Peak Cortisol Response Research Articles

Effect of a 14-day course of systemic corticosteroids on the hypothalamic-pituitary-adrenal-axis in patients with acute exacerbation of chronic obstructive pulmonary disease

BackgroundAs supra-physiological intake of corticosteroids is a well known risk factor for the development of adrenal insufficiency, we investigated the function of the hypothalamic-pituitary-adrenal (HPA) axis during a 14-day course of systemic corticosteroids in patients with acute exacerbation of chronic obstructive pulmonary disease using clinical and laboratory measures.MethodsA systematic clinical and laboratory assessment including measurement of basal cortisol levels and the response to low dose (1 μg) ACTH stimulation was performed in nine patients before, on the first and the last day of treatment, as well as 2, 7 and 21 days after corticosteroid withdrawal.ResultsAt baseline, all nine patients had normal responses to 1 μg ACTH. On the first day of steroid treatment, 78% had a blunted peak cortisol response. This percentage increased to 89% after 14 days of steroid treatment. 78%, 33% and 33% of the patients had a blunted cortisol response to ACTH 2, 7, and 21 days after corticosteroid withdrawal, respectively. ROC curve analysis revealed that only basal cortisol concentrations (AUC 0.89), but not ACTH concentrations (AUC 0.49) or clinical signs (AUC 0.47) were predictive of an impaired function of the HPA axis. Basal cortisol levels of > 400 and < 150 nmol/l were 96% and 100% sensitive for a normal or pathological response to the ACTH stimulation test, respectively.ConclusionImmediate and prolonged suppression of the HPA axis is a common finding in otherwise asymptomatic patients undergoing systemic steroid treatment for acute exacerbation of chronic obstructive pulmonary disease and can reliably be assessed with the low-dose ACTH test.

Reliability of the Low Dose Synacthen Test in Children Undergoing Pituitary Function Testing

There are few data in the paediatric literature on the normal cortisol response to stimulation during the low dose synacthen test (LDST) (1 microg). To examine the cortisol responses in children, subsequently presumed to be normal, who had an LDST during anterior pituitary function tests (APFTs). A retrospective review of results in children with short stature and normal growth hormone levels. Of 33 children tested, seven had suboptimal cortisol responses based on accepted criteria (peak <500 nmol/l)--a false positive rate of 21%. Only three of these children had a repeat LDST, which was normal in all cases. The peak cortisol response (median 633, range, 417-1052 nmol/l) was inversely correlated with age (r = -0.44, p < 0.05). One in five tests did not meet normal criteria. This false positive rate (21%) should be borne in mind when interpreting synacthen tests to prevent overdiagnosis of adrenal insufficiency.

Dehydroepiandrosterone Sulfate in the Assessment of the Hypothalamic-Pituitary-Adrenal Axis

The role of dehydroepiandrosterone-sulfate (DHEA-S) in assessing the integrity of the hypothalamic-pituitary-adrenal (HPA) axis in patients with suspected insufficiency is uncertain. The objective of the study was to prospectively evaluate the diagnostic value of DHEA-S on HPA function in consecutive patients with suspected HPA insufficiency with and without pituitary lesions at a tertiary referral center. In 70 consecutive patients, insulin tolerance test was accompanied by measurement of basal DHEA-S. Assessment of HPA axis was based on peak cortisol response in insulin tolerance test (normal > or = 550 nmol/liter). To account for the age and gender dependency of DHEA-S, a z-score was calculated using age- and gender-specific reference values of the assay. Individuals with HPA insufficiency had significantly lower z-scores than those with normal HPA function (-1.66 vs. -0.62, P < 0.0001). In individuals up to 30 yr of age, a z-score of -2.0 had 100% sensitivity and specificity regarding HPA function [area under receiver operating characteristics (ROC) curve 1.00], whereas z-scores proved less useful in older individuals. In individuals with pituitary macroadenoma, a z-score below -2.0 had 100% specificity to predict HPA insufficiency (area under ROC curve 0.82). In the absence of a pituitary adenoma, the diagnostic value of the z-score was reduced (area under ROC curve 0.71). Individuals with HPA insufficiency have lower z-scores for DHEA-S than those with normal HPA function. There is evidence that a z-score could be of diagnostic value in assessing HPA integrity, especially in younger patients and patients with pituitary macroadenoma, but further studies are needed to consolidate these findings.

