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• W1998592968 abstract "Eleven healthy, eumenorrheic, nonhirsute women underwent acute adrenal stimulation testing at monthly intervals in order to measure the responses of cortisol (F), DHEA, and androstenedione, to a 60-minute acute stimulation with 1.0 mg ACTH (1-24). When the women were subdivided into either high or low responders to ACTH stimulation (relative to the group median), the relative adrenocortical response within individual subjects was found to be highly constant over time. Eleven healthy, eumenorrheic, nonhirsute women underwent acute adrenal stimulation testing at monthly intervals in order to measure the responses of cortisol (F), DHEA, and androstenedione, to a 60-minute acute stimulation with 1.0 mg ACTH (1-24). When the women were subdivided into either high or low responders to ACTH stimulation (relative to the group median), the relative adrenocortical response within individual subjects was found to be highly constant over time. The sulfated adrenal androgen (AA) metabolite DHEAS is frequently used as a marker of AA secretion (1Lobo R.A. Paul W.L. Goebelsmann U. Serum levels of DHEAS in gynecologic endocrinopathy and infertility.Obstet Gynecol. 1981; 57: 607-612PubMed Google Scholar), and circulating DHEAS levels appear to be determined to a significant extent by heritability (2Akamine Y. Kato K. Ibayashi H. Studies on changes in the concentration of serum adrenal androgens in pubertal twins.Acta Endocrinol. 1980; 93: 356-364PubMed Google Scholar, 3Rotter J.I. Wong F.L. Lifrak E.T. Parker L.N. A genetic component to the variation of dehydroepiandrosterone sulfate.Metabol. 1985; 34: 731-736Abstract Full Text PDF PubMed Scopus (106) Google Scholar, 4Meikle A.W. Stringham J.D. Woodward M.G. Bishop D.T. Heritability of variation of plasma cortisol levels.Metabol. 1988; 37: 514-517Abstract Full Text PDF PubMed Scopus (129) Google Scholar, 5Rice T. Sprecher D.L. Borecki I.B. Mitchell L.E. Laskarzewski P.M. Rao D.C. The Cincinnati Myocardial Infarction and Hormone Family Study family resemblance for dehydroepiandrosterone sulfate in control and myocardial infarction families.Metabolism. 1993; 42: 1284-1290Abstract Full Text PDF PubMed Scopus (46) Google Scholar). In women with polycystic ovary syndrome (PCOS), DHEAS levels are supranormal in approximately 25% of patients (6Kumar A. Woods K.S. Bartolucci A.A. Azziz R. Prevalence of adrenal androgen excess in patients with the polycystic ovary syndrome (PCOS).Clin Endocrinol. 2005; 62: 644-649Crossref PubMed Scopus (175) Google Scholar), and DHEAS has been found to predict adrenocortical responsiveness of AA to ACTH stimulation in these patients (7Azziz R. Black V. Hines G.A. Fox L.M. Bradley Jr, E. Boots L.R. Adrenal androgen excess in the polycystic ovary syndrome Sensitivity and responsivity of the hypothalamic-pituitary-adrenal axis.J Clin Endocrinol Metab. 1998; 83: 2317-2323Crossref PubMed Scopus (130) Google Scholar). As would be predicted for an inherited factor, the levels of this metabolite have been found to remain relatively steady over time, at least in postmenopausal women (8Thomas G. Frenoy N. Legrain S. Sebag-Lanoe R. Baulieu E.E. Debuire B. Serum dehydroepiandrosterone sulfate levels as an individual marker.J Clin Endocrinol Metab. 1994; 79: 1273-1276Crossref PubMed Scopus (140) Google Scholar). Although DHEAS levels may be used as a marker of AA secretion, the production of AA may be more accurately determined by their response to acute ACTH stimulation. There is significant between-subject variability (approximately 60%) in the response of the adrenal androgen (AA) DHEA to ACTH stimulation in normal women compared with that of cortisol (F) (approximately 17%), suggesting significant variability in the ability of normal women to secrete AAs (9Azziz R. Fox L.M. Zacur H.A. Parker Jr, C.R. Boots L.R. Adrenocortical secretion of dehydroepiandrosterone in healthy women highly variable response to ACTH.J Clin Endocrinol Metab. 2001; 86: 2513-2517Crossref PubMed Scopus (36) Google Scholar). The response of AAs to ACTH stimulation within subjects with PCOS appears to be relatively constant over time (10Yildiz B.O. Woods K.S. Stanczyk F. Bartolucci A. Azziz R. Stability of adrenocortical steroidogenesis over time in healthy women and women with polycystic ovary syndrome.J Clin Endocrinol Metab. 2004; 89: 5558-5562Crossref PubMed Scopus (28) Google Scholar). However, it is unclear whether this same relative stability in the AA response to ACTH is observed in healthy premenopausal women. We have hypothesized that the AA response to ACTH stimulation in most healthy premenopausal women, relative to other subjects, is constant over time. To test this hypothesis we studied 11 healthy nonobese white women who had undergone repeated ACTH stimulations over a 1-year period. The mean age of the subjects was 27.5 years (range 20–35 years), the mean body mass index was 22.2 kg/m2 (range 18.2–24.4 kg/m2), and all were eumenorrheic and nonhirsute. All subjects underwent an acute stimulation with 1.0 mg ACTH (1-24), with samples obtained at baseline (combined samples obtained at −30, −15, and 0 minutes) and at 60 minutes on days 3–8 of the menstrual cycle. The tests were repeated at monthly intervals, with subjects undergoing from two to six ACTH stimulations (average 4.0). All samples were stored at −20°C until assayed for F, DHEA, and androstenedione (A4). Written and informed consent was obtained from all subjects according to the guidelines of the Institutional Review Board of the University of Alabama at Birmingham. These subjects were included as part of a previously published study (11Azziz R. Bradley Jr, E. Huth J. Parker Jr, C.R. Boots L.R. Zacur H.A. Acute adrenocorticotropin-(1-24) (ACTH) adrenal stimulation in eumenorrheic women reproducibility and effect of ACTH dose, subject weight and sampling time.J Clin Endocrinol Metab. 