ABSTRACT Objective Discrimination and bullying are common conditions among LGBT people. During schooling, these practices compromising education. The aim of this study is to evaluate educational attainment among Brazilian transgender women (TW) and how their education level affects the risk of HIV infection. Study design a cross-sectional population-based study. Subjects and methods 95 adult TW were selected. Information concerning verbal and physical aggression, school dropout, school years (SY), and educational level were assessed. HIV status was screened using a fourth-generation immunoassay followed by western blot testing. Results The mean of SY was 9.1 ± 3.8 ys. The mean age at school dropout was 16.3 ± 3.4 ys old. Verbal aggression was reported by 83%, physical by 48%, and 18% of the TW dropped out school immediately after being physically assaulted. Participants who suffered physical aggression attended school for almost 4 years less than those participants who did not suffer this abuse (OR = -3.96, p < 0.0001). A similar result was found for verbal aggression (OR = -4.35; p < 0.0001). HIV/AIDS prevalence was 18% (n = 17). The mean of SY among HIV/AIDS positive and negative individuals were 6.8 ± 43 versus 9.7 ± 3, respectively (p = 0.004). Lower education was associated with higher frequency of HIV/AIDS among TW and this relationship was sustained after adjustment for injectable drug use and sex work (OR = 0.79, p = 0.04). Conclusion Among Brazilian TW, lower education level was a risk factor associated with HIV. The reasons for low schooling among TW are multifactorial, but verbal and physical harassment strongly contribute for it.

RESUMO: Embora o aprendizado de ciências costume estar relacionado ao ambiente escolar, existem outras instituições que proporcionam acesso ao conhecimento científico, como os hospitais. Com base nesse pressuposto, realizou-se um estudo no Hospital das Clínicas da Faculdade de Medicina de São Paulo para levantar as possibilidades da divulgação científica sobre um tema pouco conhecido, as diferenças no desenvolvimento sexual (DDS). Com o objetivo de descrever a apropriação do conhecimento pelos pacientes, foram utilizadas as categorias epistemológicas de Bachelard. Os resultados preliminares obtidos a partir de entrevistas semiestruturadas com pacientes indicados pelo corpo clínico mostram que o modelo epistemológico adotado contribui de duas maneiras para a pesquisa: ao auxiliar na elaboração de texto e figuras em folhetos, guias para pais e livros de divulgação da ciência; e ao descrever o processo de aprendizagem que ocorre no hospital como etapas distintas de aquisição do conhecimento científico.

ABSTRACT: Although science learning is usually related to the school environment, other institutions, such as hospitals, promote access to scientific knowledge. Based on this assumption, an study was carried out at the Hospital das Clínicas da Faculdade de Medicina de São Paulo to raise the possibilities of scientific divulgation about a little-known subject, the differences of sex development (DSD). Aiming to describe the appropriation of knowledge by patients, the Bachelard’s epistemological categories were applied. The preliminary results obtained from semi-structured interviews with patients indicated by the clinical staff show that the epistemological model adopted contributes to the research in two ways: when assisting in the formulation of text and pictures for folders, guides for parents and science divulgation books; and when describing the learning process that happens in the hospital as distinct steps of scientific knowledge acquisition.

RESUMEN: Aunque el aprendizaje de ciencias suele relacionarse con el ambiente escolar, hay otras instituciones que proporcionan acceso al conocimiento científico, como los hospitales. Basados en ese presupuesto, se realizó un estudio en el Hospital das Clínicas de la Faculdade de Medicina de São Paulo para levantar las posibilidades de la divulgación científica acerca de un tema poco conocido: las diferencias en el desarrollo sexual (DDS). Con el objetivo de describir la apropiación del conocimiento por los pacientes, se utilizaron las categorías epistemológicas de Bachelard. Los resultados preliminares obtenidos a partir de entrevistas semiestructuradas con pacientes indicados por el cuerpo médico indican que el modelo epistemológico adoptado contribuye de dos maneras a la investigación: al ayudar en la elaboración de texto y figuras en folletos, guías para padres y libros de divulgación de la ciencia; y al describir el proceso de aprendizaje que ocurre en el hospital como etapas distintas de adquisición del conocimiento científico.

