RESUMEN
We present a boy with a genetically proven congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency. While massively elevated 17-hydroxyprogesterone (17-OHP) concentrations after birth led to the diagnosis, 17-OHP concentrations became immeasurable starting with the second year of life even though the dose of hydrocortisone was continuously decreased to â¼7 mg/m2/day. Furthermore, 17-OHP levels were immeasurable during the ACTH test and after withdrawing hydrocortisone medication. In contrast, ACTH levels increased after cessation of hydrocortisone treatment suggesting complete primary adrenal cortex failure. We discuss this case based on the differential diagnosis of complete adrenal cortex failure including other genetic causes in addition to CAH, prednisolone treatment, autoimmune adrenalitis, adrenoleukodystrophy, CMV infection, and adrenal hemorrhage infarction. The most likely disease in our boy is autoimmune adrenalitis, which is difficult to prove years after the onset of the disease. Treatment of CAH had masked the classical symptoms of complete adrenal cortex insufficiency leading to delayed diagnosis in this case.
Asunto(s)
17-alfa-Hidroxiprogesterona/sangre , Enfermedades de la Corteza Suprarrenal/diagnóstico , Hiperplasia Suprarrenal Congénita/sangre , Insuficiencia Suprarrenal/diagnóstico , Anomalías Múltiples/sangre , Anomalías Múltiples/diagnóstico , Enfermedades de la Corteza Suprarrenal/sangre , Enfermedades de la Corteza Suprarrenal/congénito , Hiperplasia Suprarrenal Congénita/diagnóstico , Insuficiencia Suprarrenal/sangre , Insuficiencia Suprarrenal/congénito , Cuidados Posteriores , Niño , Preescolar , Diagnóstico Tardío , Humanos , Hidrocortisona/uso terapéutico , Lactante , Recién Nacido , MasculinoRESUMEN
During the early phases of development, adrenal glands share a common origin with kidneys and gonads. The action of diverse transcription factors, signalling pathways and endocrine signals is required for the individualization of the adrenal primordium and its subsequent differentiation into an adult adrenal gland, with massive remodelling taking place around the time of birth in humans. Here I summarize the most important steps by which the adrenal cortex is shaped and present an overview of the current understanding of the genes and molecular pathways implicated in adrenal development and involved in the pathogenesis of its congenital diseases. Evidence is accumulating that some pivotal factors acting during adrenocortical development also play an important role to regulate the growth of adrenocortical tumors, representing promising therapeutical targets for a biology-oriented therapy.
Asunto(s)
Corteza Suprarrenal/embriología , Corteza Suprarrenal/crecimiento & desarrollo , Organogénesis , Corteza Suprarrenal/metabolismo , Enfermedades de la Corteza Suprarrenal/congénito , Enfermedades de la Corteza Suprarrenal/fisiopatología , Enfermedades de la Corteza Suprarrenal/terapia , Neoplasias de la Corteza Suprarrenal/metabolismo , Neoplasias de la Corteza Suprarrenal/fisiopatología , Neoplasias de la Corteza Suprarrenal/terapia , Animales , Humanos , Terapia Molecular Dirigida , Organogénesis/genéticaRESUMEN
Mutations of DSS (dosage sensitive sex reversal)-AHC critical region on the X chromosome, gene 1 DAX-1(NROB1)] results in X-linked adrenal hypoplasia congenita (AHC) and hypogonadotropic hypogonadism (HHG). Here we report four Japanese patients with AHC and HHG caused by the mutations of the DAX-1 gene. All patients manifested adrenal crisis at early childhood. Three patients did not show any pubertal sign and were diagnosed as having HHG. One patient manifested spontaneous pubertal development at 17 years of age. Nevertheless, his puberty did not develop further and his gonadotropin and testosterone levels decreased thereafter. Therefore, he was also diagnosed as having HHG. We performed testicular biopsy in another patient with HHG. Histological examination demonstrated Sertoli cell hypoplasia and no sperm formation in the seminiferous tubules. Molecular analysis demonstrated two novel point mutations (V269D and L278R) in two patients. Transient transfection assays showed that all these mutations (V269D, L271X, L278R, and Q395X) abolished the repression activity to both StAR and LHbeta gene promoter activation. In conclusion, we reported patients with AHC and HHG caused by the loss of function mutations of the DAX-1 gene.
