cosyntropin and Hirsutism

Moderate forms of 21-hydroxylase deficiency (D21OH-NC), the so-called non-classical or late-onset forms are a frequently reported cause of hyperandrogenism in women [1-5]. The purpose of this collective and synthetic work was to provide the endocrinologist, gynecologist and dermatologist with consensual information so as to detect the maximum cases with acceptable cost-benefit ratio and to define the main lines of optimal patient management, given the data currently available in medical literature.

Topics: Adrenal Hyperplasia, Congenital; Adrenal Insufficiency; Cosyntropin; Female; Genetic Counseling; Glucocorticoids; Hirsutism; Hormone Replacement Therapy; Humans; Hyperandrogenism; Infertility, Female; Steroid 21-Hydroxylase

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

Virilising ovarian tumours are a rare cause of hyperandrogenism in women, accounting for less than 5% of all ovarian neoplasms. It occurs most often in - and postmenopausal women. We report a case of a 64 year-old woman with signs of virilisation that had started 3 years before. Blood hormone analysis revealed increased levels of testosterone, and 17-hydroxyprogesterone. The tetracosactin test revealed 21-hydroxylase deficiency. Radiological imaging demonstrated a nodule in her left ovary. The patient was submitted to bilateral laparoscopic oophorectomy, and histopathological examination revealed a luteoma of the left ovary. Postoperative serum testosterone level and 17-hydroxyprogesterone returned to normal levels in one month. Virilism regressed within six months. Our patient also showed an elevation in 17-OHP serum levels. Normalization of 17-OHP after oophorectomy suggests a case of intratumoral 21-hydroxylase deficiency. To our knowledge, this is the first description of ovarian intratumoral 21-hydroxylase deficiency in a postmenopausal woman.

Topics: Adrenal Hyperplasia, Congenital; Cosyntropin; Female; Hirsutism; Humans; Luteoma; Middle Aged; Ovarian Neoplasms; Postmenopause; Testosterone

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

Our purpose was to establish the incidence of point mutations of the 21-hydroxylase gene (CYP21) in hyperandrogenic women with and without a 17-hydroxyprogesterone response to corticotropin stimulation above normal but below those levels associated with nonclassic adrenal hyperplasia.. We studied 22 patients with hirsutism or hyperandrogenic oligoovulation: eight with an exaggerated net increase in 17-hydroxyprogesterone (i.e., change in 17-hydroxyprogesterone between 8.8 and 36 nmol/L) and 14 with a normal change in 17-hydroxyprogesterone. Large deletions of the 21-hydroxylase gene were evaluated by laser densitometry. Point mutations were detected with the polymerase chain reaction and dot blot hybridization analysis and included 30 Leu, intron-2 (G), 8 bp deletion exon-3, 172 Asn, 236-237-239 exon-6, 281 Leu, 318 stop, 339 His, 341 Trp, 356 Trp, and 453 Ser.. Four patients with an increase in 17-hydroxyprogesterone carried a 281 Leu mutation, one patient had an intron-2 (G) mutation, and one had a complete deletion of CYP21. Only two of these patients demonstrated no obvious abnormality of CYP21. In contrast, only one of the control patients demonstrated a CYP21 abnormality, a significant difference (p < 0.001).. These findings suggest that the majority of hyperandrogenic women with an exaggerated 17-hydroxyprogesterone response to corticotropin stimulation are heterozygotes (carriers) for inherited defects of CYP21. Whether these mutations are incidental to the androgen excess or predispose to the development of this disorder remains to be determined.

Topics: 17-alpha-Hydroxyprogesterone; Adrenal Glands; Adult; Case-Control Studies; Cosyntropin; Female; Heterozygote; Hirsutism; Humans; Hydroxyprogesterones; Hyperandrogenism; Mutation; Oligomenorrhea; Peptide Fragments; Point Mutation; Steroid 21-Hydroxylase

