cortodoxone and Hirsutism

To determine if the (tttta)(n) repeat polymorphism in the promoter region of CYP11a gene is associated with hirsutism and hyperandrogenism in women from Spain.. Controlled clinical study.. Tertiary-care institutional hospital.. Ninety-two hirsute women and 33 healthy control women.. Basal and adrenocorticotropin-stimulated serum samples and genomic DNA extracted and purified from whole-blood samples were obtained during the follicular phase of the menstrual cycle.. CYP11a (tttta)(n) repeat-polymorphism genotype and serum ovarian and adrenal androgen levels.. None of the CYP11a (tttta)(n) polymorphic alleles was associated with hirsutism. The absence of the four-repeat-units allele (4R-- genotype), which has been reported by other authors to be associated with polycystic ovary syndrome (PCOS), was found in 22.4% of the women studied here and was equally distributed among patients and controls, independently of the presence of PCOS and/or ovarian or adrenal hyperandrogenism. No differences were observed in serum hormone concentrations in 4R-- individuals as compared with subjects with at least one four-repeat-units allele.. The (tttta)(n) repeat polymorphism in the promoter region of CYP11a does not appear to play any significant role in the pathogenesis of hirsutism and hyperandrogenism in women from Spain.

Topics: Adult; Base Sequence; Cholesterol Side-Chain Cleavage Enzyme; Cortodoxone; Cosyntropin; Dehydroepiandrosterone Sulfate; Dexamethasone; Estradiol; Female; Follicle Stimulating Hormone; Genotype; Hirsutism; Humans; Hyperandrogenism; Luteinizing Hormone; Menstrual Cycle; Microsatellite Repeats; Polycystic Ovary Syndrome; Polymorphism, Genetic; Progesterone; Promoter Regions, Genetic; Reference Values; Sex Hormone-Binding Globulin; Testosterone

Patients with 21-hydroxylase deficiency (21OHD) have long-term complications, resulting from poor disease control and/or glucocorticoid overtreatment. Lack of optimal biomarkers has made it challenging to tailor therapy and predict long-term outcomes.. To identify biomarkers of disease control and long-term complications in 21OHD.. Cross-sectional study of 114 patients (70 males), ages 2 to 67 years (median, 15 years), seen in a tertiary referral center.. We correlated a mass-spectrometry panel of 23 steroids, obtained before first morning medication, with bone age advancement (children), adrenal volume (adults), testicular adrenal rest tumors (TART), hirsutism, menstrual disorders, and pituitary hormones.. Total adrenal volume correlated positively with 18 steroids, most prominently 21-deoxycortisol and four 11-oxygenated-C19 (11oxC19) steroids: 11β-hydroxyandrostenedione (11OHA4), 11-ketoandrostenedione (11ketoA4), 11β-hydroxytestosterone (11OHT), and 11-ketotestosterone (11ketoT) (r ≈ 0.7, P < 0.0001). Nine steroids were significantly higher (P ≤ 0.01) in males with TART compared with those without TART, including 11OHA4 (6.8-fold), 11OHT (4.9-fold), 11ketoT (3.6-fold), 11ketoA4 (3.3-fold), and pregnenolone sulfate (PregS; 4.8-fold). PregS (28.5-fold) and 17-hydroxypregnenolone sulfate (19-fold) levels were higher (P < 0.01) in postpubertal females with menstrual disorders. In males, testosterone levels correlated positively with all 11oxC19 steroids in Tanner stages 1 and 2 (r ≈ 0.7; P < 0.001) but negatively in Tanner stage 5 (r = -0.3 and P < 0.05 for 11ketoA4 and 11ketoT). In females, testosterone level correlated positively with all four 11oxC19 steroids across all Tanner stages (r ≈ 0.8; P < 0.0001).. 11oxC19 steroids and PregS might serve as clinically useful biomarkers of disease control and long-term complications in 21OHD.

Topics: 17-alpha-Hydroxypregnenolone; Adolescent; Adrenal Glands; Adrenal Hyperplasia, Congenital; Adrenal Rest Tumor; Adult; Age Determination by Skeleton; Aged; Androgens; Androstenedione; Androstenes; Child; Child, Preschool; Cortodoxone; Cross-Sectional Studies; Female; Hirsutism; Humans; Hydroxytestosterones; Male; Menstruation Disturbances; Middle Aged; Organ Size; Pregnenolone; Testicular Neoplasms; Testosterone; Young Adult

