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
55 resultados
Resultados de Busca
Agora exibindo 1 - 10 de 55
- Myocardial Inactivation of Thyroid Hormones in Patients with Aortic Stenosis(2017) PAOLINO, Bruno S.; POMERANTZEFF, Pablo M.; DALLAN, Luis Alberto O.; GAIOTTO, Fabio A.; PREITE, Nailliw Z.; LATRONICO, Ana Claudia; NICOLAU, Jose Carlos; BIANCO, Antonio C.; GIRALDEZ, Roberto R. C. V.Objective: The human heart expresses the type 2 deiodinase (D2) that activates thyroxine (T4) to triiodothyronine (T3). At the same time, the inactivating type 3 deiodinase (D3) has been found in a rat model of right ventricular hypertrophy. It is not known whether the human myocardium metabolizes thyroid hormone. This study examined myocardial thyroid hormone metabolism in patients with aortic valve stenosis (AS) undergoing aortic valve replacement and in patients with coronary artery disease (CAD) undergoing coronary artery bypass grafting surgery. Methods: Myocardial thyroid hormone metabolism was assessed by analyzing the difference in serum thyroid hormone levels between the aortic root (incoming blood) and the coronary sinus (outgoing blood) of patients undergoing cardiac surgery. A total of 23 patients with AS and 35 patients with CAD were included. Patients received a pre-surgical echocardiogram, and pre-, during and post-surgical thyroid hormone serum levels were collected in the myocardial and peripheral circulations. Results: Patients with AS exhibited the expected left ventricle (LV) hypertrophy (i.e., 20-30% increase in LV posterior wall and interventricular septum thickness and similar to 10% increase in AS in LV diastolic diameter). Immediately before cardiopulmonary bypass, blood flowing through the AS myocardium exhibited a 4.6% reduction in T3 and 6.9% increase in rT3 levels, decreasing the serum T3/rT3 ratio by 9.6%. T4 and thyrotropin serum levels remained similar between the aortic root and coronary sinus. In contrast, no myocardial thyroid hormone metabolism was observed in CAD patients. Notably, the AS myocardium lost the ability to inactivate thyroid hormone after cardiopulmonary bypass, possibly due to myocardial stunning. Conclusions: There is accelerated thyroid hormone inactivation in the AS myocardium, which is likely the result of D3 expression. No evidence to suggest thyroid hormone activation in the myocardium was obtained in the present study.
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.- Kisspeptin and Clinical Disorders(2013) SILVEIRA, Leticia Gontijo; LATRONICO, Ana Claudia; SEMINARA, Stephanie BethThe hypothalamic hormone GnRH has traditionally been viewed as a central driver of the hypothalamic-pituitary-gonadal axis. Pulsatile GnRH release is required for pulsatile gonadotropin secretion, which then modulates gonadal steroid feedback and brings about full fertility in the adult. Pathways governing GnRH ontogeny and physiology have been discovered by studying humans with disorders of GnRH secretion. In this chapter, the human genetics of the kisspeptin signaling pathway in patients with diverse reproductive phenotypes will be explored. The discovery of defects in the kisspeptin system in several reproductive disorders has shed light on the mechanisms involved in regulating GnRH secretion, revealing the critical role played by the kisspeptin signaling pathway in pubertal initiation and reproductive function.
- Centennial Celebration: Endocrine Reviews Past Highlights for November and December(2016) LATRONICO, Ana Claudia; RICKELS, Michael R.; HANDELSMAN, David J.; SALVATORI, Roberto
- Pathogenic variants inTNRC6Bcause a genetic disorder characterised by developmental delay/intellectual disability and a spectrum of neurobehavioural phenotypes including autism and ADHD(2020) GRANADILLO, Jorge Luis; STEGMANN, Alexander P.A.; GUO, Hui; XIA, Kun; ANGLE, Brad; BONTEMPO, Kelly; RANELLS, Judith D.; NEWKIRK, Patricia; COSTIN, Carrie; VIRONT, Joleen; STUMPEL, Constanze T.; SINNEMA, Margje; PANIS, Bianca; PFUNDT, Rolph; KRAPELS, Ingrid P. C.; KLAASSENS, Merel; NICOLAI, Joost; LI, Jinliang; JIANG, Yuwu; MARCO, Elysa; CANTON, Ana; LATRONICO, Ana Claudia; MONTENEGRO, Luciana; LEHEUP, Bruno; BONNET, Celine; AMUDHAVALLI, Shivarajan M.; LAWSON, Caitlin E.; MCWALTER, Kirsty; TELEGRAFI, Aida; PEARSON, Richard; KVARNUNG, Malin; WANG, Xia; BI, Weimin; ROSENFELD, Jill Anne; SHINAWI, MarwanBackground Rare variants in hundreds of genes have been implicated in developmental delay (DD), intellectual disability (ID) and neurobehavioural phenotypes.TNRC6Bencodes a protein important for RNA silencing. Heterozygous truncating variants have been reported in three patients from large cohorts with autism, but no full phenotypic characterisation was described. Methods Clinical and molecular characterisation was performed on 17 patients withTNRC6Bvariants. Clinical data were obtained by retrospective chart review, parent interviews, direct patient interaction with providers and formal neuropsychological evaluation. Results Clinical findings included DD/ID (17/17) (speech delay in 94% (16/17), fine motor delay in 82% (14/17) and gross motor delay in 71% (12/17) of subjects), autism or autistic traits (13/17), attention deficit and hyperactivity disorder (ADHD) (11/17), other behavioural problems (7/17) and musculoskeletal findings (12/17). Other congenital malformations or clinical findings were occasionally documented. The majority of patients exhibited some dysmorphic features but no recognisable gestalt was identified. 17 heterozygousTNRC6Bvariants were identified in 12 male and five female unrelated subjects by exome sequencing (14), a targeted panel (2) and a chromosomal microarray (1). The variants were nonsense (7), frameshift (5), splice site (2), intragenic deletions (2) and missense (1). Conclusions Variants inTNRC6Bcause a novel genetic disorder characterised by recurrent neurocognitive and behavioural phenotypes featuring DD/ID, autism, ADHD and other behavioural abnormalities. Our data highly suggest that haploinsufficiency is the most likely pathogenic mechanism.TNRC6Bshould be added to the growing list of genes of the RNA-induced silencing complex associated with ID/DD, autism and ADHD.
