ELAINE MARIA FRADE COSTA
Projetos de Pesquisa
Unidades Organizacionais
Instituto Central, Hospital das Clínicas, Faculdade de Medicina
LIM/42 - Laboratório de Hormônios e Genética Molecular, Hospital das Clínicas, Faculdade de Medicina
LIM/42 - Laboratório de Hormônios e Genética Molecular, Hospital das Clínicas, Faculdade de Medicina
9 resultados
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Agora exibindo 1 - 9 de 9
- 46,XY disorder of sex development (DSD) due to 17 beta-hydroxysteroid dehydrogenase type 3 deficiency(2017) MENDONCA, Berenice B.; GOMES, Nathalia Lisboa; COSTA, Elaine M. F.; INACIO, Marlene; MARTIN, Regina M.; NISHI, Mirian Y.; CARVALHO, Filomena Marino; TIBOR, Francisco Denes; DOMENICE, Sorahia17 beta-hydroxysteroid dehydrogenase 3 deficiency consists of a defect in the last phase of steroidogenesis, in which androstenedione is converted into testosterone and estrone into estradiol. External genitalia range from female-like to atypical genitalia and most affected males are raised as females. Virilization in subjects with 17 beta-HSD3 deficiency occurs at the time of puberty and several of them change to male social sex. In male social sex patients, testes can be safely maintained, as long as they are positioned inside the scrotum The phenotype of 46,XY DSD due to 17 beta-HSD3 deficiency is extremely variable and clinically indistinguishable from other causes of 46,XY DSD such as partial androgen insensitivity syndrome and 5 alpha-reductase 2 deficiency. Laboratory diagnosis is based on a low testosterone/androstenedione ratio due to high serum levels of androstenedione and low levels of testosterone. The disorder is caused by a homozygous or compound heterozygous mutations in the HSD17B3 gene that encodes the 17 beta-HSD3 isoenzyme leading to an impairment of the conversion of 17-keto into 17-hydroxysteroids. Molecular genetic testing confirms the diagnosis and provides the orientation for genetic counseling. Our proposal in this article is to review-the previously reported cases of 17 beta-HSD3 deficiency adding our own cases. (C) 2016 Published by Elsevier Ltd.
- Management of 46,XY Differences/Disorders of Sex Development (DSD) Throughout Life(2019) WISNIEWSKI, Amy B.; BATISTA, Rafael L.; COSTA, Elaine M. F.; FINLAYSON, Courtney; SIRCILI, Maria Helena Palma; DENES, Francisco Tibor; DOMENICE, Sorahia; MENDONCA, Berenice B.Differences/disorders of sex development (DSD) are a heterogeneous group of congenital conditions that result in discordance between an individual's sex chromosomes, gonads, and/or anatomic sex. Advances in the clinical care of patients and families affected by 46,XY DSD have been achieved since publication of the original Consensusmeeting in 2006. The aims of this paper are to review what is known about morbidity and mortality, diagnostic tools and timing, sex of rearing, endocrine and surgical treatment, fertility and sexual function, and quality of life in people with 46,XY DSD. The role for interdisciplinary health care teams, importance of establishing a molecular diagnosis, and need for research collaborations using patient registries to better understand long-term outcomes of specific medical and surgical interventions are acknowledged and accepted. Topics that require further study include prevalence and incidence, understanding morbidity and mortality as these relate to specific etiologies underlying 46,XY DSD, appropriate and optimal options for genitoplasty, long-term quality of life, sexual function, involvement with intimate partners, and optimizing fertility potential.
