ANA CLAUDIA LATRONICO XAVIER
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Clínica Médica, Faculdade de Medicina - Docente
Instituto Central, Hospital das Clínicas, Faculdade de Medicina
LIM/42 - Laboratório de Hormônios e Genética Molecular, Hospital das Clínicas, Faculdade de Medicina
Instituto Central, Hospital das Clínicas, Faculdade de Medicina
LIM/42 - Laboratório de Hormônios e Genética Molecular, Hospital das Clínicas, Faculdade de Medicina
15 resultados
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conferenceObject Time Course of Central Precocious Puberty Development Caused by an MKRN3 Gene Mutation: A Prismatic Case(2016) STECCHINI, M.; MACEDO, D.; REIS, A. C.; ABREU, A. P.; MOREIRA, A.; CASTRO, M.; KAISER, U.; LATRONICO, A. C.; ANTONINI, S.- Centennial Celebration: Endocrine Reviews Past Highlights for November and December(2016) LATRONICO, Ana Claudia; RICKELS, Michael R.; HANDELSMAN, David J.; SALVATORI, Roberto
conferenceObject Whole-Exome Sequencing Reveals RAD51B Variant in Two Sisters with Primary Ovarian Failure(2016) FRANCA, Monica; FUNARI, Mariana; NISHI, Mirian; DOMENICE, Sorahia; LATRONICO, Ana Claudia; JORGE, Alexander; LERARIO, Antonio; MENDONCA, Berenice- A boy with Prader-Willi syndrome: unmasking precocious puberty during growth hormone replacement therapy(2016) LUDWIG, Natasha G.; RADAELI, Rafael F.; SILVA, Mariana M. X.; ROMERO, Camila M.; CARRILHO, Alexandre J. F.; BESSA, Danielle; MACEDO, Delanie B.; OLIVEIRA, Maria L.; LATRONICO, Ana Claudia; MAZZUCO, Tânia L.SUMMARY Prader-Willi syndrome (PWS) is a genetic disorder frequently characterized by obesity, growth hormone deficiency, genital abnormalities, and hypogonadotropic hypogonadism. Incomplete or delayed pubertal development as well as premature adrenarche are usually found in PWS, whereas central precocious puberty (CPP) is very rare. This study aimed to report the clinical and biochemical follow-up of a PWS boy with CPP and to discuss the management of pubertal growth. By the age of 6, he had obesity, short stature, and many clinical criteria of PWS diagnosis, which was confirmed by DNA methylation test. Therapy with recombinant human growth hormone (rhGH) replacement (0.15 IU/kg/day) was started. Later, he presented psychomotor agitation, aggressive behavior, and increased testicular volume. Laboratory analyses were consistent with the diagnosis of CPP (gonadorelin-stimulated LH peak 15.8 IU/L, testosterone 54.7 ng/dL). The patient was then treated with gonadotropin-releasing hormone analog (GnRHa). Hypothalamic dysfunctions have been implicated in hormonal disturbances related to pubertal development, but no morphologic abnormalities were detected in the present case. Additional methylation analysis (MS-MLPA) of the chromosome 15q11 locus confirmed PWS diagnosis. We presented the fifth case of CPP in a genetically-confirmed PWS male. Combined therapy with GnRHa and rhGH may be beneficial in this rare condition of precocious pubertal development in PWS.
- Causes, diagnosis, and treatment of central precocious puberty(2016) LATRONICO, Ana Claudia; BRITO, Vinicius Nahime; CAREL, Jean-ClaudeCentral precocious puberty results from the premature activation of the hypothalamic-pituitary-gonadal axis. It mimics physiological pubertal development, although at an inappropriate chronological age (before 8 years in girls and 9 years in boys). It can be attributable to cerebral congenital malformations or acquired insults, but the cause in most cases in girls remains unknown. MKRN3 gene defects have been identified in familial disease, with important basic and clinical results. Indeed, genetic analysis of this gene should be included in the routine clinical investigation of familial and idiopathic cases of central precocious puberty. Gonadotropin-releasing hormone agonists are the gold-standard treatment. The assessment and management of this disease remain challenging for paediatric endocrinologists. In this Series paper, we describe current challenges involving the precise diagnosis and adequate treatment of this disorder.
- Effects of Type 1 Insulin-Like Growth Factor Receptor Silencing in a Human Adrenocortical Cell Line(2016) RIBEIRO, T. C.; JORGE, A. A.; MONTENEGRO, L. R.; ALMEIDA, M. Q.; FERRAZ-DE-SOUZA, B.; NISHI, M. Y.; MENDONCA, B. B.; LATRONICO, A. C.Type 1 insulin-like growth factor receptor (IGF-1R) is overexpressed in a variety of human cancers, including adrenocortical tumors. The aim of the work was to investigate the effects of IGF-1R downregulation in a human adrenocortical cell line by small interfering RNA (siRNA). The human adrenocortical tumor cell line NCI H295R was transfected with 2 specific IGF1R siRNAs (#1 and #2) and compared with untreated cells and a negative control siRNA. IGF1R expression was determined by quantitative reverse-transcription PCR (qRTPCR) and Western blot. The effects of IGF-1R downregulation on cell proliferation and apoptosis were assessed. IGF-1R levels were significantly decreased in cells treated with IGF1R siRNA #1 or #2. Relative expression of IGF1R mRNA decreased approximately 50 % and Western blot analysis revealed a 30 % of reduction in IGF-1R protein. Downregulation of this gene resulted in 40 % reduction in cell growth in vitro and 45 % increase in apoptosis using siRNA #2. These findings demonstrate that decreasing IGF1R mRNA and protein expression in NCI H295R cells can partially inhibit adrenal tumor cell growth in vitro. Targeting IGF-1R is a promising therapy for pediatric malignant adrenocortical tumor and can still be an option for adult adrenocortical cancer based on personalized genomic tumor profiling.
