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V TEMA: DIAGNOSTICO POR LABORATORIO DE HIPERPLASIA SUPRARRENAL CONGENITA DR. MARIA CALIXTA MARTINEZ VAZQUEZ
Introduccin
Autosmica Recesiva Deficiencia 21 Hidroxilasa 90%
Hh Hh HH Hh Hh
Forma Clsica - Perdedora de sal 75% - Virilizante simple 25% No Clsica 1-2:1.000 RN vivos
1:15.000 RN vivos
Portacin 1:60-80
Clasificacion
HIPERPLASIA SUPRARRENAL CONGNITA LIPOIDEA. DEFICIENCIA DE 3HIDROXIESTEROIDE DESHIDROGENASA/4,5 ISOMERASA.
DEFICIENCIA DE 21HIDROXILASA.
DEFICIENCIA DE 11HIDROXILASA
Deficiencia de 21-hidroxilasa.
Es la causa ms frecuente de HSC. La incapacidad de 21-hidroxilar adecuadamente 17hidroxiprogesterona en 11-desoxicortisol, provocan: una deficiencia de cortisol y aldosterona. de ACTH Hiperplasia suprarrenal. de la secrecin de andrgenos suprarrenales:
17-hidroxiprogesterona Androstendiona DHEA Testosterona
Deficiencia de 21-hidroxilasa
CYP21P
CYP21
Forma Clsica
Forma Virilizante Simple
Forma NO Clsica
Pubertad Precoz Central
INFERTILIDAD
Acn Hirsutismo
Oligomenorrea
Neonato Lactante
Escolar
Adolescente
Adulto
Manifestaciones clinicas
Femenino
Genitales ambiguos
Aparicin temprana de vello pbico y axilar Crecimiento excesivo de vello
Masculino
Desarrollo precoz de caractersticas masculinas
Musculatura bien desarrollada Pene agrandado
hasta 1000ng/dl
Test de ACTH
Diagnostico forma no clasica se recomienda valores basales superiores a 5ng/mL,
Administracin de 250 g/m2 de ACTH, Determinacin de 17hidroxiprogesterona a los 60 minutos.
1000
100
10
100
1000
Hipoglucemia
Homocistinuria
Tarjeta de guthrie
Galactosemia
Fibrosis qustica.
Tamiz neonatal
17 OHP de sangre capilar normal 17 OHP > p95th Para el peso de RN normal Re-llamado
No ms investigacin
Limites 17-hidroxiprogesterona total Basada en el peso al nacer: > 3,000 g < de 17.3 ng/ml 2,500-3,000 g < de 22.7 1,500-2,500 g < de 27.3 < 1,500 g < de 45.5
HSR-NC HSR-C
Diagnostico prenatal
ltima fase del primer trimestre mediante el anlisis del ADN obtenido por biopsia de vellosidades corinicas. Durante el segundo trimestre mediante amniocentesis.
Analisis del gen CYP21P del brazo corto del cromosoma 6. PCR
CASO CLINICO
Hiperplasia Suprarrenal Congenita
Se presenta el caso de un recin nacido con fecha de nacimiento e ingreso, al Servicio de Neonatologa, del 3 de octubre del 2012 por presentar genitales ambiguos. Madre de 18 aos de edad con escolaridad preparatoria, toxicomanas negadas y sin antecedentes heredofamiliares o personales patolgicos de importancia. En unin libre, con menarca a los 14 aos. Producto de la primera gesta, resuelto por cesrea debida a presentacin plvica en la semana 36 de gestacin. Peso al nacer de 2,550 g, talla 46 cm, Apgar 99 en tiempos convencionales. A la exploracin fsica se encontraron genitales ambiguos caracterizados por hipertrofia de cltoris, fusin labioescrotal y seno urogenital abajo del falo o cltoris. No se palparon testculos y el ano estaba permeable. El resto de la exploracin se encontr sin anormalidades.
Los estudiosde laboratorio dentro de valores de referencia . El ecosonograma plvico no visualiz rganos sexuales internos femeninos. Cariotipo 46 XX. Egres del servicio para continuar estudio en la consulta externa. El paciente reingres a los 26 das de vida, al ser enviado del poblado Miguel Alemn, Hermosillo, con el diagnstico de choque hipovolmico secundario a vmito y rechazo al alimento. A su llegada se le encontr con coloracin plida, hipoactivo, hiporreactivo, con presencia de signos universales de deshidratacin, respiracin de kussmaull y llenado capilar de 3 segundos. Recibi hidratacin endovenosa con solucin salina a razn de 50 ml/kg/hora ms reanimacin con presin positiva intermitente, con lo que mejoraron sus condiciones clnicas. El sodio srico se report en 109 mEq/L, potasio 8.9 mEq/L, cloro 86 mEql/L, urea 154 mg/dL y creatinina 1.4 mg/dL. La biometra hemtica con hemoglobinade 12.8 g/dL, hematocrito de 37 5%, leucocitos en 15,300 mm3, con 71% de neutrfilos y plaquetas de 580,000 mm3. La gasometra arterial con acidosis metablica.
El manejo posterior incluy la administracin endovenosa de solucin glucoelectroltica, correccin de acidosis con bicarbonato de sodio y asociacin antimicrobiana de ampicilina/cefotaxima. El cuadro clnico se consider como caracterstico de crisis adrenal por lo que se agreg al manejo hidrocortisona endovenosa. El sodio se elev a 129 mmol/L veinticuatro horas despus y se inici mineralocorticoide (fludrocortisona) al tratamiento. En el servicio de Neonatologa se confirm el diagnstico de hiperplasia suprarrenal con la determinacin de 17OHP en cifras de 339 ng/ml. Fue dado de alta con normalizacin de electrolitos sricos y tratamiento por va oral a base de hidrocortisona (1.2 mg cada 8 horas) y fludrocortisona (0.1 mg cada 24 horas).
