RESUMO
17alpha-hydroxylase deficiency is a rare form of congenital adrenal hyperplasia (CAH) that affects both glucocorticoid and sex hormone biosynthesis. We report a case of an unambiguous female with testes and hypertension. She was found to have deficient 17alpha-hydroxylase activity. The diagnosis was not made easily, the condition being unexpected due to its rarity. The discriminating feature of this form of sex-reversal is the presence of hypertension due to the elevated serum deoxycorticosterone levels. A failure to detect this will inappropriately focus attention on other, more common causes of sex reversal such as androgen insensitivity and gonadal dysgenesis, and expose the patient to the long-term sequelae of uncontrolled arterial hypertension.
Assuntos
Hiperplasia Suprarrenal Congênita , Hiperplasia Suprarrenal Congênita/metabolismo , Hiperplasia Suprarrenal Congênita/epidemiologia , Hiperplasia Suprarrenal Congênita/patologia , Hiperplasia Suprarrenal Congênita/terapia , Austrália/epidemiologia , Criança , Feminino , Genitália Feminina/anormalidades , HumanosRESUMO
OBJECTIVE: To review experience of CYP11 beta 1 deficiency (previously known as 11 beta-hydroxylase) at the Royal Children's Hospital, Melbourne, Victoria. METHODOLOGY: A retrospective case review was conducted from 1974 to 1995 with five cases identified. RESULTS: Age of presentation ranged from 1 day to 7 years. Presentation was with ambiguous genitalia at birth (two females), simple virilization (two males) and suspected early puberty in mid childhood (one female). Associated clinical features were hypertension (three cases) and tail stature with markedly advanced bone age (four cases). Biochemical abnormalities consistent with CYP11 beta 1-deficiency were elevated urinary tetrahydro-11-deoxycortisol (n = 5) and elevated serum 11-deoxycortisol (n = 3). Additional abnormalities were elevated 17-hydroxyprogesterone (n = 3), elevated androstenedione (n = 4) and elevated dehydroepiandrosterone sulphate (n = 4). The clinical features and investigations suggested CYP11 beta 1-classical deficiency in four patients and CYP11 beta 1-non-classical deficiency in one patient. CONCLUSIONS: The five cases of CYP11 beta 1-deficiency demonstrate a spectrum of clinical abnormalities, with diagnostic difficulties in two cases and delayed presentation in three cases. Prompt diagnosis of CYP11 beta 1-deficiency is facilitated greatly by the availability of a gas chromatography-mass spectrometry instrument and is essential to avoid the long-term effects of hypertension and hyperandrogenism.
Assuntos
Hiperplasia Suprarrenal Congênita , Hiperplasia Suprarrenal Congênita/etiologia , Hiperplasia Suprarrenal Congênita/sangue , Hiperplasia Suprarrenal Congênita/urina , Criança , Pré-Escolar , Progressão da Doença , Feminino , Humanos , Hiperandrogenismo/etiologia , Hipertensão/etiologia , Lactente , Recém-Nascido , Masculino , Estudos Retrospectivos , Esteroide 11-beta-Hidroxilase/urina , Esteroides/uso terapêutico , Esteroides/urina , VitóriaRESUMO
The symptoms, auxological characteristics, and stimulated 17-hydroxyprogesterone (17-OHP) concentrations in a group of patients with non-classical 21-hydroxylase deficiency (NCCAH) were compared with those of their siblings. Ten index cases consisting of nine females and one male patient aged 3-33 years and 16 siblings were studied. In the sibling group five subjects were slightly virilised and of these, two females were found to have NCCAH according to their stimulated 17-OHP concentrations. The remaining nine siblings, who were not virilised, all had normal stimulated 17-OHP concentrations. Among the total NCCAH group (index cases and affected siblings) eight patients had the diagnosis made within two years of the onset of symptoms. In four patients diagnosis was delayed until adulthood. In seven patients investigated, bone age was significantly increased before treatment. The mean height and body mass index Z scores of the affected patients as a total group or when divided according to skeletal maturity were not significantly different from either the normal mean or from their unaffected siblings. Virilised siblings of patients with NCCAH should have stimulated 17-OHP levels measured to exclude the disease. Patients with NCCAH do not appear to be at risk of short adult stature despite increased bone age in childhood.