The insulin tolerance test (ITT) is a reproducible test for assessment of growth hormone (GH) and cortisol secretion in hypopituitary patients

The Insulin Tolerance Test (ITT) is the gold-standard for assessment of GH and ACTH reserve. GH and cortisol responses of <9mU/l and <500nmol/l respectivly have been defined as evidence of deficiency. Using these criteria we studied the reproducibility of the ITT in patients with pituitary surgery±radiotherapy. Two ITTs were performed within 7 days in 15 patients (7 men, age 22–51, 6 patients with GHD and 5 patients with cortisol deficiency). Serum GH and cortisol were measured by immunoradiometric and immunofluorimetric assay, respectivly. The CV of the assay for cortisol and GH was 5.8% and 5.9%. All patients achieved a hypoglycemia <2.2mmol/l and were symptomatic. In our series the median GH response was 13.2±18.1 mU/l with a range of 0–84.3 mU/l. The mean difference in the peak GH response between two tests was 3.6±1.3ng/ml. In 3/15 cases GH all values were undetectable on both occasions. In 2/12 cases the detected values were within 1 CV of the assay, in 3/12 cases within 2 CVs of the assay and in 7/12 cases the observed value was ≥ than 2 CVs of the assay. There was 1 case of clinical importance where the observed values around 9ng/ml was discordant in terms of defining GHD and could have led to misclassification and different therapeutic decision. The median cortisol response was 544±210 nmol/l with a range of 262–1012 nmol/l. The mean difference in the peak cortisol response was 84.8±21.3 nmol/l. In 4/15 cases the detected values were within one CV of the assay and in 5/15 cases within 2 CVs of the assay. In 6/15 cases the observed difference was bigger than explicable by 2 CVs of the assay. 5/15 cases showed conflicting values in relation to the cut off point of 500 nmol/l and were discordant in terms of defining cortisol deficiency. In our series of patients with pituitary disease conflicting GH and cortisol results during ITT were observed in 7% and 30% of patients, respectively. This shows a good reproducibility for the GH response. There was only a low number of cases of misclassification by the arbitrary definition of GH and cortisol deficiency.

Rams with poor feed efficiency are highly responsive to an exogenous adrenocorticotropin hormone (ACTH) challenge

An animal's response to a stressor is to increase metabolic rate, and thus energy consumption through the activation of the hypothalamic–pituitary–adrenal axis. Changes to energy use by an animal are likely to influence the efficiency with which it is utilised. In this study, we tested the hypothesis that less efficient sheep are more responsive to exogenous administration of adrenocorticotropin hormone. This was done by firstly determining the appropriate dose (0.4, 1.6 or 6.4 μg/kg LW) and peak serum cortisol response time (45 min) to exogenous administration of adrenocorticotropin hormone in a pilot study ( n = 3 sheep). Following this, adrenocorticotropin hormone (2.0 μg/kg LW) stimulated cortisol levels were measured in a larger group of sheep ( n = 50) of known feed efficiency (feed conversion ratio and residual feed intake values). Less efficient sheep (more positive residual feed intake values) were found to have a greater ( P < 0.001) increase in cortisol concentration in comparison to more efficient animals. Those sheep which had higher levels of cortisol also had a greater proportion ( P < 0.001) of fat tissue. These data clearly demonstrated that efficiency of energy use, when measured as residual feed intake, is significantly related to an animal's stress response. These findings have important implications for understanding the physiological mechanisms underpinning efficiency of energy use, and may be useful in successfully identifying animals which are superior in terms of feed efficiency.

