cosyntropin and Body-Weight

Recent studies suggest using lower GH cut-points for the glucagon stimulation test (GST) in diagnosing adult GH deficiency (GHD), especially in obese patients. There are limited data on evaluating GH and hypothalamic-pituitary-adrenal (HPA) axes using weight-based dosing for the GST.. To define GH and cortisol cut-points to diagnose adult GHD and secondary adrenal insufficiency (SAI) using the GST, and to compare fixed-dose (FD: 1 or 1.5 mg in patients >90 kg) with weight-based dosing (WB: 0.03 mg/kg). Response to the insulin tolerance test (ITT) was considered the gold standard, using GH and cortisol cut-points of ≥3 ng/ml and ≥18 µg/dL, respectively.. 28 Patients with hypothalamic-pituitary disease and 1-2 (n = 14) or ≥3 (n = 14) pituitary hormone deficiencies, and 14 control subjects matched for age, sex, estrogen status and body mass index (BMI) underwent the ITT, FD- and WB-GST in random order.. Age, sex ratio and BMI were comparable between the three groups. The best GH cut-point for diagnosis of GHD was 1.0 (92 % sensitivity, 100 % specificity) and 2.0 ng/mL (96 % sensitivity and 100 % specificity) for FD- and WB-GST, respectively. Age negatively correlated with peak GH during FD-GST (r = -0.32, P = 0.04), but not WB-GST. The best cortisol cut-point for diagnosis of SAI was 8.8 µg/dL (92 % sensitivity, 100 % specificity) and 11.2 µg/dL (92 % sensitivity and 100 % specificity) for FD-GST and WB-GST, respectively. Nausea was the most common side effect, and one patient had a seizure during the FD-GST.. The GST correctly classified GHD using GH cut-points of 1 ng/ml for FD-GST and 2 ng/ml for WB-GST, hence using 3 ng/ml as the GH cut-point will misclassify some GH-sufficient adults. The GST may also be an acceptable alternative to the ITT for evaluating the HPA axis utilizing cortisol cut-points of 9 µg/dL for FD-GST and 11 µg/dL for WB-GST.

Topics: Adenoma; Adrenal Insufficiency; Adult; Aged; Blood Glucose; Body Weight; Case-Control Studies; Central Nervous System Cysts; Cosyntropin; Craniopharyngioma; Dose-Response Relationship, Drug; Female; Glucagon; Hormones; Human Growth Hormone; Humans; Hydrocortisone; Hypoglycemic Agents; Hypopituitarism; Hypothalamo-Hypophyseal System; Insulin; Male; Middle Aged; Pituitary Neoplasms; Pituitary-Adrenal System; Reference Values; Sensitivity and Specificity

Body fat mass and nutrition influence secretion of the adrenocortical hormones--aldosterone and cortisol--via several mechanisms. However, there are no data on adrenocortical function following widely prescribed mild diet-induced weight loss (10%) in obese subjects. In the present study, 25 healthy obese volunteers (BMI 32.9+/-4.3 kg/m (2)) followed a 30% calorie restricted diet over 12 weeks. Hypothalamic-pituitary-adrenal (HPA) axis function was assessed by 24-hour urine free cortisol/cortisone and a 1 mcg ACTH stimulation test with measurement of total and free cortisol and corticosteroid-binding globulin (CBG). The renin-angiotensin-aldosterone system (RAAS) was assessed by measurement of plasma aldosterone and renin under salt depleted (30 mmol/d) and loading (250 mmol/d) conditions. Volunteers' weight fell by 8.5+/-0.8 kg (8.9+/-0.7%) and seated systolic blood pressure fell by 8.7+/-2.7 mmHg and diastolic blood pressure by 7.0+/-1.4 mmHg (p<0.01). Plasma aldosterone and renin levels fell significantly with weight loss (aldosterone: 853+/-156-635+/-73 pmol/l; renin: 35.4+/-7-24+/-3 mU/l, both p<0.05). The volunteers were relatively salt insensitive (mean arterial pressure change with salt intake: 4 mmHg) and this was not affected by weight loss. Moderate weight loss had no effect on 24-hour urine free cortisol/cortisone, or on basal, or ACTH-stimulated free and total cortisol, or CBG. Hence this conventional weight loss program reduces blood pressure and activity of the RAAS via an effect on renin release. Despite various described influences of fat mass and energy restriction on HPA axis function, there were no changes in basal and stimulated HPA axis function with moderate weight loss. There may be a threshold effect of weight loss/energy restriction required to alter HPA axis function, or moderate weight loss may lead to a counterbalanced effect of stimulatory and inhibitory influences on HPA axis function.

