RESUMO
El hipospadias es la localización anormal del meato urinario y es la malformación de genitales externos más frecuentemente diagnosticada. El diagnóstico prenatal es posible mediante ecografía sistemática desde la semana 20 de gestación, siendo más fácil su diagnóstico en el tercer trimestre. Las formas leves suelen ser aisladas, familiares o asociadas a disfunción placentaria o restricción de crecimiento intrauterino, mientras que las formas más graves presentan hasta un 30% de asociación a defectos fetales, anomalías cromosómicas/genéticas o anomalías del desarrollo sexual. La tríada para el diagnóstico ecográfico prenatal consiste en curvatura ventral del pene, anomalía del prepucio dorsal y punta del pene roma. La valoración de la uretra durante la micción y el aspecto del chorro miccional son de gran utilidad para clasificar el defecto. Cuando se diagnostica hipospadias peneano o escrotal es aconsejable realizar una amniocentesis para estudio genético fetal y valorar otros signos de adecuada virilización, como el descenso testicular a partir de la semana 27. El seguimiento tras el parto debe ser multidisciplinario, incluyendo urólogo y endocrinólogo infantil. En hipospadias leves el pronóstico es bueno con reparación quirúrgica en el primer año de vida, pero las formas graves pueden presentar un reto mayor para su corrección funcional y estética.
Hypospadias refers to the abnormal location of the meatus; it is the most common genital malformation detected in the fetus and newborn. Prenatal diagnosis is feasible from 20 weeks onwards with routine ultrasound; however, it is easier to diagnose during the third trimester of pregnancy. Mild defects are usually isolated, familiar o related to placental disfunction or intrauterine growth restriction, while the severe hypospadias are associated to other fetal defects, genetic or chromosomal abnormalities or disorders of sex development. In about 30% of cases. The triad of ultrasound findings prenatally is ventral curvature of the penis, redundant dorsal foreskin and blunt distal penis. The identification of the urethra during the micturition and the direction of the urinary stream help in the classification of the defect. When severe hypospadias is detected, the recommendation is to perform genetic amniocentesis and search for other ultrasound findings related to poor virilization in the fetus, as testicular descent after 27 weeks of gestation. Postnatal follow up should be multidisciplinary including infantile urologist and endocrinologist. The prognosis in distal hypospadias is usually good following surgical repair, however in severe cases surgical interventions may be more challenging in order to obtain satisfactory outcome in terms of function and esthetic.
Assuntos
Humanos , Feminino , Gravidez , Recém-Nascido , Ultrassonografia Pré-Natal , Hipospadia/diagnóstico por imagem , Diagnóstico Pré-Natal , Diagnóstico Diferencial , Retardo do Crescimento Fetal , Hipospadia/cirurgia , Hipospadia/classificação , Hipospadia/etiologiaRESUMO
We performed an exploratory study by analyzing the correlation of 46, XY disorders of sex development (46, XY DSD) with androgen receptor (AR) and steroid 5α-reductase-2 (SRD5A2) gene mutations and a safety analysis of dihydrotestosterone (DHT) gel treatment for pediatric micropenis. We collected samples from 76 pediatric patients with 46, XY DSD and 50 healthy adult men with normal fertility as the control group. The pediatric patients were treated with DHT gel (0.1-0.3 mg/kg/day) for three to six months. The extended penis length, testicular volume, and multiple blood parameters were collected before treatment and one, three, and six months after treatment. Of the 76 cases with 46, XY DSD, 31.58% had hypospadias with micropenis and 6.58% had male pseudohermaphroditism. Through AR gene screening, it was found that 14 patients had AR point mutations and 22 patients had SRD5A2 mutations. After treatment with DHT, the penis length of the patients significantly improved after one, three, and six months of treatment, with longer treatment times resulting in greater improvement. Before treatment with DHT, the average serum DHT value of patients with 46, XY DSD was 24.29 pg/mL. After one, three, and six months of treatment, this value increased to 430.71, 328.9, and 323.6 pg/mL, respectively. We conclude that for pediatric patients who have male hermaphroditism or hypospadias with micropenis, AR and SRD5A2 gene mutation detection should be performed. Local application of DHT gel can promote penis growth effectively without systemic adverse reactions.
