RESUMEN
Glucocorticoids are essential in the treatment of patients with congenital adrenal hyperplasia (CAH). The opposite actions of glucocorticoids and androgens in bone mass achievement justify a study of bone mineral density (BMD) in these patients. We evaluated BMD in patients with CAH due to classic 21-hydroxylase (CYP21A2) deficiency and investigated the involvement of clinical and laboratory factors in the BMD. This study assessed the clinical and laboratory factors involved in BMD of 45 patients at the Pediatric Unit of Endocrinology, UNICAMP, who had been diagnosed as having classical CAH due to CYP21A2 deficiency including molecular characterization. The sample consisted of 28 females and 17 males; 23 salt-wasting (SW) and 22 simple virilizing (SV) cases, with average of 9.9 years (ranges, 5.1-16.3 years) when bone densitometry was performed. The DEXA method was used for calculating the areal BMD Z score in L2-L4. The variables were analyzed with reference to the BMD for chronological age (BMD/CA), height age (BMD/HA), and bone age (BMD/BA). The mean Z score for BMD/CA was 0.08 +/- 1.21 (-2.55 to 2.64); it was 0.29 +/- 1.33 (-2.01 to 4.00) for BMD/HA, and -0.90 +/- 1.24 (-3.41 to 1.92) for BMD/BA. The BMD/CA was significantly lower in females and in patients on treatment for a long period and of more advanced chronological age. Weight and body mass index (BMI) Z scores showed a positive correlation with advanced BA. The higher the weight and BMI Z scores, the higher the BMD/HA. The BMD/BA values were significantly higher in the group in which BA was closer to CA. The BMD/BA value was significantly lower when compared to the value obtained with height and chronological ages. Sex, duration of treatment, weight, BMI, and bone age have an effect on areal BMD in patients with CAH due to CYP21A2 deficiency, which may be underestimated when evaluated in relation to CA and HA.
Asunto(s)
Hiperplasia Suprarrenal Congénita/patología , Adolescente , Hiperplasia Suprarrenal Congénita/diagnóstico , Hiperplasia Suprarrenal Congénita/etiología , Factores de Edad , Densidad Ósea , Niño , Preescolar , Estudios Transversales , Femenino , Glucocorticoides/farmacología , Humanos , Masculino , Pubertad , Factores Sexuales , Esteroide 21-Hidroxilasa/biosíntesis , Esteroide 21-Hidroxilasa/genética , Esteroide Hidroxilasas/deficienciaRESUMEN
17 alpha-Hydroxylase deficiency (17-OHDS) is a peculiar type of adrenal insufficiency because of elevated corticosterone (B) production. Episodic and circadian ACTH secretion and the responses to ovine CRH and metyrapone were examined in a female with 17-OHDS under conditions of normal sodium (NSI) and low sodium (LSI) intake. Plasma ACTH and B were higher on LSI than on NSI (mean +/- SD: ACTH, 58 +/- 20 vs. 33 +/- 14 pmol/L; B, 508 +/- 107 vs. 381 +/- 69 nmol/L). ACTH pulses were concomitant with or followed by B pulses. An increase in the amplitude, but not the number, of ACTH and B pulses was found on LSI. Circadian ACTH and B rhythms persisted on LSI. Aldosterone levels were higher on LSI than on NSI. After metyrapone, plasma B decreased in the afternoon (NSI, 220 +/- 10; LSI, 275 +/- 35 nmol/L) and rose on the following morning. Plasma ACTH increased substantially on the following morning (NSI, 135 +/- 47; LSI, 307 +/- 77 pmol/L). The ACTH peak levels after ovine CRH increased after metyrapone administration. These data indicate that B may also have a negative feedback effect at the pituitary level. In all maneuvers, there were no changes in PRA, plasma sodium and potassium, or cortisol. We conclude that in 17-OHDS, in the absence of cortisol production, ACTH and B may interact to modulate the brain-pituitary-adrenocortical system.