Topics: Adult; Aged; Aldosterone; Blood Pressure; Body Weight; Caloric Restriction; Cosyntropin; Cross-Over Studies; Diet, Reducing; Female; Humans; Hydrocortisone; Male; Middle Aged; Obesity; Pituitary-Adrenal System; Renin; Renin-Angiotensin System; Sodium Chloride, Dietary; Transcortin; Weight Loss

Following a short-term clinical trial reported elsewhere, beclomethasone dipropionate aerosol has been given to 15 children with asthma for between 2 1/2 and 3 years except for a short placebo period after the first year. Month-by-month records of wheezing, peak flow rate, and other treatments used are presented for the first 17 months, adrenocortical function tests are reported for the first 2 years, and growth is recorded for 2 1/2-3 years. The short-term clinical benefits of the treatment are confirmed in the longer term, adrenocortical function appears to be unchanged, and growth proceeds along expected lines. The main disadvantage seems to be worsening of eczema and allergic rhinitis in those children who have ceased using corticotrophin or oral steroids for the control of asthma. It is concluded that in the long term beclomethasone dipropionate aerosol provides safe and effective day-to-day control of asthma in children, although occasional recourse to systemic steroid therapy cannot be avoided. Oral candidasis has not been a clinical problem.

Topics: Adolescent; Adrenal Cortex Function Tests; Aerosols; Asthma; Beclomethasone; Body Height; Body Weight; Child; Clinical Trials as Topic; Cosyntropin; Female; Humans; Male; Methylprednisolone; Placebos; Rhinitis, Allergic, Seasonal

Controversy persists regarding the use of the low-dose adrenocorticotropic hormone (ACTH) stimulation test (LDST) for the diagnosis of adrenal insufficiency (AI) and optimal test result interpretation. However, many centers are now using the LDST to assess cortisol secretion adequacy, and some only use a 30-minute cortisol level to determine adrenal sufficiency or AI. This study examined both 30- and 60-minute cortisol levels to assess whether the interpretation of the test was affected when both cortisol levels were taken into consideration.. Data were obtained by retrospective chart review from a single pediatric endocrinology unit over a 7-year period. We identified 82 patients who completed the LDST. Their mean age was 11.7 years, and 37% were female. Cortisol levels were evaluated at baseline and 30 and 60 minutes after cosyntropin administration. A cutoff value ≥18 μg/dL was used to define adrenal sufficiency.. We found that 54% of patients reached peak cortisol levels at 60 minutes, and 11 patients who did not pass the test at 30 minutes did so at 60 minutes. The only predictive characteristic was weight status; overweight and obese individuals tended to peak at 30 minutes, and normal and underweight individuals tended to peak at 60 minutes.. Although further studies are necessary to confirm our findings, it appears that measuring cortisol both 30 and 60 minutes following synthetic ACTH administration may be necessary to avoid overdiagnosing AI.

Topics: Adolescent; Adrenal Insufficiency; Body Weight; Child; Cosyntropin; Female; Humans; Hydrocortisone; Kinetics; Male; Obesity; Overweight; Retrospective Studies; Time Factors

To determine the lowest dose of cosyntropin on a per body weight basis that would produce maximal cortisol and aldosterone secretion and the ideal timing of blood sample collection after ACTH stimulation in healthy cats.. Randomized crossover trial.. 7 adult sexually intact male purpose-bred cats.. Each cat received saline (0.9% NaCl) solution (control) and 5 doses (125 μg/cat and 10, 5, 2.5, and 1 μg/kg [4.54, 2.27, 1.14, and 0.45 μg/lb]) of cosyntropin IV with a 2-week washout period between treatments. Blood samples were obtained before (baseline) and at 15, 30, 45, 60, 75, and 90 minutes after administration of saline solution or cosyntropin.. Serum cortisol and aldosterone concentration increased significantly, compared with baseline values, after administration of all cosyntropin doses. Lower doses of cosyntropin resulted in an adrenocortical response equivalent to the traditional dose of 125 μg/cat. The lowest doses of cosyntropin that stimulated a maximal cortisol and aldosterone response were 5 and 2.5 μg/kg, respectively. Lower doses of cosyntropin resulted in a shorter interval between IV administration of cosyntropin and peak serum cortisol and aldosterone concentrations.. Low-dose ACTH stimulation testing with IV administration of cosyntropin at 5 μg/kg followed by blood sample collection at 60 to 75 minutes resulted in concurrent peak serum cortisol and aldosterone concentrations that were equivalent to those achieved following administration of cosyntropin at 125 μg/cat, the standard dose currently used.

Topics: Aldosterone; Animals; Body Weight; Cats; Cosyntropin; Dose-Response Relationship, Drug; Hormones; Hydrocortisone; Male

Disturbances in mood such as anxiety and depression are often associated with altered hypothalamo-pituitary-adrenal (HPA) axis reactivity, but also with changes in cytokine production, such as interleukin-6 (IL-6), an essential immune factor produced by macrophages and lymphocytes during inflammatory processes. The reciprocal relationship between the HPA axis and the immune system is now well established. In order to understand better the endocrine reactivity of anxious individuals faced with an immune challenge, a model of innate anxiety-related behavior, HAB and LAB rats (HABs, high and LABs, low anxiety-related behavior) was used in this study. We sought to determine whether injection of lipopolysaccharide (LPS) induced a differential HPA axis reactivity and plasma IL-6 release in HABs and LABs. After LPS injection, the plasma adrenal corticotrophic hormone increase did not differ between HABs and LABs, whereas a larger increase in plasma corticosterone levels occurred in HABs than in LABs at 2 h after injection. Moreover, basal IL-6 levels were lower in HABs than in LABs, leading to a higher IL-6 2 h/basal ratio in HABs. In conclusion, we propose for the first time a link between the endocrine and immune systems of HABs and LABs and suggest that IL-6 could be a neuroendocrine correlate of trait anxiety in HABs.