conferenceObject Clinical Presentation of Klinefelter Syndrome and Other Causes of Hypergonadotropic Hypogonadism(2016) SCHNOLL, C.; RENCK, A. Covallero; LIMA, L. Guimaraes; MENDONCA, B. Bilharinho de; LATRONICO, A. C.; SILVEIRA, L. F. G.conferenceObject Time Course of Central Precocious Puberty Development Caused by an MKRN3 Gene Mutation: A Prismatic Case(2016) STECCHINI, Monica; MACEDO, Delanie; REIS, Ana Claudia; ABREU, Ana Paula; MOREIRA, Ayrton; CASTRO, Margaret; KAISER, Ursula; LATRONICO, Ana Claudia; ANTONINI, Sonir- Time Course of Central Precocious Puberty Development Caused by an MKRN3 Gene Mutation: A Prismatic Case(2016) STECCHINI, Monica F.; MACEDO, Delanie B.; REIS, Ana Claudia S.; ABREU, Ana Paula; MOREIRA, Ayrton C.; CASTRO, Margaret; KAISER, Ursula B.; LATRONICO, Ana Claudia; ANTONINI, Sonir R.Background: Loss-of-function mutations in the imprinted gene MKRN3 represent the most common known genetic defects associated with central precocious puberty (CPP). Methods: We report the first case of a girl carrying an MKRN3 mutation detected in childhood and followed until the development of pubertal signs. Results: The girl was screened at the age of 4 years because of a positive family history; her sister had developed CPP at 6 years of age and was found to harbor the MKRN3 p.Pro161Argfs*16 mutation, inherited from their asymptomatic father. During close follow-up, she initially developed increased growth velocity at 6 years (9 cm/year), followed by a slightly increased basal luteinizing hormone level (0.4 mIU/ml) and, ultimately, clinical thelarche with rapid progression (Tanner stage 1-3) between 6.3 and 6.7 years. In the context of a loss-of-function MKRN3 mutation and a positive family history, these features established the diagnosis of CPP and supported the initiation of treatment with a gonadotropin-releasing hormone analog. The absence of significant bone age advancement, pubic or axillary hair, or behavioral or social problems could be ascribed to the early diagnosis. Conclusion: The identification of carriers of MKRN3 mutations may contribute to early diagnosis of CPP, facilitating treatment decisions and guiding genetic counseling and prompt intervention in familial cases. (C) 2016 S. Karger AG, Basel
- Misfolding Ectodomain Mutations of the Lutropin Receptor Increase Efficacy of Hormone Stimulation(2016) CHARMANDARI, E.; GUAN, R.; ZHANG, M.; SILVEIRA, L. G.; FAN, Q. R.; CHROUSOS, G. P.; SERTEDAKI, A. C.; LATRONICO, A. C.; SEGALOFF, D. L.We demonstrate 2 novel mutations of the LHCGR, each homozygous, in a 46,XY patient with severe Leydig cell hypoplasia. One is a mutation in the signal peptide (p.Gln18_Leu19ins9; referred to here as SP) that results in an alteration of the coding sequence of the N terminus of the mature mutant receptor. The other mutation (p.G71R) is also within the ectodomain. Similar to many other inactivating mutations, the cell surface expression of recombinant human LHR(SP,G71R) is greatly reduced due to intracellular retention. However, we made the unusual discovery that the intrinsic efficacy for agonist-stimulated cAMP in the reduced numbers of receptors on the cell surface was greatly increased relative to the same low number of cell surface wild-type receptor. Remarkably, this appears to be a general attribute of misfolding mutations in the ectodomains, but not serpentine domains, of the gonadotropin receptors. These findings suggest that there must be a common, shared mechanism by which disparate mutations in the ectodomain that cause misfolding and therefore reduced cell surface expression concomitantly confer increased agonist efficacy to those receptor mutants on the cell surface. Our data further suggest that, due to their increased agonist efficacy, extremely small changes in cell surface expression of misfolded ectodomain mutants cause larger than expected alterations in the cellular response to agonist. Therefore, for inactivating LHCGR mutations causing ectodomain misfolding, the numbers of cell surface mutant receptors on fetal Leydig cells of 46,XY individuals exert a more exquisite effect on the relative severity of the clinical phenotypes than already appreciated.