An oral 5-mg dose of finasteride, a 5 alpha-reductase inhibitor, was administered for 3 months to 10 hirsute women to determine the effect on gonadotropin secretion, on basal and stimulated androgen secretion, and on hair growth. Hair growth was assessed by the Ferriman-Gallwey score. All of the above determinations were evaluated before and after 1 and/or 3 months of finasteride treatment. Basal and GnRH-stimulated gonadotropin secretions were not affected. Indeed, finasteride did not modify the pulsatility of LH secretion. No change was seen in estradiol, PRL, free testosterone, androstenedione, dehydroepiandrosterone sulfate, and sex hormone-binding globulin concentrations. Serum concentrations of cortisol (F) were significantly reduced after 1 month of finasteride treatment. The F levels returned to pretreatment levels after 3 months. Plasma levels of dihydrotestosterone and 3 alpha-androstanediol glucuronide significantly decreased during finasteride treatment. A significant increase in testosterone concentrations was observed after 3 months. Finasteride did not modify the responses of testosterone, androstenedione, and dehydroepiandrosterone sulfate to ACTH-(1-24) injection. Conversely, finasteride blunted the F response to corticotropin stimulation. Three months of finasteride treatment significantly decreased the Ferriman-Gallwey score. In conclusion, finasteride significantly decreased dihydrotestosterone and hair growth in hirsute women without negatively affecting gonadotropin secretion.

Topics: 5-alpha Reductase Inhibitors; Adolescent; Adult; Androgens; Androstane-3,17-diol; Cosyntropin; Dihydrotestosterone; Female; Finasteride; Follicle Stimulating Hormone; Hair; Hirsutism; Humans; Hydrocortisone; Luteinizing Hormone; Periodicity; Testosterone

Nonclassical congenital adrenal hyperplasia (NCCAH) is well recognized among women who seek medical attention for hirsutism. However, the prevalence of this disorder among women self-referred for electrolytic treatment of hirsutism is unknown. We hypothesized that the prevalence of NCCAH among women attending an electrolysis clinic might be high. By measuring the morning salivary 17-hydroxyprogesterone (17-OHP) as a screening test for NCCAH in 46 women in the follicular phase of their menstrual cycle, we identified 12 subjects with a high basal salivary 17-OHP. Eleven agreed to have a 60-minute Cosyntropin-stimulation test, as did an additional 6 of 9 women with normal basal salivary 17-OHP, but with a particularly high hirsutism score. One of the women with high basal salivary 17-OHP had a 60-minute Cosyntropin response, which was diagnostic of NCCAH. She was of the Ashkenazi Jewish decent, a group previously reported to have a high prevalence of NCCAH. A second woman with high salivary 17-OPH had a Cosyntropin-stimulation response consistent with heterozygosity for 21-hydroxylase deficiency. None of the Cosyntropin-stimulation responses in those chosen for a high hirsutism score were diagnostic. Thus, 1 of 46 (2.2%) of the women who entered our study had unrecognized NCCAH, a prevalence only about 2-fold greater than that reported in the general population. Therefore, we recommend that electrolysis clinics advise clients from ethnic groups known to have a high frequency of NCCAH of the advisability of having a formal medical evaluation for NCCAH.

Topics: 17-alpha-Hydroxyprogesterone; Adrenal Hyperplasia, Congenital; Adult; Cosyntropin; Electrolysis; Female; Hirsutism; Humans; Hydroxyprogesterones; Middle Aged; Prevalence; Saliva