Assuntos
3-Oxo-5-alfa-Esteroide 4-Desidrogenase/genética , Transtorno 46,XY do Desenvolvimento Sexual/metabolismo , Hipospadia/metabolismo , Proteínas de Membrana/genética , Mutação , Receptores Androgênicos/genética , Adulto , Criança , China , Di-Hidrotestosterona/sangue , Di-Hidrotestosterona/uso terapêutico , Transtorno 46,XY do Desenvolvimento Sexual/complicações , Transtorno 46,XY do Desenvolvimento Sexual/genética , Testes Genéticos , Doenças dos Genitais Masculinos/sangue , Doenças dos Genitais Masculinos/tratamento farmacológico , Doenças dos Genitais Masculinos/etiologia , Humanos , Hipospadia/etiologia , Hipospadia/genética , Masculino , Pênis/anormalidadesRESUMO
We present the case of a male patient who required treaatment due to anorectal agenesis with recto urethral fistula and penoscrotal transposition with perineal hypospadias, associated with a perineal tumor. The perineal tumor was found strongly adhered and contiguous to the rectum which makes it compatible with an exstrophy of rectal duplication. Surgical reconstruction of the birth defect was performed in stages until acceptable biological function and esthetic results were obtained.
Assuntos
Anormalidades Múltiplas/patologia , Canal Anal/anormalidades , Hipospadia/patologia , Pênis/anormalidades , Reto/anormalidades , Escroto/anormalidades , Anormalidades Múltiplas/cirurgia , Cardiopatias Congênitas/cirurgia , Humanos , Hipospadia/etiologia , Hipospadia/cirurgia , Recém-Nascido , Masculino , Fístula Retal/congênito , Fístula Retal/etiologia , Fístula Retal/cirurgia , Doenças Uretrais/congênito , Doenças Uretrais/etiologia , Doenças Uretrais/cirurgia , Fístula Urinária/congênito , Fístula Urinária/etiologia , Fístula Urinária/cirurgiaRESUMO
Se presenta el caso de un paciente masculino quien requirió tratamiento por agenesia anorrectal con fístula rectouretral y transposición pene-escrotal con hipospadias perineal, acompañados de una masa perineal. La tumoración perineal se encontró íntimamente adherida y en continuidad al recto, lo que la hace compatible con una duplicación rectal extrofiada. La reconstrucción quirúrgica de la anomalía se realizó en etapas hasta lograr resultados funcionales y estéticos aceptables.
We present the case of a male patient who required treaatment due to anorectal agenesis with recto urethral fistula and penoscrotal transposition with perineal hypospadias, associated with a perineal tumor. The perineal tumor was found strongly adhered and contiguous to the rectum which makes it compatible with an exstrophy of rectal duplication. Surgical reconstruction of the birth defect was performed in stages until acceptable biological function and esthetic results were obtained.
Assuntos
Humanos , Recém-Nascido , Masculino , Anormalidades Múltiplas/patologia , Canal Anal/anormalidades , Hipospadia/patologia , Pênis/anormalidades , Reto/anormalidades , Escroto/anormalidades , Anormalidades Múltiplas/cirurgia , Cardiopatias Congênitas/cirurgia , Hipospadia/etiologia , Hipospadia/cirurgia , Fístula Retal/congênito , Fístula Retal/etiologia , Fístula Retal/cirurgia , Doenças Uretrais/congênito , Doenças Uretrais/etiologia , Doenças Uretrais/cirurgia , Fístula Urinária/congênito , Fístula Urinária/etiologia , Fístula Urinária/cirurgiaRESUMO
A male infant was diagnosed with partial androgen insensitivity caused by a novel mutation in the androgen receptor. At 3.5 months of age, he received 100 mg of testosterone intramuscularly over the course of 3 months to increase phallic size. He developed pubic hair after 5 months and signs of progressive central precocious puberty when re-examined at 17.5 months, which subsequently was suppressed with depot leuprolide.