Combining Growth Hormone Releasing Hormone-Arginine and Synacthen Testing Diminishes the Cortisol Response

The GHRH/arginine test and short synacthen test (SST) have been validated as safe alternatives to the insulin tolerance test for the assessment of the GH reserve and hypothalamic-pituitary-adrenal axis integrity, respectively. However, these two tests are usually performed separately. The objective was to see whether the synacthen and GHRH/arginine tests could be combined to save time and blood samples and minimize inconvenience to patients. Twenty-four consecutive patients with adult onset pituitary disease requiring pituitary function testing were randomized to receive sequentially and in random order a SST, a GHRH/arginine test, and a combined SST and GHRH/arginine test on three different visits separated by at least 1 wk. There was no difference in basal cortisol or ACTH values for the SST done alone or during the combined test. However, when GHRH/arginine was given with synacthen, patients had a lower peak cortisol response with a mean difference of 116 nmol/liter (95% confidence interval, 52.54 to 179.37; P < 0.001), and one patient with a normal response on the SST had a subnormal cortisol response in the combined test. Similar lower peak cortisol responses were observed in males and females with combined test. The difference between the peak cortisol responses showed no significant correlation with age (r = 0.123; P = 0.58) or with the body mass index (r = -0.376; P = 0.09). There was no difference in GH measurements between the GHRH/arginine test done alone or in combination with the SST. Combining the SST and GHRH/arginine test results in a lower cortisol response to synacthen. For this reason, the combined test cannot be recommended to assess the integrity of cortisol and GH reserve using current diagnostic criteria.

Comparison of the hypothalamic–pituitary–adrenal axis susceptibility upon single-dose i.m. depot versus long-acting i.v. triamcinolone acetonide therapy: a direct pharmacokinetic correlation

The effects of single injections of glucocorticoid (GC) depot suspension and of long-acting GC were studied in conscious dogs. Both the depot suspension GC triamcinolone-16,17-alpha-acetonide (TAA) and the long-acting triamcinolone acetonide-21-dihydrogen phosphate (TAA-DHP) decreased basal and ACTH-stimulated cortisol levels and in a specific time-dependent way. Before treatment, all dogs had normal basal and peak cortisol responses to ACTH challenge (13-15 and > 120 nmol/l at 1 h respectively). Intravenous TAA-DHP reduced cortisol levels for 12 h, i.m. TAA reduced cortisol levels as of 1.5 h and the effect lasted for at least 4 weeks. Both treatments blunted the peak response to ACTH. ACTH elevated cortisol levels to or above baseline values within 10 days following TAA-DHP treatment, but the TAA treatment suppressed an ACTH response for at least 4 weeks. Kinetic analysis of both the preparations demonstrated rapid absorption (tmax, 0.6-1.5 h) and low maximum plasma concentrations (peak Cmax, 2.99-5.51 nmol/l) of the steroids; indeed, the terminal half-life of TAA-DHP (13.9 +/- 1.3 h) was very much shorter than that of TAA (125.9 +/- 15.8 h). In addition, the mean residence time differed very much (11 vs 160 h for TAA-DHP and TAA respectively), in line with a delayed elimination of the depot compared with the long-acting formulation. Application of these TAA formulations needs careful evaluation for their surprisingly different effects on endocrine stress axis activity.

A comparison between the effects of low (1 µg) and standard dose (250 µg) ACTH stimulation tests on adrenal cortex functions with Behçet's disease

Behçet's disease is a rare, chronic disorder. The cause of Behçet's disease is unknown. It is believed to be caused by an autoimmune reaction. As in other chronic autoimmune diseases, Behçet's disease may show a subclinical adrenal failure and some changes in cortisol levels. We aimed to evaluate adrenal gland function in Behçet's disease patients. This study included 18 Behçet's disease patients and 15 healthy controls. Patient and control groups were administered i.v. 1 microg low dose test (LDT) and 250 microg standard dose test (SDT) adrenocorticotropic hormone (ACTH) stimulation test after 12 h of night fasting with an interval of 3-days and cortisol responses in the 0th, 30th and 60th minutes were evaluated. There was no statistically significant difference between basal cortisol values of Behçet's disease and control groups. Cortisol values in the 60th minute in LDT were significantly lower in Behçet's disease group than in the control group. In the peak cortisol responses to LDT, a significant decrease was found in Behçet's disease group. These findings suggest that hypothalamo-pituitary adrenal axis is partially suppressed in Behçet's disease.

