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2.
Rev. chil. endocrinol. diabetes ; 14(2): 81-89, 2021. ilus, tab
Article in Spanish | LILACS | ID: biblio-1283557

ABSTRACT

La Hiperplasia Suprarrenal Congénita (HSRC) corresponde a un grupo de defectos genéticos en la síntesis de cortisol. El 95% de ellas son debidas al déficit de 21-hidroxilasa por lo que nos referiremos solo a esta deficiencia. La hiperplasia suprarrenal congénita clásica (HSRC-C) debuta en recién nacidos o lactantes con insuficiencia suprarrenal primaria, diferentes grados de hiperandrogenismo clínico en mujeres y puede coexistir con hipotensión, hiperkalemia e hiponatremia si hay un déficit clínico de aldosterona. El objetivo de este artículo es actualizar el conocimiento y enfoques sugeridos para el manejo de la HSRC-C desde el inicio de sus controles en la etapa adulta. El diagnóstico diferencial en retrospectiva de la HSRC-C y la no clásica (HSRC-NC) a veces resulta difícil ya que esta enfermedad es un espectro fenotípico continuo. La insuficiencia suprarrenal y la dependencia a terapia corticoidal son los eventos principales para diferenciar estas dos patologías que tienen enfoques terapéuticos diferentes. El tratamiento de la HSRC-C en adultos abarca 2 objetivos primarios: la adecuada sustitución de la falla suprarrenal y el control de hiperandrogenismo mediante el uso de corticoides en sus dosis mínimas efectivas. En la mujer existen terapias complementarias para el control del hiperandrogenismo como anticonceptivos y otras que se encuentran en diferentes fases de investigación. Esto permite disminuir las dosis de corticoides en algunos casos. Es importante a la vez abordar tres objetivos secundarios: controlar el riesgo cardiometabólico propio de la enfermedad, evitar el sobre tratamiento corticoidal y manejar la infertilidad. La correcta monitorización del tratamiento en adultos tomando en cuenta los objetivos descritos permite una mejor calidad de vida en estos pacientes. Finalmente el consejo genético debe realizarse en todos los pacientes con HSRC que deseen fertilidad y en sus parejas. El estudio requiere de secuenciación del gen CYP21A2 y debe realizarse en un laboratorio de experiencia.


Congenital Adrenal Hyperplasia (CAH) are a group of genetic defects characterized by impaired cortisol synthesis. 95% of them are due to 21-hydroxylase deficiency. We will discuss only this enzyme's deficiency. Classic congenital adrenal hyperplasia (CAH-C) debuts in newborns or infants with primary adrenal insufficiency, some degree of clinical hyperandrogenism in newborn females, and can coexist with hypotension, hyperkalemia, and hyponatremia if there is a clinical aldosterone deficiency. The objective of this article is to update the knowledge and suggested approaches for the management of CAH-C from the beginning of its controls in the adult stage. The retrospective differential diagnosis of CAH-C and non-classical (CAH-NC) is sometimes difficult because this disease is a continuous phenotypic spectrum. Adrenal insufficiency and dependence on corticosteroid therapy are the main events to differentiate these two pathologies that have different therapeutic approaches. In adults, the treatment of CAH-C must include 2 primary objectives: adequate the replacement of adrenal failure and control of hyperandrogenism, through the use of corticosteroids in their minimum effective doses. In women there are complementary therapies for the control of hyperandrogenism, such as contraceptives and others that are in different phases of research. This makes it possible to reduce the doses of corticosteroids in some cases. It is important at the same time to address three secondary objectives: control the cardiometabolic risk of the disease secondary to corticosteroid treatment, avoid corticosteroid overtreatment and manage infertility. The correct monitoring of treatment in adults and taking in to account the objectives described, allows a better quality of life in these patients. Finally, genetic counseling must be carried out in all patients planning for children, with any type of CAH and in their partners. The study requires sequencing of the CYP21A2 gene and must be performed in a certified laboratory.


Subject(s)
Humans , Adrenal Hyperplasia, Congenital/therapy , Steroid 21-Hydroxylase , Adrenal Cortex Hormones/therapeutic use , Adrenal Insufficiency/etiology , Adrenal Insufficiency/therapy , Hyperandrogenism/etiology , Hyperandrogenism/therapy , Adrenal Hyperplasia, Congenital/complications , Adrenal Hyperplasia, Congenital/diagnosis , Metabolic Syndrome/prevention & control , Flutamide/therapeutic use , Genetic Counseling , Infertility/etiology , Infertility/therapy
3.
Rev. cuba. endocrinol ; 31(2): e184, tab, graf
Article in Spanish | LILACS, CUMED | ID: biblio-1138894

ABSTRACT

RESUMEN Introducción: Si bien en la mujer con hiperplasia adrenal congénita la consecución de una función gonadal y fertilidad normales requiere de una adhesión estricta al tratamiento sustitutivo, no siempre esto es suficiente y, desde la adolescencia, aparece algún grado de hiperandrogenismo ovárico que influye de manera negativa. Objetivos: Describir algunos aspectos relacionados con la sexualidad, la salud sexual y reproductiva en pacientes con hiperplasia adrenal congénita asignadas como femeninas. Métodos: Se realizó un estudio descriptivo transversal y observacional, que incluyó todas las pacientes con diagnóstico de hiperplasia adrenal congénita asignadas como femeninas, que fueron atendidas en el Instituto Nacional de Endocrinología durante el periodo 2000-2019. Exploró aspectos demográficos, historia familiar y aspectos relacionados con la salud sexual y reproductiva. Resultados: La muestra quedó constituida por 47 pacientes, con una media de edad actual de 14,76 ± 7,04 años y una edad promedio de inicio del tratamiento de 5,9 años. Se comprobó un predominio de las formas clínicas clásicas en 25 pacientes (53,19 por ciento), y 22 (46,80 por ciento) formas no clásicas. Presentaron algún grado de virilización genital 22 pacientes, de este grupo 14 (68,1 por ciento) habían recibido cirugía genital, 5(10,6 por ciento) clitoroplastia con una media de edad 2,8 ± 0,8 años y 9 (19,1 por ciento) combinado con vaginoplastia. De las 36 pacientes en edad reproductiva, 11 (37,9 por ciento) refirieron haber iniciado relaciones sexuales a los 17,8 ± 3,9 años, como promedio. Conclusiones: Es importante considerar que la subfertilidad de las mujeres con hiperplasia adrenal congénita tiene su origen desde los años peripuberales, por lo que debe ser de interés permanente del endocrinólogo pediatra para mejorar su futuro reproductivo(AU)


ABSTRACT Introduction: Although in women with congenital adrenal hyperplasia, the achievement of normal gonadal function and fertility requires strict adherence to substitution treatment, this is not always sufficient and some degree of ovarian hyperandrogenism appears with a negative effect, which is evident since adolescence. Objective: To characterize some factors related to sexual and reproductive health in patients with congenital adrenal hyperplasia and assigned as female. Methods: A cross-sectional and observational-descriptive study was carried out, including all female-assigned patients with a diagnosis of congenital adrenal hyperplasia and who were treated at the Institute of Endocrinology from 2000 to 2019. The study explored demographic aspects, family history, as well as aspects related to sexual and reproductive health Results: The sample was made up of 47 patients, with current mean age of 14.76 ± 7.04 years and average age for starting treatment of 5.9 years. Predominance of classic clinical forms was verified in 25 patients (53.19 percent), while 22 patients (46.80 percent) presented nonclassical forms. Some degree of genital virilization manifested in 22 patients; of this group, 13 (59.1 percent) had received genital surgery, four (8.5 percent) received clitoroplasty at mean age of 2.8 ± 0.8 years, and nine (19, 1 percent) received an approach combined with vaginoplasty. Of the 36 patients at reproductive age, 11 (37.9 percent) reported having started sexual intercourse relations at an average age of 17.8 ± 3.9 years old. Conclusions: It is important to consider that subfertility of women with congenital adrenal hyperplasia starts in the peripubertal years, a reason why it should be of permanent interest to the pediatric endocrinologist in order to improve their reproductive future(AU)