Assuntos
Síndrome de Resistência a Andrógenos/tratamento farmacológico , Androgênios/efeitos adversos , Puberdade Precoce/induzido quimicamente , Testosterona/análogos & derivados , Agressão/efeitos dos fármacos , Substituição de Aminoácidos , Síndrome de Resistência a Andrógenos/diagnóstico , Síndrome de Resistência a Andrógenos/genética , Androgênios/administração & dosagem , Preparações de Ação Retardada , Éxons , Hormônio Liberador de Gonadotropina/agonistas , Hemizigoto , Humanos , Hipospadia/etiologia , Recém-Nascido , Leuprolida/uso terapêutico , Hormônio Luteinizante/sangue , Masculino , Mutação , Pênis/anormalidades , Receptores Androgênicos/genética , Escroto/anormalidades , Testosterona/administração & dosagem , Testosterona/efeitos adversos , Testosterona/sangueRESUMO
BACKGROUND: The etiology of hypospadias is multifactorial. Abnormal androgenic secretion and/or action during the development of external genitalia may be involved in the etiology of this congenital malformation. This study explored CAG and GGN polymorphisms in the androgen receptor (AR) gene, which may affect its transcriptional activity, in patients with isolated hypospadias. METHODS: The length of the CAG/GGN polymorphisms was determined in 44 boys with non-severe (glandular) or severe (penile or penoscrotal) isolated hypospadias and with a normal hormonal evaluation. In addition, 79 healthy men, as controls, were studied. RESULTS: Mean CAG repeats were significantly higher in total and severe cases compared to controls (24.4 +/- 2.8 and 24.7 +/- 3.1 vs. 22.7 +/- 3.3, respectively; p<0.05, Student's t and Bonferroni test). In addition, a frequency of CAG alleles >23 was significantly different in total and severe cases compared to controls (70.5% and 74.1% vs. 39.2%, respectively, p<0.05, chi2 and Bonferroni test). The median number and the distribution of GGN polymorphisms were similar in cases and controls. CONCLUSION: Boys with isolated hypospadias have longer CAG alleles in their AR, which may be related with the development of this congenital malformation.
Assuntos
Hipospadia/genética , Polimorfismo Genético , Receptores Androgênicos/genética , Repetições de Trinucleotídeos , Criança , Humanos , Hipospadia/etiologia , MasculinoRESUMO
Children born small for gestational age (SGA) are at higher risk for perinatal morbidity, mortality and chronic diseases in later life. There is increasing evidence for a link between prenatal growth and pubertal development, but studies concerning the timing, duration and progression of puberty in these children are scarce and the results are difficult to compare due to the various methodologies employed. Most boys born SGA have normal pubertal timing, but often attain an adult height below the target height. In girls, most studies document a relationship between intra-uterine growth retardation and earlier pubertal development or normal timing but with rapid progression. This chapter will discuss the factors that could influence pubertal development in children born SGA and the information reported to date.
Assuntos
Recém-Nascido Pequeno para a Idade Gestacional , Puberdade/fisiologia , Adolescente , Animais , Composição Corporal , Criança , Criptorquidismo/etiologia , Feminino , Humanos , Hipospadia/etiologia , Recém-Nascido , Masculino , Menarca/fisiologiaRESUMO
The relationship between environmental factors and health is well known. Rural environmental influences on reproductive health have been properly proved, both in animals and humans. In Latin America, few studies have been conducted in this area. The current project is based on the description of relationships between reproductive health and environmental factors in rural populations, characterized by specific environmental characteristics. Three variables were evaluated: male-to-female birth ratio, male urogenital malformations (cryptorchidism and hypospadias), and endocrine-related cancer incidence. Five rural communities in the Pampa Humeda in Argentina were selected, and the data were compared to the national mean. Biomedical data and environmental risk factors were correlated through a geographic information system. The ratio of male to female births did not show any differences. Malformations showed very significant differences. Endocrine-related cancers showed higher incidence rates compared to the national mean, particularly in some communities. In conclusion, there is a relationship between environmental factors and reproductive health conditions in this region.