Topics: Adrenocorticotropic Hormone; Analysis of Variance; Animals; Anxiety; Behavior, Animal; Body Weight; Brain; Corticosterone; Cosyntropin; Disease Models, Animal; Interleukin-6; Lipopolysaccharides; Male; Protein Binding; Rats; Receptors, Corticotropin

The hypothalamic-pituitary-adrenal (HPA) axis has been proposed to be susceptible to fetal programming, the process by which an adverse fetal environment elicits permanent physiological and metabolic alterations predisposing to disease in later life. It is hypothesized that fetal exposure to poor circumstances alters the set point of the HPA axis, leading to increased HPA axis activity and subsequent increased cortisol concentrations. In this study, we tested the hypothesis that prenatal exposure to famine during different periods of gestation is associated with increased activity of the HPA axis.. We assessed plasma cortisol concentrations after a dexamethasone suppression and an ACTH1-24 -stimulation test in a group of 98 men and women randomly sampled from the Dutch famine birth cohort. Cohort members were born as term singletons around the 1944-1945 Dutch famine.. Cortisol profiles after dexamethasone suppression and ACTH1-24 stimulation were similar for participants exposed to famine during late, mid- or early gestation (P = 0.78). Cortisol concentrations after dexamethasone suppression test did not differ between those exposed and those unexposed to famine in utero (mean difference -2% (95% confidence interval (CI) -27 to 23)). Neither peak cortisol concentration (20 nmol/l (95% CI -27 to 66)), cortisol increment (-5 nmol/l (95% CI -56 to 47)) or cortisol area under the curve post-ACTH1-24 injection (4% (95% CI -4 to 12)) differed between exposed and unexposed participants.. Prenatal famine exposure does not seem to affect HPA axis activity at adult age, at least not at the adrenal level. This does not exclude altered HPA axis activity at the levels of the hippocampus and hypothalamus.

Topics: Adult; Anthropometry; Birth Weight; Blood Glucose; Body Weight; Cohort Studies; Cosyntropin; Dexamethasone; Female; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Insulin; Linear Models; Male; Middle Aged; Pituitary-Adrenal System; Pregnancy; Prenatal Exposure Delayed Effects; Starvation; Stimulation, Chemical

The melanocortin pathway consists of endogenous agonists, antagonists, G-protein coupled receptors, and ancillary proteins that mediate the function of the endogenous antagonists. The melanocortin-4 receptor (MC4R) is involved in the regulation of obesity and the melanocortin-2 receptor (MC2R) is involved in the regulation of steroidogenesis. Herein, we present the effects of voluntary exercise on the MC4R knockout mice in terms of bypassing the morbid obesity and hyperphagia phenotypes associated with this genetic obesity model. Additionally, a systematic truncation study of the adrenocorticotropin hormone (ACTH 1-24) has been performed and characterized at the cloned MC2R.

Topics: Animals; Body Weight; Cloning, Molecular; Cosyntropin; Eating; Ligands; Mice; Mice, Knockout; Molecular Structure; Motor Activity; Peptide Fragments; Phenotype; Receptor, Melanocortin, Type 2; Receptor, Melanocortin, Type 4; Structure-Activity Relationship

The aim of this study was to compare the response of cortisol in sheep of different sex and gonadal status to adrenal cortex stimulation by an ACTH analogue in the breeding and non-breeding season. Twenty-four adult Corriedale sheep were used in the non-breeding season, and 19 in the breeding season. Three weeks prior to the first trial (non-breeding season), six rams and six ewes were gonadectomised. In each trial, blood was obtained every 15min for 9h and the animals received 0.5mg of ACTH (Tetracosactid, Synacthen Depot i.m., after 1.5h of sampling. Sampling began at 10:00a.m. in the non-breeding season and at 9:00a.m. in the breeding season. Three main effects (sex, gonadal status and season) were evaluated, each with two levels (male and female, intact and gonadectomised, breeding and non-breeding season, respectively). In both seasons, the females showed higher cortisol levels after ACTH than males (P<0.001), though the difference seemed less marked in the non-breeding season. The cortisol response in the ewes was not affected by season. The rams, however, showed a lower response in the breeding season (P<0.03). Gonadectomy reduced the response in the ewes (P<0.001) but had no effect in the rams. Nevertheless, gonadectomy also eliminated the differences between the ewes and the rams, such that the intact rams had lower levels of cortisol compared to the intact females, with those of the gonadectomised animals of both sexes being intermediate between the gonad-intact groups. The results of this study confirm sex differences in ACTH induced cortisol secretion in intact sheep in vivo. Furthermore, by applying exogenous ACTH we have directly stimulated the adrenal cortex, indicating the existence of sex differences also at this level. The circulating gonadal steroids, which are responsible at least in part for the sex differences in the responses to stress, may influence cortisol secretion from the adrenal gland by direct action at the cortex.