ARTICULOS
Hiperplasia Suprarrenal Congenita
Confirmation of congenital adrenal hyperplasia by adrenal steroid profiling of filter paper dried blood samples using ultra-performance liquid chromatography-tandem mass spectrometry
Claudia Rossi1,2,*, Lisa Calton3, Heather A. Brown3, Scott Gillingwater3, A. Michael Wallace4, Francesca Petrucci1,2, Domenico Ciavardelli1,5, Andrea Urbani6,7, Paolo Sacchetta1,2 and Michael Morris3 1 Centre of Study on Aging (Ce.S.I.), G. dAnnunzio University Foundation, Chieti, Italy 2 Department of Biomedical Science, G. dAnnunzio University Chieti-Pescara, Italy 3 Clinical Operations Group, Waters Corporation, Atlas Park, Manchester, UK 4 Department of Clinical Biochemistry, Glasgow Royal Infirmary, Glasgow, Scotland, UK 5 Faculty of Motor and Health Sciences, Kore University of Enna, Enna, Italy 6 Department of Internal Medicine,Tor Vergata University, Rome, Italy 7 IRCCS-Santa Lucia Foundation, Rome, Italy
Clin Chem Lab Med 2011;49(4):677684 Abstract Background: The specificity of screening for congenital adrenal hyperplasia by direct measurement of 17hydroxyprogesterone in filter paper dried blood spot samples by immunoassay is low and has a high false-positive rate. In order to reduce the false-positive rate of this test, we developed a rapid, robust, specific confirmatory procedure in which cortisol, 4-androstene-3,17-dione and 17-hydroxyprogesterone were measured simultaneously by ultra-performance liquid chromatography-tandem mass spectrometry. Methods: After extraction, samples were analysed by ultraperformance liquid chromatography-tandem mass spectrometry and 17-hydroxyprogesterone was quantified accurately. Other steroids were determined using stable deuterated internal standards. In total, 25 patient blood spot samples and 92 control samples were analysed. Results: The assay was linear for 17-hydroxyprogesterone, with a coefficient of determination )0.997 and imprecision F6.5%. An upper limit of normal for 17-hydroxyprogesterone of 4.45 nmol/L was established by analysing a cohort of samples from unaffected newborns. In addition, a cut-off of3.5 for the peak areas ratio (17-hydroxyprogesteroneq4androstene-3,17-dione)/cortisol, allows confirmation of the affected steroidogenic enzyme. Conclusions: A high throughput method for the detection of steroids related to congenital adrenal hyperplasia has been developed, allowing the false-positive rate associated with screening for 17-hydroxyprogesterone by immunoassay to be determined.
Molecular testing in congenital adrenal hyperplasia due to 21-hydroxylase deficiency in the era of newborn screening
Sarafoglou K, Lorentz CP, Otten N, Oetting WS, Grebe SKG. aDepartment of Pediatrics, and bCollege of Pharmacology, Institute of Human Genetics, University of Minnesota, Minneapolis, MN, USA, and cDepartment of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA Clin Genet 2012: 82: 6470. John Wiley & Sons A/S, 2011 Abstract Newborn screening (NBS) identifies the majority of classical [salt-wasting (SW) and simple-virilizing (SV)] cases of congenital adrenal hyperplasia (CAH) due to 21-hydroxylase (21-OHase) during the first days of life. Diagnosis of classical CAH is confirmed by follow-up serum 17-hydroxyprogesterone and/or the adrenocorticotropin stimulation test; however, neither test definitively distinguishes between the classical subtypes. After confirmation, all newborns are started on hydrocortisone (glucocorticoid) and fludrocortisone (mineralocorticoid) treatment. While initiating fludrocortisone treatment in classical CAH patients, independent of subtype and before SW signs or symptoms occur, prevents a life-threatening SW crisis, it may later complicate distinguishing between the classical subtypes. Genotypephenotype correlations in 21-Ohase deficiency are excellent; however, molecular testing is not a regular part of the diagnostic workup. Molecular testing on 39 patients (25 identified by NBS) with an already established diagnosis of CAH identified 11 SW patients (8 identified by NBS) whose mutations suggested further biochemical and clinical reassessment of their subtype. Overall, SW accounted for 57.6% of our classical CAH patients, below the generally accepted figure that >75% of classical CAH are comprised of the SW form. In the era of NBS, molecular testing is a valuable supplemental tool identifying patients who may benefit from reassessment of their salt-retaining ability.
Referencias bibliograficas
Confirmation of congenital adrenal hyperplasia by adrenal steroid profiling of filter paper dried blood samples using ultra-performance liquid chromatography-tandem mass spectrometry Claudia Rossi1,2,*, Lisa Calton3, Heather A. Brown3 Clin Chem Lab Med 2011;49(4):677684 Hiperplasia suprarrenal congenita.L. Soriano Guilln, M. Velzquez de Cullar Paracchi. Unidad de Endocrinologa Infantil. Servicio de Pediatra. Fundacin Jimnez Daz. Madrid. Pediatr Integral 2007;XI(7):601-610. Resultados del tamiz neonatal ampliado, como nueva estrategia para la prevencin de los defectos al nacimiento.Antonio Velzquez,*,** Marcela Vela-Amieva,*,*** Edwin W Naylor,***Donald H Chace**** Velzquez A. y cols: Tamiz neonatal ampliado. Rev Mex Pediatr 2000; 67(5); 206-213 Hiperplasia Suprarrenal Congnita: Reporte de un caso clnico. Miguel A. MartnezMedina* Jorge I. HernndezBlanquel** Bol Clin Hosp Infant Edo Son 2007 24(1): 3841