MARCIO CARLOS MACHADO
Projetos de Pesquisa
Unidades Organizacionais
Instituto Central, Hospital das Clínicas, Faculdade de Medicina - Médico
LIM/25 - Laboratório de Endocrinologia Celular e Molecular, Hospital das Clínicas, Faculdade de Medicina - Líder
LIM/25 - Laboratório de Endocrinologia Celular e Molecular, Hospital das Clínicas, Faculdade de Medicina - Líder
4 resultados
Resultados de Busca
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- 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.
- Medical combination therapies in Cushing's disease(2015) VILAR, Lucio; NAVES, Luciana A.; MACHADO, Marcio C.; BRONSTEIN, Marcello D.Introduction There has been growing interest on medical therapy for the management of Cushing's disease (CD), particularly in cases of persistent or recurrent hypercortisolism. Ketoconazole, an inhibitor of adrenal steroidogenesis, is the most widely used drug, whereas cabergoline and pasireotide are the most promising centrally acting agents. The main purpose of this review article is to highlight the options of medical treatment for CD, with a special emphasis on combination therapies, a topic that has only been addressed by a limited number of studies. Conclusions According to the results of these studies, combination therapies involving medications with additive or synergistic effects on ACTH and cortisol secretion seem quite attractive as they yield higher probability of longterm control of the hypercortisolism at lower doses, a lower incidence of side-effects, and possibly a lower rate of treatment escapes. Currently, ketoconazole, cabergoline, and pasireotide are the best drugs to be prescribed in combination.
- Filamin A and DRD2 expression in corticotrophinomas(2019) SICKLER, Thais; TRARBACH, Ericka Barbosa; FRASSETTO, Fernando Pereira; DETTONI, Juliano Bertollo; ALVES, Venancio Avancini Ferreira; FRAGOSO, Maria Candida Barisson Villares; MACHADO, Marcio Carlos; CARDOSO, Ellison Fernando; BRONSTEIN, Marcello Delano; GLEZER, AndreaPurposeFilamin A (FLNA) expression is related to dopamine receptor type 2 (DRD2) expression in prolactinomas. Nevertheless, in corticotrophinomas, there are few studies about DRD2 expression and no data on FLNA. Therefore, we evaluated FLNA and DRD2 expression in corticotrophinomas and their association with tumor characteristics.MethodsDRD2 and FLNA expression by immunohistochemistry, using H-score, based on the percentage of positive cells in a continuous scale of 0-300, were evaluated in 23 corticotrophinomas samples from patients submitted to neurosurgery. In six patients, treatment with cabergoline was indicated after non curative surgery.ResultsTwenty-two patients were female and one male. Regarding tumor size, 10 were micro and 12 were macroadenomas. DRD2 expression was found in 89% of cases and did not correlate with FLNA expression. Moreover, the response to cabergoline, observed in 33% of the cases, did not correlate with DRD2 nor FLNA expression. FLNA expression was not associated with clinical and tumor characteristics, except for sphenoid sinus invasion.ConclusionsIn our cohort of corticotrophinomas, DRD2 expression was not associated with FLNA expression nor to the response to CAB. Nonetheless, FLNA expression could be related to tumor invasiveness.
- 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.