Androgen excess carries varied clinical manifestations in women. Although testosterone and dehydroepiandrostendionesulfate (DHEAS) determination is considered useful in diagnostic workup, there is no laboratory definition that sufficiently describes androgen excess.. We studied 464 hirsute women with a Ferriman and Gallwey score of at least 8 between 2000 and 2005. Our examination included clinical data, total testosterone (T), sex hormone-binding globulin (SHBG), the free androgen index (FAI), and DHEAS. Additionally, androstendione, 17alpha-hydroxyprogesterone (17OHP), dehydroepiandrostendione (DHEA), and 11-deoxycortisol were determined at baseline and 60min after corticotropin challenge (250microg synacthen).. Of 464 women, 77.6% fulfilled the clinical criteria for hyperandrogenemia. Of these 360 women, 78.1% had hyperandrogenic hirsutism. Of these 281 women, 43.4% showed increased stimulation of 17OHP to 250microg of synacthen. Another 37.4% showed adrenal steroid biosynthesis defects other than 21alpha-hydroxylase deficiency, such as defective 11beta-hydroxylation or 3beta-hydroxysteroid dehydrogenase malfunction. The diagnosis of polycystic ovary syndrome was applicable to 12.4%. In addition, our results show that 72% of 281 patients with secondary hirsutism had normal T concentrations, and 55% had a normal FAI. Only 5% of hirsute patients with a normal FAI had elevated DHEAS values. However, 40% showed elevated DHEA levels, while 26% of the women with normal FAI showed androstendione values over the maximal levels in the 79 controls.. Our data suggest that in addition to testosterone and FAI, androstendione and DHEA are significantly helpful parameters in diagnosing hyperandrogenemia in hirsute women. DHEAS was not found to be helpful.

Topics: 17-alpha-Hydroxyprogesterone; Adolescent; Adult; Aged; Androstenedione; Biomarkers; Cortodoxone; Dehydroepiandrosterone; Female; Follicle Stimulating Hormone; Hirsutism; Humans; Hyperandrogenism; Insulin-Like Growth Factor I; Luteinizing Hormone; Middle Aged; Polycystic Ovary Syndrome; Radioimmunoassay; Steroid 21-Hydroxylase

Late onset congenital adrenal hyperplasia (LO CAH) can be seen in association with polycystic ovary syndrome (PCOS) or idiopathic hirsutism (IH). The study aimed to find out the prevalence of LO CAH in Central Anatolia among hirsute women. Sixty-three patients with hirsutism were evaluated to determine the frequency of LO CAH by comparing them with their age and body mass index matched 28 healthy controls. Of those 63 hirsute women, 43 were diagnosed as PCOS, and 20 were diagnosed as IH. Following basal hormonal evaluation, all subjects underwent ACTH stimulation test and ACTH stimulated 17-hydroxyprogesterone (17-OH P), 11-desoxycortisol (11-DOC), cortisol (F), and dehydroepiandrosterone sulfate (DHEA-S) levels were determined in all subjects. ACTH stimulated 17-OH P, 11-DOC, and DHEA-S levels did not differ between groups. However, stimulated F levels were found to be higher in hirsute women (p<0.001). Six out of 63 (9.52%) patients with hirsutism met the criterion for 21 hydroxylase deficiency. We found no subject presumed to have 11-beta hydroxylase deficiency, but one subject in control group (3.57%) and two patients among PCOS subjects (4.65%) had exaggerated DHEA-S response which was suggestive of mild 3-beta hydroxysteroid dehydrogenase deficiency. In conclusion, the most frequent form of LO CAH seems to be due to 21 OH deficiency among women with PCOS and IH in Central Anatolia. Mild 3-beta HSD deficiency may also be an underlying cause for hirsutism and it may be seen without any clinical presentation. Adrenal hyperactivity is likely to be the main reason of hyperandrogenemia in women with hirsutism.

Topics: 17-alpha-Hydroxyprogesterone; Adrenal Hyperplasia, Congenital; Adrenocorticotropic Hormone; Age Distribution; Age of Onset; Body Mass Index; Case-Control Studies; Cortodoxone; Dehydroepiandrosterone Sulfate; Female; Hirsutism; Humans; Hydrocortisone; Polycystic Ovary Syndrome; Prevalence; Steroid 21-Hydroxylase; Turkey

To study three common polymorphisms in intron 3 of the calpain-10 gene (CAPN10) in hyperandrogenic patients.. Case-control study.. Academic hospital.. Ninety-seven hyperandrogenic patients and 37 healthy controls.. Basal and adrenocorticotropin-stimulated serum samples and genomic DNA samples were obtained during the follicular phase of the menstrual cycle.. Genotyping of the UCSNP43, UCSNP44, and UCSNP45 polymorphisms in CAPN10 and serum androgen levels.. Sixteen patients had idiopathic hirsutism, defined as normal serum androgen levels and regular menstrual cycles. Eighty-one hyperandrogenic patients (those presenting with hyperandrogenemic hirsutism or the polycystic ovary syndrome) were analyzed further. UCSNP45 alleles were distributed differently among the study groups. Heterozygosity for the uncommon C allele was increased in patients with idiopathic hirsutism (31.3%) and reduced in hyperandrogenic patients (7.4%) compared with controls (16.2%). The UCSNP44 and UCSNP43 alleles were in linkage disequilibrium, and were distributed equally among patients with idiopathic hirsutism, hyperandrogenism, and controls. However, the uncommon A allele at UCSNP43 was associated with higher hirsutism score (mean [+/- SD], 9.9 +/- 6.8, 12.7 +/- 7.7, and 14.6 +/- 8.2 in GG, GA, and AA participants, respectively). No other differences were observed in clinical and biochemical characteristics, including insulin sensitivity, by CAPN10 variant.. The C allele at the UCSNP45 locus in CAPN10 is associated with idiopathic hirsutism, and UCSNP43 influences the hirsutism score.