Topics: Adrenal Cortex; Adrenocorticotropic Hormone; Animals; Body Weight; Breeding; Cosyntropin; Female; Hydrocortisone; Kinetics; Male; Orchiectomy; Ovariectomy; Regression Analysis; Seasons; Sheep; Testosterone

Topics: Adrenal Glands; Adult; Aged; Aging; Anorexia Nervosa; Body Weight; Cosyntropin; Female; Humans; Male; Middle Aged; Obesity; Pituitary Gland

Although prior studies suggest reduced androgen levels in women with acquired immune deficiency syndrome wasting, little is known regarding the regulation of adrenal and ovarian androgen secretion in such patients. We investigated ovarian and adrenal function in 13 human immunodeficiency virus-infected women with acquired immune deficiency syndrome wasting and 21 age- and body mass index-matched healthy control subjects studied in the early follicular phase. Subjects received hCG (5000 U, im) on d 1 and Cosyntropin (0.25 mg, i.v.) on d 3 after dexamethasone (1 mg, orally, at 2400 h) pretreatment on d 2. At baseline, human immunodeficiency virus-infected subjects demonstrated significantly reduced T [18 +/- 2 vs. 25 +/- 2 ng/dl (0.6 +/- 0.1 vs. 0.9 +/- 0.1 nmol/liter); P = 0.02], free T [1.5 +/- 0.1 vs. 2.4 +/- 0.2 pg/ml (5.3 +/- 0.5 vs. 8.3 +/- 0.6 pmol/liter); P = 0.001], androstenedione [119 +/- 6 vs. 162 +/- 14 ng/dl (4.16 +/- 0.20 vs. 5.66 +/- 0.48 nmol/liter); P = 0.02], and dehydroepiandrosterone sulfate [0.96 +/- 0.17 vs. 1.55 +/- 0.19 microg/ml (2.6 +/- 0.5 vs. 4.2 +/- 0.5 micromol/liter); P = 0.047] levels compared with the control subjects. T [8 +/- 2 vs. 6 +/- 2 ng/dl (0.3 +/- 0.1 vs. 0.2 +/- 0.1 nmol/liter); P = 0.48], free T [0.5 +/- 0.2 vs. 0.4 +/- 0.1 pg/ml (1.7 +/- 0.7 vs. 1.5 +/- 0.5 pmol/liter); P = 0.85], 17 hydroxyprogesterone [0.5 +/- 0.2 vs. 0.7 +/- 0.2 microg/liter (1.6 +/- 0.6 vs. 2.0 +/- 0.6 nmol/liter); P = 0.63], and androstenedione [-1 +/- 12 vs. 8 +/- 11 ng/dl (-0.03 +/- 0.42 vs. 0.28 +/- 0.39 nmol/liter), P = 0.61] responses to hCG were not different between the groups. Cortisol responses were increased and dehydroepiandrosterone sulfate responses were decreased in the human immunodeficiency virus-infected vs. control subjects after ACTH stimulation. The ratio of DHEA to cortisol was significantly decreased at 60 (71 +/- 11 vs. 107 +/- 10; P = 0.02) and 90 (63 +/- 8 vs. 102 +/- 9; P = 0.004) min post-ACTH in the human immunodeficiency virus-infected patients compared with control subjects. Baseline urinary free cortisol levels were not different between the groups [36 +/- 9 vs. 36 +/- 5 microg/24 h (99 +/- 26 vs. 100 +/- 13 nmol/d)]. The DHEA to cortisol ratio correlated with the CD4 count (r = 0.67; P = 0.01). These data demonstrate significant shunting of adrenal steroid metabolism away from androgenic pathways and toward cortisol production in human immunodeficiency virus-infected women with the wasting syndrome. In contra

Topics: Adrenal Glands; Adult; Androgens; Area Under Curve; Body Weight; CD4 Lymphocyte Count; Chorionic Gonadotropin; Cosyntropin; Dehydroepiandrosterone Sulfate; Energy Intake; Female; HIV Infections; HIV Wasting Syndrome; Humans; Ovary

