GUSTAVO ARANTES ROSA MACIEL
Projetos de Pesquisa
Unidades Organizacionais
Instituto Central, Hospital das Clínicas, Faculdade de Medicina - Médico
LIM/58 - Laboratório de Ginecologia Estrutural e Molecular, Hospital das Clínicas, Faculdade de Medicina
LIM/58 - Laboratório de Ginecologia Estrutural e Molecular, Hospital das Clínicas, Faculdade de Medicina
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- Screening of targeted panel genes in Brazilian patients with primary ovarian insufficiency(2020) FRANCA, Monica M.; FUNARI, Mariana F. A.; LERARIO, Antonio M.; SANTOS, Mariza G.; NISHI, Mirian Y.; DOMENICE, Sorahia; MORAES, Daniela R.; COSTALONGA, Everlayny F.; MACIEL, Gustavo A. R.; MACIEL-GUERRA, Andrea T.; GUERRA-JUNIOR, Gil; MENDONCA, Berenice B.Primary ovarian insufficiency (POI) is a heterogeneous disorder associated with several genes. The majority of cases are still unsolved. Our aim was to identify the molecular diagnosis of a Brazilian cohort with POI. Genetic analysis was performed using a customized panel of targeted massively parallel sequencing (TMPS) and the candidate variants were confirmed by Sanger sequencing. Additional copy number variation (CNV) analysis of TMPS samples was performed by CONTRA. Fifty women with POI (29 primary amenorrhea and 21 secondary amenorrhea) of unknown molecular diagnosis were included in this study, which was conducted in a tertiary referral center of clinical endocrinology. A genetic defect was obtained in 70% women with POI using the customized TMPS panel. Twenty-four pathogenic variants and two CNVs were found in 48% of POI women. Of these variants, 16 genes were identified as BMP8B, CPEB1, INSL3, MCM9, GDF9, UBR2, ATM, STAG3, BMP15, BMPR2, DAZL, PRDM1, FSHR, EIF4ENIF1, NOBOX, and GATA4. Moreover, a microdeletion and microduplication in the CPEB1 and SYCE1 genes, respectively, were also identified in two distinct patients. The genetic analysis of eleven patients was classified as variants of uncertain clinical significance whereas this group of patients harbored at least two variants in different genes. Thirteen patients had benign or no rare variants, and therefore the genetic etiology remained unclear. In conclusion, next-generation sequencing (NGS) is a highly effective approach to identify the genetic diagnoses of heterogenous disorders, such as POI. A molecular etiology allowed us to improve the disease knowledge, guide decisions about prevention or treatment, and allow familial counseling avoiding future comorbidities.
- Contemporary human papillomavirus genotyping and correlations to peniscopy, cytology, and histopatology on over 1000 males(2020) TRUZZI, Jose Carlos; SILVA, Ismael Dale da; FREIRE, Marcos Paulo; NETO, Miguel Jorge; RODRIGUES, Fabio Ferro; MACIEL, Gustavo Arantes; GIRARDI, Ruana; BERTOLINI, Sissi; REIS, Leonardo O.Objectives To explore male human papillomavirus (HPV) contemporary genotyping epidemiology and correlations to peniscopy, cytology, and histopatology. Methods Medical records of patients who had been submitted to HPV infection screening with genotyping, peniscopy, cytology, and histopathology in a period of 2 years were reviewed. Frequency analysis and correlations between the diagnostic tools were established. Results Genotype of 1132 men resulted in 69.2% (784) positivity for HPV DNA, 78% classified as high risk of oncogenesis. Co-infections occurred in 429 (54.7%) and the most frequently identified types were HPV-6, HPV-42, and HPV-16, in 133 (17%), 94 (12%), and 86 (11%) patients, respectively. Positive/negative predictive values of peniscopy, cytology, and histopathology were 83/31%, 92/32%, and 87/33%, respectively. As a result, though significant, the correlations between genotype and non-molecular tests were poor. Conclusions In the current contemporary representative male cohort, over two thirds are positive for human HPV DNA, 78% of high risk and with over half co-infections. Though significant, its correlation with non-molecular tests is poor and while the positive predictive values of peniscopy, cytology, and histopatology are between 83% and 92%, their negative predictive values are as low as 31% to 33%.