Subject(s)
Humans , Female , Child, Preschool , Child , Adolescent , Adult , Hyperandrogenism/etiology , Adrenal Hyperplasia, Congenital/diagnosis , Sexual and Reproductive Health , Epidemiology, Descriptive , Cross-Sectional Studies , Observational Studies as Topic
4.
Medicina (B.Aires) ; 80(3): 197-202, jun. 2020. ilus, tab
Article in English | LILACS | ID: biblio-1125070

ABSTRACT

Congenital adrenal hyperplasia (CAH) is an autosomal recessive disorder due to a deficiency of enzymes involved in cortisol biosynthesis. In more than 90% of cases, CAH is secondary to deleterious mutations in the CYP21A2 gene leading to 21-hydroxilase deficiency (21OHD). The CYP21A2 gene is located on the short arm of chromosome 6 (6p21·3) and encodes the cytochrome P450C21 enzyme. Neonatal screening programs detect the classic forms of CAH-21OHD quantifying 17OH-progesterone in dried blood spots (DBS). This test is very sensitive, but it has a low specificity, requiring a second sample to confirm the result. In these cases, a second-tier test in the same sample may be useful. Our aim was to evaluate a DNA extraction method from DBS and assess the performance of such DNA in the molecular analysis of the CYP21A2 gene mutations. Twelve individuals, who presumably had CAH based on the initial neonatal screening results, were analyzed using DNA extracted from freshly collected blood on EDTA and DBS. The CYP21A2 gene was analyzed by automated sequencing of all exons and intron boundaries and MLPA analysis in DBS. Molecular analysis results from both extraction methods were compared. In this study, we show that DNA extracted from neonatal screening DBS is a useful tool to define CYP21A2 gene mutations in 21-OHD diagnostic confirmation for the newborn screening program and that its results are comparable to traditional genotyping.


La hiperplasia suprarrenal congénita (HSC) es un desorden autosómico recesivo producido por la deficiencia de alguna de las enzimas involucradas en la biosíntesis de cortisol. Más del 90% se debe a mutaciones en el gen CYP21A2 que genera deficiencia de 21 hidroxilasa (21OHD). Este gen se encuentra en el brazo corto del cromosoma 6 (6p21·3) y codifica para la enzima citocromo P450C21. Los programas de pesquisa neonatal detectan la forma clásica de la HSC-21OHD cuantificando 17OH-progesterona en gota de sangre en papel de filtro (GSPF). Este test es muy sensible, pero tiene baja especificidad , por lo que se utiliza una segunda muestra para confirmar el resultado. En estos casos, una segunda determinación en la misma muestra podría ser de utilidad. Nuestro objetivo fue evaluar el método de extracción de ADN y posterior análisis molecular del gen CYP21A2 en muestras de GSPF. Analizamos doce individuos presumiblemente afectados por HSC en la pesquisa neonatal usando ADN extraído de sangre fresca recolectada sobre EDTA y de GSPF. Realizamos el análisis del gen CYP21A2 mediante secuenciación automática de todos los exones y regiones intrónicas flanqueantes y MLPA en GSPF, y comparamos los resultados con ambos métodos de extracción. En este estudio demostramos que el ADN extraído de GSPF es una herramienta muy útil para analizar las mutaciones del gen CYP21A2 en la confirmación diagnóstica de 21-OHD para los programas de pesquisa neonatal y que los resultados son comparables con la genotipificación tradicional.


Subject(s)
Humans , Male , Female , Infant, Newborn , Steroid 21-Hydroxylase/genetics , Neonatal Screening/methods , Adrenal Hyperplasia, Congenital/diagnosis , Adrenal Hyperplasia, Congenital/genetics , Dried Blood Spot Testing/methods , Mutation , Reference Values , Spectrophotometry , Polymerase Chain Reaction , Reproducibility of Results , Gestational Age , 17-alpha-Hydroxyprogesterone/analysis , Alleles
5.
Rev. cuba. endocrinol ; 31(1): e187, ene.-abr. 2020. tab, graf
Article in Spanish | LILACS, CUMED | ID: biblio-1126455

ABSTRACT

RESUMEN Introducción: En la hiperplasia adrenal congénita el aumento de los niveles de andrógenos suprarrenales en las pacientes no tratadas o mal controladas, puede alterar el inicio y/o la progresión puberal (progresión puberal/progresiones puberales?). Objetivos: Describir las características puberales de pacientes con hiperplasia adrenal congénita asignadas como femeninas e identificar si existe asociación entre elementos relacionados con la enfermedad y el inicio y progresión puberales. Métodos: Se incluyeron todas las pacientes con diagnóstico de hiperplasia adrenal congénita asignadas como femeninas, que fueron atendidas en el INEN de enero 2000 a mayo 2019. Resultados: Fueron estudiadas 47 pacientes, con una media de edad de 14,76 ± 7,04 años. Se comprobó un predominio de las formas clínicas clásicas en 25 pacientes (53,19 por ciento), de ellas 11 (23,40 por ciento) fueron formas virilizantes simples, 14 (29,78 por ciento) perdedoras de sal y 22 (46,80 por ciento) formas no clásicas. El inicio del vello pubiano fue a una edad promedio de 7,78 ± 3,2 años. El comienzo de la telarquia resultó en una media de 10,09 ± 2,4 años y la menarquia a los 12,2 ± 2,3 años como promedio. De las 29 pacientes que ya habían menstruado 16 (55,2 por ciento) presentaban irregularidades menstruales. El tiempo entre el inicio puberal y la menarquia fue de 3,4 años en las formas no clásicas, 5,6 años en las perdedoras de sal y 7,0 años en las virilizantes simples. La edad al diagnóstico, la edad de inicio del tratamiento y la dosis de esteroides empleada se relacionaron con algunos aspectos puberales. Conclusiones: El diagnóstico oportuno y el ajuste cuidadoso del esquema esteroideo, constituyen pilares importantes en el inicio y progresión puberales, y en la consecución de ciclos ovulatorios regulares que aseguren desde la adolescencia, un inicio y desarrollo puberales normales y en edades reproductivas, la optimización de la fertilidad(AU)


ABSTRACT Introduction: In the congenital adrenal hyperplasia, the increased levels of adrenal androgens in patients untreated or poorly controlled can alter the start and/or pubertal progression (pubertal progression/pubertal progressions). Objectives: To describe the pubertal characteristics of patients with congenital adrenal hyperplasia assigned as females and to identify whether there is an association between elements related to the disease and the pubertal onset and progression. Methods: There were included all patients diagnosed with congenital adrenal hyperplasia assigned as females that were attended at the National Institute of Endocrinology from January 2000 to May 2019. Results: 47 patients were studied, with an average age of 14.76 ± 7.04 years. It was found a predominance of classic clinical forms in 25 patients (53.19 percent, of which 11 (23.40 percent) had simple virilization forms, 14 (29.78 percent) were salt-losers and 22 (46.80 percent) had non-classical forms. The onset of the pubic hair was at an average age of 7.78 ± 3.2 years. The beginning of the thelarche resulted in an average of 10.09 ± 2.4 years and menarche at the 12.2 ± 2.3 years on average. Of the 29 patients who had menstruated, 16 (55.2 percent) presented menstrual irregularities. The time between the puberty onset and menarche was 3.4 years in the non-classical forms, 5.6 years in the salt-losers, and 7.0 years in the simple virilizations. The age at initial diagnosis treatment and the dose of steroids used were related to some pubertal aspects. Conclusions: Early diagnosis and careful adjustment of the steroid scheme are important pillars in the pubertal onset and progression, the achievement of regular ovulatory cycles, and with it, in the optimization of fertility(AU)