Ovine parturition results from an increase in foetal cortisol secretion in late gestation which is dependent on an intact hypothalamo-pituitary connection. The cortisol surge and parturition fails in hypothalamo-pituitary disconnected (HPD) foetuses but, paradoxically, immunoreactive (ir)-ACTH concentrations and secretory dynamics appear normal. This study compares the occurrence and timing of labour, basal ir-ACTH and cortisol concentrations and adrenal responsiveness in HPD foetuses (HPD/ACTH) receiving constant ACTH(1-24) infusion (43 ng/h/kg) from surgery (114+/-1 days gestational age (GA)) with those of saline-infused HPD or intact foetuses (HPD/SAL and INT/SAL). HPD/ACTH foetuses initiated labour at 147+/-2 days GA, which was not significantly different from INT/SAL foetuses (149+/-1 day GA). HPD/SAL foetuses were killed electively at 146+/-3 days GA with no signs of labour. Foetal ir-ACTH concentrations in all groups were indistinguishable, but only HPD/ACTH and INT/SAL foetuses had a significant cortisol surge. Adrenal responsiveness to ACTH(1-24)(1 microg/kg) was greater in HPD/ACTH foetuses than in HPD/SAL or INT/SAL foetuses at all GAs studied. Adrenal responsiveness in HPD/SAL foetuses exceeded that in INT/SAL foetuses at 120 and 130 days GA but did not change with GA. In summary, the basal cortisol and parturition defect in HPD foetuses was reversed by low-dose ACTH(1-24) infusion. Basal cortisol concentrations were unrelated to adrenal responsiveness. HPD/SAL foetuses had hyper-responsive adrenals compared to those of INT/SAL foetuses until 130 days GA, suggesting that the foetal hypothalamus exerts a negative influence on adrenal cortisol responses before 130 days GA, after which time stimulatory influences predominate.

Topics: Adrenal Glands; Adrenocorticotropic Hormone; Animals; Body Weight; Cosyntropin; Female; Fetus; Gestational Age; Hydrocortisone; Hypothalamus; Labor, Obstetric; Organ Size; Pituitary Gland; Pregnancy; Sheep; Time Factors

This study was designed to examine adrenocortical function in old (30 months) and young (6 months) male Brown Norway rats. The following observations were made. First, stress induced a higher pituitary adrenocorticotropic hormone (ACTH) response in the aged male Brown Norway rats than in young rats, while peak circulating corticosterone (CORT) levels were not different. Moreover, this type of "repeated" stress involving subcutaneous injection and blood sampling at various time points by pinching the tail vein, evoked a prolonged ACTH and CORT response in the aged animal. Second, exogenous ACTH1-24 administered to dexamethasone-pretreated Brown Norway rats, used as an in vivo challenge test for adrenocortical function, resulted in a delayed CORT response in the aged rats. The termination of the CORT response to ACTH, however, was not different between young and old rats. Third, ACTH1-24 stimulation of adrenocortical cells in vitro showed a tendency to a reduced CORT output, when these cells were obtained from old animals. Fourth, adrenalectomy (ADX) differentially affected pituitary ACTH release at both ages. The initial post-ADX ACTH surge was more pronounced in the aged animals. Beyond 4 days post-ADX the old Brown Norway rats did not show the pronounced afternoon peak in circulating ACTH as was observed in the young animals. This study demonstrates that during the aging process a deficiency in adrenocortical function develops in the male Brown Norway rat. This deficiency involves a less efficient stress-induced activation of adrenocortical output of CORT having enhanced pituitary ACTH release as one of the consequences.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adrenal Cortex; Adrenalectomy; Adrenocorticotropic Hormone; Aging; Animals; Body Weight; Circadian Rhythm; Corticosterone; Cosyntropin; Culture Techniques; Dexamethasone; Feedback; Male; Organ Size; Peptide Fragments; Pilot Projects; Pituitary Gland; Rats; Sensitivity and Specificity; Stress, Physiological

To investigate whether obese subjects with abdominal obesity may be characterized by hyperactivity of the hypothalamic-pituitary-adrenal axis, we examined two groups of obese women with a waist to hip ratio (WHR) lower than 0.80 (n = 13), therefore having peripheral body fat distribution (P-BFD), or a WHR higher than 0.85 (n = 12), thus having abdominal body fat distribution (A-BFD). A group of seven normal weight healthy women served as controls. All subjects underwent the following protocol study that included 1) measurement of daily urinary free cortisol excretion rate; 2) a CRF test (human CRF, 1 microgram/kg BW, as iv bolus), with blood samples taken at regular intervals for ACTH and cortisol determination; and 3) an ACTH test, performed by administering two boli of ACTH (Synacthen, 0.2 microgram/kg BW, iv), at 90-min intervals, with blood samples taken for cortisol determination. Each woman also had a control saline study. Basal levels of both ACTH and cortisol rose significantly after CRF administration in all groups, but this increase was significantly higher in A-BFD than in P-BFD and control women. A significant correlation was found between the incremental area of cortisol and that of ACTH during the CRF test (r = 0.502), but not between these parameters and WHR values. Although the cortisol increase after the ACTH test was higher in A-BFD than in the other groups, these differences were only significant at 60 min during the test and when the analysis for repeated measures was applied. On the contrary, the incremental cortisol area after the ACTH test was not significantly different in the three groups. Moreover, it was not significantly correlated with the incremental cortisol area after CRF test or WHR values. Daily urinary free cortisol excretion rates (per g creatinine), however, were significantly higher in A-BFD than in P-BFD and control women. These results, therefore, suggest that obese women with A-BFD may have hyperactivity of the hypothalamic-pituitary-adrenal axis. This abnormality could be central in origin, due to hypersecretion of CRF or ACTH; alternatively, it could represent an adaptive phenomenon secondary to a state of functional cortisol resistance.

