Microg ACTH Research Articles

Salivary Cortisol as an alternative for serum Cortisol in the low-dose adrenocorticotropic hormone stimulation test?

Salivary cortisol is unaffected by cortisol binding globulin and reflects free serum cortisol as compared to total serum cortisol. The aim of the present study was to compare the salivary cortisol response with the serum cortisol response in a low-dose (1-microg) ACTH test in a clinical setting and to determine the optimal cut-off value of salivary cortisol as an alternative to serum cortisol. We measured serum and salivary cortisol responses to iv administration of 1-microg ACTH in 51 patients (17 males) referred to the Department of Clinical Chemistry for ACTH-testing. Serum cortisol was assessed before, 20, and 30 min after ACTH-administration, and salivary cortisol was assessed before and 30 min after ACTH administration. Mean cortisol at baseline, 20, and 30 min were 0.44 micromol/l (SD: 0.22), 0.64 micromol/l (SD: 0.24), and 0.70 micromol/l (SD: 0.25), respectively. Median basal salivary cortisol was 8.4 nmol/l [interquartile range (IQR): 3.8-14.2]. Salivary cortisol at 30 min equaled 35.9 nmol/l (IQR: 21.1-46.2). Basal salivary cortisol was significantly correlated with salivary cortisol at 30 min (r=0.53; p<0.001). Salivary cortisol at 30 min of 23.5 nmol/l had a sensitivity and specificity of 78.1% and 70.0%, respectively as compared to the serum cortisol cut-off values of >0.50 micromol/l. The salivary low-dose ACTH-test yields more dynamic responses than serum cortisol. However, the sensitivity and specificity of salivary cortisol are too low to be adequate as an alternative to the serum cortisol measurements. In women on estrogen therapy, however, the use of salivary cortisol might be superior to serum cortisol.

Perioperative Cortisol can predict hypothalamus-pituitary-adrenal status in clinically non-functioning pituitary adenomas

Peri-operative steroids are administered routinely to patients with pituitary adenoma undergoing transsphenoidal adenomectomy (TSA). To evaluate hypothalamic-pituitary-adrenal (HPA) axis before and after programmed endoscopic TSA (E-TSA) in patients with clinically non-functioning pituitary macroadenoma (NFPA). Open prospective. Tertiary referral hospitals. Seventy-two consecutive patients (20-87 yr, 37 males). Adrenal steroid replacement therapy (ASRT) was given only in patients with hypocortisolism [08:00 h cortisol (F) <8 microg/dl]. After ETSA, achieving wide (>90%) selective resection of the adenoma in all, F and clinical picture were checked at day 2. The low-dose (1 microg) ACTH test (LDACTH) was performed at 6 weeks and repeated at 12 months. Hypocortisolism was present pre-operatively in 14 patients (19.4%), persisted post-operatively in all but one, and was detected de novo at the post-operative day 2 control in 6 (10.3%). In all but one the post-operative day 2 basal F and peak F during LDACTH test were concordant. No patient whose F was > 8 microg/dl was treated with ASRT or developed symptoms of adrenal failure during the follow-up (1-11 yr, median 5). HPA function is usually preserved in NFPA and is infrequently impaired after complete tumor removal by E-TSA. The 08:00 h. plasma cortisol evaluation before and 2 days after surgery, using as cut-off the value of 8 microg/dl, allows full evaluation of HPA status. Peri-operative steroid treatment should be given only in patients with hypocortisolism.

Peri-operative adrenocortical response to low-dose (1 μg) ACTH and relation to postoperative complications in patients undergoing elective abdominal surgery

To test the hypothesis that reduced responsiveness to adrenocorticotropin (ACTH) stimulation before elective major abdominal surgery is associated with an increased incidence of postoperative complications. A low-dose (1 microg) ACTH test was performed the day before surgery, during the operation, on the first postoperative day, and before discharge from the hospital in 77 patients undergoing major abdominal surgery (age 62 [47;69] yrs [median, quartiles]; 30 female). Thirty-one patients undergoing minor, non-abdominal surgery (mostly inguinal hernia repair) (age 57 [40;66] yrs; 14 female) served as controls with minor surgical stress. A stimulated plasma cortisol concentration >or=500 nmol/l or an increment of >or=200 nmol/l in response to 1 microg ACTH was defined as normal. Scores for surgical stress and comprehensive risk, postoperative complications, and length of hospital stay (LOS) were assessed. On the day before major abdominal surgery, basal and stimulated plasma cortisol were 242 (165;299) nmol/l and 497 (404;568) nmol/l, respectively. Eighteen (23%) patients had an abnormal ACTH test, and 7 of these (39%) had complications versus 25 (42%) of the 59 patients with normal ACTH tests (P = .992). Surgical stress, comprehensive risk, and intra- and postoperative basal cortisol levels were higher and the response to ACTH stimulation smaller in patients with major abdominal compared to minor surgery. The peri-operative course of ACTH responses was not associated with complications or LOS in abdominal surgery patients. In patients scheduled for abdominal surgery, pre-operatively reduced adrenal response to stimulation with 1 microg ACTH is common but not associated with postoperative complications.