Subject(s)
Humans , Female , Child , Adolescent , Menarche/physiology , Puberty , Adrenal Hyperplasia, Congenital/diagnosis , Menstruation Disturbances/therapy , Epidemiology, Descriptive , Cross-Sectional Studies
6.
J. pediatr. (Rio J.) ; 95(3): 282-290, May-June 2019. tab, graf
Article in English | LILACS | ID: biblio-1012607

ABSTRACT

Abstract Objective: To describe the results obtained in a neonatal screening program after its implementation and to assess the clinical and molecular profiles of confirmed and suspicious congenital adrenal hyperplasia cases. Methods: A cross-sectional study was conducted. Newborns with suspected disease due to high 17-hydroxyprogesterone levels and adjusted for birth weight were selected. Classical congenital adrenal hyperplasia (salt-wasting and simple virilizing forms) was diagnosed by an increase in 17-hydroxyprogesterone levels as confirmed in the retest, clinical evaluation, and genotype determined by SNaPshot and multiplex ligation-dependent probe amplification. Results: After 24 months, 15 classic congenital adrenal hyperplasia cases were diagnosed in a total of 217,965 newborns, with an estimated incidence of 1:14,531. From 132 patients, seven non-classical and 14 heterozygous patients were screened for CYP21A2 mutations, and 96 patients presented false positives with wild type CYP21A2. On retest, increased 17-hydroxyprogesterone levels were found in classical congenital adrenal hyperplasia patients and showed significant correlation with genotype-related classical genital adrenal hyperplasia. The most frequent mutations were IVS2-13A/C>G followed by gene deletion or rearrangement events in the classical form. In non-classical and heterozygous diseases, p.Val282Leu was the most common mutation. Conclusions: The results underscore the effectiveness of congenital adrenal hyperplasia neonatal screening in the public health system and indicate that the adopted strategy was appropriate. The second sample collection along with genotyping of suspected cases helped to properly diagnose both severe and milder cases and delineate them from false positive patients.


Resumo Objetivo: Descrever os resultados obtidos em um programa de triagem neonatal após sua implementação e avaliar os perfis clínicos e moleculares de casos confirmados e suspeitos de hiperplasia adrenal congênita. Métodos: Foi feito um estudo transversal. Recém-nascidos com suspeita da doença devido aos altos níveis de 17-alfa-hidroxiprogesterona e ajustados pelo peso ao nascer foram selecionados. A hiperplasia adrenal congênita clássica (forma perdedora de sal e forma virilizante simples) foi diagnosticada por um aumento nos níveis de 17-alfa-hidroxiprogesterona confirmado no reteste, avaliação clínica e genótipo determinado com o uso do ensaio SNaPshot e amplificação multiplex de sondas dependente de ligação. Resultados: Após 24 meses, 15 casos clássicos de hiperplasia adrenal congênita foram diagnosticados em 217.965 recém-nascidos, com uma incidência estimada de 1:14.531. De 132 pacientes, sete não clássicos e 14 heterozigotos foram submetidos à triagem para mutações no gene CYP21A2 e 96 pacientes apresentaram resultados falso-positivos com CYP21A2 do tipo selvagem. No reteste, níveis aumentados de 17-alfa-hidroxiprogesterona foram encontrados em pacientes com hiperplasia adrenal congênita clássica e mostraram correlação significativa com HAC clássica relacionada ao genótipo. As mutações mais frequentes foram IVS2-13A/C>G, seguidas de deleção gênica ou eventos de rearranjo na forma clássica. Em casos de doenças não clássicas e heterozigose, a mutação p.Val282Leu foi a mais comum. Conclusões: Os resultados ressaltam a eficácia da triagem neonatal para a hiperplasia adrenal congênita no sistema público de saúde e indicam que a estratégia adotada foi adequada. A segunda coleta de amostras, juntamente com a genotipagem dos casos suspeitos, ajudou a diagnosticar adequadamente os casos graves e mais leves e diferenciá-los de pacientes com resultado falso-positivo.


Subject(s)
Humans , Male , Female , Infant, Newborn , Steroid 21-Hydroxylase/blood , Neonatal Screening/methods , Adrenal Hyperplasia, Congenital/diagnosis , 17-alpha-Hydroxyprogesterone/blood , Phenotype , Brazil/epidemiology , Biomarkers/blood , Incidence , Cross-Sectional Studies , Adrenal Hyperplasia, Congenital/genetics , Adrenal Hyperplasia, Congenital/epidemiology , Genotype , Mutation
7.
Rev. chil. endocrinol. diabetes ; 12(1): 11-15, 2019. tab, ilus
Article in Spanish | LILACS | ID: biblio-982011

ABSTRACT

Clinical case: a girl of 7 ½ years who consulted for early pubarche without thelark, with a percentile size of 75 for a genetic target size in the 10th percentile, overweight with a 90th percentile BMI, and normal blood pressure. The biochemical study showed high levels of androgens: testosterone: 7.2 ng/dL, androstenedione of 5.1 ng / ml, 17OHP: 15 ng / dL with low normal DHEAS (0.26 ug/ml), Plasma Renin Activity normal low: 0.22 ng/mL/h. Initial imaging study showed a bone age of 10 years 6 months and normal abdominal and pelvic ultrasound. Molecular study showed no pathogenic variants in the CYP21A2 gene (21 Hydroxylase). With a probable diagnosis of non-classical congenital adrenal hyperplasia (HSRNC) and no known mutation, he started treatment with hydrocortisone (12 mg/m2). At 8.7 years, pubertal development begins and braking begins with LHRH analogues, which are administered for 18 months. Despite the treatment, signs of virilization and elevation of androgens (testosterone up to 130 ng/ml) are progressively accentuated, which do not diminish when trying different corticosteroid schemes. MRI of the abdomen and pelvis shows the normal adrenal glands and a solid nodular image of 2.1 x 1.6 cm in the right ovary (Figure 2), later demonstrated with pelvic ultrasound (Figure 2). Right laparoscopic oophorectomy was performed, whose biopsy demonstrated a Leydig cell tumor. One month after surgery, all androgenic levels were normalized, so the gradual suspension of corticosteroids began. Conclusion: Although HSRNC is the most frequent pathological cause of early pubarche, when it is associated with progressive clinical and biochemical hyperandrogenism despite adequate treatment and without pathogenic variants in the CYP21A2 gene, even with high levels of 17OHP, other causes should be considered, specifically, androgen producing tumors.