One to 2% of hyperandrogenic women demonstrate a 17-hydroxyprogesterone (17-HP) level greater than 36.3 nmol/L (1200 ng/dL) after acute ACTH-(1-24) adrenal stimulation, consistent with 21-hydroxylase (21-OH) deficient late-onset adrenal hyperplasia (LOAH). The following study was undertaken to endocrinologically and genetically define hyperandrogenic patients with an exaggerated 17-HP response to ACTH stimulation, and which do not represent LOAH. Of 265 consecutive patients suffering from hirsutism and/or hyperandrogenic oligomenorrhea, 23 (8.7%) demonstrated a 17-HP level 30 min post stimulation greater than 9.6 nmol/L or 316 ng/dL (the upper 95th percentile in 41 eumenorrheic nonhirsute healthy control women). Seven patients or five separate families (1.8% of total) demonstrated poststimulation 17-HP levels consistent with LOAH. Of the remaining 16 patients, the net increment in 17-HP (delta 17-HP0-30) was within normal limits in seven (2.6%) and these women were assumed to have a normal 17-HP adrenocortical response superimposed on an elevated basal level of nonadrenal (e.g. ovarian) origin. In the remaining nine hyperandrogenic patients (3.4%) various abnormalities of adrenal response were noted in all but one patient, consistent with adrenal hyper-responsiveness. One patient demonstrated an 11-deoxycortisol poststimulation level greater than 3-fold the upper 95th percentile of normal, consistent with 11-hydroxylase LOAH and was excluded from further study. Six of these women were available for further genetic characterization, all Caucasian and unrelated. Three were heterozygotes for HLA-B14, three for B40, and one for B35 antigen, HLA-types associated with the inheritance of 21-OH deficiencies. Although, normally there are two 21-OH genes (a pseudogene and a functional gene) present in a 1:1 ratio, we have previously reported a high frequency of 21-OH gene ratio abnormalities in LOAH. All but one of our patients demonstrated an abnormal 21-OH gene ratio. In conclusion, 3.4% of our hyperandrogenic population demonstrated an exaggerated 17-HP increment after ACTH stimulation, not consistent with LOAH or increased extraadrenal 17-HP production. The increased prevalence of HLA alleles known to be linked to inherited defects of 21-OH function and the increased frequency in 21-OH gene ratio abnormalities suggest that a majority of these individuals may be carriers for these genetic disorders. However, the adrenocortical abnormalities noted were more consi

Topics: 17-alpha-Hydroxyprogesterone; Adrenal Cortex Hormones; Adrenal Glands; Adult; Androgens; Cosyntropin; Female; Genes; Hirsutism; Humans; Hydroxyprogesterones; Hyperplasia; Oligomenorrhea; Steroid 21-Hydroxylase

The aims of this study were to determine the frequency of late-onset adrenal hyperplasia due specifically to 21-hydroxylase deficiency in a group of Irish women who presented at a Dublin Clinic with symptoms of hyperandrogenism, including hirsutism, menstrual irregularities and/or cystic acne, and to determine if those with 21-hydroxylase deficiency showed particular HLA associations. 119 women had blood samples taken basally and 1 h after an injection of 0.25 mg synacthen with the following hormones profiled: 17-hydroxyprogesterone, 11-deoxycortisol, androstenedione, testosterone, DHEAS and cortisol. Blood sampling was carried out between 0900 and 1000 h during the early follicular phase of the menstrual cycle (when applicable). Ninety-six subjects were new referrals to the Clinic for investigation of hyperandrogenism and 23 were acting as controls. In this study, 6% of patients showed evidence of partial 21-hydroxylase deficiency. In addition, 3 of the 6 with partial 21-hydroxylase deficiency had normal baseline levels of 17-hydroxyprogesterone, with the biochemical abnormality becoming manifest only on synacthen stimulation. Late-onset adrenal hyperplasia due to partial deficiency of this enzyme should always be considered as a possible diagnosis in women who present with symptoms of hyperandrogenism. Synacthen stimulation is an important diagnostic tool in elucidating partial enzyme deficiency as baseline 17-hydroxyprogesterone may be normal in such patients.

Topics: Acne Vulgaris; Adolescent; Adrenal Hyperplasia, Congenital; Adult; Cosyntropin; Female; Haplotypes; Hirsutism; Humans; Hydroxyprogesterones; Menstruation Disturbances; Steroid Hydroxylases

Late-onset congenital adrenal hyperplasia is a mild genetic defect in steroidogenesis that presents with hirsutism and menstrual irregularities and responds to specific treatment with dexamethasone sodium phosphate. Its incidence as a significant cause of hirsutism or amenorrhea is controversial because it cannot be distinguished clinically from other causes. However, it is readily diagnosed by a marked increase in 17 alpha-hydroxyprogesterone levels after adrenocorticotropic hormone stimulation. Seventy-seven randomly selected women with hirsutism or amenorrhea were tested, and eight women (10.4%) were found to have late-onset congenital adrenal hyperplasia. Plasma levels of other hormones were similar in patients with and without late-onset congenital adrenal hyperplasia and were of no benefit in making the diagnosis. It is concluded that the adrenocorticotropic hormone stimulation test should be more widely utilized in patients presenting with hirsutism or menstrual dysfunction.