Asunto(s)
Hiperplasia Suprarrenal Congénita , Hiperplasia Suprarrenal Congénita/enzimología , Hormona Adrenocorticotrópica/sangre , Esteroide Hidroxilasas/deficiencia , Adolescente , Hiperplasia Suprarrenal Congénita/sangre , Hormona Adrenocorticotrópica/metabolismo , Ritmo Circadiano , Hormona Liberadora de Corticotropina , Femenino , Humanos , MetiraponaRESUMEN
From the study of HLA, complement, and glyoxalase I alleles in 82 Venezuelan individuals belonging to 19 families of mixed ethnic origin having 20 affected newborns with salt-wasting congenital adrenal hyperplasia due to 21-hydroxylase (21-OH) deficiency, a total of 38 disease haplotypes and 53 nondisease haplotypes were found. Of the pathological haplotypes 47% were found to share the HLA-B39 or -Bw62 specificities, 55% of them in combination with the BFS, C2C, C4A4, C4B2 (SC42) complotype. The frequencies of HLA-B39 and -Bw62 among the affected haplotypes were 29 and 18% as compared with 6 and 0% among the nondisease haplotypes of the same families. Statistical associations (P less than 0.01) with salt-wasting adrenal hyperplasia were found with the SC42 complotype and with the combination SC42, HLA-B39. These results are markedly different from those reported in the literature which show an "association" at the population level among many Caucasoid samples of HLA-Bw47 and the extended haplotype (HLA-Bw47, DR7,FC91,0) with the salt-wasting form of the disease. Furthermore, four of the unrelated patients reported here were homozygous for all the major histocompatibility complex loci tested, while three others were homozygous for at least two HLA loci. Analysis of the geographical origin of the grandparents indicated clustering of the deficiency carrier HLA haplotypes. This observation, together with the fact that there is an excess of homozygotes among the patients in Venezuela, strongly suggests that salt-wasting 21-OH deficiency congenital adrenal hyperplasia is mostly the result of a founder effect of relatively hyperplasia is mostly the result of a founder effect identity by descent of a few abnormal alleles at the 21-OHB locus in most cases. The mutation marked by HLA-Bw47 was not observed in this population.
Asunto(s)
Hiperplasia Suprarrenal Congénita , Hiperplasia Suprarrenal Congénita/inmunología , Cromosomas Humanos Par 6 , Antígenos HLA/genética , Complejo Mayor de Histocompatibilidad , Esteroide Hidroxilasas/deficiencia , Hiperplasia Suprarrenal Congénita/genética , Frecuencia de los Genes , Haplotipos , Heterocigoto , Humanos , Linaje , Esteroide 21-Hidroxilasa/genética , VenezuelaAsunto(s)
Humanos , Femenino , 3-Hidroxiesteroide Deshidrogenasas/deficiencia , Hiperplasia Suprarrenal Congénita/enzimología , Trastornos del Desarrollo Sexual/enzimología , Esteroide 11-beta-Hidroxilasa/deficiencia , Esteroide 21-Hidroxilasa/deficiencia , Esteroide Hidroxilasas/deficiencia , Hiperplasia Suprarrenal Congénita/tratamiento farmacológico , Trastornos del Desarrollo Sexual/genética , Glucocorticoides/uso terapéutico , FenotipoAsunto(s)
3-Hidroxiesteroide Deshidrogenasas/deficiencia , Hiperplasia Suprarrenal Congénita , Hiperplasia Suprarrenal Congénita/enzimología , Trastornos del Desarrollo Sexual/enzimología , Esteroide Hidroxilasas/deficiencia , Hiperplasia Suprarrenal Congénita/tratamiento farmacológico , Trastornos del Desarrollo Sexual/genética , Femenino , Glucocorticoides/uso terapéutico , Humanos , FenotipoAsunto(s)
Hiperplasia Suprarrenal Congénita , Hiperplasia Suprarrenal Congénita/etiología , Esteroide Hidroxilasas/deficiencia , Hiperplasia Suprarrenal Congénita/diagnóstico , Hiperplasia Suprarrenal Congénita/genética , Niño , Preescolar , Femenino , Antígenos HLA/genética , Humanos , Hidrocortisona/uso terapéutico , Hidroxiprogesteronas/sangre , Lactante , Recién Nacido , Masculino , Mutación , Esteroide 21-Hidroxilasa/genética , Virilismo/etiologíaRESUMEN
In an attempt to prevent in utero virilization of female fetuses with 21-hydroxylase deficiency, six mothers at risk were treated with either hydrocortisone (n = 1) or dexamethasone (n = 5) in early pregnancy. Treatment was continued to term in the two pregnancies in which the diagnosis of an affected female fetus was confirmed. In patient 1 (hydrocortisone treatment) fetal adrenal suppression was only partial but the external genitalia were only slightly abnormal. In patient 2 (dexamethasone treatment) fetal adrenal suppression was achieved and the external genitalia were normal at birth. These encouraging results open a new prospect for treating congenital adrenal hyperplasia in utero.
