VINICIUS NAHIME DE BRITO
Projetos de Pesquisa
Unidades Organizacionais
LIM/42 - Laboratório de Hormônios e Genética Molecular, Hospital das Clínicas, Faculdade de Medicina
10 resultados
Resultados de Busca
Agora exibindo 1 - 10 de 10
- Successful Pregnancies After Adequate Hormonal Replacement in Patients With Combined Pituitary Hormone Deficiencies(2017) CORREA, Fernanda A.; BIANCHI, Paulo H. M.; FRANCA, Marcela M.; OTTO, Aline P.; RODRIGUES, Rodrigo J. M.; EJZENBERG, Dani; SERAFINI, Paulo C.; BARACAT, Edmundo Chada; FRANCISCO, Rossana P. V.; BRITO, Vinicius N.; ARNHOLD, Ivo J. P.; MENDONCA, Berenice B.; CARVALHO, Luciani R.Context: Women with hypopituitarism have lower pregnancy rates after ovulation induction. Associated pituitary hormone deficiencies might play a role in this poorer outcome. Objective: We evaluated fertility treatment and pregnancy outcomes in five women with childhoodonset combined pituitary hormone deficiencies (CPHD). Patients and Methods: Five women with CPHD were referred for fertility treatment after adequacy of hormone replacement was determined. Patients were subjected to controlled ovarian stimulation (COS) for timed intercourse, intrauterine insemination, or in vitro fertilization, according to the presence or absence of other infertility factors (male or tubal). Results: All women became pregnant. The number of COS attempts until pregnancy was achieved varied between 1 and 5. The duration of COS resulting in at least one dominant follicle varied between 9 and 28 days, and total gonadotropin consumed varied between 1200 and 3450 IU. Two patients with severely suppressed basal gonadotropin levels since an early age had a cancelled COS cycle. All pregnancies were singleton except one (monochorionic twin gestation). The gestational ages at birth ranged from 35 weeks to 39 weeks and 4 days; three patients underwent cesarean section, and two had vaginal deliveries. Only one newborn was small for gestational age (delivered at 35 weeks). Conclusion: Adequate hormonal replacement prior to ovarian stimulation resulted in successful pregnancies in patients with childhood-onset CPHD, indicating that hormone replacement, including growth hormone, is an important step prior to fertility treatments in these patients.
- High Frequency of MKRN3 Mutations in Male Central Precocious Puberty Previously Classified as Idiopathic(2017) BESSA, Danielle S.; MACEDO, Delanie B.; BRITO, Vinicius N.; FRANCA, Monica M.; MONTENEGRO, Luciana R.; CUNHA-SILVA, Marina; SILVEIRA, Leticia G.; HUMMEL, Tiago; BERGADA, Ignacio; BRASLAVSKY, Debora; ABREU, Ana Paula; DAUBER, Andrew; MENDONCA, Berenice B.; KAISER, Ursula B.; LATRONICO, Ana ClaudiaBackground/Aims: Recently, loss-of-function mutations in the MKRN3 gene have been implicated in the etiology of familial central precocious puberty (CPP) in both sexes. We aimed to analyze the frequency of MKRN3 mutations in boys with CPP and to compare the clinical and hormonal features of boys with and without MKRN3 mutations. Methods: This was a retrospective review of clinical, hormonal and genetic features of 20 male patients with idiopathic CPP evaluated at an academic medical center. The entire coding regions of MKRN3, KISS1 and KISS1R genes were sequenced. Results: We studied 20 boys from 17 families with CPP. All of them had normal brain magnetic resonance imaging. Eight boys from 5 families harbored four distinct heterozygous MKRN3 mutations predicted to be deleterious for protein function, p.Ala162Glyfs*14, p.Arg213Glyfs*73, p.Arg328Cys