Adrenal responses to low dose synthetic ACTH (Synacthen) in children receiving high dose inhaled fluticasone

Background and Aims: Clinical adrenal insufficiency has been reported with doses of inhaled fluticasone proprionate (FP) >400 μg/day, the maximum dose licensed for use in children with asthma. Following two...

The effect of inhaled budesonide on adrenal and growth suppression in asthmatic children

The present authors evaluated adrenal reserve in asthmatic children on long-term inhaled corticosteroids and whether possible adrenal suppression could be predicted by growth retardation. Low-dose synacthen test (0.5 microg x 1.73 m(-2)) was performed in 72 asthmatic children with a median age of 9.4 (range 4.2-15.7) yrs on long-term treatment (median 18 (range 6-84) months) with low-to-moderate doses (median 363 (range 127-1012) microg x m(-2)) of inhaled budesonide, as well as in 30 controls. Adrenal suppression was considered as a peak serum cortisol <495 nmol x L(-1). The current authors calculated height standard deviation score (HSDS) at the time of testing and height velocity SDS (HVSDS) in the preceding year. Mean HSDS was 0.06+/-1.3 and HVSDS was -0.9+/-2.3. Adrenal suppression was disclosed in 15 asthmatic children (20.8%). There were no differences in HSDS and HVSDS between children with and without adrenal suppression. There was no correlation between peak cortisol response and dose or duration of treatment. However, a positive relationship between HVSDS and duration of treatment was noted. These data suggest that long-term treatment of asthmatic children with low and moderate doses of inhaled budesonide may result in mild adrenal suppression that cannot be predicted by growth deceleration. The negative influence of inhaled corticosteroids on growth becomes less the longer the duration of treatment.

Effect of carprofen administration during banding or burdizzo castration of bulls on plasma cortisol, in vitro interferon-γ production, acute-phase proteins, feed intake, and growth1

The objective of this study was to determine the effect of carprofen (C) administration before banding or burdizzo castration of bulls on cortisol, in vitro interferon-gamma (IFN-gamma) production, acute-phase proteins, feed intake, and growth. Fifty Holstein Friesian bulls (5.5 mo old; 191 +/- 3.7 kg) were blocked by weight and assigned randomly to 1 of 5 treatments (n = 10/treatment): 1) untreated control (2) banding castration at 0 min (Band); 3) Band following an i.v. injection of 1.4 mg/kg of BW of C at -20 min (Band+C); 4) Burdizzo castration at 0 min (Burd); or 5) Burd following 1.4 mg/kg of BW of C at -20 min (Burd+C). Castration acutely increased plasma cortisol concentrations compared with control; no significant differences occurred in peak and interval to peak cortisol responses between Band and Band+C or Burd and Burd+C groups. The administration of C in Band+C reduced (P < 0.05) the cortisol concentration between 6 and 12 h postcastration compared with Band animals. Overall, the integrated cortisol response was greater (P < 0.05) in the castrates than in control, whereas C treatments tended to reduce this response compared with Band (P = 0.08) and Burd (P = 0.07), respectively. Plasma fibrinogen was elevated in Band animals on d 14 and in Burd animals on d 3 and 14. Carprofen administration reduced Band- and Burd-induced fibrinogen production on d 14 and 3, respectively. Plasma haptoglobin was elevated in Band animals on d 3 and 35 compared with control, and C administration was effective in reducing the haptoglobin elevation on d 35 in Band+C compared with Band. There were no differences among treatments in in vitro IFN-gamma production induced by concanavalin A and phytohemagglutinin on d 1 and 2. Overall from d -1 to 16, there were no DMI differences among treatments. From d -1 to 35, there were no ADG differences among treatments. In conclusion, banding and burdizzo castration increased plasma cortisol with no change in in vitro IFN-gamma production. Carprofen (1.4 mg/kg of BW) tended to reduce the integrated cortisol response, and it reduced cortisol secretion in banded animals between 6 and 12 h postcastration. There was an increased acute-phase protein production following castration; this response was effectively moderated by the administration of C before castration.