Topics: 17-alpha-Hydroxyprogesterone; Adolescent; Adrenal Hyperplasia, Congenital; Adult; Amenorrhea; Cosyntropin; Female; Hirsutism; Humans; Hydroxyprogesterones; Mass Screening

ACTH tests were performed with and without dexamethasone (dex) pretreatment to clarify the nature of the relationship between the absolute and incremental response (delta) to ACTH in normal men and women, hirsute women, adrenarchal children, and women heterozygous for congenital adrenal hyperplasia (CAH). The purposes were to test the effect of dex preparation on adrenal responsiveness to ACTH and the efficacy of the dex-pretreated ACTH test in detecting heterozygosity for CAH. Cosyntropin was given as a 10 micrograms/m2 iv bolus dose at 0800-1000 h; dex (1 mg/m2) was given at 2200-2400 h the night before. Dex did not alter the absolute plasma steroid levels achieved in response to ACTH. However, since post-dex baseline concentrations of adrenal steroids were lower, the delta to ACTH was significantly greater for the major adrenal secretory products, 17 alpha-hydroxypregnenolone (3 beta, 17 alpha-dihydroxypregn-5-ene-20-one), dehydroepiandrosterone, and cortisol (F). For example, for all paired tests, the mean plasma F values achieved 30 min post-ACTH were 26.0 +/- 4.4 (+/- SD) micrograms/dl without dex and 23.8 +/- 5.5 micrograms/dl after dex. In contrast, the mean delta of plasma F 30 min post-ACTH was less without (13.3 +/- 4.8 micrograms/dl) than after (19.4 +/- 3.3 micrograms/dl) dex (P less than 0.001). Apparent 21-hydroxylase efficiency, computed from dex-prepared tests, was found in follicular phase women to have a markedly skewed distribution without clear demarcation between 15% of the population and CAH heterozygotes. Luteal phase responses differed from follicular phase responses in dex-pretreated women in the magnitude of the 17-hydroxyprogesterone response. In the luteal phase, although the plasma 17-hydroxyprogesterone level at 30 min was higher, a response to ACTH was not consistently found, averaging only 22 +/- 26 ng/dl, in contrast to the consistent 52 +/- 15 ng/dl response in the follicular phase. These findings have practical implications for interpreting rapid ACTH test results. The absolute plasma F level achieved post-ACTH is more important as an index of adrenocortical reserve than the increment. Dex pretreatment appears to offer no practical advantage in ACTH testing for mild defects in 21-hydroxylation; we postulate that this is because of considerable normal variability in the efficiency of 21-hydroxylation.

Topics: Adolescent; Adrenal Cortex Hormones; Adrenal Hyperplasia, Congenital; Adrenocorticotropic Hormone; Adult; Androgens; Child; Cosyntropin; Dexamethasone; Drug Administration Schedule; Female; Genetic Carrier Screening; Hirsutism; Humans; Male; Menstrual Cycle; Progesterone; Steroid Hydroxylases

The plasma 17 alpha-hydroxyprogesterone (17-OHP) concentration was determined in the basal state and 60 minutes after cosyntropin, 0.25 mg, in 139 patients with idiopathic hirsutism (IH) and polycystic ovarian disease (PCOD). Although there was an increased response of 17-OHP in subjects with PCOD when compared with IH subjects, in no instance was stimulated 17-OHP abnormal in the presence of normal basal 17-OHP. Two subjects with 21-hydroxylase (21-OH) deficiency were discovered; both demonstrated elevated basal levels of 17-OHP. We therefore conclude that routine adrenocorticotropic hormone testing is not a useful tool in detecting 21-OH deficiency in hyperandrogenic women.