Topics: Abdomen; Adipose Tissue; Adrenocorticotropic Hormone; Adult; Analysis of Variance; Body Height; Body Weight; Corticotropin-Releasing Hormone; Cosyntropin; Female; Hip; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Obesity; Pituitary-Adrenal System; Regression Analysis; Time Factors

Assessment of adrenal reserve and the diagnosis of adrenal insufficiency by acute adrenocortical stimulation with ACTH-(1-24) has been well established. Alternatively, estimation of adrenocortical enzymatic activities by this method for the detection of inherited or acquired biosynthetic abnormalities has been less well characterized. Some of the discrepancies between studies estimating adrenocortical enzymatic activities in different pathological conditions (e.g. hyperandrogenism) may result from the different stimulation protocols used. The objective of this prospective study was to establish the inherent variability of the adrenal response to acute ACTH-(1-24) stimulation and to determine the effect of sampling time, stimulation dose, and subject weight on the same. Forty-one normal female volunteers were recruited (mean age, 29.1 yr), 30 within 90-110% ideal body weight and 11 weighing more than 120% ideal body weight. Three protocols were designed to study 1) the effects of sampling time, ACTH-(1-24) dose, and subject weight on adrenal response; 2) the effect of time of the day on the variability of basal steroid levels and the adrenal response to stimulation; and 3) the long term reproducibility of the adrenal response to ACTH-(1-24). Androstenedione, 17-hydroxyprogesterone, 11-deoxycortisol, dehydroepiandrosterone, and cortisol were measured in serum under basal and stimulated conditions. All subjects had normal basal levels of testosterone, androstenedione, dehydroepiandrosterone sulfate, and PRL. The acute iv administration of 0.10, 0.25, and 1.0 mg ACTH-(1-24) elicited similar and maximal steroid responses, with all steroid levels reaching a plateau 60-90 min poststimulation regardless of subject weight. Sampling of basal steroid levels every 5 min in the morning (AM; beginning 0700-0900 h) or evening (PM; 1500-1700 h) did not reveal any difference in steroid variability. Only the mean basal cortisol level was higher in AM than PM testing (P less than 0.03). Although the mean levels of dehydroepiandrosterone and 17-hydroxyprogesterone 60 min after stimulation were significantly higher in AM than PM studies, these differences were minimal. Ten volunteers underwent an average of four (range, 2-6) adrenal stimulation studies using 1.0 mg ACTH-(1-24) over a 1-yr period. The long term coefficient of variation (CV) for basal steroid levels ranged from 15-28%. Calculations of net adrenal response (delta steroid O-T and area delta steroid O-T) were less

Topics: 17-alpha-Hydroxyprogesterone; Adrenal Glands; Adrenal Insufficiency; Adult; Analysis of Variance; Androstenedione; Body Weight; Circadian Rhythm; Cortodoxone; Cosyntropin; Dehydroepiandrosterone; Female; Humans; Hydrocortisone; Hydroxyprogesterones; Menstrual Cycle; Prospective Studies; Reproducibility of Results; Time Factors

Previous work has demonstrated that 4-week protein restriction of the domestic fowl (Gallus gallus domesticus) increases both adrenocortical cell sensitivity to ACTH and corticosteroidogenic capacity. In the present study we examined the transience (study 1) and the persistence (study 2) of this effect of protein restriction. In study 1, two strains of domestic fowl were used: a slower-growing White Leghorn strain and a faster-growing Cobb broiler strain. Cockerels (2 weeks old) were fed isocaloric diets containing either low (L; 5% or 8%) or control (C; 20%) levels of soy protein for 2 weeks, and then were either switched to the alternate diet (C-L, L-C) or maintained on the initial diet (C-C, L-L) for an additional 2 weeks. Cockerels were killed at 6 weeks of age. In study 2, White Leghorn cockerels (2 weeks old) were fed either diet for 4 weeks and then switched to or maintained on the control diet for an additional 4 weeks (i.e. C vs. restriction followed by repletion). In this study cockerels were killed at 10 weeks of age. In both studies highly enriched populations of adrenocortical cells were isolated from cockerel adrenal glands, and their steroidogenic properties (basal and maximally induced corticosterone and cAMP production; steroidogenic agent ED50 values) were evaluated in 2-h suspension incubations. In study 1, regardless of strain, the greater the length of the restriction period, the greater the magnitude of maximal cellular corticosterone production induced by ACTH; the average value for 4-week restriction (L-L) was 39.5% greater than that for 2-week restriction (L-C, C-L) and 117.5% greater than that for control (C-C). In addition, the value for restriction from 4-6 weeks of age (C-L) was 34% greater than that for restriction from 2-4 weeks of age (L-C), suggesting that the enhancement of maximal ACTH-induced corticosterone production after a 2-week restriction interval might be transient. Although there were no strain differences in the effect of protein restriction on maximal ACTH-induced corticosterone production, there were strain differences in its effect on cellular sensitivity to ACTH, as indicated by the ACTH ED50 values (the lower the ED50 value, the greater tha cellular sensitivity). With the White Leghorn strain, the greater the duration of protein restriction, the greater the adrenocortical cell sensitivity to ACTH; the sensitivity of L-L cells was 3.0 times the sensitivities of L-C and C-L cells and 4.1 times the sensitivit