and p. Arg365Ser. One boy carried a previously described KISS1-activating mutation (p.Pro74Ser). The frequency of MKRN3 mutations among these boys with idiopathic CPP was significantly higher than previously reported female data (40 vs. 6.4%, respectively, p < 0.001). Boys with MKRN3 mutations had typical clinical and hormonal features of CPP. Notably, they had later pubertal onset than boys without MKRN3 abnormalities (median age 8.2 vs. 7.0 years, respectively, p = 0.033). Conclusion: We demonstrated a high frequency of MKRN3 mutations in boys with CPP, previously classified as idiopathic, suggesting the importance of genetic analysis in this group. The boys with CPP due to MKRN3 mutations had classical features of CPP, but with puberty initiation at a borderline age. (C) 2016 S. Karger AG, Basel
conferenceObject PATERNALLY INHERITED DLK1 DELETION AS A NOVEL CAUSE OF FAMILIAL CENTRAL PRECOCIOUS PUBERTY(2017) DAUBER, Andrew; CUNHA-SILVA, Marina; MACEDO, Delanie; BRITO, Vinicius; ABREU, Ana Paula; ROBERTS, Stephanie; MONTENEGRO, Luciana; ANDREW, Melissa; KRIBY, Andrew; WEIRAUCH, Matthew; LABILLOY, Guillaume; BESSA, Danielle; CARROLL, Rona; JACOBS, Dakota; CHAPPELL, Patrick; MENDONCA, Berenice B.; HAIG, David; KAISER, Ursula; LATRONICO, Ana Claudia- Paternally Inherited DLK1 Deletion Associated With Familial Central Precocious Puberty(2017) DAUBER, Andrew; CUNHA-SILVA, Marina; MACEDO, Delanie B.; BRITO, Vinicius N.; ABREU, Ana Paula; ROBERTS, Stephanie A.; MONTENEGRO, Luciana R.; ANDREW, Melissa; KIRBY, Andrew; WEIRAUCH, Matthew T.; LABILLOY, Guillaume; BESSA, Danielle S.; CARROLL, Rona S.; JACOBS, Dakota C.; CHAPPELL, Patrick E.; MENDONCA, Berenice B.; HAIG, David; KAISER, Ursula B.; LATRONICO, Ana ClaudiaContext: Central precocious puberty (CPP) results from premature activation of the hypothalamic-pituitary- gonadal axis. Few genetic causes of CPP have been identified, with the most common being mutations in the paternally expressed imprinted gene MKRN3. Objective: To identify the genetic etiology of CPP in a large multigenerational family. Design: Linkage analysis followed by whole-genome sequencing was performed in a family with five female members with nonsyndromic CPP. Detailed phenotyping was performed at the time of initial diagnosis and long-term follow-up, and circulating levels of Delta-like 1 homolog (DLK1) were measured in affected individuals. Expression of DLK1 was measured in mouse hypothalamus and in kisspeptin-secreting neuronal cell lines in vitro. Setting: Endocrine clinic of an academic medical center. Patients: Patients with familial CPP were studied. Results: A complex defect of DLK1 (similar to 14-kb deletion and 269-bp duplication) was identified in this family. This deletion included the 50 untranslated region and the first exon of DLK1, including the translational start site. Only family members who inherited the defect from their father have precocious puberty, consistent with the known imprinting of DLK1. The patients did not demonstrate additional features of the imprinted disorder Temple syndrome except for increased fat mass. Serum DLK1 levels were undetectable in all affected individuals. Dlk1 was expressed in mouse hypothalamus and in kisspeptin neuron-derived cell lines. Conclusion: We identified a genomic defect in DLK1 associated with isolated familial CPP. MKRN3 and DLK1 are both paternally expressed imprinted genes. These findings suggest a role of genomic imprinting in regulating the timing of human puberty.
