Cytochrome b5 (b5) in the developing rhesus adrenal.
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Adrenal Glands↗
Biomedical subjects
C R Parker
Publications and source records attributed to C R Parker.
Alendronate in the treatment of primary hyperparathyroid-related osteoporosis: a 2-year study.
We investigated the effect of alendronate on calcium, PTH, and bone mineral density in 27 female and 5 male patients with primary hyperparathyroidism. The treatment group [n = 14; T score < or = -2.5 SD at the femoral neck (FN) or T < or = -1.0 SD plus previous nonvertebral fracture] was given alendronate 10 mg/d for 24 months. The second group (n = 18; T score > -2.5 SD at the FN) was untreated. Biochemistry was repeated at 1.5, 3, 6, 12, 18, and 24 months, and dual-energy x-ray absorptiometry at 12 and 24 months. There were no significant between-group baseline differences in calcium, creatinine, or PTH. Alendronate-treated patients gained bone at all sites [lumbar spine (LS), 1 yr gain, +7.3 +/- 1.7%; P < 0.001; 2 yr, +7.3 +/- 3.1%; P = 0.04). Untreated patients gained bone at the LS over 2 yr (+4.0 +/- 1.8%; P = 0.03) but lost bone elsewhere. Calcium fell nonsignificantly in the alendronate group between baseline (2.84 +/- 0.12 mmol/liter) and 6 wk (2.76 +/- 0.09 mmol/liter), with a nonsignificant rise in PTH (baseline, 103.5 +/- 14.6 ng/liter; 6 wk, 116.7 +/- 15.6 ng/liter). By 3 months, values had reverted to baseline. In primary hyperparathyroidism, alendronate is well tolerated and significantly improves bone mineral density at the LS (with lesser gains at FN and radius), especially within the first year of treatment. Short-term changes in calcium and PTH resolve by 3 months.
Absorptiometry, Photon↗
Adrenocortical secretion of dehydroepiandrosterone in healthy women: highly variable response to adrenocorticotropin.
Excess adrenal androgen (AA) levels are observed in 25--50% of women with the polycystic ovary syndrome (PCOS), and AA excess in PCOS may represent selection bias. Thus, it is possible that AA secretion among the general population is highly variable, and that those women who are predisposed to secreting greater amounts of AA have a greater probability of having PCOS. We now hypothesize that the levels of AAs are highly variable among normal nonhyperandrogenic women, and that this heterogeneity is the result of a variable response of AAs to ACTH stimulation. To test this hypothesis we prospectively studied the response of dehydroepiandrosterone (DHA) and cortisol (F) to a 60-min acute stimulation with ACTH-(1--24) in 56 healthy eumenorrheic nonhirsute healthy women with a mean age of 28.9 yr (range, 20--37 yr.) and a mean body mass index (BMI) of 29.2 kg/m(2) (18.2--46.2 kg/m(2)). Baseline samples and poststimulation samples were assayed for DHA and F. The basal and ACTH-stimulated levels of DHA, but not those of F, were negatively correlated with age, although neither the basal nor ACTH-stimulated responses of DHA and F varied with BMI. After controlling for age, the basal F level was negatively correlated to its net increment (i.e. Delta F; r = -0.54; P < 0.001), whereas there was no significant relationship between basal DHA and Delta DHA. We also compared the intersubject variability (coefficient of variation) for basal and stimulated levels of DHA and F. For basal (DHA(0)), 60 min (DHA(60)), and net increment in (Delta DHA) DHA levels, the coefficients of variation were 67.9%, 61.4%, and 76.0%, respectively; for F(0), F(60), and Delta F, they were 40.4%, 16.9%, and 31.3%, respectively. The variance in Delta DHA was significantly higher, and the variance in F(60) was significantly lower than that in all other variables; DHA(0), DHA(60), F(0), and Delta F had similar variances. In conclusion, in our population of healthy reproductive-aged women we observed that both basal and ACTH-stimulated levels of DHA after ACTH-(1--24) stimulation had significantly greater intersubject variance (approximately 60--70%) compared with the basal and poststimulation levels of F (approximately 15--40%). These data support the hypothesis that among normal women, AA (i.e. DHA) levels are highly variable compared to those of F. In addition, the intersubject variability in DHA levels is at least in part due to a variable response of AAs to ACTH stimulation. Whether the AA excess frequently observed in PCOS is due to the greater risk of those women with higher AA levels, basally and after ACTH stimulation, remains to be confirmed.