ABSTRACT The first description of patients with combined pituitary hormone deficiencies (CPHD) caused by PROP1 mutations was made 20 years ago. Here we updated the clinical and genetic characteristics of patients with PROP1 mutations and summarized the phenotypes of 14 patients with 7 different pathogenic PROP1 mutations followed at the Hospital das Clínicas of the University of Sao Paulo. In addition to deficiencies in GH, TSH, PRL and gonadotropins some patients develop late ACTH deficiency. Therefore, patients with PROP1 mutations require permanent surveillance. On magnetic resonance imaging, the pituitary stalk is normal, and the posterior lobe is in the normal position. The anterior lobe in patients with PROP1 mutations is usually hypoplastic but may be normal or even enlarged. Bi-allelic PROP1 mutations are currently the most frequently recognized genetic cause of CPHD worldwide. PROP1 defects occur more frequently among offspring of consanguineous parents and familial cases, but they also occur in sporadic cases, especially in countries in which the prevalence of PROP1 mutations is relatively high. We classified all reported PROP1 variants described to date according to the American College of Medical Genetics and Genomics and the Association for Molecular Pathology (ACMG-AMP) guidelines: 29 were pathogenic, 2 were likely pathogenic, and 2 were of unknown significance. An expansion of the phenotype of patients with PROP1 mutations was observed since the first description 20 years ago: variable anterior pituitary size, different pathogenic mutations, and late development of ACTH deficiency. PROP1 mutations are the most common cause of autosomal recessive CPHD with a topic posterior pituitary lobe. Arch Endocrinol Metab. 2019;63(2):167-74

ABSTRACT Polycystic ovary syndrome (PCOS) is a common and complex endocrine disorder that affects 5-20% of reproductive age women. PCOS clinical symptoms include hirsutism, menstrual dysfunction, infertility, obesity and metabolic syndrome. There is a wide heterogeneity in clinical manifestations and metabolic complications. The pathogenesis of PCOS is not fully elucidated, but four aspects seem to contribute to the syndrome to different degrees: increased ovarian and/or adrenal androgen secretion, partial folliculogenesis arrest, insulin resistance and neuroendocrine axis dysfunction. A definitive etiology remains to be elucidated, but PCOS has a strong heritable component indicated by familial clustering and twin studies. Genome Wide Association Studies (GWAS) have identified several new risk loci and candidate genes for PCOS. Despite these findings, the association studies have explained less than 10% of heritability. Therefore, we could speculate that different phenotypes and subphenotypes are caused by rare private genetic variants. Modern genetic studies, such as whole exome and genome sequencing, will help to clarify the contribution of these rare genetic variants on different PCOS phenotypes. Arch Endocrinol Metab. 2018;62(3):352-61

OBJECTIVES: Unfavorable predicted adult height and psychosocial inadequacy represent parameters used to guide therapeutic intervention in girls with central precocious puberty. Gonadotropin-releasing hormone analog is the first-line treatment. The aim of this study was to compare two methods used to predict adult height and assess a validated tool for predicting the age at menarche in girls with central precocious puberty. METHODS: The predicted adult height of 48 girls with central precocious puberty was calculated at diagnosis using the Bayley-Pinneau method based on average and advanced bone age tables and compared with the predicted adult height calculated using a mathematical model. In addition, the age at spontaneous menarche was predicted using the new formulae. After Gonadotropin-releasing hormone analog treatment, the predicted adult height was calculated using only the Bayley-Pinneau tables. RESULTS: The achieved adult height was within the target height range in all treated girls with central precocious puberty. At diagnosis, the predicted adult height using the Bayley-Pinneau tables was lower than that using the mathematical model. After the Gonadotropin-releasing hormone analog treatment, the predicted adult height using the Bayley-Pinneau method with the average bone age tables was the closest to the achieved adult height. Using the formulae, the predicted age at spontaneous menarche was 10.1±0.5 yr. The Gonadotropin-releasing hormone analog treatment significantly postponed this event until 11.9±0.7 yr in these “idiopathic” central precocious puberty girls, highlighting the beneficial effect of this treatment. CONCLUSION: Both initial adult height prediction methods are limited and must be used with caution. The prediction of the age at spontaneous menarche represents an innovative tool that can help in clinical decisions regarding pubertal suppression.

