17-hydroxylation deficiency in man.

Abstract

The biosynthesis of steroid hormones 1 requires a number of hydroxylating enzymes. Deficiency of these enzymes is demonstrated by increased or decreased amounts of certain steroid metabolites in blood and urine and is best exemplified by the deficiency of 11,8-hydroxylase (1) and 21-hydroxylase (2) in patients with congenital adrenal hyperplasia. 17a-Hydroxylase activity is present in these disorders because of the increases in secretion of androgens and excretion of pregnanetriol. In addition, a lack of 3-hydroxysteroid dehydrogenase has also been described (3). 17-Hydroxylation is essential not only to the biosynthesis of cortisol but also to the formation of * Submitted for publication July 19, 1966; accepted September 7, 1966 androstenedione = 4-androsten-3,17-dione; compound S= li-deoxycortisol = 4-pregnen-17a,21-diol-3,20-dione; dehydroepiandrosterone = 5-androsten -3,8 -ol -17 -one; dexamethasone = 1,4-pregnandien-9-fluoro-16a-methyl-1 ll,17a, 21-triol-3,20-dione; etiocholanolone = 5,B-androstan-3a-ol-17-one; pregnanediol = 5,8-pregnan-3a,20a-diol; pregnanetriol = 5p6-pregnan-3a,11a,20a-triol; stilbestrol = diethylstilbestrol = aca'diethyl-4,4'stilbenediol; tetrahydroaldosterone = TH aldosterone = 5,8-pregnan-3a,11p,21-trihydroxy-20 keto-18-ol; tetrahydrocortisol = THF = 5fi-pregnan-3a,1llf,17a,21-tetrol-20-one; tetrahydrocortisone = THE = 5fi-pregnan-3a,17a,21-triol-11,20-dione; tetrahydrodeoxycorticosterone = THDOC = 5#-pregnan-3a, 21-diol-20-one; tetrahydro-ll-deoxycortisol = 5,0-pregnan3a,17a,21-triol-20-one; and tetrahydro-18-OH-dehydrocorticosterone = TH-18-OH compound A = 5#-pregnan3a,18,21-trihydroxy-11,20-dione.gonadal hormones (4, 5), the androgenic steroids, androstenedione, testosterone, and, eventually, estrogens (6). Deficiency of this enzyme system should be manifested clinically in both adrenal and gonadal abnormalities if the enzyme is similar in both glands. Furthermore, it is reasonable to assume that lack of 1 7-hydroxylated steroids would allow uninhibited release of adrenocorticotropin. In such a circumstance in which cortisol secretion is absent, prolonged survival would not be anticipated because mineralocorticoids would be the only adrenal steroids produced. We will describe and discuss a patient with deficiency in 17a-hydroxylase activity with possibly a second defect in production of aldosterone. MethodsCase report The female patient M. H. was the product of a full-term normal pregnancy and weighed 7 pounds at birth. Several severe episodes of bronchitis occurred before 5 years of age. The patient was hospitalized for an influenza-like syndrome when she was 5 years old; the mother (29 years) and one sibling (11 months) died from "influenza" at this time. From 5 to 10 years of age the patient was absent from school about one-third of the time because of infections of the upper respiratory tract. She was hospitalized at age 9 for severe upper respiratory infection, high fever, and unconsciousness. Intravenous glucose therapy promptly restored consciousness, and hypoglycemia was d...

Two Cases of Pseudoaldosteronism (Liddle's Syndrome) in Siblings

“…In the syndrome of 17-hydroxylase deficiency, elevated blood pressure and hypokalemia are usually glucocorticoid remediable (Biglieri et al, 1966;New and Peterson, 1967).…”

Genetics of Congenital Adrenal Hyperplasia

“…17α-hydroxylase deficiency 17α-hydroxylase deficiency (17-OHD) (OMIM 202110) results from a defective CYP17A1 and accounts for approximately 1% of all CAH cases. 77 The CYP17A1 enzyme is a microsomal P450 type II enzyme that catalyzes two different enzymatic reactions; 17-α hydroxylation of pregnenolone and progesterone, and the conversion of 17-hydroxypregnenolone to dehydroepiandrosterone and, with lesser efficiency, of 17-OHP to androstenedione through the 17,20 lyase reaction. Thus, 17-OHD results in glucocorticoid and sex steroid deficiency, and impairs both adrenal and gonadal function.…”

Hiperplasia adrenal congênita: deficiência de 17alfa-hidroxilase

“…Os altos níveis de DOC causam supressão da renina e redução dos níveis circulantes de aldosterona e clinicamente se manifesta por quadro hipertensivo, hipocalemia e alcalose metabólica (1,5,8). A diminuição da síntese de esteróides sexuais leva a distúrbios no desenvolvimento sexual.…”

“…Em homens (46XY), o defeito enzimático manifesta-se por quadro de pseudo-hermafroditismo masculino (5,7,8), com genitália externa feminina, vagina em fundo cego e ausência de estruturas mullerianas ( 1 / 3 superior da vagina, útero e tubas uterinas), bem como ausência de pêlos axilares e pubianos.…”