- Wide spectrum of NR5A1-related phenotypes in 46,XY and 46,XX individuals(2016) DOMENICE, Sorahia; MACHADO, Aline Zamboni; FERREIRA, Frederico Moraes; FERRAZ-DE-SOUZA, Bruno; LERARIO, Antonio Marcondes; LIN, Lin; NISHI, Mirian Yumie; GOMES, Nathalia Lisboa; SILVA, Thatiana Evelin da; SILVA, Rosana Barbosa; CORREA, Rafaela Vieira; MONTENEGRO, Luciana Ribeiro; NARCISO, Amanda; COSTA, Elaine Maria Frade; ACHERMANN, John C.; MENDONCA, Berenice BilharinhoSteroidogenic factor 1 (NR5A1, SF-1, Ad4BP) is a transcriptional regulator of genes involved in adrenal and gonadal development and function. Mutations in NR5A1 have been among the most frequently identified genetic causes of gonadal development disorders and are associated with a wide phenotypic spectrum. In 46,XY individuals, NR5A1-related phenotypes may range from disorders of sex development (DSD) to oligo/azoospermia, and in 46,XX individuals, from 46,XX ovotesticular and testicular DSD to primary ovarian insufficiency (POI). The most common 46,XY phenotype is atypical or female external genitalia with clitoromegaly, palpable gonads, and absence of Mullerian derivatives. Notably, an undervirilized external genitalia is frequently seen at birth, while spontaneous virilization may occur later, at puberty. In 46,XX individuals, NR5A1 mutations are a rare genetic cause of POI, manifesting as primary or secondary amenorrhea, infertility, hypoestrogenism, and elevated gonadotropin levels. Mothers and sisters of 46,XY DSD patients carrying heterozygous NR5A1 mutations may develop POI, and therefore require appropriate counseling. Moreover, the recurrent heterozygous p.Arg92Trp NR5A1 mutation is associated with variable degrees of testis development in 46,XX patients. A clear genotype-phenotype correlation is not seen in patients bearing NR5A1 mutations, suggesting that genetic modifiers, such as pathogenic variants in other testis/ovarian-determining genes, may contribute to the phenotypic expression. Here, we review the published literature on NR5A1-related disease, and discuss our findings at a single tertiary center in Brazil, including ten novel NR5A1 mutations identified in 46,XY DSD patients. The ever-expanding phenotypic range associated with NR5A1 variants in XY and XX individuals confirms its pivotal role in reproductive biology, and should alert clinicians to the possibility of NR5A1 defects in a variety of phenotypes presenting with gonadal dysfunction. Birth Defects Research (Part C) 108:309-320, 2016. (c) 2016 The Authors Birth Defects Research Part C: Embryo Today: Reviews Published by Wiley Periodicals, Inc.
- Effects of endocrine disruptors in the development of the female reproductive tract(2014) COSTA, Elaine Maria Frade; SPRITZER, Poli Mara; HOHL, Alexandre; BACHEGA, Tania A. S. S.Environmental agencies have identified a growing number of environmental contaminants that have endocrine disrupting activity, and these can become a major public health problem. It is suggested that endocrine disruptors could account for the higher-than-expected increase in the prevalence of some non-communicable diseases, such as obesity, diabetes, thyroid diseases, and some cancers. Several endocrine Disrupting Chemicals (EDCs), such as pesticides, bisphenol A, phthalates, dioxins, and phytoestrogens, can interact with the female reproductive system and lead to endocrine disruption. Initially, it was assumed that EDCs exert their effects by binding to hormone receptors and transcription factors, but it is currently known that they may also alter the expression of enzymes involved in the synthesis or catabolism of steroids. Biomonitoring studies have identified these compounds in adults, children, pregnant women, and fetuses. Among the diseases of the female reproductive tract associated with EDCs exposure are the following: precocious puberty, polycystic ovary syndrome, and premature ovarian failure. The different populations of the world are exposed to a great number of chemicals through different routes of infection; despite the various available studies, there is still much doubt regarding the additive effect of a mixture of EDCs with similar mechanisms of action.
- A systematic review on the role of infrared thermography in the Brown adipose tissue assessment(2020) BRASIL, Sergio; RENCK, Alessandra C.; MENECK, Franciele de; BRIOSCHI, Marcos L.; COSTA, Elaine F.; TEIXEIRA, Manoel J.Brown adipose tissue (BAT) is an endocrine adipose tissue with attributes to dissipate energy as heat in response to changes in temperature and diet. Infrared thermography (IRT) has been studied in recent years in the assessment of BAT thermogenesis, as an option to positron emission tomography - computed tomography (PET-CT), because of several advantages. We performed a systematic review on the use of IRT in BAT assessment. Comprehensive online search was performed in different databases. The QUADAS 2 tool was used to evaluate studies' quality. 12 studies fit the inclusion criteria, whereas only one of these was considered of low risk of bias. 10 studies were favorable to IRT appliance in BAT evaluation, observing elevation of supraclavicular skin temperature correlated with BAT activity. Studies were heterogeneous in design, and a meta-analysis was precluded. Further studies with similar methodologies are needed. Conclusion: Despite the large number of published methodologies, IRT is a promising method for detecting BAT activation. Current knowledge already allows a better understanding of thermography to improve and standardize the technique.
