingrid Quevedo; MARIANI, Beatriz Marinho de Paula; FRASSETTO, Fernando Pereira; SIQUEIRA, Sheila Aparecida Coelho; MUSOLINO, Nina Rosa de Castro; CUNHA-NETO, Malebranche Berardo Carneiro; OCHMAN, Gilberto; CESCATO, Valter Angelo Sperling; MACHADO, Marcio Carlos; TRARBACH, Ericka Barbosa; BRONSTEIN, Marcello Delano; FRAGOSO, Maria Candida Barisson VillaresPurposeCushing's disease (CD) is a severe illness generally caused by microcorticotropinomas (MICs) and in approximately 7-20% of patients by macrocorticotropinomas (MACs). USP8-mutations have been identified as a major genetic cause of CD (50%). Few studies have reported the distribution between MICs-MACs related to USP8-mutations and their genotype-phenotype correlations. Therefore, we aimed to evaluate USP8-mutations in a cohort of MICs-MACs from a unique center and to perform a systematic review and meta-analysis.MethodsDNA-tumor-tissues from 47 corticotropinomas (16 MICs and 31 MACs) were sequenced. Clinical-biochemical data, radiological imaging data and remission/recurrence rates were evaluated. In addition, we performed a meta-analysis of nine published series (n=630).ResultsWe identified four different USP8-mutations previously described, in 11 out of 47 (23.4%) corticotropinomas; 8 out of 11 were MACs. The urinary cortisol levels of our patients with corticotrophin USP8-mutated-alleles were lower than those of patients with wild-type (WT) alleles (p <= 0.017). The frequency of USP8-mutated-alleles among the series was approximately 30% with a higher prevalence in female-patients (p<0.1x10(-4)). Among the 5 series, the remission rates were higher in patients with USP8-mutated-alleles than in those with the USP8-WT-alleles (p<0.1x10(-4)).ConclusionOur data, as well as the retrospective review of CD series associated with USP8-mutated alleles, show heterogeneous findings among the series. Several drawbacks included the lack of a systematic protocol to evaluate these patients before surgery and follow-up. Further prospective studies using a systematic protocol will provide more consistent information about the influence of the corticotropinomas with USP8-mutated alleles on the phenotype, responses to treatment and outcome of patients with CD.
- Cushing disease due to a somatic USP8 mutation in a patient with evolving pituitary hormone deficiencies due to a germline GH1 splicing variant(2022) LABELLO, Julia Haddad; BENEDETTI, Anna Flavia Figueredo; AZEVEDO, Bruna Viscardi; JORGE, Alexander Augusto de Lima; CESCATO, Valter Angelo Sperling; ROSEMBERG, Sergio; FRASSETO, Fernando Pereira; ARNHOLD, Ivo Jorge Prado; CARVALHO, Luciani Renata Silveira deWe present the unique case of an adult Brazilian woman with severe short stature due to growth hormone deficiency with a heterozygous G to T substitution in the donor splice site of intron 3 of the growth hormone 1 (GH1) gene (c.291+1G>T). In this autosomal dominant form of growth hormone deficiency (type II), exon 3 skipping results in expression of the 17.5 kDa isoform of growth hormone, which has a dominant negative effect over the bioactive isoform, is retained in the endoplasmic reticulum, disrupts the Golgi apparatus, and impairs the secretion of other pituitary hormones in addition to growth hormone deficiency.This mechanism led to the progression of central hypothyroidism in the same patient. After 5 years of growth and thyroid hormone replacement, at the age of 33, laboratory evaluation for increased weight gain revealed high serum and urine cortisol concentrations, which could not be suppressed with dexamethasone. Magnetic resonance imaging of the sella turcica detected a pituitary macroadenoma, which was surgically removed. Histological examination confirmed an adrenocorticotropic hormone (ACTH)-secreting pituitary macroadenoma. A ubiquitin-specific peptidase 8 (USP8) somatic pathogenic variant (c.2159C>G/p.Pro720Arg) was found in the tumor. In conclusion, we report progression of isolated growth hormone deficiency due to a germline GH1 variant to combined pituitary hormone deficiency followed by hypercortisolism due to an ACTH-secreting macroadenoma with a somatic variant in USP8 in the same patient. Genetic studies allowed etiologic diagnosis and prognosis of this unique case.