- Kisspeptin Influence on Polycystic Ovary Syndrome-a Mini Review(2020) ARAUJO, Bruna Silva; BARACAT, Maria Candida P.; SIMOES, Ricardo dos Santos; NUNES, Camila de Oliveira; MACIEL, Gustavo Arantes Rosa; LOBO, Rogerio A.; JR, Jose Maria Soares; BARACAT, Edmund ChadaPolycystic ovary syndrome (PCOS) affects 6% to 20% of reproductive age women and is the most frequent cause of anovulatory infertility. Its physiopathology may result in part from hypothalamic alterations in the pulsatile secretion of gonadotropin-releasing hormone (GnRH). The neuropeptide kisspeptin participates in the mechanism through stimulation of the hormone's production. The purpose of this study was to review the articles which compared kisspeptin levels in women with PCOS with those of controls. A systematic review of observational studies was conducted in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) recommendations. The selected studies encompassed a population of patients with PCOS and controls, whose serum kisspeptin levels were evaluated. The studies were retrieved from the Medline, Cochrane, and Embase databases, and four of them were chosen for the review. In most studies, the serum kisspeptin levels were higher in women with PCOS than in controls notwithstanding the BMI. One of the articles showed that circulating plasma levels of kisspeptin were significantly higher in women with PCOS whose BMI was lower than 25 than in obese and overweight women. Our data suggest a higher concentration of serum kisspeptin in women with PCOS irrespective of their BMI. Further experimental and clinical studies are needed to ascertain the role of kisspeptin in PCOS.
- Steroid Screening Tools Differentiating Nonclassical Congenital Adrenal Hyperplasia and Polycystic Ovary Syndrome(2020) MAFFAZIOLI, Giovana D. N.; BACHEGA, Tania A. S. S.; HAYASHIDA, Sylvia A. Y.; GOMES, Larissa G.; VALASSI, Helena P. L.; MARCONDES, Jose A. M.; MENDONCA, Berenice B.; BARACAT, Edmund C.; MACIEL, Gustavo A. R.Purpose: To analyze the performance of basal 17OH-progesterone (17OHP) levels versus the basal 17OHP/cortisol ratio in nonclassical congenital adrenal hyperplasia (NCAH) and polycystic ovary syndrome (PCOS) differential diagnosis. Basal 17OHP levels >10 ng/mL have been used to confirm NCAH diagnosis without the adrenocorticotropic hormone (ACTH) test; however, the optimal cutoff value is a matter of debate. Methods: A cross-sectional study was performed at the endocrinology and gynecological endocrinology outpatient clinics of a tertiary hospital. A total of 361 patients with PCOS (age 25.0 +/- 5.3 years) and 113 (age 19.0 +/- 13.6 years) patients with NCAH were enrolled. Basal and ACTH-17OHP levels were measured by radioimmunoassay, and CYP21A2 molecular analysis was performed to confirm hormonal NCAH diagnosis. Receiver operating characteristic curve analysis compared basal 17OHP levels and the 17OHP/cortisol ratio between NCAH and PCOS patients. Results: Basal 17OHP levels were higher in NCAH patients than in those with PCOS (8.85 [4.20-17.30] vs 1.00 [0.70-1.50] ng/mL; P < 0.0001), along with 17OHP/cortisol ratio (0.86 [0.47-1.5]) vs 0.12 [0.07-0.19]; P < 0.0001, respectively). Basal 17OHP levels and the 170HP/cortisol ratio were strongly correlated in both groups (rho = 0.82; P < 0.0001). Areas under the curves for basal 17OHP levels (0.9528) and the 17OHP/cortisol ratio (0.9455) were not different to discriminate NCAH and PCOS (P > 0.05). Basal 17OHP level >5.4 ng/mL and 17OHP/cortisol ratio >2.90 had 100% specificity to identify NCAH. Main Conclusions: Basal 17OHP levels >5.4 ng/mL can be used to perform differential diagnoses between NCAH and PCOS, dismissing the ACTH test. The basal 17OHP/cortisol ratio was not superior to basal 17OHP levels in this scenario.