- Clinical management of transsexual subjects(2014) COSTA, Elaine Maria Frade; MENDONCA, Berenice BilharinhoTranssexual subjects are individuals who have a desire to live and be accepted as a member of the opposite sex, usually accompanied by a sense of discomfort with, or inappropriateness of, one's anatomic sex, and a wish to have surgery and hormonal treatment to make one's body as congruent as possible with one's preferred sex. They seek to develop the physical characteristics of the desired gender, and should undergo an effective and safe treatment regimen. The goal of treatment is to rehabilitate the individual as a member of society in the gender he or she identifies with. Sex reassignment procedures necessary for the treatment of transsexual patients are allowed in our country, at Medical Services that have a multidisciplinary team composed of a psychologist, a social worker, a psychiatrist, an endocrinologist and surgeons (gynecologists, plastic surgeons, and urologists). Patients must be between 21 to 75 years old and in psychological and hormonal treatment for at least 2 years. Testosterone is the principal agent used to induce male characteristics in female transsexual patients, and the estrogen is the chosen hormone used to induce the female sexual characteristics in male transsexual patients. Based on our 15 years of experience, we can conclude that testosterone and estradiol treatment in physiological doses are effective and safe in female and male transsexual patients, respectively.
- Quality of life of patients with 46,XX and 46,XY disorders of sex development(2015) AMARAL, Rita Cassia; INACIO, Marlene; BRITO, Vinicius N.; BACHEGA, Tania A. S. S.; DOMENICE, Sorahia; ARNHOLD, Ivo J. P.; MADUREIRA, Guiomar; GOMES, Larissa; COSTA, Elaine M. F.; MENDONCA, Berenice B.Disorders of sex development (DSD) result from abnormalities in the complex process of sex determination and differentiation. An important consideration to guide the assignment of social sex in newborns with ambiguous genitalia is the quality of life (QoL) of these patients in adulthood. The rarity of most DSD conditions makes it difficult to conduct a long-term follow-up of affected patients through adulthood. This review of papers on the QoL of DSD patients evaluated in developing and developed countries by qualitative and quantitative instruments revealed a large spectrum of QoL, ranging from very poor to similar to, or even better than, the normal population. A more adequate QoL was found in patients from tertiary centres, indicating that the medical care of DSD patients should be multidisciplinary and carried out by specialized teams.
- Steroid 5 alpha-reductase 2 deficiency(2016) MENDONCA, Berenice B.; BATISTA, Rafael Loch; DOMENICE, Sorahia; COSTA, Elaine M. F.; ARNHOLD, Ivo J. P.; RUSSELL, David W.; WILSON, Jean D.Dihydrotestosterone is a potent androgen metabolite formed from testosterone by action of 5 alpha-reductase isoenzymes. Mutations in the type 2 isoenzyme cause a disorder of 46,XY sex development, termed 5a-reductase type 2 deficiency and that was described forty years ago. Many mutations in the encoding gene have been reported in different ethnic groups. In affected 46,XY individuals, female external genitalia are common, but Mullerian ducts regress, and the internal urogenital tract is male. Most affected males are raised as females, but virilization occurs at puberty, and male social sex develops thereafter with high frequency. Fertility can be achieved in some affected males with assisted reproduction techniques, and adults with male social sex report a more satisfactory sex life and quality of life as compared to affected individuals with female social sex.
- Androgen insensitivity syndrome: a review(2018) BATISTA, Rafael Loch; COSTA, Elaine M. Frade; RODRIGUES, Andresa de Santi; GOMES, Nathalia Lisboa; FARIA JR., Jose Antonio; NISHI, Mirian Y.; ARNHOLD, Ivo Jorge Prado; DOMENICE, Sorahia; MENDONCA, Berenice Bilharinho deAndrogenic insensitivity syndrome is the most common cause of disorders of sexual differentiation in 46, XY individuals. It results from alterations in the androgen receptor gene, leading to a frame of hormonal resistance, which may present clinically under 3 phenotypes: complete (CAIS), partial (PAIS) or mild (MAIS). The androgen receptor gene has 8 exons and 3 domains, and allelic variants in this gene occur in all domains and exons, regardless of phenotype, providing a poor genotype phenotype correlation in this syndrome. Typically, laboratory diagnosis is made through elevated levels of LH and testosterone, with little or no virilization. Treatment depends on the phenotype and social sex of the individual. Open issues in the management of androgen insensitivity syndromes includes decisions on sex assignment, timing of gonadectomy, fertility, physcological outcomes and genetic counseling.