Topics: 17-alpha-Hydroxyprogesterone; Adolescent; Adrenal Hyperplasia, Congenital; Adrenocorticotropic Hormone; Adult; Cosyntropin; Female; Hirsutism; Humans; Hydroxyprogesterones; Middle Aged; Polycystic Ovary Syndrome; Stimulation, Chemical

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

Because severe hirsutism is difficult to reverse, the evaluation of the adolescent girl with progressive hirsutism should aim at the pathophysiology of androgen excess in order to select appropriate therapies. A prospective study was undertaken to determine the occurrence of late-onset 21-hydroxylase deficiency among adolescents with androgen excess. Twenty-two young women (mean age 17.3 +/- 2.6 years) with androgen excess had serum 17-hydroxyprogesterone measured before and after bolus intravenous infusion of synthetic ACTH (Cortrosyn), 0.25 mg. Two patients, aged 13 and 19 years old, had elevated base line 17-hydroxyprogesterone and 30- and 60-minute responses to Cortrosyn consistent with 21-hydroxylase deficiency. Chromosome 6p haplotypes provided supportive evidence of 21-hydroxylase deficiency. The base line androgen levels, clinical presentation, and a four-day dexamethasone test did not distinguish patients with 21-hydroxylase deficiency from other hirsute adolescents. The Cortrosyn test identifies a population of adolescents who need long-term corticosteroid therapy. The use of major histocompatibility complex haplotypes could be of help in identifying affected siblings prior to the development of significant hirsutism.

Topics: Adolescent; Adrenal Hyperplasia, Congenital; Adrenocorticotropic Hormone; Adult; Androgens; Child; Chromosomes, Human, 6-12 and X; Cosyntropin; Dexamethasone; Female; Follicular Phase; Hirsutism; HLA Antigens; Humans; Hydroxyprogesterones; Prospective Studies; Steroid Hydroxylases; Time Factors

It seemed to us worth while when taking plasma samples to prove the presence or absence of ovulation and the presence or absence of a 21-hydroxylase block by estimating the levels of 17-hydroxyprogesterone under stimulation with tetracosactide. The results are as delta hydroxyprogesterone (ng/dl/mn). Eighteen women were studied in this way in the follicular phase (delta OHP: 1.21 +/- 0.71 ng/dl/mn) and 9 women in the luteal phase (delta OHP: 0.76 +/- 0.55 ng/dl/mn). This, while reliable, was not significant statistically. The explanation seems to be linked to anovulation. In the five cases with anovulation delta OHP was 0.233 ng/dl/mn, while in other cases where ovulation was proved to exist it was 1 ng/dl/mn. It seems to us that the so-called "luteal phase" should not have been retained when we wanted to test for a hormonal block, except where ovulation has been proved previously to be present, because of the possibility of anovulation. The interrelationships between the polycystic ovary syndrome and the therapeutic implications are discussed.

Topics: 17-alpha-Hydroxyprogesterone; Androstenedione; Cosyntropin; Desoxycorticosterone; Enzyme Repression; Female; Follicular Phase; Hirsutism; Humans; Hydroxyprogesterones; Luteal Phase; Menstruation; Testosterone

Detection of heterozygote carriers for congenital adrenal hyperplasia by use of a modified tetracosactide (a synthetic corticotropin) stimulation test with prior overnight dexamethasone suppression proved to have a diagnostic accuracy of 95%. Discrimination of heterozygotes from normals was best when we used a criterion based on the ratios of 17 alpha-hydroxyprogesterone to cortisol at baseline and at 30 min after intravenous administration of 250 micrograms of tetracosactide.

Topics: 17-alpha-Hydroxyprogesterone; Adrenal Hyperplasia, Congenital; Cosyntropin; Dexamethasone; Female; Genetic Carrier Screening; Hirsutism; Humans; Hydrocortisone; Hydroxyprogesterones; Male; Polycystic Ovary Syndrome; Radioimmunoassay; Time Factors

We studied the simultaneous responses of four serum androgens (testosterone, androstenedione, dehydroepiandrosterone, and dehydroepiandrosterone sulfate) and five other steroids (deoxycorticosterone, corticosterone, 11-deoxycortisol, cortisol, and 17 alpha-hydroxyprogesterone) to the infusion of small amounts of cosyntropin in eight patients with idiopathic hirsutism and in six normal women. Serum testosterone and androstenedione concentrations were significantly higher in hirsute women after graded cosyntropin infusions than in controls, as were concentrations of plasma deoxycorticosterone and 11-deoxycortisol. Analysis of the substrate/product ratios 11-deoxycortisol/cortisol and deoxycorticosterone/corticosterone revealed defective 11 beta-hydroxylation in women with hirsutism. The presence of increased circulating androgen levels in response to physiologic amounts of adrenocorticotropic hormone thus appears to be a common response in women with idiopathic hirsutism, and, together with impaired adrenal 11 beta-hydroxylation, points to an adrenal defect as important components of this disorder.