Caso clínico: niña de 7½ años que consulta por pubarquia precoz sin telarquia, con talla en percentil 75 para una talla objetivo genético en percentil 10, sobrepeso con IMC percentil 90 y presión arterial normal. El estudio bioquímico mostró niveles elevados de andrógenos: testosterona: 7,2 ng/dL, androstenediona de 5,1 ng/ml, 17OHP: 15 ng/dL con DHEAS normal baja (0,26 ug/ml), Actividad de Renina Plasmática normal baja: 0.22 ng/ mL/h. Estudio de imágenes inicial mostró una edad ósea de 10 años 6 meses y ecografía abdominal y pelviana normales. Estudio molecular no mostró variantes patogénicas en el gen CYP21A2 (21 Hidroxilasa). Con diagnosticó probable de hiperplasia suprarrenal congénita no clásica (HSRNC) y sin mutación conocida,inició el tratamiento con hidrocortisona (12 mg/m2). A los 8.7 años comienza desarrollo puberal y se inicia frenación con análogos de LHRH, los cuales se administran por 18 meses. A pesar del tratamiento se acentúan progresivamente los signos de virilización y hayelevación de los andrógenos (testosterona hasta 130 ng/ml), que no disminuyen intentando diferentes esquemas de corticoides. Se realiza RM de abdomen y pelvis que muestra las glándulas suprarrenales normales y una imagen nodular sólida de 2.1 x 1.6 cm en el ovario derecho (Figura 2), demostrada posteriormente con Ecografía pelviana (Figura 2). Se realiza ooforectomía derecha por vía laparoscópica, cuya biopsia demostró un tumor de células de Leydig. Un mes después de la cirugía, se normalizan todos los niveles androgénicos por lo que se inició la suspensión gradual de los corticoides. Conclusión: Aunque la HSRNC es la causa patológica más frecuente de la pubarquia precoz, cuando se asocia con un hiperandrogenismo clínico y bioquímico progresivo a pesar de un tratamiento adecuado y sin variantes patógenicas en el gen CYP21A2, incluso con niveles elevados de 17OHP, otras causas deben ser consideradas, específicamente tumores productores de andrógenos.


Subject(s)
Humans , Female , Child , Ovarian Neoplasms/complications , Ovarian Neoplasms/diagnosis , Puberty, Precocious/etiology , Leydig Cell Tumor/complications , Leydig Cell Tumor/diagnosis , Testosterone/analysis , Hyperandrogenism/etiology , Adrenal Hyperplasia, Congenital/diagnosis , 17-alpha-Hydroxyprogesterone/analysis , Hirsutism/etiology , Androgens/analysis , Androstenedione/analysis
8.
Rev. cuba. endocrinol ; 25(3): 141-148, sep.-dic. 2014.
Article in Spanish | LILACS, CUMED | ID: lil-736988

ABSTRACT

La hiperplasia adrenal congénita es una de las endocrinopatías más frecuentes en la infancia. Resulta desde el punto de vista clínico en un trastorno del desarrollo sexual asociado o no a un cuadro de pérdida salina en la etapa neonatal, manifestaciones de hiperandrogenismo en la adolescencia u oligomenorrea y trastornos de la fertilidad en la adultez. Las posibilidades de diagnóstico en el periodo prenatal han marcado un nuevo hito en el manejo y el pronóstico de estas personas, de ahí el interés por su conocimiento y domínio(AU)


Congenital adrenal hyperplasia is one of the most frequent endocrinopathies in childhood. It is from the clinical viewpoint a sexual development disorder associated or not to salt loss condition in the neonatal phase, hyperandrogenism manifestations in adolescence and oligomenorrhea and fertility disorders in the adulthood. The diagnostic possibilities in the prenatal period has marked new milestone in management and prognosis of these patients, hence the interest of professionals for gaining more knowledge about this disorder(AU)


Subject(s)
Humans , Female , Pregnancy , Adrenal Hyperplasia, Congenital/diagnosis , Prenatal Diagnosis/methods , Disorders of Sex Development/etiology , Hyperandrogenism
9.
Arq. bras. endocrinol. metab ; 58(7): 765-771, 10/2014. tab, graf
Article in English | LILACS | ID: lil-726265

ABSTRACT

Objective Evaluate the Neonatal Screening Program (NSP) for congenital adrenal hyperplasia (CAH) of the Department of Health of the State of Santa Catarina (Secretaria de Estado da Saúde de Santa Catarina, SES/SC), and provide information to improve the program. Subjects and methods Descriptive, retrospective study of 748,395 children screened between January 2001 and December 2010. We analyzed the coverage of the NSP-SES/SC prevalence of CAH, child’s age when the first sample for 17-hydroxyprogesterone (17OHP) measurement was collected, levels of 17OHP, mean age at treatment onset and main clinical manifestations. Results The NSP-SES/SC covered 89% of the live newborns in the State. It diagnosed 50 cases of CAH, yielding an incidence of 1:14,967. Mean age at collection of the first sample was 7.3 days and mean level of 17OHP was 152.9 ng/mL. The most frequent manifestations were virilized genitalia with nonpalpable gonads, clitoromegaly and genital hyperpigmentation. In three girls, the genre established at birth was incorrect. The salt-wasting form was present in 74% of the cases. There was no occurrence of shock or death. Mean age at treatment onset in the salt-wasting form was 17.4 days compared with 54.9 days in those without the salt-wasting form of the disease. All children were treated with hydrocortisone, and those with salt-wasting CAH were also treated with fludrocortisone. Conclusions The incidence of CAH was 1 case to 14,967 live newborns. Collection of the first sample occurred outside the recommended time, resulting in delays in treatment onset. .


Objetivo Avaliar o Programa de Triagem Neonatal da Secretaria de Estado da Saúde de Santa Catarina (PTN-SES/SC) em relação à hiperplasia adrenal congênita (HAC) e fornecer subsídios que possibilitem seu aperfeiçoamento. Sujeitos e métodos Estudo descritivo e retrospectivo de 748.395 crianças triadas no período de janeiro de 2001 a dezembro de 2010, sendo analisados a cobertura do PTN-SES/SC, a prevalência da HAC, a idade na coleta da primeira amostra para 17-hidroxiprogesterona (17OHP), os níveis de 17OHP, a idade média de início de tratamento e as principais manifestações clínicas. Resultados A cobertura do PTN-SES/SC foi de 89% dos recém-nascidos vivos no Estado. Foram diagnosticados 50 casos de HAC, com incidência de 1:14.967. A média de idade na coleta da primeira amostra foi de 7,3 dias e a de 17OHP, de 152,9 ng/mL. As manifestações mais frequentes foram genitália virilizada sem gônadas palpáveis, clitoromegalia e hiperpigmentação genital. Em três meninas ocorreu erro no estabelecimento de gênero ao nascimento. A forma perdedora de sal foi encontrada em 74% dos casos. Nenhum caso de choque ou óbito foi verificado. A média de idade no início do tratamento nos perdedores de sal foi de 17,4 dias e nos não perdedores, de 54,9 dias. Todas as crianças foram tratadas com hidrocortisona e, nos casos com a forma perdedora de sal, associou-se fludrocortisona. Conclusões A incidência de HAC foi de 1 caso para 14.967 recém-nascidos vivos. A coleta da primeira amostra ainda ocorreu fora do tempo preconizado, acarretando atraso no início do tratamento. .


Subject(s)
Animals , Female , Humans , Infant, Newborn , Male , /blood , Adrenal Hyperplasia, Congenital/diagnosis , Birth Weight/physiology , Neonatal Screening , Adrenal Hyperplasia, Congenital/classification , Adrenal Hyperplasia, Congenital/drug therapy , Adrenal Hyperplasia, Congenital/epidemiology , Brazil/epidemiology , Heel , Incidence , Program Evaluation , Retrospective Studies
10.
Arq. bras. endocrinol. metab ; 58(7): 701-708, 10/2014. tab, graf
Article in English | LILACS | ID: lil-726266

ABSTRACT

Congenital adrenal hyperplasia (CAH) is an autossomic recessive disorder caused by impaired steroidogenesis. Patients with CAH may present adrenal insufficiency with or without salt-wasting, as well as various degrees of virilization and fertility impairment, carrying a high incidence of testicular adrenal rest tumors and increased incidence of adrenal tumors. The diagnosis of CAH is made based on the adrenocortical profile hormonal evaluation and genotyping, in selected cases. Follow-up is mainly based on hormonal and clinical evaluation. Utility of imaging in this clinical setting may be helpful for the diagnosis, management, and follow-up of the patients, although recommendations according to most guidelines are weak when present. Thus, the authors aimed to conduct a narrative synthesis of how imaging can help in the management of patients with CAH, especially focused on genitography, ultrasonography, computed tomography, and magnetic resonance imaging.