Malignancy must be considered in the management of adrenal lesions, including those incidentally identified on imaging studies. Adrenocortical carcinomas (ACCs) are rare tumors with an estimated annual incidence of 0.7-2 cases per year and a worldwide prevalence of 4-12 cases per million/year. However, a much higher incidence of these tumors (>15 times) has been demonstrated in south and southeastern Brazil. Most ACCs cause hypersecretion of steroids including glucocorticoids and androgens. ACC patients have a very poor prognosis with a 5-year overall survival (OS) below 30% in most series. Pheochromocytoma or paraganglioma (PPGL) is a metabolically active tumor originating from the chromaffin cells of the adrenal medulla. The incidence of PPGL is 0.2 to 0.9 cases per 100,000 individuals per year. Pheochromocytomas are present in approximately 4-7% of patients with adrenal incidentalomas. Classically, PPGL manifests as paroxysmal attacks of the following 4 symptoms: headaches, diaphoresis, palpitations, and severe hypertensive episodes. The diagnosis of malignant PPGL relies on the presence of local invasion or metastasis. In this review, we present the clinical and biochemical characteristics and pathogenesis of malignant primary lesions that affect the cortex and medulla of human adrenal glands.

ABSTRACT Purpose: To evaluate the role of ARDT after surgical resection of ACC. Materials and Methods: Records of patients from our institutional ACC database were retrospectively assessed. A paired comparison analysis was used to evaluate the oncological outcomes between patients treated with surgery followed by ARDT or surgery only (control). The endpoints were LRFS, RFS, and OS. A systematic review of the literature and meta-analysis was also performed to evaluate local recurrence of ACC when ARDT was used. Results: Ten patients were included in each Group. The median follow-up times were 32 months and 35 months for the ARDT and control Groups, respectively. The results for LRFS (p=0.11), RFS (p=0.92), and OS (p=0.47) were similar among subsets. The mean time to present with local recurrence was significantly longer in the ARDT group compared with the control Group (419±206 days vs. 181±86 days, respectively; p=0.03). ARDT was well tolerated by the patients; there were no reports of late toxicity. The meta-analysis, which included four retrospective series, revealed that ARDT had a protective effect on LRFS (HR=0.4; CI=0.17-0.94). Conclusions: ARDT may reduce the chance and prolong the time to ACC local recurrence. However, there were no benefits for disease recurrence control or overall survival for patients who underwent this complementary therapy.

Objetivo : Nosso objetivo foi comparar duas técnicas de dosagem do 11-desoxicortisol: a técnica de radioimunoensaio iodado, a qual foi validada neste trabalho, e a cromatografia líquida de alta performance seguida por espectrometria de massa em tandem (LC-MS/MS), sendo a última considerada o padrão-ouro para dosagem dos hormônios esteroides. Materiais e métodos : Para a comparação entre os resultados de 11-desoxicortisol, foram selecionadas 88 amostras. Resultados : A sensibilidade analítica do radioimunoensaio foi de 0,30 ng/mL, com linearidade e perfil de precisão inadequado (34% das amostras com CV ≥ 20%). Das 88 amostras selecionadas, apenas 54 apresentaram resultados mensuráveis em ambos os métodos. A comparação desses resultados, por meio da regressão de Deming, resultou em um coeficiente de correlação de 0,610, inclinação de 3,751, intercepção de 0,145, evidenciando a pobre correlação entre os resultados e a superestimação dos resultados pelo RIA. Conclusão : Concluímos que o método de dosagem de 11-desoxicortisol por radioimunoensaio iodado apresentou resultados inadequados nos diversos parâmetros avaliados, inviabilizando sua utilização como método de dosagem do 11-desoxicortisol. Arq Bras Endocrinol Metab. 2014;58(3):232-6