Topics: 8-Bromo Cyclic Adenosine Monophosphate; Adrenal Cortex; Aldosterone; Animals; Body Weight; Chickens; Corticosterone; Cosyntropin; Cyclic AMP; Dietary Proteins; Hydroxycholesterols; Kinetics; Male; Organ Size; Protein-Energy Malnutrition; Species Specificity; Stress, Physiological

Topics: Adipose Tissue; Animals; Body Weight; Cosyntropin; Diet; Fatty Acids, Essential; Linoleic Acids; Rats

Administration of pharmacological doses of glucocorticoid to male rats in vivo suppresses adrenal steroidogenesis and inhibits testicular steroidogenesis by inhibiting the anterior pituitary secretion of LH. In contrast, administration of ACTH to these pharmacologically-suppressed rats stimulates the adrenal secretion of progesterone and testicular steroidogenesis. The mechanism by which ACTH increases testicular steroidogenesis is dependent on the presence of the adrenal gland and is reproduced by the administration of progesterone. The conclusion from these data is that the adrenal gland has an important role in generating external signals that modulate the hypothalamic-pituitary-gonadal axis in male rats. The adrenal secretion of glucocorticoid acts as a negative signal to testicular steroidogenesis whereas progesterone acts as a positive signal. The adrenal secretion of progesterone and its conversion to testosterone by steroidogenic enzymes in the cytoplasm of the Leydig cell may provide an alternative pathway for testosterone biosynthesis and may account for the increased plasma testosterone levels during the acute phase of stress and mating.

Topics: Adrenalectomy; Animals; Body Weight; Corticosterone; Cosyntropin; Dexamethasone; Luteinizing Hormone; Male; Orchiectomy; Pituitary Gland, Anterior; Progesterone; Rats; Rats, Inbred Strains; Reference Values; Testosterone

Adrenal responsiveness to Cosyntropin (synthetic ACTH) was investigated in five patients with major depression and five individually matched normal subjects. Three hours following suppression of endogenous ACTH secretion with dexamethasone (1 mg orally), the adrenal response to a 10-min infusion of Cosyntropin (0.05 micrograms/kg body weight) was monitored for 2 1/2 hr by plasma cortisol measured at 15-min intervals. The depressed patients had significantly higher baseline plasma cortisol, but not higher baseline ACTH, than the controls. During the 3-hr post-dexamethasone (and prior to Cosyntropin infusion), the depressed patients maintained significantly higher cortisol secretion, but not higher ACTH secretion, than the controls. After Cosyntropin infusion, there were no differences in ACTH and cortisol increases between the two groups. These findings stand in contrast to previous reports of enhanced adrenal responsiveness to the administration of much larger amounts of Cosyntropin in major depression.

Topics: Adrenocorticotropic Hormone; Adult; Age Factors; Body Weight; Cosyntropin; Depressive Disorder; Dexamethasone; Female; Humans; Hydrocortisone; Male; Middle Aged; Sex Factors

An excessive insulin releasing effect of adrenocorticotropic hormone (ACTH) and ACTH fragments has been considered as a possible factor contributing to the hyperinsulinaemia of genetically obese hyperglycaemic (ob/ob) mice. To investigate this possibility, plasma glucose and insulin responses of 11- to 14-week-old fed lean and ob/ob mice were examined after intraperitoneal administration of ACTH 1-39, ACTH 1-24 and ACTH 18-39, each at a dose of 25 nmol/mouse (50-115 micrograms/mouse). ACTH 1-39 produced a marked and rapid increase of plasma insulin in both lean and ob/ob mice, the effect being much greater in the ob/ob mutant (maximum increases of 5.5 +/- 1.5 and 46.1 +/- 4.1 ng/ml at 10 min in lean and ob/ob mice respectively, P less than 0.001). In lean mice plasma glucose concentrations showed a protracted decreased (maximum decrease of 3.7 +/- 0.5 mmol/l at 120 min), whereas glucose concentrations were increased (maximum increase of 4.2 +/- 1.3 mmol/l at 60 min) in ob/ob mice. ACTH 1-24 produced qualitatively similar but generally smaller effects than ACTH 1-39, while ACTH 18-39 did not significantly affect glucose and insulin concentrations. In 24 h fasted mice, ACTH 1-39 produced similar but generally smaller effects than in fed mice. The results suggest that the effects of ACTH on glucose and insulin homoeostasis are conferred by the N-terminal 1-24 sequence, and ACTH may exert acute effects which contribute to the hyperinsulinaemia and hyperglycaemia of ob/ob mice.