Topics: 17-alpha-Hydroxyprogesterone; Adrenocorticotropic Hormone; Adult; Calpain; Case-Control Studies; Cortodoxone; DNA; Female; Follicular Phase; Hirsutism; Humans; Hydrocortisone; Introns; Polymerase Chain Reaction; Polymorphism, Single Nucleotide; Sequence Analysis, DNA; Sex Hormone-Binding Globulin; Statistics, Nonparametric; Testosterone

To test the hypothesis that patients with nonclassic adrenal hyperplasia (NCAH) exhibit a generalized exaggeration in their response to ACTH stimulation that favors the normal production of F. Patients with 21-hydroxylase (21-OH)-deficient NCAH do not demonstrate cortisol (F) deficiency.. Prospective controlled study.. Tertiary university clinic.. Twenty-four untreated patients with NCAH diagnosed by a 17 alpha-hydroxyprogesterone (17-HP) level of >30.3 nmol/L (>10 ng/mL), and 37 age- and body mass-matched healthy eumenorrheic nonhirsute controls.. All study subjects underwent a 60 minute acute stimulation using 0.25 mg of ACTH-(1-24) i.v.. Basal and stimulated serum levels of pregnenolone (PREG), 17-hydroxypregnenolone (17-HPREG), dehydroepiandrosterone (DHA), progesterone (P4), 17-HP, androstenedione (A4), 11-deoxycortisol (S), and cortisol (F).. The median basal (i.e., Steroid(0)) or ACTH-stimulated (i. e., Steroid(60)) serum levels of PREG, 17-HPREG, DHA, P4, 17-HP, A4 and, most importantly, S were higher in NCAH patients than in controls. In contrast, the levels of F at either 0 minute or 60 minutes of stimulation were similar between NCAH and control women. The proportion of NCAH patients with stimulated steroids levels of >the 95th percentile of controls were as follows: 84.21% for PREG(60), 87.5% for 17-HPREG(60), 95.8% for DHA(60), 89.5% for P4(60), 100% for 17-HP(60), 91.7% for A4(60), 29.2% for S(60), and 4. 1% for F(60).. A generalized adrenocortical hyperresponsivity to ACTH stimulation seems to be present in patients with 21-OH-deficient NCAH, with an exaggerated production of S evident in approximately 30%. The excess production of S in these NCAH patients may, in part, account for their normal F production.

Topics: 17-alpha-Hydroxypregnenolone; Adrenal Cortex; Adrenal Hyperplasia, Congenital; Adrenocorticotropic Hormone; Adult; Androstenedione; Case-Control Studies; Cortodoxone; Dehydroepiandrosterone; Female; Hirsutism; Humans; Hydrocortisone; Pregnenolone; Progesterone; Prospective Studies; Steroid 21-Hydroxylase

To determine the frequency and the type of adrenal steroidogenic abnormalities in hirsute women.. ACTH test was performed during follicular phase in 127 hirsute and 40 normal (control) women. Before ACTH injection we measured in serum by RIA: 17-OH-pregnenolone (17-OH-P5), 17-OH-progesterone (17-OH-P4), androstenedione (AN), cortisol (CT), 11-deoxycortisol (DCT), dehydroepiandrosterone (DHEA) and its sulphate (DHEAS), total (TT) and free (FT) testosterone, oestradiol (E2), progesterone (PR), androstenediol glucuronide (AG), LH, FSH and prolactin. After 60 min of ACTH injection 17-OH-P5, 17-OH-P4, AN, DHEA, CT and DCT were measured. Net increment of stimulated steroids and the ratios 17-OH-P5/17-OH-P4, DHEA/AN, 17-OH-P4/CT, 17-OH-P5/CT and DCT/CT were calculated. Pelvic ultrasonographic exploration was done when irregular menses were reported.. Up to 31% of the patients presented enzymatic defects in adrenal steroidogenesis. Diagnostic criteria for enzyme defects were established. Late-onset 21-hydroxylase deficiency was diagnosed in 6 (4.5%) patients, HLA typing of these patients demonstrated that 4 out of 6 had B14-DR1. Sixteen women (12.6%) displayed a 17-OH-P4 response and the net increment 2 SD above the normal mean concentration, which are diagnostic criteria for late-onset 21-hydroxylase deficiency carriers. We diagnosed a 3 beta-hydroxysteroid dehydrogenase defect when 17-OH-P5 and DHEA responses, their net increment and the 17-OH-P5/17-OH-P4 and 17-OH-P5/CT ratios were 2 SD above the normal mean after ACTH: 14 women were diagnosed. 11 beta-hydroxylase deficiency diagnosis was made when DCT response, its net increment and the DCT/CT ratio after ACTH were 2 SD above the normal mean: 7 women were detected. Associated biosynthetic defects were described.. One third of our patients with hirsutism presented anomalous response to ACTH, consistent with enzymatic abnormalities in adrenal steroidogenesis.