Assuntos
Hiperplasia Suprarrenal Congênita/genética , Estatura , Índice de Massa Corporal , Hidroxiprogesteronas/sangue , 17-alfa-Hidroxiprogesterona , Adolescente , Hiperplasia Suprarrenal Congênita/sangue , Hiperplasia Suprarrenal Congênita/fisiopatologia , Adulto , Fatores Etários , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Linhagem , Fatores de Tempo , Resultado do Tratamento , Virilismo/etiologiaRESUMO
OBJECTIVES: The study was designed to assess the reliability of measurement of 24-hour urinary 17 alpha-hydroxyprogesterone (17-OHP) by radio-immunoassay (RIA) as an alternative biochemical assessment for monitoring the treatment of congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21-OHD) and to assess the need for sample purification by column chromatography to improve assay specificity. METHODOLOGY: Morning serum 17-OHP was measured using RIA and 24-hour urinary pregnanetriol using gas chromatography. Twenty-four-hour urinary 17-OHP was measured in samples from 17 prepubertal patients with CAH due to 21-OHD, and 20 normal prepubertal children as controls. In 24 urine samples, RIA of 17-OHP was performed with and without column chromatography. RESULTS: There was a good correlation between 24-hour urinary 17-OHP and 24-hour urinary pregnanetriol (r = 0.962, P < 0.01) and between 24-hour urinary 17-OHP and morning serum 17-OHP (r = 0.955, P < 0.01). There was no significant difference in the RIA of the urine samples with and without purification by column chromatography. CONCLUSIONS: The measurement of 24-hour urinary 17-OHP is a reliable alternative for the biochemical monitoring of 21-OHD, and RIA specificity is unaffected by omission of column chromatography.
Assuntos
Hiperplasia Suprarrenal Congênita , Hiperplasia Suprarrenal Congênita/terapia , Glucocorticoides/administração & dosagem , Hidroxiprogesteronas/urina , 17-alfa-Hidroxiprogesterona , Hiperplasia Suprarrenal Congênita/urina , Estudos de Casos e Controles , Criança , Pré-Escolar , Cromatografia Gasosa/economia , Ritmo Circadiano , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Hidroxiprogesteronas/sangue , Lactente , Masculino , Valor Preditivo dos Testes , Pregnanotriol/urina , Radioimunoensaio/economiaAssuntos
18-Hidroxicorticosterona/sangue , Citocromo P-450 CYP11B2 , Erros Inatos do Metabolismo/sangue , Erros Inatos do Metabolismo/diagnóstico , Oxigenases de Função Mista/deficiência , 18-Hidroxicorticosterona/análogos & derivados , 18-Hidroxicorticosterona/urina , Aldosterona/sangue , Diagnóstico Diferencial , Fludrocortisona/uso terapêutico , Humanos , Hidroxiprogesteronas/sangue , Lactente , Masculino , Erros Inatos do Metabolismo/tratamento farmacológico , Renina/sangueRESUMO
Three infants with congenital adrenal hypoplasia are described. The two surviving infants were detected and successfully treated in the neonatal period due to a suggestive family history (Case 1) and antenatal maternal oestriol screening (Case 2). The modes of inheritance, diverse clinical presentation, associated conditions, diagnostic work-up and pathology of congenital adrenal hypoplasia in these three infants is discussed.