Evaluation of pituitary function in the fatigued patient: a review of 59 cases

The aim of this study was to review the results of dynamic pituitary testing in patients presenting with fatigue. We reviewed clinical histories and insulin tolerance test (ITT) results of 59 patients who presented with fatigue and other symptoms of glucocorticoid insufficiency over a 4-year period. All patients referred for ITT had an early-morning cortisol level of <400 nM and a low or normal ACTH level. Peak cortisol and GH responses following insulin-induced hypoglycaemia were normal in only seven patients (12%). Median age of the remaining 52 patients was 47 years (range, 17-67 years); all but five were female. Common presenting symptoms were neuroglycopaenia (n = 47), depression (n = 37), arthralgia and myalgia (n = 28), weight gain (n = 25), weight loss (n = 9), postural dizziness (n = 15) and headaches (n = 13). Other medical history included autoimmune disease (n = 20; particularly Hashimoto's thyroiditis, Graves' disease and coeliac disease), postpartum (n = 8) and gastrointestinal (n = 2) haemorrhage and hyperprolactinaemia (n = 13). 31 subjects had peak cortisol levels of <500 nM (suggestive of ACTH deficiency; 18 of whom had levels < 400 nM) and a further six had indeterminate results (500-550 nM). The remaining 15 subjects had normal cortisol responses (median 654 nM; range, 553-1062 nM) but had low GH levels following hypoglycaemic stimulation (5.9 mU/l; 3-11.6 mU/l). Our results suggest that patients presenting with fatigue and symptoms suggestive of hypocortisolism should be considered for screening for secondary adrenal insufficiency, particularly in the presence of autoimmune disease or a history of postpartum or gastrointestinal haemorrhage. Whether physiological glucocorticoid replacement improves symptoms in this patient group is yet to be established.

Low-dose glucose infusion after achieving critical hypoglycemia during insulin tolerance testing: effects on time of hypoglycemia, neuroendocrine stress response and patient’s discomfort in a pilot study

The insulin tolerance test (ITT) is regarded as the gold standard for the evaluation of pituitary ACTH and growth hormone reserve. However, the intended critical hypoglycemia results in considerable discomfort and requires close surveillance during the test. In a pilot study, we evaluated whether the ITT could be markedly simplified, made less hazardous and more convenient by routine i.v. low-dose glucose administration after hypoglycemia has been achieved. Sixteen healthy subjects (three females, 13 males) were tested twice in a randomized, single-blinded fashion, receiving 0.15 IU insulin/kg body weight as an i.v. bolus. After hypoglycemia (serum glucose less than 2.2 mmol/l) had been achieved, 500 ml isotonic saline (protocol A (A)), or 500 ml 5% glucose solution (protocol B (B)) were infused over 30 min. Compared with saline, glucose infusion shortened the period of hypoglycemia from 31 + 14 to 17 + 6 min (P < 0.01). In addition, prolonged duration of hypoglycemia (>45 min) was reduced (6 subjects in protocol A vs none in protocol B). Despite shorter duration of hypoglycemia, all subjects had adequate stimulated cortisol (>500 nmol/l) and hGH (>5 microg/l) levels. Mean peak concentrations of plasma ACTH (24 +/- 12 pmol/l (A) vs 21 +/- 8 pmol/l (B)), serum cortisol (690 +/- 83 nmol/l vs 634 +/- 83 nmol/l) and serum hGH (26 +/- 16 microg/l vs 22 +/- 13 microg/l) were slightly, but not significantly lower. In contrast, glucose infusion significantly reduced peak plasma epinephrine levels at 45 min (4.96 +/- 4.91 pmol/l (A) vs 1.53 +/- 1.1 pmol/l (B), P < 0.05) and ameliorated discomfort, as evaluated by a visual analog scale (P < 0.05). Taken together, our pilot study suggests that, while the duration of hypoglycemia is shortened and acute epinephrine response is reduced, low-dose infusion of glucose does not significantly alter peak cortisol and growth hormone responses during ITT. Studies with a larger number of subjects and patients with suspected hypopituitarism are needed to further evaluate this modified protocol.