Assuntos
Neoplasias da Mama/epidemiologia , Criptorquidismo/epidemiologia , Neoplasias das Glândulas Endócrinas/epidemiologia , Poluentes Ambientais/efeitos adversos , Hipospadia/epidemiologia , Neoplasias da Próstata/epidemiologia , Argentina/epidemiologia , Neoplasias da Mama/etiologia , Criptorquidismo/etiologia , Neoplasias das Glândulas Endócrinas/etiologia , Feminino , Humanos , Hipospadia/etiologia , Incidência , Masculino , Neoplasias da Próstata/etiologia , Reprodução , Fatores de Risco , Saúde da População Rural , População Rural , Razão de MasculinidadeRESUMO
La relación entre factores ambientales y salud es un hecho reconocido. La influencia de ambientes rurales sobre la salud reproductiva ha sido fehacientemente probada en diferentes regiones del mundo, tanto en la fauna como en humanos. En América Latina pocas investigaciones han sido realizadas en este campo. El presente proyecto se establece sobre la base de la describir las relaciones entre salud reproductiva y factores ambientales en poblaciones rurales, caracterizada por aspectos ambientales particulares. Tres variables han sido evaluadas: relación de nacimientos masculinos/femeninos; incidencia de malformaciones uro-genitales masculinas (hipospadias y criptorquidias); e incidencia de cánceres hormono-dependientes. Se seleccionaron cinco comunidades rurales de la Pampa Húmeda de Argentina, comparándose los datos obtenidos con medias nacionales. Los datos bio-médicos y las fuentes ambientales de riesgo fueron relacionados entre sí a través de un sistema de geo-referenciación. La relación de nacimientos no mostró significación. Las malformaciones presentaron una muy significativa incidencia. Los cánceres hormono-dependientes presentaron incidencia mayores a las medias nacionales, particularmente en algunas de las comunidades estudiadas. Se concluye que existe una relación entre condiciones de salud reproductiva y factores ambientales en esta región.
The relationship between environmental factors and health is well known. Rural environmental influences on reproductive health have been properly proved, both in animals and humans. In Latin America, few studies have been conducted in this area. The current project is based on the description of relationships between reproductive health and environmental factors in rural populations, characterized by specific environmental characteristics. Three variables were evaluated: male-to-female birth ratio, male urogenital malformations (cryptorchidism and hypospadias), and endocrine-related cancer incidence. Five rural communities in the Pampa Humeda in Argentina were selected, and the data were compared to the national mean. Biomedical data and environmental risk factors were correlated through a geographic information system. The ratio of male to female births did not show any differences. Malformations showed very significant differences. Endocrine-related cancers showed higher incidence rates compared to the national mean, particularly in some communities. In conclusion, there is a relationship between environmental factors and reproductive health conditions in this region.
Assuntos
Feminino , Humanos , Masculino , Neoplasias da Mama/epidemiologia , Criptorquidismo/epidemiologia , Neoplasias das Glândulas Endócrinas/epidemiologia , Poluentes Ambientais/efeitos adversos , Hipospadia/epidemiologia , Neoplasias da Próstata/epidemiologia , Argentina/epidemiologia , Neoplasias da Mama/etiologia , Criptorquidismo/etiologia , Neoplasias das Glândulas Endócrinas/etiologia , Hipospadia/etiologia , Incidência , Neoplasias da Próstata/etiologia , Reprodução , Fatores de Risco , Saúde da População Rural , População Rural , Razão de MasculinidadeRESUMO
Las hipospadias son el arresta en el desarrollo ventral del pene. Puede ser una malformación que se presenta de forma aislada o asociada a otras alteraciones como lo es la presencia de una curvatura ventral anormal del pene, criptorquidia, hernias inguinales, entre otras. En todos los casos es importante considerar las hipospadias como un grado leve de feminización. Actualmente no existe prevención para el desarrollo de las hipospadias y el único manejo es la corrección quirúrgica de la lesión. Grandes avances se han logrado en el estudio de los procesos moleculares asociados en el desarrollo de las hipospadias. Los receptores androgénicos (RA), alteraciones endocrinas se han postulado como fenómenos influyentes en el desarrollo de ésta patología. El objetivo del presente artículo es determinar los eventos moleculares asociados en el desarrollo de las hipospadias.