Assuntos
Glândulas Suprarrenais/anormalidades , Hiponatremia/etiologia , Cortisona/uso terapêutico , Feminino , Fludrocortisona/uso terapêutico , Cromatografia Gasosa-Espectrometria de Massas , Doenças Genéticas Inatas/sangue , Doenças Genéticas Inatas/diagnóstico , Doenças Genéticas Inatas/mortalidade , Doenças Genéticas Inatas/urina , Humanos , Hiponatremia/diagnóstico , Hiponatremia/tratamento farmacológico , Recém-Nascido , Masculino , Esteroides/urinaRESUMO
Serum sulphates of 5-androstene-3 beta,17 beta-diol (5-ADIOL-S), 5 alpha-androstane-3 alpha,17 beta-diol (3 alpha-DIOL-S) and dehydroepiandrosterone (DHEA-S), as well as 5 alpha-androstane-3 alpha,17 beta-diol glucuronide (3 alpha-DIOL-G) and unconjugated androstenedione (AD) and testosterone (T), sex hormone binding globulin (SHBG), free androgen index (FAI) and 17 alpha-hydroxyprogester-one (17OHP) were measured by specific radioimmunoassays (RIA) in 14 women with late-onset 21-hydroxylase deficiency (LOCAH), and in normal women (n = 73). The diagnosis of LOCAH was made on the finding of a (17OHP) response level greater than 30 nmol/l following ACTH stimulation, and/or an elevation of urinary metabolites of 17OHP. Mean values for serum concentrations of all steroids measured and the free androgen index (100 X T nmol/l divided by SHBG nmol/l) were significantly elevated, and SHBG levels depressed in patients with LOCAH. These studies show that in LOCAH, in addition to the unconjugated steroids AD and T, the sulphoconjugated steroids DHEA-S, 5-ADIOL-S and 3 alpha-DIOL-S are increased, as is the glucuronide conjugate 3 alpha-DIOL-G and the index of bioavailable testosterone (FAI), and that mean SHBG levels are depressed. These data suggest that as well as AD, 5-ADIOL-S and DHEA-S may act as pro-hormones for more potent steroids (T and 5 alpha-dihydrotestosterone) in peripheral tissues, while 3 alpha-DIOL-S and 3 alpha-DIOL-G may both reflect peripheral androgen metabolism in patients with LOCAH.
Assuntos
Hiperplasia Suprarrenal Congênita , Androstano-3,17-diol/sangue , Androstenodiol/sangue , Glucuronatos/sangue , Sulfatos/sangue , 17-alfa-Hidroxiprogesterona , Hormônio Adrenocorticotrópico , Adulto , Androstenodiona/sangue , Desidroepiandrosterona/análogos & derivados , Desidroepiandrosterona/sangue , Sulfato de Desidroepiandrosterona , Feminino , Hirsutismo/sangue , Humanos , Hidroxiprogesteronas/sangue , Hidroxiprogesteronas/urina , Globulina de Ligação a Hormônio Sexual/metabolismo , Testosterona/sangueRESUMO
Serum sulphates of 5-androstene-3 beta,17 beta-diol (5-ADIOL-S), 5 alpha-androstane-3 alpha,17 beta-diol (3 alpha-DIOL-S) and dehydroepiandrosterone (DHEA-S), unconjugated androstene-dione (AD) and testosterone (T), sex hormone binding globulin (SHBG), free androgen index (FAI), 17 alpha-hydroxyprogesterone (17OHP), luteinising hormone (LH) and follicle stimulating hormone (FSH) were measured by specific radioimmunoassay in 28 hirsute women with polycystic ovarian disease (PCO) and in normal women (n = 73). Mean levels of steroids measured were significantly elevated, and SHBG significantly depressed, in the women with PCO with values (mean +/- SE) for 5-ADIOL-S (516 +/- 51 vs 267 +/- 10 nmol/l), 3 alpha-DIOL-S (130 +/- 9 vs 52 +/- 2 nmol/l), DHEA-S (7.3 +/- 0.5 vs 4.4 +/- 0.2 mumol/l), AD (11.3 +/- 1.1 vs 3.4 +/- 0.2 nmol/l), T (3.3 +/- 0.2 vs 1.5 +/- 0.1 nmol/l) and 17OHP (5.1 +/- 0.8 vs 2.8 +/- 0.2 nmol/l). SHBG levels were 31 +/- 2.9 vs 65 +/- 2.5 nmol/l, and the free androgen index [100 x T (nmol/l) divided by (SHBG nmol/l)] was 12.5 +/- 1.4 vs 2.4 +/- 0.1. The mean LH to FSH ratio was also elevated at 2.8 +/- 0.3. These studies suggest that the measurement of 5-ADIOL-S and DHEA-S may indicate adrenal gland involvement in PCO while 3 alpha-DIOL-S appears to be a reflection of peripheral androgen metabolism. A comprehensive biochemical profile of PCO should thus include the analysis of these sulphoconjugates as well as unconjugated steroids.