- Genetic Syndromes Presenting in Childhood Affecting Gonadotropin Function(2019) CLOSE, S.; LATRONICO, A. C.; CUNHA-SILVA, M.This chapter will focus on two genetic syndromes affecting gonadotropin function that typically present in childhood, Klinefelter syndrome, and testotoxicosis. Klinefelter syndrome (47, XXY) is the most common sex chromosome aneuploidy with a prevalence of 1 in 450-500 male births. Unless detected by prenatal screening or prenatal diagnosis, this chromosome variation diagnosis is frequently missed in children. Physical, neurocognitive, and psychosocial phenotypes of boys with 47, XXY are extremely variable, making a typical case difficult to characterize. Health care needs of boys born with 47, XXY are complex including the need for monitoring growth, pubertal development, optimization of reproductive capacity, bone health, and acknowledgement of physical symptoms such as fatigue, hypotonic muscle strength, tremors, tics, and pain. Physical health risks associated with 47, XXY include: metabolic syndrome, Type II diabetes, cardiovascular disease, immunological issues, bone loss, and certain types of malignancies. Boys with 47, XXY frequently show executive function issues, language-based learning difficulties, problems with communication, and struggles with behavior that contribute to stressors for the boys as well as for their families. Psychosocial manifestations of these stressors include low self-esteem, increased risk for depression, difficulties maintaining personal relationships, and adverse quality of life. There is a general lack of awareness in the health care community about the complexities of care required for families who have sons with 47, XXY. Since puberty is a sentinel time for diagnosing and monitoring hypogonadism, families often depend on professionals in the specialty of endocrinology to address their many concerns. Families seeking anticipatory guidance about how 47, XXY will influence the growth and development of their sons often look to the specialty of endocrinology to help them navigate a health care environment that is confusing to them. This chapter will describe the physical, neurocognitive, and psychosocial phenotype of 47, XXY in childhood and provide suggestions for endocrine-related health surveillance for advanced practice nurses (APRN). APRNs in endocrinology practice are perfectly positioned to assess, coordinate, and provide family-centered navigation for health surveillance according to child’s level of development. Testotoxicosis or familial male-limited precocious puberty is a rare dominant form of gonadotropin-independent precocious puberty caused by constitutively activating mutations of the luteinizing hormone receptor. Affected males present premature and progressive virilization associated with accelerated growth and advanced bone age between 2 and 4 years of age. Hormonal profile is characterized by elevated testosterone levels, despite prepubertal levels of luteinizing hormone. Treatment typically consists of reducing hyperandrogenism with ketoconazole or a combination of antiandrogens and aromatase inhibitors. © Springer Nature Switzerland AG 2019.
- Mutational analysis of TAC3 and TACR3 genes in patients with idiopathic central pubertal disorders(2012) TUSSET, Cintia; NOEL, Sekoni D.; TRARBACH, Ericka B.; SILVEIRA, Leticia F. G.; JORGE, Alexander A. L.; BRITO, Vinicius N.; CUKIER, Priscila; SEMINARA, Stephanie B.; MENDONCA, Berenice B. de; KAISER, Ursula B.; LATRONICO, Ana ClaudiaObjective: To investigate the presence of variants in the TAC3 and TACR3 genes, which encode NKB and its receptor (NK3R), respectively, in a large cohort of patients with idiopathic central pubertal disorders. Subjects and methods: Two hundred and thirty seven patients were studied: 114 with central precocious puberty (CPP), 73 with normosmic isolated hypogonadotropic hypogonadism (IHH), and 50 with constitutional delay of growth and puberty (CDGP). The control group consisted of 150 Brazilian individuals with normal pubertal development. Genomic DNA was extracted from peripheral blood and the entire coding region of both TAC3 and TACR3 genes were amplified and automatically sequenced. Results: We identified one variant (p.A63P) in NKB and four variants, p.G18D, p.L58L (c.172C > T), p.W275* and p.A449S in NK3R, which were absent in the control group. The p.A63P variant was identified in a girl with CPP, and p.A449S in a girl with CDGP. The known p.G18D, p.L58L, and p.W275* variants were identified in three unrelated males with normosmic IHH. Conclusion: Rare variants in the TAC3 and TACR3 genes were identified in patients with central pubertal disorders. Loss-of-function variants of TACR3 were associated with the normosmic IHH phenotype.