Asunto(s)
Enfermedades de la Corteza Suprarrenal/genética , Proteínas de Unión al ADN/genética , Regulación hacia Abajo/genética , Hipogonadismo/genética , Hormona Luteinizante de Subunidad beta/genética , Fosfoproteínas/genética , Regiones Promotoras Genéticas , Receptores de Ácido Retinoico/genética , Proteínas Represoras/genética , Adolescente , Enfermedades de la Corteza Suprarrenal/complicaciones , Enfermedades de la Corteza Suprarrenal/congénito , Adulto , Animales , Secuencia de Bases , Células Cultivadas , Receptor Nuclear Huérfano DAX-1 , Análisis Mutacional de ADN , Proteínas de Unión al ADN/fisiología , Humanos , Hipogonadismo/complicaciones , Japón , Masculino , Ratones , Proteínas Mutantes/fisiología , Mutación , Receptores de Ácido Retinoico/fisiología , Proteínas Represoras/fisiología , TransfecciónAsunto(s)
Enfermedades de la Corteza Suprarrenal/genética , Enfermedades Autoinmunes/genética , Enfermedad de Addison/congénito , Enfermedad de Addison/genética , Enfermedades de la Corteza Suprarrenal/congénito , Hiperplasia Suprarrenal Congénita/genética , Hormona Adrenocorticotrópica/metabolismo , Enfermedades Autoinmunes/congénito , ADN Mitocondrial , Femenino , Eliminación de Gen , Predisposición Genética a la Enfermedad , Antígenos HLA/genética , Humanos , Síndrome de Kearns-Sayre/genética , Masculino , Mutación , Poliendocrinopatías Autoinmunes/congénito , Poliendocrinopatías Autoinmunes/genética , Factores de Transcripción/genética , Cromosoma X , Proteína AIREAsunto(s)
Enfermedades de la Corteza Suprarrenal/diagnóstico , Síndrome de Beckwith-Wiedemann/diagnóstico , Quistes/diagnóstico , Hemorragia/diagnóstico , Enfermedades de la Corteza Suprarrenal/complicaciones , Enfermedades de la Corteza Suprarrenal/congénito , Síndrome de Beckwith-Wiedemann/complicaciones , Quistes/complicaciones , Quistes/congénito , Hemorragia/complicaciones , Hemorragia/congénito , Humanos , Recién Nacido , Imagen por Resonancia Magnética , MasculinoRESUMEN
Adrenal abnormalities are rarely recognized in association with the nephrotic syndrome. This report describes the hospital course of an 11-week-old child with congenital nephrotic syndrome secondary to diffuse mesangial sclerosis, in addition to hypothyroidism and hypoadrenocorticism.
Asunto(s)
Enfermedades de la Corteza Suprarrenal/congénito , Insuficiencia Suprarrenal/congénito , Hipotiroidismo Congénito , Síndrome Nefrótico/congénito , Enfermedades de la Corteza Suprarrenal/diagnóstico por imagen , Enfermedades de la Corteza Suprarrenal/patología , Insuficiencia Suprarrenal/diagnóstico por imagen , Insuficiencia Suprarrenal/patología , Femenino , Humanos , Hipotiroidismo/diagnóstico por imagen , Hipotiroidismo/patología , Lactante , Síndrome Nefrótico/diagnóstico por imagen , Síndrome Nefrótico/patología , Tomografía Computarizada por Rayos XRESUMEN
We report two children of a family with congenital adrenocortical unresponsiveness to ACTH. Repeated stimulation of the adrenal by Synthetic 1-24 ACTH (Synacthen) failed to increase cortisol secretion, but produced significant rises of serum aldosterone. This was, however, associated with increased plasma renin activity. Only when the renin-angiotensin effect was eliminated, by a converting enzyme blocker, did Synacthen fail to affect serum aldosterone. These data support the view that glucocorticoid deficiency in this disorder results from unresponsiveness to ACTH and that development of the zona glomerulosa and normal aldosterone secretion is achieved by action of the renin-angiotensin system.