Topics: Adolescent; Adrenal Cortex; Adrenal Cortex Hormones; Adult; Androgens; Cosyntropin; Dexamethasone; Female; Hirsutism; Humans; Steroid 11-beta-Hydroxylase; Steroid Hydroxylases

Topics: Adolescent; Adrenalectomy; Adult; Aged; Aging; Androgens; Androstane-3,17-diol; Androstanols; Cosyntropin; Cushing Syndrome; Female; Glucuronates; Hirsutism; Humans; Male; Menopause; Middle Aged

The variations in plasma cortisol, testosterone and 17-hydroxyprogesterone (17-OHP) induced by an im injection of 0.25 mg cosyntrophin were studied in three groups of subjects: 16 healthy women, 16 hirsute women (HW) and 10 mild cases of congenital adrenal hyperplasia (CAH). The basal values of cortisol and testosterone were comparable between the three groups. In the patients with mild CAH, the mean 17-OHP concentration was increased: 483.9 ng/100 ml (113-1200 ng), but it should be noted that the individual values could overlap with the normal concentrations found in the controls and the HW during the luteal phase of the cycle. One hour after the injection of cosyntropin, a massive response of 17-OHP was observed in the mild cases of CAH, the mean basal concentration was multiplied by ten: 4843 ng/100 ml. The minimum concentration reached was 1740 ng/100 ml which is still 3-fold the highest level seen either in normal women (400 ng/ml) or in hirsute women (550 ng/100 ml). Determination of 17-OHP following a short-term ACTH stimulation, therefore provides evidence of partial 21-hydroxylase deficiency.

Topics: Adrenal Hyperplasia, Congenital; Adrenocortical Hyperfunction; Adrenocorticotropic Hormone; Adult; Cosyntropin; Female; Hirsutism; Humans; Hydrocortisone; Hydroxyprogesterones; Testosterone

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

Adrenal effluent concentrations of aldosterone were measured along with testosterone, androstenedione, and cortisol in 17 women with idiopathic hirsutism. In the basal state, aldosterone secretion (higher concentrations vs peripheral blood) was demonstrated in 14 out of 16 of the women, in contrast to 8 out of 16 who demonstrated cortisol gradients. Nine women received 0.25 mgm beta 1-24 ACTH im and serial adrenal venous blood samples were obtained over the next 30 minutes. Parallel 30-40-fold increments were noted in aldosterone, androstenedione, and cortisol; testosterone increased only 8-fold. These marked changes in adrenal effluents were not observed in simultaneously monitored peripheral blood. Minimal changes in these steroid concentrations were noted in adrenal and peripheral blood in 7 women who received 2,000 IU hCG. One woman received a pressor dose of angiotensin II, resulting in a marked increase in adrenal vein aldosterone and a simultaneous decrease in cortisol. Since adrenal androgen secretion parallels cortisol, quantification of adrenal androgen secretion rates can be achieved by sampling the adrenal effluent and relating the androgen gradient to that of cortisol at any given time. In contrast, aldosterone secretion is often independent of cortisol, and thus cannot be estimated by comparison of adrenal gradients. ACTH administration, however, invariably stimulated aldosterone secretion, enabling us to quantify the "ACTH-related aldosterone secretion rate" from a comparison of maximal adrenal gradients of aldosterone vs cortisol. In 6 women, "ACTH-related aldosterone" secretion rate averaged 40 mug/day, roughly 20% of the total daily aldosterone secretion rate.

Topics: Adrenal Glands; Aldosterone; Androgens; Androstenedione; Angiotensin II; Chorionic Gonadotropin; Cosyntropin; Female; Hirsutism; Humans; Hydrocortisone; Testosterone; Veins