cortodoxone and Adrenal-Cortex-Diseases

Topics: Adrenal Cortex Diseases; Adrenal Hyperplasia, Congenital; Biomarkers; Cortodoxone; Cushing Syndrome; Humans; Hyperaldosteronism; Radioimmunoassay; Reference Values; Specimen Handling

Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to measure 6 metabolic compounds of the adrenocorticosteroid pathway simultaneously on residual specimens from patients who had previously been previously diagnosed, on the basis of immunoassays, as having congenital adrenal hyperplasia (CAH), 11 beta-hydroxylase deficiency, 21-hydroxylase deficiency, or Addison disease (adrenal insufficiency). Two subjects with normal adrenal function had serum cortisol values of 13.6 and 8.9 micrograms/dL and serum cortisone values of 2.1 and 0.6 microgram/dL, but the rest of the compounds were undetectable. Two patients with 11 beta-hydroxylase deficiency had serum 11 beta-deoxycortisol values of 14.9 and 10.0 micrograms/dL and serum 11-deoxycorticosterone values of 3.9 and 1.0 microgram/dL, but their serum levels of cortisol and cortisone were diminished. A patient with 21-hydroxylase deficiency had a highly increased serum 17-hydroxyprogesterone concentration of 28.5 micrograms/dL (or 28,500 ng/dL, the traditional unit to report this assay) and a serum 21-deoxycortisol concentration of 6.9 ug/dL (this is a pathologic marker of 21-hydroxylase deficiency that is nondetectable in sera of healthy subjects). This patient also had diminished concentrations of serum cortisol and cortisone (0.9 and 0.3 microgram/dL, respectively). At 30 and 60 min after corticotropin (ACTH) stimulation, serum cortisol was the only compound that showed a dramatic increase in the normal subjects; the patient with 21-hydroxylase deficiency showed an increase of serum 17-hydroxyprogesterone level, but no increase of serum cortisol level; the patient with Addison disease showed no increase in the levels of serum cortisol or other compounds. Metyprapone, which blocks 11 beta-hydroxylase activity, increased the serum 11-deoxycorticosteroid levels and decreased the serum cortisol level. This pilot study demonstrates that it is feasible to use LC-MS/MS for the laboratory diagnosis of adrenal cortical dysfunction. The authors envision that LC-MS/MS may soon become an ideal analytical technique for the diagnosis of such endocrine diseases.

Topics: 17-alpha-Hydroxyprogesterone; Addison Disease; Adrenal Cortex Diseases; Adrenal Hyperplasia, Congenital; Adrenocorticotropic Hormone; Adult; Aged; Chromatography, Liquid; Cortisone; Cortodoxone; Desoxycorticosterone; Female; Humans; Hydrocortisone; Male; Mass Spectrometry; Metyrapone; Middle Aged

A radioimmunoassay of three deoxycorticoids, namely 11 beta,17 alpha-dihydroxy-4-pregnene-3,20-dione (21-deoxycortisol), 17 alpha,21-dihydroxy-4-pregnene-3,20-dione (11-deoxycortisol), and 21-hydroxy-4-pregnene-3,20-dione (11-deoxycorticosterone) which are important for differential diagnosis of congenital adrenal disorders, is described and evaluated. Antisera against 3-(O-carboxymethyl)oximes conjugated to bovine serum albumin were raised in rabbits. The radioligands were prepared by radioiodination of previously synthesized homologous tyrosine methyl ester derivatives. Following diethyl ether extraction, the steroids were separated from each other and from cross-reactants by HPLC using a Nucleosil C8 reverse-phase column and a methanol-water mixture (7:5, v/v) as an eluent. Normal levels of analyzed steroids ranged from 0.02 to 0.348, 0.185 to 3.80, and 0.013 to 0.299 nmol/l, for 21-deoxycortisol, 11-deoxycortisol and 11-deoxycorticosterone, respectively. The levels of both deoxycortisols rose significantly after ACTH treatment. Data are given with respect to the concentrations of these steroids in some pathological situations such as 21-hydroxylase and 11 beta-hydroxylase block, hyperaldosteronism, and polycystic ovary syndrome.

Topics: Adolescent; Adrenal Cortex Diseases; Adult; Child; Child, Preschool; Chromatography, High Pressure Liquid; Cortodoxone; Desoxycorticosterone; Evaluation Studies as Topic; Female; Humans; Male; Middle Aged; Radioimmunoassay; Reproducibility of Results

Premature pubarche is characterized by pubic hair, adult type body odor, acne, and axillary hair before 8 yr of age in girls and 9.5 yr of age in boys. Causes of this premature virilization include premature adrenarche, mild errors of steroidogenesis, precocious puberty, and adrenal and gonadal tumors. To determine whether any clinical parameters are helpful in distinguishing which children should undergo further evaluation for mild congenital adrenal hyperplasia, we performed ACTH stimulation tests in 69 children with premature pubarche and 8 pubertal controls. Patients were categorized as having typical (pubic hair with or without axillary hair and body odor) or atypical (pubic hair and genital enlargement) premature pubarche. Blood samples, before and 30 min after iv bolus administration of synthetic ACTH, were obtained for progesterone, 17-hydroxypregnenolone, 17-hydroxyprogesterone, dehydroepiandrosterone, androstenedione, 11-deoxycortisol, and cortisol measurements. The patients were divided into 4 groups based on their individual responses to ACTH stimulation: premature adrenarche (no apparent defect in steroidogenesis), possible decreased 21-hydroxylase activity, possible decreased 3 beta-hydroxysteroid dehydrogenase activity, and indeterminate responses. Five of 11 (45%) children with atypical premature pubarche and 7 of 58 (12%) children with typical premature pubarche were found to have evidence of mild defects in steroidogenesis. Similar to previous reports in postpubertal women, only responses to ACTH stimulation allowed accurate classification of these patients.

Topics: 17-alpha-Hydroxypregnenolone; 17-alpha-Hydroxyprogesterone; Adrenal Cortex Diseases; Adrenocorticotropic Hormone; Androstenedione; Child; Cortodoxone; Dehydroepiandrosterone; Female; Genitalia, Female; Genitalia, Male; Hirsutism; Humans; Hydrocortisone; Hydroxyprogesterones; Male; Progesterone; Reference Values