- Reproductive Outcomes in Cases of Subclinical Hypothyroidism and Thyroid Autoimmunity: A Narrative Review(2020) CARVALHO, Bruno Ramalho de; NACUL, Andrea Prestes; BENETTI-PINTO, Cristina Laguna; ROSA-E-SILVA, Ana Carolina Japur de Sa; SOARES JUNIOR, Jose Maria; MACIEL, Gustavo Arantes Rosa; BARACAT, Edmund ChadaThyroid diseases are relatively common in women in the reproductive period. It is currently understood that clinically-evident thyroid disorders may impair ovulation and, consequently, fertility. However, to date it has not been proven that high serum levels of thyroid-stimulating hormone and/or positivity for antithyroid antibodies are associated to a reduction in fertility, mainly in the absence of altered thyroxine levels. The present comprehensive review aims to present current data on the association between subclinical hypothyroidism and/ or thyroid autoimmunity and reproductive outcomes.
- Nutritional and dietary aspects in polycystic ovary syndrome: insights into the biology of nutritional interventions(2020) NEVES, Luisa Pinheiro Pimenta; MARCONDES, Rodrigo Rodrigues; MAFFAZIOLI, Giovana De Nardo; SIMOES, Ricardo Santos; MACIEL, Gustavo Arantes Rosa; JR, Jose Maria Soares; BARACAT, Edmund ChadaPolycystic Ovary Syndrome (PCOS) is a complex endocrine disorder, which affects 5-17% of reproductive age women and is often associated with obesity and metabolic impairment. Common treatment strategies are based on exercise, diet and nutrient supplementation since PCOS is often linked with obesity and metabolic impairment. Studies have recommended that nutrition is a key factor in the health maintenance of women with PCOS, however, little is known about the subject in the context of such a disease. This narrative review aims to identify dietary and nutritional aspects of PCOS and discuss the role of nutrients in management of polycystic ovary syndrome in view of clinical trials.
- Premature ovarian insufficiency: A hormonal treatment approach(2020) BENETTI-PINTO, Cristina Laguna; SOARES JUNIOR, Jose Maria; MACIEL, Gustavo Arantes; NACUL, Andrea Prestes; YELA, Daniela Angerame; SILVA, Ana Carolina Japur Sa Rosa e
conferenceObject Variation of Antimullerian Hormone (AMH) Measurements and Its Impact on Prescription and Predicted Response in Controlled Ovarian Stimulation(2020) MACIEL, G.; MAFFAZIOLI, G.; HEIRICH, V.; LOPES, C.; BISCOLLA, R. P.; SA, J. De; FERRER, C.; VIEIRA, J.; BARACAT, E.- Prevalence of metabolic disturbances among women with polycystic ovary syndrome in different regions of Brazil(2020) MAFFAZIOLI, Giovana D. N.; LOPES, Caroline P.; HEINRICH-OLIVEIRA, Vanessa; LOBO, Rogerio A.; HAYASHIDA, Sylvia A. Y.; SOARES JR., Jose Maria; MACIEL, Gustavo A. R.; BARACAT, Edmund C.Objective To describe the prevalence of metabolic disturbances in a large cohort of women with polycystic ovary syndrome (PCOS) in southeastern Brazil and to compare the findings with other cohorts of Brazilian women with PCOS. Methods A retrospective study analyzing clinical and laboratory data of 462 women with PCOS treated at an outpatient clinic in a tertiary hospital in southeastern Brazil. Prevalence of insulin resistance, glucose intolerance, type 2 diabetes, dyslipidemia, central obesity, hypertension, and metabolic syndrome was compared to that of other cohorts of age and body mass index-matched Brazilian women with PCOS. Results Women with PCOS had a median age of 25.0 (21.0-29.0) years and BMI of 28.7 (23.9-34.0) kg/m(2). Prevalence of insulin resistance, glucose intolerance, and type 2 diabetes varied from 39.6% to 55.0%, 7.2% to 28.1%, and 2.0% to 4.1%, respectively. Prevalence of central obesity, dyslipidemia due to decreased high-density lipoprotein cholesterol, hypertriglyceridemia, and metabolic syndrome ranged from 57.8% to 66.4%, 54.1% to 70.4%, 22.9% to 35.1%, and 27.4% to 38.3%, respectively, which did not differ among regions in Brazil. Conclusion Prevalence of metabolic disturbances was high among Brazilian women with PCOS. This study suggests that, from a public health perspective, authorities in Brazil should be aware of and encourage screening for metabolic dysfunction in women with PCOS in all regions of the country.