1990; 70: 1273-1279Crossref PubMed Scopus (62) Google Scholar). For each steroid, subjects were divided into two groups according to the response of their first ACTH stimulation: [1] those individuals whose response to their first ACTH stimulation was above the group median (“high responders”); and [2] those whose response to their first ACTH stimulation was below the group median (“low-responders”). Our results indicated 83.3% (35/42), 84.1% (37/44), and 90.9% (40/44) of the basal F, DHEA, and A4 values, respectively, were distributed to the same relative area above or below the median value. Similarly, 76.2% (32/42), 97.6% (41/42), and 88.6% (39/44) of the ACTH-stimulated (peak 60 minutes) F, DHEA, and A4 values, respectively, were distributed to the same relative area above or below the median value. For the 60-minute ACTH-stimulated values we also calculated the interclass correlation, i.e., the average correlation across all cycles, which were 0.87 for DHEA and 0.88 for A4 but only 0.24 for F. The high positive correlation for DHEA and A4 indicated that the order of the subjects (from highest to lowest) did not change significantly across cycles for these AAs. A similar concept can be seen in Figure 1, such that the repeat stimulation values for DHEA and A4 in each study subject tend to cluster together, with high responders remaining so, and vice versa; less consistency was observed for F. In Figure 1, it can also be observed that, with few exceptions, the responses of A4 and DHEA correspond closely. In fact, there was a high degree of correlation between the responses of A4, DHEA, and F in these subjects. Of basal levels, 79.5% (35/44), 64.3% (27/42), and 66.7% (28/42) of the time both A4 and DHEA, A4 and F, and DHEA and F levels, respectively, in the same subject were distributed to the same region above or below the median value. Likewise, 73.2% (30/41), 60.5% (26/43), and 66.7% (28/42) of ACTH-stimulated A4 and DHEA, A4 and F, and DHEA and F levels, respectively, in the same subject were distributed to the same region above or below the median value. A dose of 1.0 mg of ACTH (1-24) was used in this study to ensure maximum stimulation of the adrenal regardless of body mass, and it is possible that a lower pulsed dose may not demonstrate a similar stability in response. However, we have previously demonstrated that a dose of 1.0 mg of ACTH (1-24) affords similar stimulation to the commonly clinically used dose of 0.25 mg (11Azziz R. Bradley Jr, E. Huth J. Parker Jr, C.R. Boots L.R. Zacur H.A. Acute adrenocorticotropin-(1-24) (ACTH) adrenal stimulation in eumenorrheic women reproducibility and effect of ACTH dose, subject weight and sampling time.J Clin Endocrinol Metab. 1990; 70: 1273-1279Crossref PubMed Scopus (62) Google Scholar), suggesting that the stability of response observed in this study would be similar for the lower more commonly used dose of ACTH (1-24). These results suggest that adrenocortical function, and in particular AA secretion in response to ACTH, in normal women is relatively stable over time. These results are consistent with those recently observed among women with PCOS (10Yildiz B.O. Woods K.S. Stanczyk F. Bartolucci A. Azziz R. Stability of adrenocortical steroidogenesis over time in healthy women and women with polycystic ovary syndrome.J Clin Endocrinol Metab. 2004; 89: 5558-5562Crossref PubMed Scopus (28) Google Scholar). More important, these data lend support to the concept that AA secretion is determined to a significant degree by inheritance, as has been observed for circulating basal levels of DHEAS and F (2Akamine Y. Kato K. Ibayashi H. Studies on changes in the concentration of serum adrenal androgens in pubertal twins.Acta Endocrinol. 1980; 93: 356-364PubMed Google Scholar, 3Rotter J.I. Wong F.L. Lifrak E.T. Parker L.N. A genetic component to the variation of dehydroepiandrosterone sulfate.Metabol. 1985; 34: 731-736Abstract Full Text PDF PubMed Scopus (106) Google Scholar, 4Meikle A.W. Stringham J.D. Woodward M.G. Bishop D.T. Heritability of variation of plasma cortisol levels.Metabol. 1988; 37: 514-517Abstract Full Text PDF PubMed Scopus (129) Google Scholar, 5Rice T. Sprecher D.L. Borecki I.B. Mitchell L.E. Laskarzewski P.M. Rao D.C. The Cincinnati Myocardial Infarction and Hormone Family Study family resemblance for dehydroepiandrosterone sulfate in control and myocardial infarction families.Metabolism. 1993; 42: 1284-1290Abstract Full Text PDF PubMed Scopus (46) Google Scholar). These data also lend support to the hypothesis that among women (and possibly men) there exists a wide variation in the individual potential for AA secretion, such that those women who secrete greater amounts of AAs do so consistently, and may be at greater risk for developing hyperandrogenism, such as PCOS." @default.
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• W1998592968 title "Reproducibility of the adrenal androgen response to adrenocorticotropic hormone stimulation" @default.
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