Assuntos
Androstano-3,17-diol/sangue , Androstanóis/sangue , Androstenodiol/sangue , Androstenodióis/sangue , Hirsutismo/sangue , Síndrome do Ovário Policístico/diagnóstico , Adulto , Androgênios/metabolismo , Feminino , Hirsutismo/complicações , Hirsutismo/diagnóstico , Humanos , Técnicas In Vitro , Síndrome do Ovário Policístico/complicações , Radioimunoensaio , Globulina de Ligação a Hormônio Sexual/metabolismoRESUMO
Female pattern androgenic alopecia (AA) is a relatively common endocrine abnormality in premenopausal women. However, unlike hirsutism, little is known about the androgen metabolism and plasma C19 steroid sulphate profiles in this disorder. We have therefore measured the plasma levels of dehydroepiandrosterone sulphate (DHEA-S), 5-androstene-3 beta,17 beta-diol sulphate (5-ADIOL-S), 5 alpha-androstane-3 alpha, 17 beta-diol sulphate (3 alpha-DIOL-S), androstenedione (AD), total testosterone (T), free testosterone (FT), sex hormone binding globulin (SHBG), non-SHBG bound T, luteinizing hormone (LH) and follicle stimulating hormone (FSH), and have calculated the free androgen index (FAI): 100 x T (nmol/l) divided by SHBG (nmol/l), in premenopausal women with AA (n = 25-45) and in normal premenopausal women (n = 17-73). While mean plasma concentrations of DHEA-S and T were not significantly different from controls, mean SHBG concentrations were significantly lower (47 +/- 3 vs 64 +/- 3 nmol/l) and the mean free androgen index (4.4 +/- 0.4 vs 2.4 +/- 0.2), and mean concentrations of free testosterone (45 +/- 5 vs 26 +/- 1.4 pmol/l), non-SHBG bound T (0.9 +/- 0.2 vs 0.6 +/- 0.1 nmol/l) and androstenedione (4.3 +/- 0.3 vs 3.4 +/- 0.2 nmol/l) were significantly elevated in women with AA. Furthermore, mean plasma concentrations of 5-ADIOL-S (512 +/- 42 nmol/l) and 3 alpha-DIOL-S (76 +/- 7 nmol/l) were significantly higher than levels found in normal women (272 +/- 12 nmol/l and 52 +/- 2 nmol/l respectively). The nature of the hyperandrogenism associated with AA may thus only be revealed by a comprehensive plasma androgen and androgen sulphate profile, which may explain apparently aberrant data for a given patient. In addition, 5-ADIOL-S and 3 alpha-DIOL-S may serve as excellent plasma markers of both the existence of the disorder and the efficacy of its treatment.
Assuntos
Alopecia/metabolismo , Androgênios/metabolismo , Adolescente , Adulto , Androstano-3,17-diol/análogos & derivados , Androstano-3,17-diol/sangue , Androstenodiol/análogos & derivados , Androstenodiol/sangue , Androstenodiona/sangue , Disponibilidade Biológica , Desidroepiandrosterona/análogos & derivados , Desidroepiandrosterona/sangue , Sulfato de Desidroepiandrosterona , Feminino , Hormônio Foliculoestimulante/sangue , Humanos , Hormônio Luteinizante/sangue , Pessoa de Meia-Idade , Radioimunoensaio/métodos , Globulina de Ligação a Hormônio Sexual/análise , Testosterona/sangueRESUMO
Serum sex hormone binding globulin (SHBG), testosterone (T), DHEA sulphate (DHEA-S), androstenedione (AD) and delta 5-androstene-3 beta,17 beta-diol sulphate (5-ADIOL-S) levels were measured by specific radioimmunoassay in 16 girls presenting with premature adrenarche (PA) and in 14 normal girls. Mean levels of steroids measured were elevated, and SHBG significantly depressed, in the girls with PA, with values (mean +/- SE) for DHEA-S (1.73 +/- 0.17 vs 0.25 +/- 0.06 mumol/l), 5-ADIOL-S (104 +/- 8 vs 31 +/- 4 nmol/l), AD (0.89 +/- 0.06 vs 0.62 +/- 0.04 nmol/l), and T (0.49 +/- 0.03 vs 0.23 +/- 0.06 nmol/l). SHBG levels were 68 +/- 6 vs 108 +/- 5 nmol/l, and the free androgen index [100 x T (nmol/l) divided by SHBG (nmol/l)] was 0.89 +/- 0.17 vs 0.22 +/- 0.01. These studies show that SHBG is depressed in girls with premature adrenarche; with the increased testosterone levels, this results in a markedly elevated free androgen index, a measure of testosterone which is bioavailable to target tissue. This may be compounded by the elevated levels of 5-ADIOL-S in girls with PA since its role may be as a prohormone for more potent androgens (testosterone, 5 alpha-dihydrotestosterone) in target tissues such as pubic skin.