Topics: Adrenocorticotropic Hormone; Animals; Blood Glucose; Body Weight; Corticotropin-Like Intermediate Lobe Peptide; Cosyntropin; Drug Evaluation; Hyperglycemia; Insulin; Male; Mice; Mice, Inbred Strains; Mice, Obese; Obesity; Peptide Fragments

A slight but significant natriuretic action of 1-24 ACTH was confirmed both in trained conscious nonhydrated rats and in anaesthetized rats with sustained water diuresis. This action was compared with a strongly effective oxytocin analogue, nacartocin.

Topics: Adrenocorticotropic Hormone; Animals; Body Weight; Cosyntropin; Dose-Response Relationship, Drug; Male; Natriuresis; Oxytocin; Potassium; Rats; Rats, Inbred Strains; Sodium

Hypercortisolism was induced in rats by the administration of a corticotrophin analogue (Synacthen depot). The effect of this treatment during different periods was studied in normally fed and overnight-fasted rats. The activity of liver-type lipases, i.e., of lipases similar to the heparin-releasable lipase of rat liver (liver lipase), was determined in the adrenal gland and in the liver. Short-term (16 h) treatment had no effect on the lipase activity in the adrenal gland. During prolonged treatment, however, the lipase activity rose to 600-700% of control values in 10 days and from then on remained constant. The effect was similar in fed and overnight-fasted rats. The lipase activity in the liver decreased upon Synacthen administration. In the fed rats a decrease of 25% of the initial value was found after 16 h, 40% after 3 days and 50% after 20 days of treatment. In overnight-fasted rats the lowering of the lipase activity was less marked than in fasted controls. Serum lipid levels and high-density lipoprotein (HDL) subclass concentrations were also measured. The cholesterol concentration in the lipoproteins with a density greater than 1.050 g/ml (HDL) was elevated in rats treated for 3-20 days. If the rats were treated for longer than 10 days, overnight fasting led to a normalization of the HDL-cholesterol levels. After separation of the HDL into two subfractions, a relatively 'light' apolipoprotein E-rich fraction and a more 'heavy' apolipoprotein A-I-rich fraction, in fed and fasted animals treated with Synacthen for 3 days both HDL subfractions were elevated. After 10 days treatment only the apolipoprotein A-I-rich HDL fraction was still enhanced in both fed and fasted rats.

Topics: Adrenal Glands; Adrenocorticotropic Hormone; Animals; Body Weight; Chemical Phenomena; Chemistry; Cholesterol; Cosyntropin; Fasting; Lipase; Lipoproteins, HDL; Liver; Male; Rats; Rats, Inbred Strains

Prolonged low-dose ACTH infusion (5 or 10 iU/24h) leads to a transient increase in plasma renin activity and angiotensin II concentration in normal man. In order to find out whether the increase in angiotensin II stimulates aldosterone secretion, 12 normal men received ACTH (10 IU/24h) for 34 hours altogether, 6 with and 6 without simultaneous administration of captopril, 50 mg every 6 hours. Captopril prevented the increase in plasma angiotensin II during ACTH infusion and lowered its levels below those on the control day two hours after a new dose of the converting enzyme inhibitor was given. The increase in plasma cortisol was similar in both groups. The increase in plasma aldosterone was significantly blunted by captopril. The early blood pressure rise and the kaliuresis during ACTH infusion were also significantly decreased in the captopril group. These results suggest that angiotensin II mediates in part the effect of ACTH on aldosterone and blood pressure during the first 2 days of infusion. Since captopril reduced plasma angiotensin II for some time below normal, it is alternatively possible that ACTH requires normal plasma angiotensin II levels for a full effect on aldosterone secretion.

Topics: Adrenocorticotropic Hormone; Adult; Aldosterone; Angiotensin II; Angiotensin III; Blood Pressure; Body Weight; Captopril; Cosyntropin; Humans; Hydrocortisone; Kinetics; Male; Potassium; Proline; Renin; Sodium

Topics: Adrenal Cortex; Adrenocorticotropic Hormone; Aldosterone; Animals; Body Weight; Corticosterone; Cosyntropin; Delayed-Action Preparations; Dose-Response Relationship, Drug; Female; Hyperplasia; Injections, Subcutaneous; Mitosis; Rats

Topics: Adrenocorticotropic Hormone; Age Factors; Animals; Animals, Newborn; Body Weight; Cosyntropin; Eye; Female; Male; Rats; Rats, Inbred Strains; Sex Factors; Structure-Activity Relationship; Vagina