Topics: 17-alpha-Hydroxypregnenolone; 17-alpha-Hydroxyprogesterone; Adolescent; Adrenal Cortex Hormones; Adrenal Hyperplasia, Congenital; Adrenocorticotropic Hormone; Adult; Anabolic Agents; Androstenediol; Androstenedione; Cortodoxone; Dehydroepiandrosterone; Dehydroepiandrosterone Sulfate; Estradiol; Female; Follicle Stimulating Hormone; Hirsutism; Humans; Hydrocortisone; Hydroxysteroid Dehydrogenases; Luteinizing Hormone; Menstrual Cycle; Middle Aged; Progesterone; Prolactin; Radioimmunoassay; Testosterone

To investigate the presence of a dysregulation in steroid biosynthesis in women from southern Italy.. Controlled clinical study.. Normal and hyperandrogenic women referred to the Endocrinology Unit of Federico II University Medical School of Naples.. One hundred fifty untreated young hyperandrogenic women and 50 normal age-matched women.. Morning (basal) blood samples obtained in the early follicular phase and after a long (360 minute) ACTH stimulation test.. The adrenal maximal response was calculated as stimulus under curve areas (AUCa), and all steroids were assayed using RIA methods.. A dysregulation of 21-hydroxylase was found in 22 patients (14.7%), with a prevalent increase of 17 alpha-hydroxyprogesterone AUC, whereas in 9 hirsute women (6%), there was a prevalent significant increase in 11-deoxycortisol AUC. In 5 women (3.3%), DHEA and DHEAS basal and AUCs plasma levels were increased, suggesting an impaired 3 beta-olo-dehydrogenase activity. The remaining 114 hyperandrogenic women (76%) compose the nonadrenal group, with a probable diagnosis of primitive functional ovarian hyperandrogenism.. Considering the high prevalence of hirsutism and oligomenorrhea in our female hyperandrogenic population, we suggest an adrenal hyperresponsiveness likely due to a dysregulation in enzymes related to androgen adrenal steroidogenesis.

Topics: 17-alpha-Hydroxyprogesterone; Adolescent; Adrenal Cortex Hormones; Adrenocorticotropic Hormone; Adult; Cortodoxone; Dehydroepiandrosterone; Dehydroepiandrosterone Sulfate; Desoxycorticosterone; Female; Hirsutism; Homeostasis; Humans; Hyperandrogenism; Italy; Polycystic Ovary Syndrome; Steroid 21-Hydroxylase

To study ovarian and adrenal steroid profiles of women with idiopathic hirsutism, we compared sex steroid and basal and corticotropin (ACTH)-stimulated adrenal steroid levels before and after ovarian suppression induced by a long-acting gonadotropin-releasing hormone agonist analog (GnRH-a) in 24 hirsute women without hyperandrogenemia. Twelve healthy women served as controls for basal and ACTH-stimulated adrenal steroid levels. Serum levels of testosterone (T), sex hormone-binding globulin (SHBG), estradiol (E2), basal and ACTH-stimulated 17-hydroxyprogesterone (17OHP), dehydroepiandrosterone (DHEA), DHEA sulfate (DHEAS), delta 4-androstenedione (delta 4-A), 11-deoxycortisol (S) and cortisol (F), and basal and luteinizing hormone-releasing hormone (LHRH)-stimulated gonadotropin levels were measured before and 21 days after 3.75 mg intramuscular triptorelin in hirsute women. Basal T levels and basal and ACTH-stimulated delta 4-A, DHEA, and DHEAS levels were not different in hirsute women with respect to controls. Basal and ACTH-stimulated 17OHP was elevated, and decreased to normal after ovarian suppression with triptorelin. Although basal and ACTH-stimulated delta 4-A levels were normal, the delta delta 4-A/delta F and delta delta 4-A/delta 17OHP ratios were elevated and remained elevated after ovarian suppression, suggesting enhanced adrenal delta 4-17,20-lyase activity. T, F, S, and DHEAS levels were not affected by ovarian suppression. Basal and ACTH-stimulated 17OHP and delta 4-A, and stimulated DHEA concentrations were reduced with ovarian suppression, but their net increment and ratio to the increase of F in response to ACTH remained unchanged, reflecting the ovarian contribution to the secretion of these steroids. We conclude that idiopathic hirsute women with normoandrogenemia show an increase in ovarian secretion of 17OHP and a minimally increased adrenal delta 4-17, 20-lyase activity, suggesting that mild forms of ovarian and adrenal functional hyperandrogenism may be present in these patients with otherwise unexplained hirsutism.