Blunted Hormone Responses to Ipsapirone are Associated with Trait Impulsivity in Personality Disorder Patients

Impulsive aggression is associated with central serotonergic dysfunction. Animal models particularly implicate the 5-HT(1A) receptor in this behavior. We tested the hypothesis that central 5-HT(1A) receptor function is impaired in impulsive aggressive personality disorder patients. A total of 52 individuals with DSM-III-R personality disorders, all medically healthy adult outpatients without concurrent psychiatric medication treatment, underwent serial plasma cortisol, prolactin, and temperature measurements before and after ipsapirone 20 mg oral administration. Subjects completed self-report measures of impulsivity, hostility, depression and anxiety, and childhood maltreatment. Stepwise regression analysis revealed impulsivity alone among symptom measures to be associated with significantly decreased peak cortisol and prolactin responses. Diagnoses of borderline personality disorder (BPD) and intermittent explosive disorder-revised (IED-R) were associated with significantly increased and decreased cortisol responses, respectively. However, post hoc analyses indicated that impulsivity was significantly negatively correlated with cortisol responses in the BPD group, and may mediate the association of both BPD and IED-R with altered cortisol responses. Temperature response was associated with neither diagnostic nor symptom measures. Neither diagnostic nor dimensional measures of depression or anxiety, nor severity of childhood maltreatment, were significantly associated with cortisol, prolactin, or temperature responses. Impulsivity is related to impaired function at (or downstream to) postsynaptic 5-HT(1A) receptors, and this relationship may be partly responsible for the association of impaired serotonergic function with diagnoses such as BPD and IED-R. In addition, D(2) receptor dysfunction may play a role in impulsivity, whereas 5-HT(1A) cell-body autoreceptor function may be spared in these disorders.

Delayed response and lack of habituation in plasma interleukin-6 to acute mental stress in men

Acute mental stress induces a significant increase in plasma interleukin (IL)-6 levels as a possible mechanism for how psychological stress might contribute to atherosclerosis. We investigated whether the IL-6 response would habituate in response to a repetitively applied mental stressor and whether cortisol reactivity would show a relationship with IL-6 reactivity. Study participants were 21 reasonably healthy men (mean age 46 ± 7 years) who underwent the Trier Social Stress Test (combination of a 3-min preparation, 5-min speech, and 5-min mental arithmetic) three times with an interval of 1 week. Plasma IL-6 and free salivary cortisol were measured immediately before and after stress, and at 45 and 105 min of recovery from stress. Cortisol samples were also obtained 15 and 30 min after stress. Compared to non-stressed controls, IL-6 significantly increased between rest and 45 min post-stress ( p = .022) and between rest and 105 min post-stress ( p = .001). Peak cortisol ( p = .034) and systolic blood pressure ( p = .009) responses to stress both habituated between weeks one and three. No adaptation occurred in diastolic blood pressure, heart rate, and IL-6 responses to stress. The areas under the curve integrating the stress-induced changes in cortisol and IL-6 reactivity were negatively correlated at visit three ( r = −.54, p = .011), but not at visit one. The IL-6 response to acute mental stress occurs delayed and shows no adaptation to repeated moderate mental stress. The hypothalamus–pituitary–adrenal axis may attenuate stress reactivity of IL-6. The lack of habituation in IL-6 responses to daily stress could subject at-risk individuals to higher atherosclerotic morbidity and mortality.

Evaluation of the pituitary–adrenal axis function following single intraarticular injection of methylprednisolone