Adrenal Cortex↗
Gene profiling of human fetal and adult adrenals.
The mechanisms that lead to the steroidogenic differences in the human fetal adrenal (HFA) and adult adrenal gland are not known. However, gene expression clearly plays a critical role in defining their distinct steroidogenic and structural phenotypes. We used DNA microarrays to compare expression levels of several thousand transcripts between the HFA and adult adrenal gland. Total RNA was isolated from 18 HFA and 12 adult adrenal glands. Samples of total RNA were used to make five pools of poly A+ RNA (mRNA). Gene profiling was done using five independent microarrays that contained between 7075 and 9182 cDNA elements. Sixty-nine transcripts were found to have a greater than 2.5-fold difference in expression between HFA and adult adrenals. The largest differences were observed for transcripts that encode IGF-II (25-fold higher in HFA) and 3beta-hydroxysteroid dehydrogenase (24-fold higher in adult). Among the other genes, transcripts related to sterol biosynthesis or to growth and development were higher in the HFA than adult adrenals. Transcripts concerned with cellular immunity and signal transduction were preferentially expressed in the adult adrenal. The vast majority of the 69 transcripts have not been studied with regard to adrenal function. Thus, these gene profiles provide valuable information that could help define the mechanisms that control adrenal function.
3-Hydroxysteroid Dehydrogenases↗
Effects of aging on adrenal function in the human: responsiveness and sensitivity of adrenal androgens and cortisol to adrenocorticotropin in premenopausal and postmenopausal women.
We sought to determine the effects of aging on several aspects of adrenal steroidogenesis in the hopes of characterizing the possible causes of adrenal androgen deficiency in elderly women. To this end, we quantified basal morning concentrations of cortisol (F), dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DS), and androstenedione (A4) and then evaluated the effects of overnight dexamethasone (DEX) suppression followed by adrenal responses to graded hourly infusions of ACTH, ranging from 20-1280 ng/1.5 m2 x h. Finally, we performed a standard 0.25-mg ACTH bolus stimulation test, with sampling at 1 h thereafter. Basal serum levels of DHEA, DS, and A4 were significantly reduced (approximately 50% each) in a group of 35 healthy postmenopausal women, 55-68 yr old, compared to those in 30 healthy, regularly menstruating women, 20-25 yr old. Post-DEX levels of these C19 steroids also were significantly lower in the older women than in the younger women; the percent decrease after DEX for A4 was greater in the older women, whereas those in DHEA and DS were not age related. Basal and post-DEX levels of F were similar in both groups. Secretory responses of DS to ACTH were not informative due to its large plasma pool and slow clearance rate. The maximally stimulated levels of DHEA after ACTH bolus were significantly lower in the older women than in younger women; those of A4 were similar in both age groups, and the maximally achieved levels of F were higher in the older women than in the younger women. The sensitivity of adrenal DHEA, A4, and F to ACTH (defined as the minimal dose of ACTH required to significantly increase the steroid levels above basal post-DEX values) was similar in older and younger women. The responsiveness of the steroids of interest to ACTH (defined as the slope of the dose-response curve over the linear portion of the dose-response curve) also was similar among younger and older women. These data demonstrate that the deficiency in adrenal androgen production in women is restricted to the delta5-pathway steroid products (DHEA and DS), whereas there is no reduction in the capacity of the adrenal to produce A4 or cortisol. As DHEA and DS are likely to be produced mainly in the zona reticularis of the adrenal cortex, we propose that these data point to an alteration in that cortical zone as the cause of adrenal androgen deficiency in aging. The reductions in A4 in aging are probably due to reduced ovarian secretion after menopause.
Adrenal Glands↗
The localization of DHEA sulfotransferase in steroidogenic and steroid metabolizing tissues of the adult rhesus macaque monkey.