Hiperplasia congênita de suprarrenal (CAH) é uma doença autossômica recessiva causada por deficiências enzimáticas na esteroidogênese. Clinicamente, os pacientes com CAH podem apresentar insuficiência adrenal com ou sem perda de sal, vários graus de virilização e diminuição na fertilidade, alta incidência de restos adrenais testiculares e de tumores adrenais. O diagnóstico de CAH é feito baseado nos resultados da avaliação hormonal e genotípica, em casos selecionados. O seguimento dos pacientes é principalmente feito com avaliação clínica e hormonal. Métodos de diagnóstico por imagem podem ser muito úteis não só no diagnóstico como no manejo e seguimento dos pacientes com CAH. Porém, as recomendações, de acordo com a maioria dos consensos, quando existem, são escassas. Nesse contexto, com base em uma revisão sistemática, o objetivo deste artigo foi sintetizar a literatura em relação a como os métodos de diagnóstico por imagem podem ser úteis no manejo dos pacientes com CAH, com foco em genitografia, ultrassonografia, tomografia computadorizada e ressonância magnética.


Subject(s)
Humans , Adrenal Hyperplasia, Congenital/diagnosis , Diagnostic Imaging/methods , Adrenal Hyperplasia, Congenital , Follow-Up Studies , Magnetic Resonance Imaging/methods , Tomography, X-Ray Computed/methods
11.
Rev. cuba. pediatr ; 86(3): 381-389, jul.-set. 2014. ilus
Article in Spanish | LILACS, CUMED | ID: lil-725124

ABSTRACT

El déficit de 21-hidroxilasa es la forma más frecuente de hiperplasia adrenal congénita, que forma parte de los desórdenes de la diferenciación sexual. Se presentan 3 casos. El primero, un recién nacido de 19 días que es llevado a consulta por presentar desórdenes de los genitales externos. Al examen físico presentaba un clítoris aumentado de tamaño, con orificio uretral en su base y engrosamiento de los rodetes labioescrotales. El diagnóstico se realizó por ultrasonido ginecológico, cromatina sexual, estudios hormonales y cariotipo. El segundo caso, un recién nacido de 15 días que también es llevado a consulta por desórdenes de los genitales externos, con examen físico similar al primer caso, y se le realizaron los mismos complementarios para su diagnóstico. El tercer caso, un lactante de 2 meses de edad, que es llevado a consulta por igual motivo, y que al examen físico se encontró hiperplasia del clítoris, con orificio en su base, y engrosamiento de los labios mayores que estaban fusionados en la línea media. Se le indicaron iguales complementarios. Se diagnosticó en los 3 casos una hiperplasia adrenal virilizante, y se realizó tratamiento sustitutivo hormonal y cirugía reconstructiva de los genitales externos.


Steroid 21-hydroxylase is the most frequent form of congenital adrenal hyperplasia that is part of the sexual differentiation disorders. This article reported 3 cases. The first one was a 19 days-old infant who was taken to the doctor´s because of external genitalia disorders. The physical exam revealed augmented clitoris with urethral orifice in its basis and thickening of the labioscrotal swellings. The patient was diagnosed by means of gynecological ultrasound, sexual chromatin, hormonal studies and karyotype. The second case was a 15 days-old newborn, who was also taken to the doctor´s for external genitalia disorders. The physical exam was similar to that of the first case and the same complementary tests were performed for diagnosis. The third case was a 2 months-old infant who was taken to the medical service for the same reasons, and his physical exam showed clitoris hyperplasia, orifice in its base and thickening of labia majora that fused in the midline. The same complementary tests were indicated. The final diagnosis in these three cases was virilizing adrenal hyperplasia. They were all treated with hormone replacement therapy and reconstructive surgery of their external genitalia.


Subject(s)
Humans , Disorders of Sex Development/diagnosis , Adrenal Hyperplasia, Congenital , Adrenal Hyperplasia, Congenital/diagnosis , Case Reports
12.
Arq. bras. endocrinol. metab ; 58(6): 650-655, 08/2014. graf
Article in English | LILACS | ID: lil-721391

ABSTRACT

3b-hydroxysteroid dehydrogenase II (3β-HSD) deficiency represents a rare CAH variant. Newborns affected with its classic form have salt wasting in early infancy and genital ambiguity in both sexes. High levels of 17-hydroxypregnenolone (Δ517OHP) are characteristic, but extra-adrenal conversion to 17-hydroxyprogesterone (17OHP) may lead to positive results on newborn screening tests. Filter paper 17OHP on newborn screening test was performed by immunofluorometric assay, and serum determinations of 17OHP and Δ517OHP, by radioimmunoassay. A 46,XY infant with genital ambiguity and adrenal crisis at three months of age presented a positive result on newborn screening for CAH. Serum determinations of 17OHP and Δ517OHP were elevated, and a high Δ517OHP/cortisol relation was compatible with the diagnosis of 3β-HSD deficiency. Molecular analysis of the HSD3B2 gene from the affected case revealed the presence of the homozygous p.P222Q mutation, whereas his parents were heterozygous for it. We present the first report of 3β-HSD type II deficiency genotype-proven detected at the Newborn Screening Program in Brazil. The case described herein corroborates the strong genotype-phenotype correlation associated with the HSD3B2 p.P222Q mutation, which leads to a classic salt-wasting 3β-HSD deficiency. Further evaluation of 17OHP assays used in newborn screening tests would aid in determining their reproducibility, as well as the potential significance of moderately elevated 17OHP levels as an early indicator to the diagnosis of other forms of classic CAH, beyond 21-hydroxylase deficiency.


A deficiência da enzima 3β-hidroxiesteroide desidrogenase tipo 2 (3β-HSD) representa variante rara de hiperplasia adrenal congenital (HAC). Recém-nascidos afetados com a forma clássica apresentam perda de sal nas primeiras semanas de vida e ambiguidade genital em ambos os sexos. Concentrações elevadas de 17-hidroxipregnenolona (Δ517OHP) são características, porém sua conversão extra-adrenal a 17-hidroxiprogesterona (17OHP) pode resultar em resultados positivos no teste de triagem neonatal. A determinação da concentração de 17OHP obtida em amostra de sangue colhida em papel-filtro para triagem neonatal foi realizada por ensaio imunofluorimétrico, e as concentrações séricas de 17OHP and Δ517OHP, por radioimunoensaio. Um menino, 46,XY, com ambiguidade genital e crise adrenal aos 3 meses de vida, apresentou teste positivo na triagem neonatal para HAC. As concentrações séricas de 17OHP e Δ517OHP estavam aumentadas, bem como a relação Δ517OHP/cortisol, o que foi compatível com o diagnóstico de deficiência de 3β-HSD. A análise molecular do gene HSD3B2 revelou a mutação p.P222Q em homozigose na criança afetada e em heterozigose em seus pais, o que confirmou a deficiência de 3β-HSD com resultado moderadamente elevado na dosagem de 17OHP no “Teste do Pezinho” (Programa de Triagem Neonatal do Distrito Federal, Brasil). Esse caso corrobora a forte correlação genótipo-fenótipo associada à mutação p.P222Q no gene HSD3B2. Estudos futuros para avaliação dos ensaios utilizados na triagem neonatal para determinação de 17OHP poderão auxiliar na determinação do significado potencial de concentrações moderadamente elevadas de 17OHP como um indicador precoce para o diagnóstico de outras formas de HAC clássicas, além da deficiência de 21-hidroxilase.