Objective : Our aim was to correlate 11-deoxycortisol levels obtained by two currently available techniques for 11-deoxycortisol measurement: radioimmunoassay, and high performance liquid chromatography followed by tandem mass spectrometry (MS/MS). The latter is the gold standard method for steroid hormone measurement. Materials and methods : We selected 88 samples and the results of these two methods were compared by Deming regression. Results : The analytical sensitivity of the RIA was 0.30 ng/mL, with inadequate linearity and inadequate precision profile (34% of the samples had a CV ≥ 20%). From the selected samples, 54 had measurable levels of 11-deoxycortisol in both methods and were used in the comparison. The comparison of RIA with LC-MS/MS showed an overestimation of the results by RIA. The correlation coefficient was 0.610; linear regression slope was 3.751; and the intercept was 0.145, indicating a poor correlation between the two methods. Conclusion : We concluded that 11-deoxycortisol measured by radioimmunoassay, despite a good analytical sensitivity, showed very low specificity, precluding its use as a reliable method for 11-deoxycortisol measurement. Arq Bras Endocrinol Metab. 2014;58(3):232-6

OBJECTIVES: We aimed to investigate whether glucocorticoid receptor gene polymorphisms are associated with clinical and metabolic profiles in patients with polycystic ovary syndrome. Polycystic ovary syndrome is a complex endocrine disease that affects 5-8% of women and may be associated with metabolic syndrome, which is a risk factor for cardiovascular disease. Cortisol action and dysregulation account for metabolic syndrome development in the general population. As glucocorticoid receptor gene (NR3C1) polymorphisms regulate cortisol sensitivity, we hypothesized that variants of this gene may be involved in the adverse metabolic profiles of patients with polycystic ovary syndrome. METHOD: Clinical, metabolic and hormonal profiles were evaluated in 97 patients with polycystic ovary syndrome who were diagnosed according to the Rotterdam criteria. The alleles of the glucocorticoid gene were genotyped. Association analyses were performed using the appropriate statistical tests. RESULTS: Obesity and metabolic syndrome were observed in 42.3% and 26.8% of patients, respectively. Body mass index was positively correlated with blood pressure, triglyceride, LDL-c, total cholesterol, glucose and insulin levels as well as HOMA-IR values and inversely correlated with HDL-c and SHBG levels. The BclI and A3669G variants were found in 24.7% and 13.4% of alleles, respectively. BclI carriers presented a lower frequency of insulin resistance compared with wild-type subjects. CONCLUSION: The BclI variant is associated with a lower frequency of insulin resistance in women with polycystic ovary syndrome. Glucocorticoid gene polymorphism screening during treatment of the syndrome may be useful for identifying subgroups of at-risk patients who would benefit the most from personalized treatment.