Dehydroepiandrosterone sulfate is a major secretory product of the human adrenal cortex during intrauterine development as well as during adulthood. There are few animal experimental models that share this characteristic pattern of adrenal cortical steroidogenesis, which probably accounts for the relative paucity of information about the control of development and function of the adrenal androgen secretory apparatus. Adrenal androgen production in the rhesus macaque shares many similarities with that of the human. We sought to determine the tissue distribution of the enzyme DHEA sulfotransferase (DST) in the rhesus. Tissues were harvested at the time of autopsy from 7 adult monkeys (5 M, 2 F) ranging from 8-15 yrs old, and were fixed in 4% paraformaldehyde, embedded in paraffin, and sectioned at 5 mu thickness. Tissue sections were immunostained for DST with an anti-human liver DST antibody. DST was not detected in the testis or ovary. In the liver, immunoreactive DST was detected only in hepatocytes and in the kidney, DST was found only in the epithelial cells lining the collecting tubules. In the adrenal, DST was present in the cells of the zona reticularis but was not found in the cells of the medulla, zona fasciculata or in the very prominent zona glomerulosa. DST was most prominent in cells that were closest to the reticularis-medullary border. In most adrenals evaluated, the immunopositive cells were scattered, rather than forming a continuous band of cells around the medulla. The tissue distribution of DST in the adult rhesus macaque is qualitatively similar that observed in the adult human. These data aresuggestive that the rhesus might be an excellent model for the exploration of factors that regulate adrenal androgen production during development, aging, and in response to illness and stress, all of which have been found to be associated with variations in DHEA and DHEA sulfate production in the human.
Adrenal Glands↗
Corticotropin-releasing hormone stimulates steroidogenesis in cultured human adrenal cells.
The effects of corticotropin releasing hormone (CRH) on steroid production by cultures of human fetal adrenal cells was investigated. We found that CRH, at concentrations that have been reported to exist in human fetal serum, stimulated dehydroepiandrosterone sulfate (DS) and cortisol production by cultured fetal zone and neocortical zone cells. A dose-dependent increase in secretion of both steroids was noted, with the cortisol pathway being preferentially enhanced by CRH at high concentrations. Pretreatment of adrenal cells for 3 days made them more responsive to ACTH stimulation and such effects were dose-dependent also. Inclusion of the antagonist, alpha-helical CRH (9-41) blocked CRH-induced stimulation of DS and cortisol over a broad dose range and also interfered with the augmentation of cortisol secretion noted after ACTH in CRH treated cells. CRH had no effects on adrenal cell proliferation or total cell protein. These studies are suggestive that CRH, either of systemic origin or else produced within the adrenal itself, has the potential to be a modulator of adrenal steroid production in the human.
Adrenal Cortex↗
Dehydroepiandrosterone and dehydroepiandrosterone sulfate production in the human adrenal during development and aging.
Dehydroepiandrosterone (DHEA) is produced in prodigious quantities by the human adrenal, principally as the 3-sulfoconjugate DHEA sulfate (DS) during intrauterine life. The fetal zone and neocortex cells of the fetal adrenal express large amounts of DHEA sulfotransferase and minimal amounts, at least until very near the end of gestation, of 3beta-hydroxysteroid dehydrogenase. This pattern of enzyme expression favors substantial secretion of DHEA/DS with minimal cortisol produced; the DHEA/DS serves as the major precursor for placental estrogen formation in human pregnancy. Aside from adrenocorticotropin, other physiologic regulators of growth and steroidogenesis in the fetal adrenal have been postulated to exist, but have yet to be identified. Whereas intrauterine stressors may activate adrenal cortisol secretion, the fetal adrenal responds to many pregnancy conditions by suppressing DHEA/DS formation. After birth, the human adrenal undergoes reorganization whereby the large, inner fetal zone regresses, and DHEA/DS production is diminished. Just prior to gonadal maturation, the human adrenal undergoes morphologic and functional changes (adrenarche) that give rise to a prominent zona reticularis that is characterized by the presence of DHEA sulfotransferase, the absence of 3beta-hydroxysteroid dehydrogenase, and an enhancement of DHEA/DS production. The adrenal of the adult responds to stress in many instances like that of the fetus: increased cortisol secretion and diminished DHEA/DS secretion. The mechanisms for this divergence in the adrenocortical pathway is unknown. With aging, there is suppression of DHEA/DS secretion, possibly as the consequence of an involution of the zona reticularis, but corticosteroid production continues unabated.