To determine the effects of a single session of intraarticular methylprednisolone (IA-MP) injections on the function of the pituitary-adrenal axis. Twenty-five patients with rheumatic diseases were treated with a single IA-MP injection. The dose varied between 20 and 160 mg. The basal cortisol level and the response to 1 microg adrenocorticotropic hormone (ACTH) stimulation were determined before treatment, at 1 day, and at 1 week after IA-MP injections. Further tests were carried out for up to 6 weeks in patients with blunted cortisol response. Results were compared with those obtained in a group of 22 healthy subjects. Before treatment, all patients had normal basal and peak cortisol responses to ACTH (>396 nmoles/liter at 30 minutes). Reduced fasting cortisol levels (<147 nmoles/liter) were detected in 12 of 25 patients (48%) after 1 day, in 1 of 25 patients (4%) after 1 week, and in 1 of 25 patients (4%) 2 weeks after IA-MP injections. Blunted peak cortisol response (<396 nmoles/liter at 30 minutes) was observed in 1 of 25 patients (4%) after 1 day, in 3 of 25 patients (12%) after 1 week, and in 1 of 25 patients (4%) 2 weeks after IA-MP injections. Decreased fasting levels and peak cortisol responses to ACTH stimulation were more common in patients with inflammatory diseases and in those injected with 80-160 mg MP. Single-session IA-MP injection(s) are associated with systemic absorption of MP, causing impaired adrenocortical reserve. Recovery is expected in most patients after 1-2 weeks. Only a few patients exhibited suppression for up to 2 weeks. The magnitude of this suppression depends on the dose injected, and is more common in patients with inflammatory joint diseases. Caution is required if repeated large doses of IA-MP are considered in these patients.

Investigation of the Hypothalamo-pituitary-adrenal Axis and Changes in the Size of Adrenal Glands in Acute Brucellosis

The aim of the study was to investigate the hypothalamo-pituitary-adrenal (HPA) axis by ACTH stimulation test and the changes in adrenal size in acute brucellosis before and after therapy in a prospective study. Sixteen patients with acute brucellosis and 15 healthy subjects were included in the study during the last two years. Cortisol levels were assessed before, 30 and 60 minutes after ACTH (250 microg i.v.) injection and the size of the adrenals was measured in both groups. Mean basal cortisol levels in the patients before the therapy and after the therapy were 22.1 +/- 6.9 microg/dL and 11.3 +/- 6.0 microg/dL, respectively. The difference was statistically significant (p<0.001). There was also statistically significant difference for basal cortisol levels between the healthy subjects (12.2 +/- 4.6 microg/dL) and the patients before the therapy (p<0.001). Peak cortisol responses to ACTH were higher before the therapy in the patients with acute brucellosis (39.3 +/- 10.7 microg/dL) than in the healthy subjects (30.4 +/- 4.8 microg/dL, p = 0.014). However, there was no significant difference for peak cortisol levels in the patients before and after the therapy (32.7 +/- 8.0 microg/dL). Mean basal cortisol levels and peak cortisol responses to ACTH between the patients after the therapy and the healthy controls were similar. Both the maximum width of the adrenal glands and the width of the adrenal limbs were significantly greater before the therapy compared to healthy subjects and post-treatment period. We concluded that the HPA axis is activated and the adrenal glands are enlarged in acute brucellosis, which is reduced after appropriate therapy.

A Comparison Between the Effects of Low (1 μg) and Standard Dose (250 μg) ACTH Stimulation Tests on Adrenal Cortex Functions with Leprosy Patients

Leprosy is a chronic granulomatous disease that either remains localized or widespread depending on the immunological status of the affected patient. It can lead to clinical or subclinical adrenal failure by influencing adrenal steroidogenesis. In the present study, 26 patients (21 males and 5 females) who were diagnosed with lepromatous leprosy and 15 healthy individuals who were compatible with the patients in terms of age and sex were subjected to an adrenocorticotrophic hormone (ACTH) stimulation test.The leprosy and control groups were subjected to 1 μg low dose (LDT) and 250 μg intravenous standard dose (SDT) ACTH stimulation tests after 12-hour nocturnal fasting with an interval of three days. Cortisol responses in 0, 30, and 60 minutes were examined.There was no difference between leprosy and control groups in terms of mean baseline cortisol values. Mean value of the peak cortisol response to both LDT and SDT was found to be significantly lower in the leprosy group than in the control group (p < 0.001 and p < 0.01, respectively). Peak cortisol response to LDT in the leprosy group was found below 20 μg/dL in 9 patients (34.6%). As for the peak cortisol response to SDT, it was lower than 20 μg/dL in 5 patients (19.23%). It was found that LDT response was abnormally low in 4 patients (15.38%) who responded normally to SDT.It was observed that there could be a decrease in adrenocortical reserve capacity although baseline adrenocortical functions were normal in patients with leprosy. It was seen that LDT was more sensitive than SDT in identifying this decrease.