FUNDAMENTO: Hiperglicemia na fase aguda do infarto do miocárdio é importante fator prognóstico. Entretanto, sua fisiopatologia não está completamente elucidada. OBJETIVO: Analisar simultaneamente correlação entre hiperglicemia e marcadores bioquímicos relacionados ao estresse,metabolismo glicídico e lipídico, coagulação, inflamação e necrose miocárdica. MÉTODOS: Oitenta pacientes com infarto agudo do miocárdio foram incluídos prospectivamente. Os parâmetros analisados foram: glicose, hormônios do estresse (cortisol e norepinefrina), fatores do metabolismo glicídico [hemoglobina glicada (HbA1c), insulina], lipoproteínas (colesterol total, LDL, HDL, LDL eletronegativa minimamente modificada e adiponectina), glicerídeos (triglicérides, VLDL e ácido graxo), fatores da coagulação (fator VII, fibrinogênio,inibidor do ativador do plasminogênio-1), inflamação (proteína C reativa ultrassensível) e necrose miocárdica (CK-MB e troponina). Variáveis contínuas foram convertidas em graus de pertinência por intermédio de lógica fuzzy. RESULTADOS: Houve correlação significativa entre hiperglicemia e metabolismo glicídico (p < 0,001), lipoproteínas (p = 0,03) e fatores de necrose (p = 0,03). Na análise multivariada, somente metabolismo glicídico (OR = 4,3; IC = 2,1-68,9 e p < 0,001) e necrose miocárdica (OR = 22,5; IC = 2-253 e p = 0,012) mantiveram correlação independente e significativa.Para análise da influência da história de diabetes mellitus , modelo de regressão, incluindo somente pacientes sem diabetes mellitus foi desenvolvido, e os resultados não alteraram. Finalmente, no modelo ajustado para idade, sexo e variáveis clínicas(história de diabetes mellitus, hipertensão arterial e dislipidemia), três variáveis mantiveram associação significativa e independente com hiperglicemia: metabolismo glicídico (OR = 24,1; IC = 4,8-122,1 e p < 0,001) necrose miocárdica (OR = 21,9; IC = 1,3-360,9 e p = 0,03) e história de DM (OR = 27, IC = 3,7-195,7 e p = 0,001). CONCLUSÃO: Marcadores do metabolismo glicídico e necrose miocárdica foram os melhores preditores de hiperglicemia em pacientes com infarto agudo do miocárdio.

BACKGROUND: Hyperglycemia in the acute phase of myocardial infarction is an important prognostic factor. However, its pathophysiology is not fully understood. OBJECTIVE: To analyze simultaneously the correlation between hyperglycemia and biochemical markers related to stress, glucose and lipid metabolism, coagulation, inflammation, and myocardial necrosis. METHODS Eighty patients with acute myocardial infarction were prospectively included. The following parameters were analyzed: blood glucose; stress hormones (cortisol and norepinephrine); glucose metabolism factors [glycated hemoglobin (HbA1c); insulin]; lipoproteins (total cholesterol, LDL, HDL, minimally modified electronegative LDL, and adiponectin); glycerides (triglycerides, VLDL and fatty acids); coagulation factors (factor VII, fibrinogen, plasminogen activator inhibitor-1); inflammation (high-sensitivity C reactive protein); and myocardial necrosis (CK-MB and troponin). Continuous variables were converted into degrees of relevance using fuzzy logic. RESULTS: Significant correlation was observed between hyperglycemia and glucose metabolism (p < 0.001), lipoproteins (p = 0.03), and necrosis factors (p = 0.03). In the multivariate analysis, only glucose metabolism (OR = 4.3; CI = 2.1-68.9; and p < 0.001) and myocardial necrosis (OR = 22.5; CI = 2-253; and p = 0.012) showed independent and significant correlation. For the analysis of the influence of history of diabetes mellitus, a regression model including only patients without diabetes mellitus was developed, and the results did not change. Finally, in the model adjusted for age, gender, and clinical variables (history of diabetes mellitus, hypertension and dyslipidemia), three variables maintained a significant and independent association with hyperglycemia: glucose metabolism (OR = 24.1; CI = 4.8-122.1; and p < 0.001), myocardial necrosis (OR = 21.9; CI = 1.3-360.9; and p = 0.03), and history of DM (OR = 27; CI = 3.7-195.7; and p = 0.001). CONCLUSION: Glucose metabolism and myocardial necrosis markers were the best predictors of hyperglycemia in patients with acute myocardial infarction.