Adrenal Glands↗
Cross-sectional analysis of renal transplantation osteoporosis.
We report a cross-sectional study of 54 adult female renal transplant recipients. We measured bone mineral density (BMD) of the lumbar spine, femoral neck, total hip, and mid- and total radius, and 38 patients underwent transiliac crest bone biopsy. Osteopenia was widespread with 31/54 (57%) of patients osteoporotic at one or more sites. Seventeen out of 54 (32%) of the patients had a prevalent low-trauma fracture. There was a clear trend in BMD reduction across spine, hip and midradius, with the predominantly cortical midradial site showing the greatest loss. We found no relationship between BMD and body mass index, parathyroid hormone (PTH), dose of immunosuppressant, years since transplantation, age at menopause, or years since menopause. Histologically, abnormal biopsies could be classified into three categories: hyperparathyroid (n = 20), adynamic (n = 14), and osteomalacic (n = 2). Mean PTH was lower (p = NS) and mean cumulative prednisolone dose was higher (p = 0.04) in the adynamic group compared with the hyperparathyroid group, but because of overlap between groups neither was an effective discriminator of histology. We suggest that bone biopsy is indicated in these patients to direct appropriate treatment. At the cellular level, there were significant negative correlations between osteoclast function (eroded surface, r = 0.47, p = 0.003) and osteoblast numbers (osteoblast surface, r = -0.40, p = 0.01) and cumulative exposure to prednisolone. We postulate that suppression of osteoblast function by prednisolone with unopposed bone resorption may result in relative hypercalcaemia and low PTH. This progressive reduction in bone turnover may promote or prolong the adynamic state.
Adult↗
The relationship between salivary cortisol concentrations in frozen versus mailed samples.
Saliva, popular for the measurement of cortisol concentrations, can be easily and painlessly obtained, so that study participants or medical patients may collect their own samples. This raises the question of whether cortisol concentrations are stable if samples are mailed unfrozen. Seventeen adult subjects (five males, 12 females, mean age = 27.82, SD = 7.55) participated in this study. One saliva sample from each subject was split. Half were frozen within 1 h. The other was exposed to conditions that would mimic a postal trip, including wide variations in temperature and movement over 5 days. A statistically significant positive correlation between cortisol concentration in the frozen and nonfrozen saliva samples was found (R2 = 0.92, p < .001). A paired t-test revealed no significant difference between samples (t(16) = 1.56, n.s.). This indicates that cortisol concentrations are stable during extended periods without freezing when exposed to widely varying temperatures and movement.
Adult↗
The effects of dehydroepiandrosterone (DHEA) on the thymus, spleen, and adrenals of prepubertal and adult female rats.
Administration of dehydroepiandrosterone (DHEA) to female rats produces a condition of reproductive failure and ovarian cysts similar to that seen in women having polycystic ovarian disease. On the other hand, DHEA may have beneficial effects on the immune system. We sought to determine the effect of DHEA, when administered in pharmacological amounts, on the thymus and spleen of prepubertal (25 day old) and young adult (60 day old) female rats. Since the adrenal, by means of its production of corticosteroids, also is known to modulate the immune system, we also evaluated the effects of DHEA administration on this gland. The daily SC administration of DHEA (6 mg/100g BW) to young adult female rats led to progressive and striking reductions in thymic weights (greater than 85% suppression after 20 days compared to vehicle treated animals). There were no effects of DHEA on body weights or the weights of the spleen. DHEA treatment also led to significantly reduced weights of the adrenals , which was sustained at about 15-20% below normal over 5-20 days treatment. Ovariectomy of the rats 5 days before initiation of DHEA or vehicle treatment gave rise to significant increases in thymic and spleenic weights in control animals and strikingly blunted the inhibitory effects of DHEA treatment for 10 days on the thymus; DHEA had no effect on the ovariectomy-induced rise in the weight of the spleen. Ovariectomy also had no effect on the inhibitory effects of DHEA on adrenal weight. Similar, albeit quantitatively less striking, responses were noted to occur after DHEA treatment in immature female rats. These data indicate that DHEA in doses sufficient to interfere with ovarian cyclicity also has potentially adverse effects on the adrenal and thymus. The ovary appears to play an independent role in maintenance of the size of the thymus and spleen and also may mediate some of the effects of DHEA on the thymus but not those on the adrenals.