- Hypothalamic miR-30 regulates puberty onset via repression of the puberty-suppressing factor, Mkrn3(2019) HERAS, Violeta; SANGIAO-ALVARELLOS, Susana; MANFREDI-LOZANO, Maria; SANCHEZ-TAPIA, Maria J.; RUIZ-PINO, Francisco; ROA, Juan; LARA-CHICA, Maribel; MORRUGARES-CARMONA, Rosario; JOUY, Nathalie; ABREU, Ana P.; PREVOT, Vincent; BELSHAM, Denise; VAZQUEZ, Maria J.; CALZADO, Marco A.; PINILLA, Leonor; GAYTAN, Francisco; LATRONICO, Ana C.; KAISER, Ursula B.; CASTELLANO, Juan M.; TENA-SEMPERE, ManuelMkrn3, the maternally imprinted gene encoding the makorin RING-finger protein-3, has recently emerged as putative pubertal repressor, as evidenced by central precocity caused by MKRN3 mutations in humans; yet, the molecular underpinnings of this key regulatory action remain largely unexplored. We report herein that the microRNA, miR-30, with three binding sites in a highly conserved region of its 3 ' UTR, operates as repressor of Mkrn3 to control pubertal onset. Hypothalamic miR-30b expression increased, while Mkrn3 mRNA and protein content decreased, during rat postnatal maturation. Neonatal estrogen exposure, causing pubertal alterations, enhanced hypothalamic Mkrn3 and suppressed miR-30b expression in female rats. Functional in vitro analyses demonstrated a strong repressive action of miR-30b on Mkrn3 3 ' UTR. Moreover, central infusion during the juvenile period of target site blockers, tailored to prevent miR-30 binding to Mkrn3 3 ' UTR, reversed the prepubertal down-regulation of hypothalamic Mkrn3 protein and delayed female puberty. Collectively, our data unveil a novel hypothalamic miRNA pathway, involving miR-30, with a prominent role in the control of puberty via Mkrn3 repression. These findings expand our current understanding of the molecular basis of puberty and its disease states.
conferenceObject Genetic evaluation in children with self-limited pubertal delay discloses new candidate genes(2023) REZENDE, Raissa; SCHAFER, Evan; KAISINGER, Lena; HE, Wen; ANDRADE, Nathalia; DANTAS, Naiara; CELLIN, Laurana; QUEDAS, Elisangela; PERRY, John; HOWARD, Sasha; LATRONICO, Ana Claudia; CHAN, Yee-Ming; JORGE, Alexander- The Congenital and Acquired Mechanisms Implicated in the Etiology of Central Precocious Puberty(2023) BRITO, Vinicius N.; CANTON, Ana P. M.; SERAPHIM, Carlos Eduardo; ABREU, Ana Paula; MACEDO, Delanie B.; MENDONCA, Berenice B.; KAISER, Ursula B.; ARGENTE, Jesus; LATRONICO, Ana ClaudiaThe etiology of central precocious puberty (CPP) is multiple and heterogeneous, including congenital and acquired causes that can be associated with structural or functional brain alterations. All causes of CPP culminate in the premature pulsatile secretion of hypothalamic GnRH and, consequently, in the premature reactivation of hypothalamic-pituitary-gonadal axis. The activation of excitatory factors or suppression of inhibitory factors during childhood represent the 2 major mechanisms of CPP, revealing a delicate balance of these opposing neuronal pathways. Hypothalamic hamartoma (HH) is the most well-known congenital cause of CPP with central nervous system abnormalities. Several mechanisms by which hamartoma causes CPP have been proposed, including an anatomical connection to the anterior hypothalamus, autonomous neuroendocrine activity in GnRH neurons, trophic factors secreted by HH, and mechanical pressure applied to the hypothalamus. The importance of genetic and/or epigenetic factors in the underlying mechanisms of CPP has grown significantly in the last decade, as demonstrated by the evidence of genetic abnormalities in hypothalamic structural lesions (eg, hamartomas, gliomas), syndromic disorders associated with CPP (Temple, Prader-Willi, Silver-Russell, and Rett syndromes), and isolated CPP from monogenic defects (MKRN3 and DLK1 loss-of-function mutations). Genetic and epigenetic discoveries involving the etiology of CPP have had influence on the diagnosis and familial counseling providing bases for potential prevention of premature sexual development and new treatment targets in the future. Global preventive actions inducing healthy lifestyle habits and less exposure to endocrine-disrupting chemicals during the lifespan are desirable because they are potentially associated with CPP.