OBJETIVO: Investigar a presença de variantes nos genes TAC3 e TACR3, os quais codificam a NKB e seu receptor (NK3R), respectivamente, em uma coorte de pacientes com distúrbios puberais centrais idiopáticos. SUJEITOS E MÉTODOS: Duzentos e trinta e sete pacientes foram estudados: 114 com puberdade precoce central (PPC), 73 com hipogonadismo hipogonadotrófico isolado normósmico (HHI) e 50 com retardo constitucional do crescimento e desenvolvimento (RCCD). O grupo controle consistiu de 150 indivíduos brasileiros que apresentaram desenvolvimento puberal normal. O DNA genômico foi extraído de sangue periférico, e as regiões codificadoras dos genes TAC3 e TACR3 foram amplificadas e sequenciadas automaticamente. RESULTADOS: Uma variante (p.A63P) foi identificada na NKB, e quatro variantes, p.G18D, p.L58L (c.172C>T), p.W275X e p.A449S, foram identificadas no NK3R, as quais foram ausentes no grupo controle. A variante p.A63P foi identificada em uma menina com PPC, e a variante p.A449S, em uma menina com RCCD. As variantes previamente descritas, p.G18D, p.L58L e p.W275X, foram identificadas em três indivíduos com HHI normósmico do sexo masculino não relacionados. CONCLUSÃO: Variantes raras nos genes TAC3 e TACR3 foram identificadas em pacientes com distúrbios puberais centrais idiopáticos. Mutações de perda de função no gene TACR3 foram associadas com o fenótipo de HHI normósmico. Arq Bras Endocrinol Metab. 2012;56(9):646-52

OBJECTIVE: 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. Arq Bras Endocrinol Metab. 2012;56(9):646-52

INTRODUCTION: Activating mutations in exon 3 of the β-catenin gene are involved in the pathogenesis of adamantinomatous craniopharyngiomas. Recently, the interaction between β-catenin and PROP1 has been shown to be responsible for pituitary cell lineage determination. We hypothesized that dysregulated PROP1 expression could also be involved in the pathogenesis of craniopharyngiomas OBJECTIVES: To determine whether dysregulated gene expression was responsible for tumor pathogenesis in adamantinomatous craniopharyngiomas, the β-catenin gene was screened for mutations, and the expression of the β-catenin gene and PROP1 was evaluated. β-catenin gene was amplified and sequenced from 14 samples of adamantinomatous craniopharyngiomas. PROP1 and β-catenin gene expression was assessed by real-time RT-PCR from 12 samples, and β-catenin immunohistochemistry was performed on 11 samples. RESULTS: Mutations in the β-catenin gene were identified in 64% of the adamantinomatous craniopharyngiomas samples. Evidence of β-catenin gene overexpression was found in 71% of the tumors with β-catenin mutations and in 40% of the tumors without mutations, and β-catenin immunohistochemistry revealed a nuclear staining pattern for each of the analyzed samples. PROP1 expression was undetectable in all of the tumor samples. CONCLUSION: We found evidence of β-catenin gene overexpression in the majority of adamantinomatous craniopharyngiomas, and we also detected a nuclear β-catenin staining pattern regardless of the presence of a bcatenin gene mutation. These results suggest that WNT signaling activation plays an important role in the pathogenesis of adamantinomatous craniopharyngiomas. Additionally, this study was the first to evaluate PROP1 expression in adamantinomatous craniopharyngiomas, and the absence of PROP1 expression indicates that this gene is not involved in the pathogenesis of this tumor, at least in this cohort.