Assuntos
Doenças do Sistema Endócrino , Estrogênios , Hipospadia/classificação , Hipospadia/etiologia , Receptores Androgênicos/fisiologiaRESUMO
CONTEXT: Isolated hypospadias may result from impaired testicular function or androgen end-organ defects or, alternatively, from hormone-independent abnormalities of morphogenetic events responsible for urethral seam. OBJECTIVE: The objective was to evaluate the relative prevalence of hormone-dependent etiologies in boys with isolated hypospadias. DESIGN, PATIENTS, AND MAIN OUTCOME MEASURES: We studied endocrine testicular capacity in 61 patients with isolated hypospadias and 28 with hypospadias associated with micropenis, cryptorchidism, or ambiguous genitalia. Serum anti-Müllerian hormone and inhibin B were used as Sertoli cell markers. A human chorionic gonadotropin test was performed to evaluate Leydig cell function. RESULTS: Testicular dysfunction was observed in 57.1% and androgen end-organ defects in 7.2% of patients with hypospadias associated with cryptorchidism, micropenis, or ambiguous genitalia. In the remaining 35.7%, the disorder was idiopathic. The presence of ambiguous genitalia predicted the existence of testicular or end-organ dysfunction with 81.8% specificity. Isolated hypospadias was associated in 14.8% of patients with testicular dysfunction and in 6.5% of cases with end-organ defects; in 78.7% of cases, the condition was idiopathic. The occurrence of isolated hypospadias ruled out the existence of testicular or end-organ disorders with 80.0% sensitivity. Altogether our data indicate that the risk for the existence of an underlying testicular or end-organ dysfunction is low in patients with isolated hypospadias (odds ratio, 0.13; 95% confidence interval, 0.05-0.36; P < 0.001). CONCLUSIONS: Boys with isolated hypospadias are more likely to have normal endocrine testicular and androgen end-organ functions, suggesting that transient disruption of morphogenetic events in early fetal life may be the predominant underlying cause.
Assuntos
Hipospadia/fisiopatologia , Células Intersticiais do Testículo/fisiologia , Células de Sertoli/fisiologia , Testículo/fisiopatologia , Hormônio Antimülleriano , Gonadotropina Coriônica/farmacologia , Di-Hidrotestosterona/sangue , Glicoproteínas/sangue , Humanos , Hipospadia/etiologia , Masculino , Risco , Hormônios Testiculares/sangue , Testosterona/sangue , Uretra/embriologiaRESUMO
A fertilização in vitro tem sido associada com um aumento na incidência das hipospádias, e alguns hormônios esteróides usados em seus protocolos têm sido implicados neste processo. Para testar essas hipóteses em um modelo animal, descrevemos neste trabalho as alterações morfológicas ocorridas no tubérculo genital de camundongos, expostos à progesterona durante a vida intrauterina. Foi administrado acetato de medroxiprogesterona por via subcutânea no período pré-natal em animais normais e animais desprovidos de receptores androgênicos (Tfm). A progesterona induziu a formação de hipospádia nos animais do sexo masculino, virilização nos do sexo feminino e não causou alterações nos animais Tfm.
In vitro fertilization (IVF) has been associated with an increase incidence of hypospadias. IVF protocols require the maternal use of progesterone which may be a factor in causing hypospadias. To test these hypotheses in an animal model, we describe the effects of maternal progesterone exposure on genital development in mice. Medroxyprogesterone acetate (MPA) was administered by subcutaneous injection during the pre-natal period to wild type mice and animals knockout to androgen receptors (Tfm mice). Progesterone caused hypospadias in male mice fetuses, a virilizing effect in the female mice genitalia and didn't have any effect in Tfm animals.
Assuntos
Animais , Camundongos , Fertilização in vitro , Hipospadia/embriologia , Hipospadia/etiologia , Hipospadia/induzido quimicamente , Camundongos , Camundongos Knockout , Progesterona , VirilismoRESUMO
Male pseudohermaphroditism caused by steroid 5alpha-reductase deficiency is an autosomal recessive disorder. The enzyme steroid 5alpha-reductase 2 (encoded by the SRD5A2 gene) catalyses the conversion of testosterone to dihydrotestosterone, which is required for normal differentiation of the external male genitalia. This report describes the molecular analysis of the 5alpha-reductase type 2 gene in a Brazilian patient who was raised as a female, underwent a reversal of gender role behavior, and is now a married man. This patient is a compound heterozygote bearing an A-->G mutation within exon 2, changing codon 126 from Glu to Arg on one allele and a novel single base deletion (418delT) causing a frameshift mutation at codon 140 in the same exon, on the other allele. This last mutation probably leads to the synthesis of a truncated protein, because a premature termination signal is created at codon 159.