Asunto(s)
Enfermedades de la Corteza Suprarrenal/congénito , Corteza Suprarrenal/fisiopatología , Corteza Suprarrenal/efectos de los fármacos , Enfermedades de la Corteza Suprarrenal/fisiopatología , Pruebas de Función de la Corteza Suprarrenal , Aldosterona/sangre , Captopril/farmacología , Cosintropina/farmacología , Glucocorticoides/deficiencia , Humanos , Hidrocortisona/sangre , Lactante , Recién Nacido , Masculino , Renina/sangre , SíndromeAsunto(s)
Enfermedades de la Corteza Suprarrenal/diagnóstico , Adolescente , Enfermedades de la Corteza Suprarrenal/congénito , Enfermedades de la Corteza Suprarrenal/tratamiento farmacológico , Pruebas de Función de la Corteza Suprarrenal , Niño , Diagnóstico Diferencial , Femenino , Humanos , MasculinoAsunto(s)
Enfermedades de la Corteza Suprarrenal/diagnóstico , Enfermedades de la Corteza Suprarrenal/congénito , Enfermedades de la Corteza Suprarrenal/terapia , Neoplasias de las Glándulas Suprarrenales/diagnóstico , Insuficiencia Suprarrenal/diagnóstico , Hiperfunción de las Glándulas Suprarrenales/diagnóstico , Hiperfunción de las Glándulas Suprarrenales/genética , Hiperfunción de las Glándulas Suprarrenales/terapia , Síndrome de Cushing/diagnóstico , Síndrome de Cushing/etiología , Femenino , Antígenos HLA/análisis , Humanos , Hiperaldosteronismo/diagnóstico , Hiperaldosteronismo/terapia , Lactante , Masculino , LinajeRESUMEN
Study of prolactin secretion in patients with congenital adrenal cortex dysfunction demonstrated that the majority of untreated patients displayed elevated blood prolactin content. Blood prolactin level fell after treatment with glucocorticosteroids. Blood prolactin level was elevated, irrespective of normal or increased 24-hour 17-CS excretion in patients with congenital adrenal gland dysfunction treated with glucocorticosteroids and with persistent disturbances of ovarian function.
Asunto(s)
Enfermedades de la Corteza Suprarrenal/congénito , Prolactina/sangre , 17-Cetosteroides/orina , Adolescente , Corteza Suprarrenal/fisiopatología , Enfermedades de la Corteza Suprarrenal/sangre , Enfermedades de la Corteza Suprarrenal/fisiopatología , Adulto , Ritmo Circadiano , Femenino , Humanos , Masculino , Ovario/fisiopatologíaAsunto(s)
Enfermedades de las Glándulas Suprarrenales/diagnóstico , Enfermedades de la Corteza Suprarrenal/congénito , Enfermedades de la Corteza Suprarrenal/diagnóstico , Neoplasias de las Glándulas Suprarrenales/diagnóstico , Niño , Preescolar , Femenino , Humanos , Lactante , Recién Nacido , MasculinoRESUMEN
This is the first description of a connatal case of adrenoleukodystrophy. The clinical picture consisted of severe psychomotor retardation, convulsions and hypsarrhythmia, but no obvious signs of adrenal insufficiency. Pathologically, the adrenals were small. The entire cortex was largely replaced by large round cells. Ultrastructurally, some cells in the adrenal cortex contained inclusions with electron-lucent clefts surrounded by a membrane. The anterior pituitary lobe could be demonstrated to have produced ACTH. The central nervous system showed extensive zones of demyelination in the brainstem, the cerebellum and the right-sided capsula interna. In the demyelinated areas there was sudanophilic breakdown and an intense gliosis. Ongoing demyelination could also be demonstrated by the chemical analysis. In the gray matter there waere micropolygyria of the insular cortex and swollen nerve cells in the nucleus arcuatus. Ultrastructure revealed the type of inclusions in the microglia of the same type as in the adrenals, and a different type of inclusions in unidentifiable cells, possibly neurons. These latter inclusions consisted of loosely stacked lamellar material. The findings are interpreted as further evidence of storage taking place in this disease.