Topics: 17-alpha-Hydroxyprogesterone; Adrenocorticotropic Hormone; Adult; Androgens; Androstenedione; Case-Control Studies; Cortodoxone; Dehydroepiandrosterone; Dehydroepiandrosterone Sulfate; Estradiol; Female; Follicle Stimulating Hormone; Gonadal Steroid Hormones; Gonadotropins; Hirsutism; Humans; Hydrocortisone; Luteinizing Hormone; Luteolytic Agents; Ovary; Sex Hormone-Binding Globulin; Testosterone; Time Factors; Triptorelin Pamoate

21-hydroxylase (21-OH) deficiency accounts for the vast majority of nonclassic (NC) forms of congenital adrenal hyperplasia (CAH), and is associated with symptoms detectable either in childhood (precocious puberty) or sometimes only later in adulthood (hirsutism, acne, amenorrhea). While the severe forms of the disease responsible for salt wasting or simple virilization have been extensively studied, the NC 21-OH deficiency is less well characterized, especially in adults. We studied the 21-OH gene (CYP21) in a population of 69 unrelated hyperandrogenic subjects suspected to be homozygous or heterozygous for NC 21-OH deficiency, based on basal and adrenocorticotrophin (ACTH)-stimulated plasma 17-hydroxyprogesterone (17-OHP, 17-OHPSI) and 21-desoxycortisol (21-DOF, 21-DOFSI) levels. To identify all mutations involved, determination of the whole gene sequence, including exons, exon-intron junctions, and promoter region, was performed, followed by a study of large rearrangements and identification of compound heterozygotes. Alterations were identified in at least one allele of 55 hyperandrogenic subjects. Two NC alterations, Val282Leu and Pro454Ser, were detected in 68% and 7% of the affected alleles, respectively, whereas mutations involved in severe forms were identified in 21% of them. These results document the utility of a molecular diagnosis in hyperandrogenic women suspected of being either heterozygous or homozygous for NC 21-OH deficiency and clearly indicate the importance of genetic counseling in such a population.

Topics: 17-alpha-Hydroxyprogesterone; Adolescent; Adrenal Hyperplasia, Congenital; Adrenocorticotropic Hormone; Adult; Alleles; Base Sequence; Child; Cortodoxone; DNA Primers; Female; Genetic Counseling; Genetic Testing; Genotype; Heterozygote; Hirsutism; Homozygote; Humans; Hyperandrogenism; Middle Aged; Mutation; Phenotype; Polymerase Chain Reaction; Steroid 21-Hydroxylase

We describe a patient with signs and symptoms of virilization caused by 21-hydroxylase deficiency. The patient, a Hispanic woman, first sought medical attention at age 24, when she presented to a medical clinic with an uncomplicated urinary tract infection. At that time several signs of virilization were noted and she was referred to the endocrinology clinic. Evaluation revealed temporal balding, hyperpigmentation, acne, absent breast development, a muscular habitus, and clitoromegaly. Radiological studies revealed bilaterally enlarged adrenal glands and ovaries. Laboratory evaluation revealed markedly increased concentrations of 17-hydroxyprogesterone, androstenedione, and testosterone. The patient was diagnosed with congenital adrenal hyperplasia (CAH) and received hormone therapy. In her sister, encouraged to undergo testing for this autosomal recessive disorder, HLA testing demonstrated that certain haplotypes in this family were associated with CAH. The case highlights key steps in the laboratory diagnosis and genetics of CAH.

Topics: 17-alpha-Hydroxyprogesterone; Acne Vulgaris; Adrenal Hyperplasia, Congenital; Adult; Androstenedione; Clitoris; Cortodoxone; Dehydroepiandrosterone; Female; Gonadal Steroid Hormones; Hirsutism; Histocompatibility Testing; Humans; Hydroxyprogesterones; Hyperpigmentation; Testosterone; Urinary Tract Infections

The present study was designed to determine the prevalence of 11 beta-hydroxylase deficiency in adult women with hirsutism in a Turkish population.. One hundred and twenty-four consecutive unselected hirsute patients were studied. An ACTH stimulation test was performed in the midfollicular phase of the cycle on the patients and 20 age-matched controls by administration of a single bolus of 0.25 mg ACTH (1-24) at 0900 h.. Serum 11-deoxycortisol levels were measured before, 30 and 60 minutes after ACTH injection. Basal free testosterone (fT), SHBG, cortisol and androstenedione (A) were also measured. The diagnosis of 11 beta-hydroxylase deficiency has been presumed when the serum 11-deoxycortisol response to ACTH stimulation exceeded three times the 95th percentile of controls.. Basal hormone levels including fT and A were significantly higher in the hirsute women than in the healthy women. SHBG was significantly lower in the hirsute patients. Basal and ACTH stimulated 11-deoxycortisol levels were found to be significantly increased in the patients compared with the controls. Eight patients (6.5%) had an 11-deoxycortisol response higher than three times the upper normal limit.. Using stringent diagnostic criteria, we have found that 6.5% of the hirsute women in a Turkish population could be presumed to have 11 beta-hydroxylase deficiency.