Subject(s)
Humans , Infant, Newborn , Male , /blood , Adrenal Hyperplasia, Congenital/diagnosis , Neonatal Screening/methods , Progesterone Reductase/deficiency , Disorders of Sex Development , Homozygote , Mutation , Progesterone Reductase/genetics , Rare Diseases
13.
J. pediatr. (Rio J.) ; 90(3): 300-307, May-Jun/2014. tab, graf
Article in English | LILACS | ID: lil-713020

ABSTRACT

OBJECTIVE: congenital adrenal hyperplasia (CAH) newborn screening can prevent neonatal mortality in children with the salt-wasting form of the disease and prevent incorrect gender assignments, which can occur in females. However, the occurrence of false-positive results in preterm or low-birth-weight newborns creates some diagnostic difficulties, with consequent therapeutic implications. This study aimed to report the results of a pilot project for neonatal CAH screening conducted in the state of Minas Gerais, Brazil from 09/2007 to 05/2008 with a three-year follow-up. METHODS: dried blood specimens were collected on filter paper cards three to seven days after birth of all newborns in the period. Samples were analyzed for 17-hydroxyprogesterone using an enzyme-linked immunosorbent assay (ELISA). RESULTS: a total of 159,415 children were screened. The apparent incidence of the classic variant of the disease was 1:9,963, based on initial diagnoses following newborn screening. During the follow-up period, eight of 16 children initially diagnosed with CAH were reclassified as unaffected, resulting in a revised incidence of 1:19,927. The false-positive rate was 0.31%, and the positive predictive value was 2.1%. Sensitivity and specificity were 100% and 99.7%, respectively. CONCLUSIONS: newborn screening is an important public health policy in developing countries such as Brazil, where CAH remains underdiagnosed. It has great potential to identify children with the disease who otherwise cannot be diagnosed earlier. Long-term follow-up and monitoring of all children with positive screening results are crucial to ensure a correct diagnosis and to calculate a reliable incidence ratio of the disease. .


OBJETIVO: a triagem neonatal para hiperplasia adrenal congênita (HAC) pode evitar a morte de recém-nascidos com a forma perdedora de sal e o registro civil incorreto das meninas. Entretanto, a ocorrência de resultados falso-positivos em recém-nascidos pré-termos ou com baixo peso ao nascer gera dificuldades diagnósticas, com consequentes implicações terapêuticas. O objetivo do estudo foi avaliar os resultados do projeto piloto de triagem neonatal para HAC realizado no estado de Minas Gerais, Brasil, de setembro de 2007 a maio de 2008 com acompanhamento de três anos. MÉTODOS: a dosagem da 17-hidroxiprogesterona foi realizada por ensaio imunoenzimático (ELISA), em amostras de sangue seco coletadas em papel-filtro, três a sete dias após o nascimento de todos os recém-nascidos no período. RESULTADOS: foram triadas 159.415 crianças. Observou-se incidência de 1:9.963 para a forma clássica da doença, baseando-se nos diagnósticos iniciais. Durante o período de acompanhamento, 8 de 16 crianças inicialmente diagnosticadas com HAC foram reclassificadas como não afetadas, resultando em uma incidência corrigida de 1:19.927. A taxa de falsos positivos foi de 0,31%, e o valor preditivo positivo foi de 2,1%. A sensibilidade e a especificidade foram 100% e 99,7%, respectivamente. CONCLUSÕES: a triagem neonatal é uma importante política de saúde pública para países em desenvolvimento como o Brasil, onde a HAC continua subdiagnosticada. Ela possui grande potencial para identificar crianças que poderiam não ter a doença reconhecida precocemente. O acompanhamento em longo prazo e o monitoramento de todas as crianças com resultados positivos na triagem são cruciais para confirmação diagnóstica e para o correto cálculo da incidência da doença. .


Subject(s)
Child, Preschool , Female , Humans , Infant , Infant, Newborn , Male , Adrenal Hyperplasia, Congenital/diagnosis , Neonatal Screening/methods , /blood , Adrenal Hyperplasia, Congenital/complications , Adrenal Hyperplasia, Congenital/epidemiology , Birth Weight , Brazil/epidemiology , Early Diagnosis , Enzyme-Linked Immunosorbent Assay , False Positive Reactions , Follow-Up Studies , Incidence , Pilot Projects , Predictive Value of Tests , Sensitivity and Specificity , Virilism/etiology
14.
Arq. bras. endocrinol. metab ; 58(3): 232-236, abr. 2014. graf
Article in Portuguese | LILACS | ID: lil-709345

ABSTRACT

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 .


Subject(s)
Humans , Adrenal Hyperplasia, Congenital/diagnosis , Cortodoxone/blood , Iodine Radioisotopes , Reagent Kits, Diagnostic/standards , /analysis , Bias , Biomarkers/blood , Chromatography, High Pressure Liquid , Reference Standards , Reproducibility of Results , Radioimmunoassay/methods , Sensitivity and Specificity , Tandem Mass Spectrometry
15.
Arq. bras. endocrinol. metab ; 58(2): 124-131, 03/2014. graf
Article in Portuguese | LILACS | ID: lil-709338

ABSTRACT

Graças ao significativo avanço na conduta e no tratamento de pacientes com as diversas formas de hiperplasia adrenal congênita por deficiência de 21-hidroxilase (D21OH) durante a infância e a adolescência, essas mulheres puderam atingir a idade adulta. Dessa maneira, o manejo nessa fase tornou-se ainda mais complexo, originando novos desafios. Tanto a exposição continuada à corticoterapia (pelo uso de doses muitas vezes suprafisiológicas), quanto ao hiperandrogenismo (pelo tratamento irregular ou uso de doses insuficientes), pode causar resultados pouco favoráveis à saúde e à qualidade de vida dessas mulheres, como: osteoporose, complicações metabólicas com risco cardiovascular, prejuízos cosméticos, infertilidade e alterações psicossociais e psicossexuais. No entanto, há poucos estudos de seguimento de longo prazo nas pacientes adultas. Nessa revisão procuramos abordar alguns aspectos importantes e mesmo controversos no seguimento de mulheres adultas com D21OH, recomendando a adoção de terapia individualizada e de caráter multidisciplinar, enquanto novos estudos não proponham atitudes mais bem definidas e consensuais visando à melhora da qualidade de vida dessas mulheres.


Due to major improvements in the management and therapy of patients with congenital adrenal hyperplasia owing to 21-hydroxylase deficiency (21OHD) along childhood and adolescence, affected women are able to reach adulthood. Therefore, management throughout adult life became even more complex, leading to new challenges. Both the protracted use of corticosteroids (sometimes in supraphysiologic doses), and excess androgen (due to irregular treatment and/or inadequate dosage) may impair the quality of life and health outcomes in affected adult women, causing osteoporosis, metabolic disturbances with high cardiovascular risk, cosmetic damage, infertility, and psychosocial and psychosexual changes. However, long-term follow-up studies with 21OHD adult women are still required. In this review, we discuss some important and controversial aspects of the follow-up of adult women with 21OHD, and recommend the use of a customized multi-disciplinary therapeutic approach while further studies with these patients do not provide distinct understanding and well-defined attitudes towards better quality of life.