- Diagnostic power and clinical impact of exome sequencing in a cohort of 500 patients with rare diseases(2020) QUAIO, Caio Robledo D'Angioli Costa; MOREIRA, Caroline Monaco; NOVO-FILHO, Gil Monteiro; SACRAMENTO-BOBOTIS, Patricia Rossi; PENNA, Michele Groenner; PERAZZIO, Sandro Felix; DUTRA, Aurelio Pimenta; SILVA, Rafael Alves da; SANTOS, Monize Nakamoto Provisor; ARRUDA, Vanessa Yurie Nozaki de; FREITAS, Vanessa Galdeno; PEREIRA, Vinicius Ceola; PINTAO, Maria Carolina; FORNARI, Alexandre Ricardo dos Santos; BUZOLIN, Ana Ligia; OKU, Andre Yuji; BURGER, Matheus; RAMALHO, Rodrigo Fernandes; ANTONIO, David Santos Marco; FERREIRA, Elisa Napolitano e; PEREIRA, Otavio Jose Eulalio; CANTAGALLI, Vanessa Dionisio; TRINDADE, Ana Carolina Gomes; SOUSA, Rafaela Rogerio Floriano de; FURUZAWA, Cintia Reys; VERZINI, Fernanda; MATALHANA, Shirley Dezan; ROMANO, Naiade; PAIXAO, Daniele; OLIVATI, Caroline; SPOLADOR, Gustavo Marquezani; MACIEL, Gustavo Arantes Rosa; ROCHA, Viviane Zorzanelli; MIGUELEZ, Javier; CARVALHO, Mario Henrique Burlacchini de; SOUZA, Alexandre Wagner Silva de; ANDRADE, Luis Eduardo Coelho; CHAUFFAILLE, Maria de Lourdes; PERAZZIO, Aline dos Santos Borgo; CATELANI, Ana Lucia Pereira Monteiro; MITNE-NETO, Miguel; KIM, Chong Ae; BARATELA, Wagner Antonio da RosaRare diseases comprise a diverse group of conditions, most of which involve genetic causes. We describe the variable spectrum of findings and clinical impacts of exome sequencing (ES) in a cohort of 500 patients with rare diseases. In total, 164 primary findings were reported in 158 patients, representing an overall diagnostic yield of 31.6%. Most of the findings (61.6%) corresponded to autosomal dominant conditions, followed by autosomal recessive (25.6%) and X-linked (12.8%) conditions. These patients harbored 195 variants, among which 43.6% are novel in the literature. The rate of molecular diagnosis was considerably higher for prenatal samples (67%; 4/6), younger children (44%; 24/55), consanguinity (50%; 3/6), gastrointestinal/liver disease (44%; 16/36) and syndromic/malformative conditions (41%; 72/175). For 15.6% of the cohort patients, we observed a direct potential for the redirection of care with targeted therapy, tumor screening, medication adjustment and monitoring for disease-specific complications. Secondary findings were reported in 37 patients (7.4%). Based on cost-effectiveness studies in the literature, we speculate that the reports of secondary findings may influence an increase of 123.2 years in the life expectancy for our cohort, or 0.246 years/cohort patient. ES is a powerful method to identify the molecular bases of monogenic disorders and redirect clinical care.