Topics: Adolescent; Adrenal Hyperplasia, Congenital; Adult; Androstenedione; Cortodoxone; Cosyntropin; Female; Hirsutism; Humans; Prevalence; Testosterone; Turkey

We developed and validated a coordinated set of RIAs for the following eight steroids in single small aliquots (< or = 1 mL) of plasma: androstenedione, dehydroepiandrosterone, 11-deoxycortisol, 21-deoxycortisol (21-DF), 11 beta-hydroxyandrostenedione, 17 alpha-hydroxypregnenolone (17-Hpreg), 17 alpha-hydroxyprogesterone, and testosterone. Samples were extracted and then chromatographed on celite microcolumns. Radioiodinated tracers were used for two of the assays (17-Hpreg and 21-DF). Tritiated tracers and scintillation proximity assay counting were used to give separation-free procedures for the other six assays, which considerably improved their practicability and reproducibility. The basal and postadrenocorticotropic hormone plasma values for these steroids in normal women sampled in the follicular phase are presented. Finally, the measurement of the eight steroids as a diagnostic method is evaluated with reference to data from 203 patients with hirsutism and (or) acne.

Topics: 17-alpha-Hydroxypregnenolone; 17-alpha-Hydroxyprogesterone; Acne Vulgaris; Adolescent; Adult; Androstenedione; Cortodoxone; Dehydroepiandrosterone; Female; Follicular Phase; Hirsutism; Humans; Hydroxyprogesterones; Radioimmunoassay; Reference Values; Sensitivity and Specificity; Steroids; Testosterone

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

to determine the 11-deoxycortisol (S) response and incidence of 11 beta-hydroxylase deficiency in hyperandrogenism.. Hyperandrogenic women prospectively and consecutively underwent acute adrenal stimulation studies.. Tertiary institution.. Two hundred sixty women complaining of hirsutism and/or hyperandrogenic oligomenorrhea were studied, excluding five unrelated families (1.9% of total) suffering from 21-hydroxylase deficient late-onset adrenal hyperplasia. Forty-one healthy premenopausal eumenorrheic women served as controls.. Only two unrelated women (0.8%) had a poststimulation or net increment S level value greater than or equal to threefold the upper 95th percentile of controls and were presumed to suffer from 11 beta-hydroxylase deficient late-onset adrenal hyperplasia. One hundred nine (42%) of hyperandrogenic women had at least one S value above the 95th percentile of controls. These women also demonstrated higher basal (F0) and stimulated cortisol levels, but a similar increment compared with controls.. Patients with high S measures had higher testosterone, dehydroepiandrosterone sulfate, and androstenedione levels, but similar luteinizing hormone/follicle-stimulating hormone ratios, than hyperandrogenic cohorts with no abnormal S measures. Basal values of S (S0), F0, or S0/F0 were not useful to predict an abnormal S response to stimulation.. Although adrenocortical hyperactivity was present in 42% of our hyperandrogenic patients, only 0.8% were presumed to suffer from 11 beta-hydroxylase deficient late-onset adrenal hyperplasia. A systemic search for this deficiency in hyperandrogenism is probably unwarranted.

Topics: Adrenal Glands; Adrenal Hyperplasia, Congenital; Adult; Androgens; Cortodoxone; Female; Hirsutism; Hormones; Humans; Hyperplasia; Menstruation Disturbances; Predictive Value of Tests; Prospective Studies; Reference Values

Hirsutism in women is a clinical manifestation of excessive production of androgens. The source of the excess androgen may be either the ovaries or the adrenal glands, and distinguishing between these sources may be difficult.. To determine whether measurements of plasma dehydroepiandrosterone (DHEA) sulfate and ACTH stimulation tests, both widely used in the evaluation of hirsutism in women, provide useful information, we performed both tests in 22 normal women and 31 female patients with hirsutism. The hormones measured in plasma during the ACTH stimulation tests were progesterone, 17-hydroxypregnenolone, 17-hydroxyprogesterone, DHEA, androstenedione, 11-deoxycortisol, and cortisol.. The women with hirsutism were divided into four groups based on their individual responses to ACTH stimulation: patients with a possible 3 beta-hydroxy-delta 5-steroid dehydrogenase deficiency, those with a possible 21-hydroxylase deficiency, those with a possible 11 beta-hydroxylase deficiency, and those with no apparent defect in steroidogenesis. The results in 19 patients (61 percent) suggested subtle defects in adrenal steroidogenesis. There was no significant correlation between the basal plasma DHEA sulfate levels and the hormonal response to ACTH, nor were the basal levels of hormones predictive of the levels after ACTH stimulation. Eleven patients had significantly elevated basal levels of plasma DHEA sulfate; only 5 of these 11 had responses to ACTH suggestive of compromised steroidogenesis. Thirteen patients who had responses suggestive of defective steroidogenesis had DHEA sulfate levels within the normal range.. A substantial proportion of women with hirsutism have mild defects in adrenal steroidogenesis, revealed by an ACTH stimulation test, that are indicative of late-onset (nonclassic) congenital adrenal hyperplasia. Measurements of basal steroid levels are not helpful in differentiating among the causes of increased androgen production in such patients and may be misleading.