Adrenal Glands↗
The effect of 17 beta-estradiol on adrenocortical sensitivity, responsiveness, and steroidogenesis in postmenopausal women.
Aging in women is associated with reduced production of adrenal androgens (AAs); this decrease may in part be the result of menopausal hypoestrogenism. To determine the effects of physiological concentrations of estradiol (E2) on adrenocortical sensitivity and responsiveness in postmenopausal women, we determined steroid responses to a continuous incremental ACTH-(1-24) infusion (0, 20, 40 80, 160, 320, 640, and 1280 ng/1.5 m2/h), followed by an ACTH-(1-24) bolus of 0.25 mg, after overnight dexamethasone suppression before and after 3 months of E2 therapy (transdermal E2, 0.05 mg/day) in 14 postmenopausal women. After E2 treatment, subjects demonstrated an increase in serum E2 concentrations from 29.8 +/- 2.6 to 49.9 +/- 6.0 pg/mL (P < 0.005) and a decline in mean FSH levels from 83.1 +/- 24.4 to 57.5 +/- 17.3 mIU/mL (P < 0.004). E2 administration had no effect on basal, postdexamethasone, or maximally stimulated serum levels of cortisol (F), dehydroepiandrosterone (DHEA), androstenedione (A4), or 17-hydroxyprogesterone (17-OHP). Furthermore, E2 did not affect adrenal sensitivity or responsiveness to ACTH-(1-24) stimulation. Finally, the steroid ratios reflecting 3 beta-hydroxysteroid dehydrogenase (i.e. the A4/DHEA ratio) and delta 417,20-lyase (i.e. the A4/17-OHP ratio) activities also were unaffected by E2 therapy. The responsiveness of F to ACTH was significantly greater than that of DHEA, A4, or 17-OHP regardless of the circulating E2 levels. Furthermore, F and A4 were significantly more sensitive to ACTH stimulation than were 17-OHP and DHEA, and this was not altered by E2 administration. We conclude that transdermal E2 replacement to postmenopausal women does not significantly alter AA sensitivity or responsiveness to ACTH. Hence, it is unlikely that the hypoestrogenism of menopause contributes to the decline in AAs noted with age. Furthermore, menopausal estrogen replacement, at least in physiological amounts administered transdermally, cannot be expected to reverse the suppressed production of these androgens.
17-alpha-Hydroxyprogesterone↗
Expression and subcellular distribution of the beta-isoform of the human glucocorticoid receptor.
Alternative splicing of the human glucocorticoid receptor (hGR) primary transcript produces two highly homologous protein isoforms, termed hGR alpha and hGRbeta, that differ at their carboxy-termini. In contrast to the well characterized hGR alpha isoform, which modulates gene expression in a hormone-dependent fashion, the biological significance of hGRbeta has only recently begun to emerge. We and others have shown that the hGRbeta messenger RNA transcript is widely expressed in human tissues and that the hGRbeta protein functions as a dominant negative inhibitor of hGR alpha in transfected cells. Unfortunately, these initial studies did not determine whether the hGRbeta protein was made in vivo. Such analyses are hindered because available anti-hGR antibodies cannot discriminate between the similarly sized hGR alpha and hGRbeta proteins. Therefore, to investigate the expression of the hGRbeta protein, we have produced an antipeptide, hGRbeta-specific antibody termed BShGR. This antibody was made against the unique 15-amino acid peptide at the carboxy-terminus of hGRbeta and recognizes both the native and denatured conformations of hGRbeta, but does not cross-react with hGR alpha. Using BShGR on Western blots and in immunoprecipitation experiments, we detected the hGRbeta protein in a variety of human cell lines and tissues. Immunocytochemistry was then performed with BShGR on HeLa S3 and CEM-C7 cells and on tissue sections prepared from lung, thymus, and liver to assess the cellular and subcellular distribution of hGRbeta. In all immunopositive cells, hGRbeta was found in the nucleus independent of glucocorticoid treatment. Within tissues, the hGRbeta protein was expressed most abundantly in the epithelial cells lining the terminal bronchiole of the lung, forming the outer layer of Hassall's corpuscle in the thymus, and lining the bile duct in the liver. As a potential in vivo inhibitor of hGR alpha activity, expression of hGRbeta may be an important factor regulating target cell responsiveness to glucocorticoids.