Asunto(s)
Hiperplasia Suprarrenal Congénita/tratamiento farmacológico , Atención Prenatal , Esteroide Hidroxilasas/deficiencia , 17-alfa-Hidroxiprogesterona , Adulto , Líquido Amniótico/análisis , Dexametasona/uso terapéutico , Femenino , Humanos , Hidrocortisona/uso terapéutico , Hidroxiprogesteronas/sangre , Recién Nacido , EmbarazoAsunto(s)
Hiperplasia Suprarrenal Congénita , Hiperplasia Suprarrenal Congénita/complicaciones , Hirsutismo/etiología , Esteroide Hidroxilasas/deficiencia , 17-Cetosteroides/orina , Adolescente , Hiperplasia Suprarrenal Congénita/diagnóstico , Deshidroepiandrosterona/sangre , Femenino , Humanos , Testosterona/sangreAsunto(s)
Hiperplasia Suprarrenal Congénita , Hiperfunción de las Glándulas Suprarrenales/genética , Tamización de Portadores Genéticos , Esteroide Hidroxilasas/deficiencia , Hiperfunción de las Glándulas Suprarrenales/sangre , Hiperfunción de las Glándulas Suprarrenales/etiología , Hormona Adrenocorticotrópica , Homocigoto , Humanos , Hidroxiprogesteronas/sangre , Progesterona/sangreRESUMEN
Ninety-eight females with congenital adrenal hyperplasia due to a defect in either the 21-hydroxylase or the 11 beta-hydroxylase enzyme were evaluated to determine the effects of glucocorticoid treatment on growth, pubertal development, and fertility. When treatment was begun prior to one year of age, mean final height was 157.4 +/- 7.3 com, well within the normal adult female range, and significantly (p less than 0.001) greater than the mean final height of 150.9 +/- 4.3 cm found in untreated patients. The mean age of menarche in patients treated prior to the age of six years was 13.8 +/- 3.7 years which is significantly (p less than 0.01) delayed compared to that in the normal population of the United States. However, 92% of patients with menstrual delay had inadequate suppression of adrenal androgens and urinary excretion of 17 ketosteroids larger than 7.0 mg/24hours. The increased production of adrenal androgens was the result of poor compliance or an insufficient prescribed dose of glucocorticoids. The fertility rate in patients first treated between six and 20 years of age was 64%. The excretion of urinary 17 KS at the time of pregnancy was 2.5 to 5.3 mg/24 hours. All of the patients who delivered term infants required delivery by cesarean section because of cephalopelvic disproportion. The major problems encountered in the management of adolescent patients were patient noncompliance and physician failure to increase the glucocorticoid dose as the patient's body size increased.
Asunto(s)
Hiperfunción de las Glándulas Suprarrenales/tratamiento farmacológico , Glucocorticoides/uso terapéutico , 17-Cetosteroides/orina , Adolescente , Estatura/efectos de los fármacos , Mama/crecimiento & desarrollo , Niño , Preescolar , Cortisona/farmacología , Cortisona/uso terapéutico , Desoxicorticosterona/farmacología , Desoxicorticosterona/uso terapéutico , Femenino , Fertilidad/efectos de los fármacos , Glucocorticoides/farmacología , Humanos , Hidrocortisona/farmacología , Hidrocortisona/uso terapéutico , Lactante , Menarquia/efectos de los fármacos , Prednisona/farmacología , Prednisona/uso terapéutico , Embarazo , Pubertad/efectos de los fármacos , Maduración Sexual/efectos de los fármacos , Esteroide Hidroxilasas/deficiencia , Factores de TiempoRESUMEN
The response to administered adrenocorticotropin (ACTH, Cortrosyn) of 26 heterozygotes (parents of children with adrenal 21-hydroxylase deficiency) and of 14 controls are compared. The mean plasma levels of 4-pregnene-3, 20-dione-17, 21-diol (17-OH progesterone) were significantly greater in the heterozygotes 60 minutes (p less than 0.02) and 90 minutes (p less than 0.05) after stimulation with Cortrosyn than in controls. There is, however, considerable overlap. The results would indicate a partial enzyme deficiency in the parents of diseased subjects. There was no significant difference in the response of plasma cortisol.
Asunto(s)
Hiperfunción de las Glándulas Suprarrenales/genética , Heterocigoto , Hidroxiprogesteronas/sangre , Hiperfunción de las Glándulas Suprarrenales/sangre , Femenino , Humanos , Hidrocortisona/sangre , Masculino , Radioinmunoensayo , Esteroide Hidroxilasas/deficienciaRESUMEN
In a 19-year-old phenotypic female (46, XY) with hypertension and hypokalemia, studies confirmed 17-alpha-hydroxylase deficiency. Prior to diagnosis she had been considered to have testicular feminization. Increased plasma progesterone and urinary pregnanediol levels were present before treatment. Increased secretion rates of deoxycorticosterone and corticosterone and abnormally low production of cortisol and aldosterone were present. Following treatment with hydrocortisone, plasma progesterone, serum potassium, and urinary pregnanediol levels and DOC and B secretions were normal. Aldosterone secretion six months after treatment remained low. Normal blood pressure measurements were achieved during treatment with hydrocortisone and oral estrogen with the patient at rest; however, mild elevations in blood pressure (130/90 mm Hg) have been noted despite continued hydrocortisone therapy.