17-ketosteroids and 11-hydroxyandrostenedione

The authors divided forty children and adolescents with inborn adrenal hyperplasia caused by a block of 21-hydroxylase of steroids (CAH) according to clinical criteria into adequately and inadequately treated. Substitution treatment with hydrocortisone or hydrocortisone combined with fludrocortisone was administered three times a day in individual doses. In order to find an adequate indicator of the adequacy of therapy, the authors assessed in addition to total urinary 17-oxosteroids also 17 alpha-hydroxyprogesterone, androstenedione and 11 beta-hydroxyandrostenedione in serum. The values of urinary 17-oxosteroids did not correspond to the clinical condition of the children; in younger children three was a high percentage of falsely positive and in older children of falsely negative results. As to serum steroids, the most suitable indicator for monitoring was 17-hydroxyprogesterone. The authors consider its levels above 30 nmol/l as a basis for consideration of raising therapeutic doses, while levels below 2.2 nmol/l signalize possible overdosage of the drug. Concurrently elevated levels of 17-hydroxyprogesterone and androstenedione are found in particularly inadequately treated children. 11 beta-hydroxyandrostenedione is not a useful indicator for monitoring of CAH treatment. In any case it is necessary, when controlling CAH therapy, to select an individual procedure and to evaluate results in the context with the patient's clinical condition.

Topics: 17-alpha-Hydroxyprogesterone; 17-Ketosteroids; Adolescent; Adrenal Cortex Hormones; Adrenal Hyperplasia, Congenital; Adult; Androstenedione; Child; Child, Preschool; Humans; Hydroxyprogesterones; Infant

A six-month-old 46,XY infant with a female phenotype and ambiguous genitalia was evaluated for male pseudohermaphroditism. The principal findings were (1) low basal plasma levels of all measured C19 steroids and their sulfates, which were unchanged or only minimally increased after stimulation with human chorionic gonadotropin or ACTH, (2) no urinary metabolites of C19 11-deoxy steroids, and decreased amounts of C19 11-oxosteroids, (3) normal basal plasma cortisol levels and normal urinary excretion of cortisol metabolites, (4) high plasma corticosterone and deoxycorticosterone levels and elevated urinary excretion of their metabolites, (5) high plasma progesterone and pregnenolone levels and increased urinary excretion of pregnanediol and pregnenediol, (6) high plasma 17 alpha-hydroxyprogesterone and 21-deoxycortisol levels and increased urinary excretion of pregnanetriol, 17 alpha-hydroxypregnanolone, and pregnenetriolone, (7) high plasma and urinary levels of 5-pregnene-3 beta,20 alpha-diol sulfate, (8) low plasma levels of 21-hydroxy-pregnenolone and 5-pregnene-3 beta,17 alpha, 20 alpha-triol sulfate, (9) high plasma ACTH levels, and (10) suppression of the high plasma steroid levels by dexamethasone. The unusual pattern of plasma and urinary steroids indicated that this child had multiple abnormalities of steroid-biosynthetic microsomal mixed-function oxidases--21-hydroxylase, 17 alpha-hydroxylase, and 17,20 desmolase. The deficit in the activities of the first two enzymes resulted in decreased cortisol synthesis with subsequent increased ACTH secretion and adrenocortical hyperplasia. The male pseudohermaphroditism resulted from deficient testosterone synthesis due to deficiency of 17 alpha-hydroxylase and 17,20 desmolase. The mother and two sisters of the affected child had evidence of mild 17 alpha-hydroxylase deficiency.

Topics: 17-Hydroxycorticosteroids; 17-Ketosteroids; 18-Hydroxycorticosterone; 18-Hydroxydesoxycorticosterone; Adrenal Hyperplasia, Congenital; Aldehyde-Lyases; Aldosterone; Androstenedione; Corticosterone; Cortodoxone; Dehydroepiandrosterone; Dehydroepiandrosterone Sulfate; Desoxycorticosterone; Dihydrotestosterone; Disorders of Sex Development; Humans; Hydrocortisone; Infant; Male; Mixed Function Oxygenases; Pregnenolone; Progesterone; Steroid Hydroxylases; Testosterone