Antibodies↗
Aging alters zonation in the adrenal cortex of men.
Whereas aging has been shown to be associated with striking reductions in circulating levels of adrenal androgens in humans, the alteration in adrenal function that occurs in aging has not been identified. We sought to determine if there are changes in the zonation of the adrenal in aging men by performing histomorphologic analyses of adrenal specimens that had been obtained at autopsy following sudden death due to trauma. We evaluated adrenals from 21 young men (20-29 yrs) and 12 older men (54-90 yrs); inclusion criteria required the presence of medullary tissue in the specimen and fixation within the first 24 hrs postmortem. Sections stained with H/E were examined microscopically and areas of the cortex that included adjacent medullary tissue were chosen for quantitative evaluation by use of a computerized image analysis system. The average width (arbitrary units, pixels) of the zona reticularis and that of the combined zonae fasciculata/glomerulosa were determined from sections stained for reticulum fibers. The zona reticularis represented 37.1 +/- 1.9% of the total cortical width in the young men, which was significantly greater than that of the older men (27.1 +/- 3.3%, P = 0.0082). The zona fasciculata/glomerulosa to zona reticularis ratio in the young men (1.84 +/- 0.15) was significantly less that that of the older men (3.29 +/- 0.47, P = 0.0011). There was no significant difference in the total width of the cortex in young compared to older men. These data suggest that aging results in alterations within the cortex of the adrenals in men such that there is a reduction in the size of the zona reticularis and a relative increase in the outer cortical zones. A reduced mass of the zona reticularis could be responsible for the diminished production of dehydroepiandrosterone and dehydroepiandrosterone sulfate that occurs during aging.
Adrenal Cortex↗
Dynamics of the fetal adrenal, cholesterol, and apolipoprotein B responses to antenatal betamethasone therapy.
OBJECTIVE: Prior studies suggest that fetal plasma cholesterol is regulated in part by the rate of uptake and utilization of low-density lipoprotein cholesterol by the fetal adrenals for use in steroid biosynthesis. Direct evidence for this phenomenon and the kinetics of this process is, however, virtually impossible to obtain in a controlled experiment in the developing human. In the current study we sought to take advantage of the anticipated transient inhibition of the hypothalamic-pituitary-adrenal axis that occurs after antenatal therapy with glucocorticosteroids, to evaluate the temporal relationship between fetal adrenal steroids and plasma lipoprotein cholesterol levels in umbilical cord blood at delivery. STUDY DESIGN: Umbilical cord serum was obtained at delivery from 136 infants (30.5 +/- 2.7 weeks' gestation) who previously had been treated in utero with betamethasone, 12 mg per 12 or 24 hours for one or two doses and from 308 preterm infants (30.5 +/- 2.1 weeks) who had not been exposed to such therapy. We quantified the concentrations of dehydroepiandrosterone sulfate and cortisol as representative fetal adrenal steroids and also measured the total cholesterol and apolipoprotein B; the relationship between the steroids and lipids as a function of the interval between initial treatment and delivery was analyzed. RESULTS: Umbilical cord levels of dehydroepiandrosterone sulfate and cortisol were significantly reduced within the first 24 hours after initial treatment and remained significantly lower than in control infants through 4 days after initial treatment. In contrast, serum levels of cholesterol were significantly increased 3 to 4 days after treatment but fell on day 5. Serum levels of apolipoprotein B generally followed the same pattern as cholesterol. Cholesterol levels also were higher than normal in infants delivered >1 week after initial betamethasone treatment. CONCLUSIONS: The results of this study are consistent with the view that the plasma cholesterol pool in the fetus is regulated, at least in part, by the rate of uptake of low-density lipoprotein cholesterol and utilization by the fetal adrenals as substrate for steroidogenesis. Betamethasone also may influence cholesterol and lipoprotein synthesis in the fetus.
Apolipoproteins B↗
Diagnosis of personality disorder: a radical behavioral alternative.