Estudos realizados em pacientes portadores de deleções parciais dos cromossomos sexuais permitiram a caracterização do SHOX, gene localizado na região pseudoautossômica no braço curto dos cromossomos sexuais, fundamental na determinação da altura normal. A perda de uma cópia deste gene na síndrome de Turner (ST) explica dois terços da baixa estatura observada nesta síndrome. A haploinsuficiência do SHOX é detectada em 77% dos pacientes com discondrosteose de Leri-Weill, uma forma comum de displasia esquelética de herança autossômica dominante e em 3% das crianças com baixa estatura idiopática (BEI), tornando os defeitos neste gene a principal causa monogênica de baixa estatura. A medida da altura sentada em relação à altura total (Z da AS/AT para idade e sexo) é uma forma simples de identificar a desproporção corpórea e, associada ao exame cuidadoso do paciente e de outros membros da família, auxilia na seleção de pacientes para o estudo molecular do SHOX. O uso de hormônio de crescimento (GH) está bem estabelecido na ST e em razão da causa comum da baixa estatura com o de crianças com defeitos isolados do SHOX o tratamento destes pacientes com GH é também proposto. Neste artigo será revisado os aspectos clínicos, moleculares e terapêuticos da haploinsuficiência do SHOX.

Studies involving patients with short stature and partial deletion of sex chromosomes identified SHOX gene in the pseudoautosomal region of the X and Y chromosomes. SHOX haploinsufficiency is an important cause of short stature in a diversity of clinical conditions. It explains 2/3 of short stature observed in Turner syndrome (TS) patients. Heterozygous mutations in SHOX are observed in 77% of patients with Leri-Weill dyschondrosteosis, a common dominant inherited skeletal dysplasia and in 3% of children with idiopathic short stature, indicating that SHOX defects are the most frequent monogenetic cause of short stature. The sitting height/height ratio (SH/H) standard deviation score is a simple way to assess body proportions and together with a careful exam of other family members, effectively selected a group of patients that presented a high frequency of SHOX mutations. Growth hormone treatment of short stature due to TS is well established and considering the common etiology of short stature in patients with isolated defects of SHOX gene, this treatment is also proposed for these patients. Here, we review clinical, molecular and therapeutic aspects of SHOX haploinsufficiency.

A síndrome de Noonan (SN) é uma síndrome genética comum que constitui importante diagnóstico diferencial em pacientes com baixa estatura, atraso puberal ou criptorquidia. A SN apresenta grande variabilidade fenotípica e é caracterizada principalmente por dismorfismo facial, cardiopatia congênita e baixa estatura. A herança é autossômica dominante com penetrância completa. O diagnóstico é clínico, com base em critérios propostos por van der Burgt, em 1994. Recentemente, diversos genes envolvidos na via de sinalização RAS-MAPK foram identificados como causadores da SN: PTPN11, KRAS, SOS1, RAF1 e MEK1. O tratamento com hormônio de crescimento (hrGH) é proposto para corrigir a baixa estatura observada nestes pacientes. Estudos recentes apontam que pacientes com SN por mutações no gene PTPN11 apresentam pior resposta ao tratamento com hrGH quando comparado com pacientes sem mutações no PTPN11. Este artigo revisará os aspectos clínicos, moleculares e do tratamento da baixa estatura de crianças com SN com hrGH.

Noonan Syndrome (NS) is one of the most common genetic syndromes and it is an important differential diagnosis in children with short stature, delayed puberty and cryptorchidism. NS is characterized by dysmorphic facial features, congenital heart defects and short stature, but there is a great variability in phenotype. NS may occur in a pattern consistent with autosomal dominant inheritance with almost complete penetrance. The diagnosis is based on a clinical score system proposed by van der Burgt e cols. in 1994. In recent years, germline mutations in the components of RAS-MAPK (mitogen activated protein kinase) pathway have been shown to be involved in the pathogenesis of NS. Mutations in PTPN11, KRAS, SOS1, RAF1 e MEK1 can explain 60-70% of NS molecular cause. Growth hormone therapy is proposed to correct the short stature observed in these patients. Recent studies suggest that the presence of PTPN11 mutations in patients with NS indicates a reduced growth response to short-term hrGH treatment. In this article, it is reviewed clinical and molecular aspects of NS and hrGH treatment for short stature.