Topics: 17-alpha-Hydroxypregnenolone; 17-alpha-Hydroxyprogesterone; Adolescent; Adrenal Hyperplasia, Congenital; Adrenocorticotropic Hormone; Adult; Androstenedione; Cortodoxone; Dehydroepiandrosterone; Dehydroepiandrosterone Sulfate; Diagnosis, Differential; Female; Hirsutism; Humans; Hydrocortisone; Hydroxyprogesterones; Progesterone

The present study was undertaken to characterize further the adrenal abnormalities in the polycystic ovary syndrome (PCOS) and idiopathic hirsutism (IH). We have previously reported the close association of elevated estrone levels with amenorrhea in hyperandrogenemic patients. In addition we have suggested that high estrone levels in PCOS occur as a consequence of the provision of excess substrate, androstenedione, for conversion to estrone. In the present study plasma estrone levels rose following endogenous adrenal stimulation induced using metyrapone; the highest plasma estrone levels achieved were seen in patients with PCOS and occurred later than peak androstenedione levels. These findings are consistent with the hypothesis that elevated estrone levels occurring in PCOS may arise as a consequence of increased adrenal androgen secretion. In addition, we have examined ACTH and other pro-opiomelanocortin (POMC) fragments in an attempt to identify a factor responsible for the excessive adrenal androgen secretion occurring in hirsute patients. Plasma levels of ACTH, and of immunoreactive beta-endorphin and h-lipotropin were not elevated when androgen levels were raised prior to therapy, although these POMC fragments, and also the 16K fragment, rose in response to metyrapone treatment as did androgen levels. Following treatment with dexamethasone there was more profound suppression of the 16K, beta-endorphin and h-lipotropin responses to metyrapone stimulation, than of the ACTH response, as indicated by decreased POMC-fragment/ACTH ratios; this parallels the dissociation of cortisol from androgens in hirsute patients under similar conditions. However, we have not identified a POMC fragment which consistently parallels changes in androgen levels in patients with idiopathic hirsutism or PCOS.

Topics: Administration, Oral; Adolescent; Adrenal Glands; Adrenocorticotropic Hormone; Adult; Androstenedione; beta-Endorphin; beta-Lipotropin; Cortodoxone; Dexamethasone; Estradiol; Estrone; Female; Hirsutism; Humans; Metyrapone; Peptide Fragments; Pro-Opiomelanocortin; Testosterone

The effect of spironolactone on adrenal androgen and cortisol production was studied in six hirsute women. Hirsute women were evaluated before and 1 month after receiving 200 mg of spironolactone daily. Basal levels of serum androgens, 17-hydroxyprogesterone (17-OHP), cortisol (F), corticosteroid-binding globulin, and plasma adrenocorticotropic hormone (ACTH) were normal and did not change with therapy. The delta maximum (delta max) responses after dexamethasone suppression and ACTH administration of dehydroepiandrosterone (DHEA), androstenedione (delta 4A), 17-hydroxypregnenolone, and 17-OHP were similar in hirsute women and ovulatory control subjects. After spironolactone administration, the delta max DHEA response was unchanged, whereas the delta max delta 4A response was decreased (P less than 0.05). The delta max ratios of DHEA/delta 4A and 17-OHP/delta 4A were significantly increased after spironolactone in hirsute women, which suggested inhibitions of 3 beta-ol-dehydrogenase-isomerase and delta 4 17,20 desmolase activities. A significant reduction in delta max F occurred after spironolactone administration (P less than 0.05). Although baseline 11-desoxycortisol (S) and the plasma S/ACTH ratio were unaltered, the delta max S/F ratio increased after treatment (P less than 0.01), suggesting an inhibition of 11 beta-hydroxylase activity. Inhibition of adrenal androgen production occurs with spironolactone, but only serum levels of delta 4A are decreased, whereas DHEA and its sulfate (DHEA-S) levels remain unchanged.

Topics: 17-alpha-Hydroxyprogesterone; Adrenal Glands; Adrenocorticotropic Hormone; Adult; Androgens; Androstenedione; Cortodoxone; Dehydroepiandrosterone; Dehydroepiandrosterone Sulfate; Female; Hirsutism; Humans; Hydrocortisone; Hydroxyprogesterones; Spironolactone; Steroids; Time Factors

Specific 21-deoxycortisol (21-DF) antiserum was raised in New Zealand white rabbits using a 21-DF-3,20-oxime-bovine serum albumin complex. Plasma radioimmunoassay of 21-DF was developed and used together with a radioimmunoassay of 17-hydroxyprogesterone (17-OH-P) for diagnosis of patients with 21-hydroxylase deficiency of congenital and postpubertal forms. The assays were performed in plasma extracts after isolation by paper chromatography. The response of plasma 21-DF and 17-OH-P to i.v. ACTH (25 IU) was studied in 15 adult controls and compared to 8 women with the late onset form of 21-hydroxylase deficiency and 23 women with idiopathic hirsutism. Normal 21-DF values for women were 6.9 +/- 3.6 ng/dl and for men 9.71 +/- 2.73 ng/dl. Newborn children (age: 3-10 days) had a value of 8.3 +/- 4.8 ng/dl. These values are definitely lower than the lowest value ever published. This is possibly due to the specificity of the antibody. During the menstrual cycle the 21-DF values did not change. The baseline and post-stimulated concentrations of hormone were similar in controls and women with hirsutism but were significantly higher in women with the late onset form of 21-hydroxylase deficiency. In the congenital form of 21-hydroxylase deficiency the 21-DF values (baseline) were high. In general, the 21-DF and 17-OH-P values have shown parallel changes. However, one case of 21-hydroxylase deficiency with elevated 21-DF but normal 17-OH-P was observed. The use of 21-DF for the diagnosis of 21-hydroxylase deficiency is suggested.

