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Biomedical subjects

J Helke

Publications and source records attributed to J Helke.

5 recordsLinked to original sources
PubMed1986

Adrenal androgen hyperresponsiveness to adrenocorticotropin in women with acne and/or hirsutism: adrenal enzyme defects and exaggerated adrenarche.

To determine the adrenal contribution to elevated plasma androgens in 31 young hyperandrogenemic women with acne and/or hirsutism, we compared their responses to ACTH with those of 14 normal women. Each subject was given a low dose (10 micrograms/m2) of synthetic ACTH-(1-24) (Cortrosyn) after administration of 1.5 mg dexamethasone the night before the test. Thirty and 60 min responses of plasma 17 alpha-hydroxypregnenolone (17-Preg), 17 alpha-hydroxyprogesterone, (17-prog), dehydroepiandrosterone (DHEA), androstenedione, 11-deoxycortisol, and cortisol were measured. Eighteen (58%) patients had increased responses of at least one 17-ketosteroid or adrenal androgen precursor. All patients had cortisol responses within the range of those of the 14 normal subjects. Nine patients (29%) had evidence of steroid biosynthetic enzyme deficiencies, either mild congenital adrenal hyperplasia or the heterozygote state; after ACTH, 4 of these patients had elevated 17-prog in the range of values in heterozygote carriers of 21-hydroxylase deficiency, 2 had elevated levels of 11-deoxycortisol compatible with 11 beta-hydroxylase deficiency, and 3 had elevated levels of 17-Preg and DHEA, suggestive of 3 beta-hydroxysteroid dehydrogenase deficiency. Another 9 subjects (29%) had 17-ketosteroid (DHEA and/or androstenedione) hyperresponsiveness to ACTH with associated elevated 17-Preg responses. As a group, their patterns suggested relatively deficient 3 beta-hydroxysteroid dehydrogenase and relatively hyperactive C lyase without impairment of cortisol secretion. This pattern resembles exaggerated adrenarche, and we postulate that these 9 patients have hyperplasia of the zona reticularis. Neither basal levels of plasma androgens (free testosterone and DHEA sulfate) nor menstrual history predicted which patients would have abnormal ACTH responses. Although 5 of 11 (45%) patients with acne alone had abnormal responses to ACTH, 10 of 14 patients with acne and hirsutism (71%) had abnormal responses to ACTH. We conclude that an adrenal contribution is found in about half of hyperandrogenemic women with acne and/or hirsutism. This adrenal androgen hyperresponsiveness is heterogeneous. Some patients may have mild forms of congenital adrenal hyperplasia. However, functional androgenic hyperresponsiveness to ACTH, which resembles an exaggeration of adrenarche, is the most common abnormality found. Such findings may provide an explanation for the clinical observation of exacerbations of acne with stress.

3-Hydroxysteroid Dehydrogenases↗
PubMed1985

Dexamethasone preparation does not alter corticoid and androgen responses to adrenocorticotropin.

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.

Adolescent↗
PubMed1982

Multiple androgenic abnormalities, including elevated free testosterone, in hyperprolactinemic women.

To investigate the basis of the hirsutism and elevated plasma dehydroepiandrosterone (DHA) and/or DHA sulfate (DHAS) in hyperprolactinemic women, we measured androgen binding parameters and an extensive profile of plasma androgens in normal (NL) and hyperprolactinemic women (HYPRL). ACTH tests and dexamethasone (dex) suppression tests were performed in subgroups. Free testosterone levels were higher in HYPRL (13.1 +/- 23.3 vs. 7.18 +/- 0.72 pg/ml; P less than 0.025), although total testosterone was comparable. This disparity was related to plasma testosterone-estradiol-binding globulin (TEBG) levels being one third lower in HYPRL (mean +/- SE, 27.4 +/- 4.0 nM) than in NL (41.2 +/- 3.7 nM; P less than 0.0125). Less striking elevations of plasma DHAS, androstenedione, and 11-deoxycortisol were found in HYPRL. Plasma total dihydrotestosterone [17 beta-hydroxy-5 alpha-androstan-3-one (tDHT)] was nearly 30% lower in HYPRL (11.2 +/- 2.6 ng/dl) than in NL (15.6 +/- 1.3 ng/dl; P less than 0.025), whereas free DHT was normal. Ratios of tDHT to precursors were lower in HYPRL (P less than 0.005). After ACTH stimulation, hyperresponsiveness of 17-hydroxyprogesterone and androstenedione were observed. Apparent adrenal enzyme efficiencies, judged from post-ACTH product to precursor ratios, were normal in HYPRL with one exception: the ratio of tDHT to total testosterone at 4 h was lower (P less than 0.05). Dex suppression normalized androgens and obliterated the abnormal tDHT to precursor ratios. These findings suggest an ACTH dependency of the abnormalities. In summary, we find that about 40% of HYPRL have an androgenic abnormality, and the most characteristic abnormality is an elevated free testosterone level (abnormal in 43%). Depressed TEBG and high DHAS levels were found with lesser frequency (19-21%). The plasma tDHT concentration was low, both in absolute terms and relative to its precursors. Dex suppressibility of the hyperandrogenemia was also observed. We postulate that PRL may exert multiple effects on steroid secretion and metabolism. Possibilities include the inhibition of the TEBG level.

Adolescent↗
PubMedDate not supplied

Is an immunoassay available for the measurement of bioactive LH in serum?

An in vitro bioassay for luteinizing hormone (LH) is in our opinion the "gold standard" bioassay. The rodent interstitial cell testosterone assay (RICT) is specific for bioactive LH and very sensitive, accurate, and reproducible. Diverse LH standards consistently display parallel dose-response characteristics. Sera also manifest parallel dose-response characteristics throughout reproductive life, with the exception of basal samples from prepubertal children. This indicates that all known hormones with LH bioactivity have a similar bioactive site. The in vivo bioassays for LH used for calibration of World Health Organization standards are more cumbersome and less precise and accurate than the in vitro bioassay. The ovarian ascorbic acid depletion assay corresponds better than the seminal vesicle weight assay with in vitro bioassay. Variation in the ratio of bioactive to immunoreactive LH (B/I) principally reflects variation in LH immunoassay dose-response characteristics, rather than a change in the bioactive moiety of LH. The varying B/I ratio is due to molecular heterogeneity at multiple levels. Different LH standards contain different proportions of nonbioactive but immunoreactive material. The immunoreactive LH isoforms in serum contain different proportions of bioactive material and the isoform distribution differs with reproductive status. Furthermore, the antibodies comprising the various immunoassay systems detect heterogeneous epitopes on LH, which are not necessarily bioactive. B/I ratio disparities indicate lack of specificity of immunoassays for bioactive LH. Polyclonal antibody-based radioimmunoassay requires the use of purified reagents, including a bioactive tracer, in order to achieve high specificity for bioactive LH. The new generation of monoclonal antibody-based immunometric assays yields results that are lower than, but correlate with, LH measured by the in vitro bioassay. The purest of standards, even a recombinant standard, yields results that differ up to 50% or more from one immunoassay to another. Serum LH levels also differ up to two-fold among assays. The immunometric assays have the advantage of being more sensitive and more specific for low levels of LH in serum than radioimmunoassays, but B/I ratio discrepancies remain great. An immunoassay specific for the bioactive "docking site" of human LH isoforms is still needed.

Antibodies↗