Subject(s)
Adult , Female , Humans , Adrenal Hyperplasia, Congenital/drug therapy , Algorithms , Adrenal Hyperplasia, Congenital/complications , Adrenal Hyperplasia, Congenital/diagnosis , Adrenal Hyperplasia, Congenital/epidemiology , Adrenal Hyperplasia, Congenital/etiology , Adrenal Hyperplasia, Congenital/psychology , Fertility/drug effects , Guidelines as Topic , Glucocorticoids/adverse effects , Glucocorticoids/therapeutic use , Incidence , Quality of Life/psychology
17.
Rev. ANACEM (Impresa) ; 7(1): 38-40, abr. 2013. ilus, tab
Article in Spanish | LILACS | ID: lil-716199

ABSTRACT

INTRODUCCIÓN: La Hiperplasia suprarrenal congénita (HSC) es una enfermedad autosómica recesiva cuya principal causa es la deficiencia de 21-hidroxilasa, quien participa en la síntesis del cortisol y aldosterona. Se describen dos formas de HSC, una clásica y otra no clásica, siendo la primera el objetivo de análisis a lo largo del caso clínico. Sus manifestaciones clínicas varían en gravedad, dependiendo del nivel de deficiencia hormonal. Dentro de la clásica se describe la forma perdedora de sal, cuyas consecuencias son el exceso de andrógenos e insuficiencia de cortisol y mineral o corticoides. Así esta se puede manifestar como un trastorno de la diferenciación sexual (virilización de los genitales externos si el feto es femenino) e insuficiencia suprarrenal. Para su diagnóstico se consideran los antecedentes familiares, manifestaciones clínicas, medición de los niveles de 17-hidroxiprogesterona y la detección de la alteración genética. PRESENTACIÓN DEL CASO: Paciente con antecedentes familiares de hermano con HSC, nace con un trastorno de la diferenciación sexual y es dado de alta con sexo legal masculino. Después de 3 meses desarrolla una insuficiencia suprarrenal, diagnosticándose HSC forma clásica perdedora de sal y por cariotipo se determina sexo femenino. DISCUSIÓN: Los pilares del manejo de la HSC son el consejo genético en las familias con riesgo, el tratamiento antenatal con dexametasona, terapia postnatal con glucocorticoides y el tratamiento quirúrgico de las alteraciones de los genitales externos, junto con las nuevas investigaciones en base a terapia genética y el uso de células madre, requiriendo de este modo la HSC una vista integral.


INTRODUCTION: Congenital adrenal hyperplasia (CAH) is an autosomal recessive disease whose main cause is the deficiency of 21-hydroxylase, an enzyme involved in the synthesis of cortisol and aldosterone. There are two forms of CAH, a classical and nonclassical form, being the first objective of analysis in the clinical case. Its clinical manifestations vary in severity, depending on the level of hormone deficiency. Within the classic is described the salt-wasting form, whose consequences are androgen excess and insufficiency of cortisol and mineral o corticoids. So this may manifest as a sex differentiation disorder (virilization of the external genitalia if the fetus is female) and adrenal insufficiency. For diagnosis are considered the family history, clinical manifestations, measuring 17-hydroxyprogesterone levels and detection of genetic alteration. CASE REPORT: Patient with a family history of a brother with HSC brother, born with a disorder of sexual differentiation and is discharged with legal male sex. After three months develops adrenal insufficiency and was diagnosed with classical HSC salt-wasting form and determined female karyotype. DISCUSSION: The Pillars of the HSC are handling genetic counseling in families at risk, prenatal treatment with dexamethasone, postnatal glucocorticoid therapy and surgical treatment of disorders of the external genitalia, along with new research based therapy gene and the use of stem cells, requiring this way an integral view of HSC.


Subject(s)
Humans , Female , Infant , Adrenal Hyperplasia, Congenital/diagnosis , Adrenal Hyperplasia, Congenital/therapy , Disorders of Sex Development/etiology , Genetic Counseling , Hydrocortisone/therapeutic use
18.
Rev. Assoc. Med. Bras. (1992) ; 58(4): 459-464, July-Aug. 2012. ilus
Article in Portuguese | LILACS | ID: lil-646888

ABSTRACT

OBJETIVO: A eficácia da triagem neonatal para redução de morbimortalidade das crianças com hiperplasia adrenal congênita (HAC) é a principal justificativa para sua implantação. Um dos desafios para sua realização é a determinação do ponto de corte para a medida laboratorial da 17-hidroxiprogesterona (17OHP) que apresente adequado custo/benefício. Neste estudo foram identificados fatores intervenientes nos resultados do projeto-piloto de triagem neonatal para HAC, realizado em Minas Gerais. MÉTODOS: Rastreamento neonatal entre 09/2007 e 05/2008, com dosagens da 17OHP de amostras de sangue colhidas no calcanhar, no 5º dia de vida (papel-filtro), processadas pelo método UMELISA 17-OH Progesterona NEONATAL®. Os pontos de corte foram 80 e 160 nmol/L, para crianças saudáveis ou não, respectivamente. RESULTADOS: A incidência de HAC foi 1:19.939 em 159.415 crianças triadas. O percentil 99 (p99) da 17OHP, na primeira amostra, foi 108 nmol/L. Em 13.298 recém-nascidos com peso informado, os p99 da 17OHP foram, respectivamente, 344 nmol/L para <1500 g, 260 nmol/L para 1500 a 1999 g, 221 nmol/L para 2000 a 2499 g, e 109 nmol/L para > 2500 g. A taxa de reconvocação para consulta médica foi 0,31%. A sensibilidade do teste foi 100%, a especificidade, 99,6% e o valor preditivo positivo, 2,2%. Ajustando-se o ponto de corte da 17OHP para 110 nmol/L e 220 nmol/L, projetou-se redução em 76% dos encaminhamentos para consulta. CONCLUSÃO: Adoção dos pontos de corte para 17OHP, considerando peso de nascimento, apresentou-se como medida custo-efetiva para redução de falso-positivos. Os resultados desse estudo piloto sugerem que a triagem para HAC possa beneficiar a população infantil.


OBJECTIVE: The effectiveness of neonatal screening for reducing morbimortality in children with congenital adrenal hyperplasia (CAH) is the main justification for its implementation. One of the challenges for its implementation is to determine the cutoff value for laboratory measurement of 17-hydroxyprogesterone (17OHP) with appropriate cost-effectiveness. This study identified factors affecting the results of the pilot project of newborn screening for CAH, performed in the state of Minas Gerais, Brazil. METHODS: Neonatal screening performed between September, 2007 and May, 2008, with 17OHP measurements performed in blood samples taken from the heel (filter paper), on the 5th day of life, processed by the UMELISA 17-OH Progesterona NEONATAL® method. The cutoff value was 80 and 160 nmol/L for healthy children or not, respectively. RESULTS: The incidence of CAH was 1:19,939 in 159,415 children screened. The 99th percentile (p99) of 17OHP in the first sample was 108 nmol/L. In 13,298 newborns whose weight had been reported, the p99 of 17OHP were, respectively: 344 nmol/L for weight < 1,500 g; 260 nmol/L for weight between 1,500 and 1,999 g; 221 nmol/L for weight between 2,000 and 2,499 g; 109 nmol/L for weight > 2,500g. The rate of recall for medical consultation was 0.31%. The test sensitivity was 100%, specificity was 99.6%, and the positive predictive value was 2.2%. By adjusting the cutoff values of 17OHP to 110 nmol/L and 220 nmol/L, a 76% decrease in consultation referrals was projected. CONCLUSION: The use of 17OHP cutoff values, considering birth weight, was a cost-effective measure to reduce false positives. The results of this pilot study suggest that screening for CAH might benefit the pediatric population.