Relationship between stress hormones and testosterone with prolonged endurance exercise

Previous pharmacological and pathological studies have reported negative relationships between circulating testosterone and certain stress hormones (i.e., cortisol and prolactin) in humans. These relationships have subsequently been used in hypotheses explaining the subclinical resting testosterone levels often found in some endurance-trained males, but as of yet no one has specifically examined these relationships as they relate to exercise. Thus, we examined the relationship between total and free testosterone levels and cortisol, and between total and free testosterone and prolactin following prolonged endurance exercise in trained males. Twenty-two endurance-trained males volunteered to run at 100% of their ventilatory threshold (VT) on a treadmill until volitional fatigue. Blood samples were taken at pre-exercise baseline (B0); volitional fatigue (F0); 30 min (F30), 60 min (F60), and 90 min (F90) into recovery; and at 24 h post-baseline (P24 h). At F0 [mean running time = 84.8 (3.8) min], exercise induced significant changes (P<0.05) from B0 in total testosterone, cortisol and prolactin. All three of these hormones were still significantly elevated at F30; but at F60 only cortisol and prolactin were greater than their respective B0 values. Free testosterone displayed no significant changes from B0 at F0, F30, or the F60 time point. At F90, neither cortisol nor prolactin was significantly different from their B0 values, but total and free testosterone were reduced significantly from B0. Cortisol, total testosterone and free testosterone at P24 h were significantly lower than their respective B0 levels. Negative relationships existed between peak cortisol response (at time F30) versus total testosterone (at F90, r=-0.53, P<0.05; and at P24 h, r=-0.60, P<0.01). There were no significant relationships between prolactin and total or free testosterone. In conclusion, the present findings give credence to the hypothesis suggesting a linkage between the low resting testosterone found in endurance-trained runners and stress hormones, with respect to cortisol.

Technical note: effect of corticotropin-releasing hormone on adrenocorticotropic hormone and cortisol in steers.

The objective of this study was to determine an appropriate exogenous dose of bovine corticotropin-releasing hormone (bCRH) to stimulate the physiological effects of the hypothalamic-pituitary-adrenal axis in steers as a method to test the sensitivity of the pituitary and adrenal gland. Twenty 14-mo-old Holstein-Friesian steers were blocked by weight (443.7+/-2.5 kg) and randomly allotted to receive either saline (control) or bCRH (0.1, 0.3, 1.0, or 1.5 microg/kg BW). Animals were housed in a slatted-floor facility (n = 5 per pen). Indwelling jugular catheters, for both the administration of bCRH and blood collection, were fitted on d -1 of the experiment. Saline and bCRH were administered i.v. at time 0. Serial blood samples were collected at -15, 0, 15, 30, 45, 60, 75, 90, 105, 120, 135, 150, 165, and 180 min relative to time 0. Following administration of 0.1 microg of bCRH/kg BW, the peak ACTH response was not significantly different from pretreatment baseline concentrations (mean concentrations as measured at -15 and 0 min before bCRH administration). Mean ACTH concentrations from 0 to 180 min following 0.1 microg of bCRH/kg BW were not significantly different (P = 0.177) from controls. Administration of 0.3, 1.0, and 1.5 microg of bCRH/kg BW increased (P < 0.05) peak ACTH above pretreatment concentrations, and mean ACTH from 0 to 180 min for these treatments were greater (P < 0.05) than for controls. Peak cortisol responses to all bCRH treatments were greater (P < 0.05) than those to pretreatment concentrations. Mean cortisol concentrations from 0 to 180 min were greater (P < 0.05) in all bCRH-treated steers than in controls, but there were no significant differences among the bCRH treatments. The ratio of mean cortisol to mean ACTH for all bCRH doses tested differed (P < 0.05) from control values, indicating reactivity of the adrenals. In conclusion, bCRH challenge may be a useful method for testing the sensitivity of the hypothalamic-pituitary-adrenal axis in steers subjected to stressful husbandry conditions, and a minimum dose of 0.3 microg of bCRH/kg BW is required to stimulate physiological effects of stressor hormones.