From a radical behavioral perspective, a single, diagnostic system is unlikely to serve diverse purposes. Instead, ideal diagnostic systems should be developed to serve specific purposes. For example, the crucial proof required of a classification system designed to improve the outcome of psychosocial intervention would be that it enhance the clinician's influence on processes associated with client change. This means, in turn, that the change processes must be known or theoretically specified. As an illustration of this general approach to diagnostic classification, a specific behavioral theory is used to articulate processes of change in psychotherapy. The Axis II of the Diagnostic and Statistical Manual of Mental Disorders (4th ed.; American Psychiatric Association, 1994) is then evaluated with respect to its ability to enhance clinicians' influence of these processes, found problematic, and an alternative classification criterion is proposed.
Behavior Therapy↗
Adrenal androgen production in response to adrenocorticotropin infusions in men.
The responses of several adrenal steroids to adrenocorticotropin (ACTH) were investigated in a group of healthy young men. The protocol consisted of overnight adrenal suppression with dexamethasone followed by 1 hr infusions of ACTH in increasing (4X) doses ranging from 30-30,720 ng/1.5M2 followed by 0.25 mg ACTH/1.5M2. Whereas cortisol, androstenedione and androstenediol concentrations tended to plateau at the higher ACTH infusion rates, those of dehydroepiandrosterone (DHEA) and 17-hydroxyprogesterone (17-OH P) did not. The cortisol concentration achieved after the highest dose of ACTH was over 50 fold higher than that at baseline. DHEA levels rose to values about 13 times baseline whereas the other steroids increased to lesser extents (3-5 fold). The ACTH infusion rate required to significantly increase each steroid over the baseline level was extrapolated from dose response curves and was considered to be an index of the sensitivity of each steroid to ACTH. Cortisol was the most sensitive, rising significantly at approximately 35 ng ACTH/1.5M2, followed by androstenediol, DHEA, androstenedione and 17-OH P.
17-alpha-Hydroxyprogesterone↗
The dexamethasone suppression test in patients with mood disorders.
BACKGROUND: This study was undertaken to (1) determine whether the endogenous/nonendogenous mood disorder dichotomy is validated by the dexamethasone suppression test (DST); (2) determine whether other subtyping schemes (unipolar/bipolar, DSM-III melancholic/nonmelancholic, Winokur's family history subtypes) relate to the DST; (3) evaluate the relative contributions of symptom severity, weight loss, and other factors to DST status; and (4) assess the relative sensitivity of various post-dexamethasone cortisol determinations in the detection of dexamethasone nonsuppression. METHOD: 487 consecutive adult inpatients (N = 131) and outpatients (N = 356) with unipolar (N = 422) or bipolar disorder (N = 65) underwent the 1.0-mg DST. Nonsuppression was defined as at least one post-dexamethasone cortisol measurement > 4.0 micrograms/dL. RESULTS: Nonsuppression occurred in 27% of all patients with major depression and 43% of all bipolar depressed phase patients. For outpatients, dexamethasone nonsuppression occurred in 35.2% of subjects with endogenous (unipolar + bipolar; N = 145) and 9.0% of those with nonendogenous (unipolar only; N = 211) depressions (single 4 p.m. post-dexamethasone cortisol). For inpatients, dexamethasone nonsuppression was found in 61.5% of subjects with endogenous (N = 104) and 18.5% of those with nonendogenous (N = 27) depressions (three post-dexamethasone cortisol determinations). For the inpatient and outpatient sample together, the DST had a sensitivity of 46.2% and a specificity of 89.9% in differentiating endogenous from nonendogenous major depressive episodes. Weight loss, gender, and symptom severity added little to the endogenous/nonendogenous dichotomy. The Research Diagnostic Criteria (RDC) primary/secondary and Winokur and colleagues' family history subtypes for unipolar depression were not strongly validated by the DST. The 4 p.m. and 11 p.m. samples together detected 91.0% of those inpatients with abnormal three-sample DST results. The 8 a.m. sample alone detected 30% of those, the 4 p.m. sample alone detected 67%, and the 11 p.m. sample alone detected 62%. CONCLUSION: The RDC endogenous/nonendogenous dichotomy was validated by the DST.
Adult↗