Subject(s)
Female , Humans , Infant, Newborn , Male , /blood , Adrenal Hyperplasia, Congenital/diagnosis , Birth Weight/physiology , Neonatal Screening/economics , Adrenal Hyperplasia, Congenital/epidemiology , Brazil/epidemiology , Cost-Benefit Analysis , Feasibility Studies , Follow-Up Studies , Incidence , Pilot Projects , Predictive Value of Tests , Radioimmunoassay , Reference Values
19.
Rev. cuba. endocrinol ; 23(1): 1-18, ene.-abr. 2012.
Article in Spanish | LILACS, CUMED | ID: lil-628235

ABSTRACT

Introducción: los costos económicos y psicosociales asociados con los resultados falsos positivos de la pesquisa neonatal de hiperplasia adrenal congénita son altos. Objetivos: identificar los factores perinatales que intervienen en la elevación y en el tiempo de normalización de los valores de 17 hidroxiprogesterona (17OHP), en pacientes no afectados por hiperplasia adrenal congénita. Métodos: se realizó un estudio descriptivo longitudinal retrospectivo en 1 114 pacientes procedentes de Ciudad de La Habana y La Habana, con resultados falsos positivos en la pesquisa, desde enero/2007 hasta junio/2010. Se identificaron las diferencias en la frecuencia de los factores perinatales reconocidos en este grupo con una muestra de población general, y otra integrada por enfermos de hiperplasia adrenal congénita. Resultados: de los pacientes falsos positivos, el 50,7 por ciento pertenecía al sexo masculino y 49,3 por ciento al femenino. El 54,7 por ciento nació por cesárea, y el 82 por ciento no presentó sufrimiento fetal agudo, aquellos con menor edad gestacional y peso al nacer más bajo presentaron niveles medios de 17OHP más elevados. El 68,1 por ciento normalizó la 17OHP al cumplir un mes de vida, independientemente del tipo de parto y de la presencia de sufrimiento fetal agudo; pero la edad gestacional y el peso al nacer tuvieron correlación inversa con la persistencia de su elevación. Predominó el parto eutócico en los neonatos enfermos y normales, y la cesárea en los falsos positivos. La media de la edad gestacional y del peso al nacer fue significativamente menor en los casos en el primer grupo, comparada con la de los grupos restantes. Conclusiones: la prematuridad y el bajo peso al nacer tuvieron una influencia significativa sobre la elevación y la persistencia de los valores de 17OHP, no así el tipo de parto y el sufrimiento fetal agudo(AU)


Introduction: the psychosocial and economic costs associated with the false-positive results of the neonatal screening of congenital adrenal hyperplasia are high. Objectives: to identify the perinatal factors to get involved in the rise and in the normalization time of values of 17 hydroprogesterone (17OHP) in patients not involved by a congenital adrenal hyperplasia. Methods: a retrospective, longitudinal and descriptive study was conducted in 1 114 patients from Ciudad de La Habana and La Habana with false-positive results according to screening from January, 2007 to June, 2010. Authors identified the differences in frequency of perinatal factors recognized in this group with a sample of general population, and other including congenital adrenal hyperplasia patients. Results: from the false-positive patients, the 50,7 percent was of male sex and the 49,3 percent to the female one. The 54,7 percent was born by cesarean section and the 82 percent has not acute fetal suffering, those small for the gestational age and lower birth weight had mean levels of 17OHP higher. The 68,1 percent normalized the OHP at one month of life, independently the type of labor and of the presence of acute fetal suffering but the gestational age and the birth weight had an inverse correlation with the persistence of its rise. There was predominance of eutocia labor in the sick and normal neonates and the cesarean section in the false-positive ones. The mean of gestational age and of the birth weight was significantly minor in the cases of the first group, compared with the remaining groups. Conclusions: the prematurity and the low birth weight had a significant influence on the rise and the persistence of values of 17OHP, but not the type of labor and the acute fetal suffering(AU)


Subject(s)
Humans , Male , Female , Infant, Newborn , Neonatal Screening/adverse effects , Adrenal Hyperplasia, Congenital/diagnosis , Health Care Costs , Infant, Low Birth Weight , Epidemiology, Descriptive , Retrospective Studies , Longitudinal Studies , False Positive Reactions
20.
Arq. bras. endocrinol. metab ; 55(8): 632-637, nov. 2011. tab
Article in English | LILACS | ID: lil-610466

ABSTRACT

OBJECTIVE: To evaluate weight-adjusted strategy for levels of neonatal-17OHP in order to improve newborn screening (NBS) efficiency. SUBJECTS AND METHODS: Blood samples collected between 2-7 days of age from 67,640 newborns were evaluated. When N17OHP levels were > 20 ng/mL, and a second sample was requested. We retrospectively analyzed neonatal-17OHP levels measured by Auto DELFIA- B024-112 assay, grouped according to birth-weight: G1: < 1,500 g, G2: 1,501-2,000 g, G3: 2,000-2,500 g and G4: > 2,500 g. 17OHP cutoff values were determined for each group using the 97.5th, 99th, 99.5th and 99.8th percentiles. RESULTS: 0.5 percent of newborns presented false-positive results using the cutoff level > 20 ng/mL for all groups. Neonates of low birthweight made up 69 percent of this group. Seven full-term newborns presented congenital adrenal hyperplasia (CAH) and, except for one of them, 17OHP levels were > 120 ng/mL. Only the 99.8th percentile presented higher predictive positive value (2 percent), and lower rate of false-positives in all groups. CONCLUSIONS: We suggest the use of 99.8th percentile obtained by weight-adjusted N17OHP values of healthy newborns to reduce the rate of false-positive results in NBS.


OBJETIVO: Avaliamos retrospectivamente os valores da 17OHP ajustados para o peso ao nascimento para melhorar a eficiência da triagem neonatal. SUJEITOS E MÉTODOS: 67.640 recém-nascidos com amostras coletadas entre 2-7 dias de vida. Uma segunda amostra foi solicitada na presença de testes com valores da 17OHP > 20 ng/mL. 17OHP dosada pelo método DELFIA- B024-112 e correlacionada com o peso ao nascimento: G1 < 1.500 g, G2 1.501-2.000 g, G3 2.000-2.500 g e G4 > 2.500 g. Pontos de corte da 17OHP foram determinados para cada grupo usando os percentis 97,5th, 99th, 99,5th e 99,8th. RESULTADOS: Falso-positivos ocorreram em 5 por cento dos resultados com o ponto de corte > 20 ng/mL, dos quais 69 por cento eram prematuros. Sete recém-nascidos apresentaram deficiência da 21-hidroxilase e, exceto em um, os valores da 17OHP foram > 120 ng/mL. Somente o valor da 17OHP do 99,8th apresentou maior valor preditivo positivo (2 por cento) e menor índice de falso-positivos. CONCLUSÕES: Sugerimos o valor da 17OHP do 99,8th ajustado para o peso ao nascimento para se reduzir a taxa de resultados falso-positivos da triagem neonatal.


Subject(s)
Female , Humans , Infant, Newborn , Male , /blood , Adrenal Hyperplasia, Congenital/diagnosis , Birth Weight , Neonatal Screening/methods , Brazil/epidemiology , False Positive Reactions , Fluoroimmunoassay/methods , Predictive Value of Tests , Reference Values , Retrospective Studies , Statistics, Nonparametric
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