Topics: 17-alpha-Hydroxyprogesterone; 17-Hydroxycorticosteroids; Adolescent; Adrenocorticotropic Hormone; Adult; Child; Child, Preschool; Clinical Laboratory Techniques; Cortodoxone; Female; Hirsutism; Humans; Hydroxyprogesterones; Infant; Infant, Newborn; Lipid Metabolism, Inborn Errors; Male; Radioimmunoassay; Reference Values; Steroid Hydroxylases

The effect of cyproterone acetate (CA) on adrenal glucocorticoid secretion was studied in 35 women with hirsutism. Patients were treated for 9 months with 100 mg CA orally 10 days each month, administered in reverse sequence with 21 days of a combination oral contraceptive containing 50 micrograms ethinyloestradiol and 2 mg CA. During treatment one patient had a mildly impaired plasma cortisol response to insulin-induced hypoglycaemia and 2 patients showed slight reduction of the plasma cortisol response to ACTH. Responses to metyrapone were normal in all patients tested. Overall, the mean response to these tests was significantly greater during CA treatment compared with pre-treatment measurements, probably due to effects of oestrogen on cortisol-binding globulin. In all patients urinary cortisol excretion remained normal and no patient demonstrated any features of steroid insufficiency. Thus it appears that CA has no untoward effect upon glucocorticoid secretion when given in high dosage for prolonged periods to hirsute women.

Topics: 17-Hydroxycorticosteroids; Contraceptives, Oral, Combined; Cortodoxone; Cosyntropin; Cyproterone; Cyproterone Acetate; Ethinyl Estradiol; Female; Hirsutism; Humans; Hydrocortisone

Thirty-one women with idiopathic hirsutism were evaluated for partial 11- and 21-hydroxylase adrenocortical enzyme deficencies. Twenty-four hour urine collections for 17-ketosteroids, 17-hydroxycorticoids, tetrahydro compound S (THS), and -pregnanetriol were obtained basally and following a continuous 24 hours infusion of alpha 1-24 ACTH (cosyntropin). The results were compared to those in eight normal, nonhirsute women studied under identical conditions. Normal control subjects and 18 of 31 hirsute female patients (Group I) showed similar small increments in the excretion of THS and pregnanetriol following the infusion of cosyntropin. Thirteen hirsute women (Group II) showed cosyntropin-stimulated increments in either THS and/or pregnanetriol that were significantly greater than the mean response of the control group. The cosyntropin-stimulated increments in 17-ketosteroid excertion and basal sebum production rates were also significantly greater in Group II. The results are consistent with partial II - and/or 21-adrenocortical hydroxylase deficiencies in some hirsute women whose condition would have previously been designated as "idiopathic." Thus, prolonged ACTH stimulation testing may identify patients who might benefit from glucocorticoid suppression therapy.

Topics: 17-Hydroxycorticosteroids; 17-Ketosteroids; Adolescent; Adult; Cortodoxone; Cosyntropin; Female; Hirsutism; Humans; Middle Aged; Mixed Function Oxygenases; Pregnanetriol; Sebum

It has been postulated that hirsute patients may have a relative deficiency in 11beta-hydroxylase activity of the adrenal cortex. In order to test this postulate, we have measured the serum levels of cortisol (Cp F) and 11-desoxycortisol (Cp S) and estimated the Cp S/Cp F ratio in 9 nonhirsute and 34 hirsute premenopausal women. As a group, the hirsute patients had significantly elevated (P less than 0.05) mean Cp F and Cp S levels but the mean Cp S/Cp F ratio was not significantly different from normal. Considered individually, only 3 hirsute patients had a Cp S/Cp F ratio greater than 2 SD above the mean normal levels. These ratios were 0.0218, 0.0139, and 0.023. If there is indeed an 11beta-hydroxylase deficiency in these 3 patients, it must be relatively minor, since a patient with documented 11beta-hydroxylase deficiency had Cp S levels of 218 ng/ml and a Cp S/Cp F ratio of 0.7. Our data suggest that 11beta-hydroxylase deficiency is not a common cause of hirsutism.

Topics: 17-Hydroxycorticosteroids; Adult; Chromatography; Cortodoxone; Female; Hirsutism; Humans; Hydrocortisone; Male; Metyrapone; Mixed Function Oxygenases; Radioimmunoassay

Topics: 17-Hydroxycorticosteroids; Adrenocorticotropic Hormone; Cortodoxone; Female; Hirsutism; Humans; Hydrocortisone; Hydroxylation; Hydroxyprogesterones; Polycystic Ovary Syndrome