conferenceObject ANTHROPOMETRIC, METABOLIC AND REPRODUCTIVE OUTCOME OF PATIENTS WITH CENTRAL PRECOCIOUS PUBERTY DUE TO HYPOTHALAMIC HAMARTOMA IN ADULT LIFE(2017) RAMOS, Carolina O.; LATRONICO, Ana Claudia; CUKIER, Priscila; MACEDO, Delanie; BESSA, Danielle S.; SILVA, Marina C.; ARNHOLD, Ivo J.; MENDONCA, Berenice B.; BRITO, Vinicius N.article 2 Citação(ões) na Scopus Underdiagnosis of central precocious puberty in boys with loss-of-function mutations of MKRN3(2017) BRITO, Vinicius Nahime; LATRONICO, Ana ClaudiaconferenceObject PREMATURE PUBARCHE CAN BE CAUSED BY EXOGENOUS TESTOSTERONE GEL OR DIAPER RASH PREVENTION CREAM(2017) RAMOS, Carolina O.; MACEDO, Delanie; BACHEGA, Tania S. S.; LEE, Juliana C.; NASCIMENTO, Marilza L.; MADUREIA, Guiomar; BRITO, Vinicius N.; LATRONICO, Ana Claudia; MENDONCA, Berenice B.- Neonatal 17-hydroxyprogesterone levels adjusted according to age at sample collection and birthweight improve the efficacy of congenital adrenal hyperplasia newborn screening(2017) HAYASHI, Giselle Y.; CARVALHO, Daniel F.; MIRANDA, Mirela C. de; FAURE, Claudia; VALLEJOS, Carla; BRITO, Vinicius N.; RODRIGUES, Andresa De Santi; MADUREIRA, Guiomar; MENDONCA, Berenice B.; BACHEGA, Tania A. S. S.IntroductionThe primary concern related to congenital adrenal hyperplasia (CAH) newborn screening (NBS) is the high rate of false-positive results (FPR) associated with prematurity; false-negative results (FNR) can also occur due to precocious sample collection. ObjectiveTo determine the neonatal 17-hydroxyprogesterone (N17OHP) normal range in newborns in Sao Paulo using different references according to age and birthweight (BW) and to establish the optimal NBS cut-off levels. MethodsNeonatal 17-hydroxyprogesterone levels from 271 810 newborns (NBs) according to sample collection time (G1: 48-<72 h and G2: 72 h) and BW (1500 g, 1501-2000 g, 2001-2500 and >2500 g) were evaluated. N17OHP was measured by an fluoroimmunoassay, and serum 17OHP was measured by liquid chromatography-mass spectrometry. Affected and asymptomatic NBs with persistently increased 17OHP levels were submitted to CYP21A2-sequencing. ResultsNeonatal 17-hydroxyprogesterone levels in G1 were lower than G2 in all BW groups (P < 0001). The FPR rate in G1/G2 was 02% using the 998th and 05% using the 995th percentile. The 998th percentile N17OHP value was the best cut-off for distinguishing between unaffected and affected NBs. Forty-four salt wasters, and five simple virilisers were diagnosed; N17OHP levels ranged from 933 to 22098 nmol/l, and no affected neonates with FNR were identified. The positive predictive value in G1 and G2 using the 998th percentile was 56% and 141%, respectively, and 23% and 7%, respectively, using the 995th percentile. Molecular tests identified two NBs with the nonclassical form among the 29 FPR. ConclusionNeonatal 17-hydroxyprogesterone levels adjusted to sample collection age and birthweight reduced the FPR, and the use of N17OHP values based upon the 998th percentile improved the NBS efficacy.
conferenceObject OUTCOMES OF GIRLS WITH IDIOPATHIC CENTRAL PRECOCIOUS PUBERTY TREATED WITH 1-AND 3-MONTH GONADOTROPIN-RELEASING HORMONE ANALOG FORMULATIONS(2017) RAMOS, Carolina O.; SILVA, Marina C.; SALLES, Priscila; MENDONCA, Berenice B.; LATRONICO, Ana Claudia; BRITO, Vinicius N.bookPart Puberdade normal e precoce(2017) BRITO, Vinicius Nahime de; LATRONICO, Ana Cláudia; SILVEIRA, Letícia Ferreira Gontijo; MENDONçA, Berenice Bilharinho de