Assuntos
Androgênios/sangue , Androstenodiol/sangue , Androstenodióis/sangue , Puberdade Precoce/sangue , Globulina de Ligação a Hormônio Sexual/análise , Animais , Bovinos , Criança , Pré-Escolar , Humanos , Radioimunoensaio , Esteroides/sangueAssuntos
Di-Hidrotestosterona/sangue , Hirsutismo/sangue , Feminino , Humanos , Radioimunoensaio/métodosRESUMO
Serum sulphates of 5-androstene-3 beta, 17 beta-diol (5-ADIOL-S), 5 alpha-androstane-3 alpha,17 beta-diol (3 alpha-DIOL-S) and dehydroepiandrosterone (DHEA-S), as well as unconjugated androstenedione (AD), testosterone (T) and 17 alpha-hydroxyprogesterone (17OHP), sex hormone binding globulin (SHBG) and the free androgen index (FAI) were measured by specific radioimmunoassay in girls with premature adrenarche (n = 9-16), and in hirsute women with (1) late onset 21 hydroxylase deficiency (n = 14), (2) polycystic ovarian disease (n = 28) and (3) idiopathic hirsutism (n = 74). Levels were also determined in females with androgenic alopecia (n = 35-45), in normal prepubertal girls (n = 9-14) and in normal adult women (n = 50-73). Mean serum concentrations of 5-ADIOL-S, 3 alpha-DIOL-S, DHEA-S, AD, T, and FAI were elevated and SHBG depressed, in all patient groups compared with controls, except for DHEA-S and T in patients with alopecia. We conclude that in addition to DHEA-S, 5-ADIOL-S may have a role as a pro-hormone in the synthesis of more potent androgens (T, DHT) in peripheral tissues such as skin; in addition, 3 alpha-DIOL-S may be a marker of peripheral androgen metabolism.
Assuntos
Androgênios/sangue , Hirsutismo/sangue , Puberdade Precoce/sangue , Ácidos Sulfúricos/sangue , Adolescente , Adulto , Criança , Pré-Escolar , Desidroepiandrosterona/análogos & derivados , Desidroepiandrosterona/sangue , Sulfato de Desidroepiandrosterona , Feminino , Humanos , Menarca , Radioimunoensaio , Globulina de Ligação a Hormônio Sexual/análiseRESUMO
In a study using gas chromatography-mass spectrometry (GC-MS) on urine specimens from 16 normal infants and 16 infants with congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (aged 1 day to 4 weeks), the major steroids recognized in all infants were: 16 alpha-hydroxy-dehydroepiandrosterone, 16 beta-hydroxy-dehydroepiandrosterone, 16-oxo-androstenediol, androstenetriol, 15 beta,17 alpha-dihydroxy-pregnenolone and 16 alpha-hydroxy-pregnenolone. Pregnanetriol was detectable in three normal infants (aged 3, 6 and 15 days) but the levels seen in 15 CAH patients were in a higher range. Pregnanetriolone, 5 beta-17-hydroxy-pregnanolone and 15 beta,17 alpha-dihydroxy-pregnanolone were present in the urine of 15 CAH patients, but were not detectable in any of the normal infants. The older the patient, the higher the level was of each of these four steroids. The results indicate that, even on day 1, patients with CAH due to 21-hydroxylase deficiency may be positively identified using GC-MS of urine specimens. This does not preclude the possibility that a minority of patients with CAH, most likely those with mild 21-hydroxylase deficiency, may not exhibit the characteristic GC-MS findings on day 1, as seen in one of the 16 CAH patients.