Effect of very low LDL-cholesterol on cortisol synthesis

Cardiovascular disease is the most common cause of mortality around the world. The relationship between coronary artery disease and serum LDL-cholesterol levels has become obvious in recent years and statin treatment has been used more commonly. However, influence of intensive statin treatment on steroidal hormonal functions has remained unclear. In this paper, we evaluated the effect of very low LDL levels (<70 mg/dl) on serum cortisol concentrations, which is mainly synthesized from cholesterol. Forty-one patients with serum LDL-cholesterol levels below 70 mg/dl were included in the study. The control group consisted of 38 healthy people. Adrenal axis was evaluated by means of cortisol response to 1 microg ACTH test. The mean age of patients was 52.45+/-10.74 yr. Of 41 patients, 19 (46.9%) were female. There were statistically significant differences between the study and control group according to their serum cholesterol and LDL levels. Main serum LDL levels were 58+/-11.4 mg/dl and 131+/-25.8 mg/dl in the study and control group, respectively. There were no statistically significant differences in response to 1 microg ACTH stimulation test at basal, 30 min and 60 min among both study and control group. Atorvastatin treatment was generally well tolerated. Our data reflect that having serum LDL-cholesterol levels below 70 mg/dl did not affect the adrenal axis function in terms of cortisol.

Respuesta hemodinámica precoz a los corticoides en el shock séptico

Treatment with low dose steroids (LDST) in patients with septic shock treated with vasoactive agents has been related to earlier shock reversal. Patients with low baseline cortisol and a blunted response to the corticotropin test are more likely to benefit from LDST, so we compared the immediate hemodynamic response in patients with septic shock who received LDST with that of those who did not receive LDST.Retrospective study.Intensive Care Unit (ICU) of a tertiary university hospital.We studied 96 patients admitted to the ICU. Patients were classified in two groups of 48 patients: group A received LDST and group B did not; patients were matched according to baseline cortisol levels and norepinephrine requirements.All patients underwent a short corticotropin test (250 microg ACTH) within 72 h of septic shock onset.Baseline cortisol, delta cortisol, peak cortisol, norepinephrine reduction after LDST, and duration of shock.The two groups were comparable: baseline and stimulated cortisol levels before corticotropin test were similar, and there were no differences in the norepinephrine dose before and 24 h after testing adrenal response (p = 0.98 and p = 0.53, respectively). Norepinephrine reduction at 24 h after testing was not correlated with baseline cortisol or with adrenal response to the corticotropin test.LDST was not associated to improved 24-hour hemodynamic response, irrespective of the baseline and stimulated cortisol levels.

Hypothalamic-pituitary-adrenal axis in patients with ankylosing spondylitis

To investigate the hypothalamic-pituitary-adrenal (HPA) axis via the insulin-tolerance test (ITT), standard-dose (250 microg) ACTH test (SDT) and low-dose (1 microg) ACTH test (LDT) in patients with ankylosing spondylitis (AS). The study group included 13 male patients with AS who were diagnosed according to the Modified New York criteria, and 8 healthy male subjects and was carried out at the Department of Physical Medicine and Rehabilitation, Erciyes University Medical School. ACTH stimulation tests were carried out by using 1 microg and 250 microg i.v. ACTH as a bolus injection, and blood samples were drawn at 0, 30 and 60 min. ITT was performed by using intravenous (i.v.) soluble insulin, and serum glucose and cortisol levels were measured before and after 30, 60, 90 and 120 min. All of the tests were performed consecutively with 3-day intervals, after an overnight fast. There were no significant differences between the patients with AS (mean age 36.9+/-6.7 years) and the healthy subjects (mean age 37.4+/-5.7 years) in terms of age. The basal cortisol levels in the AS group measured during LDT, SDT and ITT (556+/-204 nmol/l; 524+/-169 nmol/l; 418+/-232 nmol/l, respectively) were comparable to the values of the control group (572+/-199 nmol/l; 520+/-182 nmol/l; 424+/-194 nmol/l, respectively). There were also no significant differences in peak cortisol responses between the two groups using LDT (patients 1025+/-339 nmol/l; controls 844+/-236 nmol/l), SDT (patients 1082+/-243 nmol/l; controls 1120+/-131 nmol/l) and ITT (patients 834+/-256 nmol/; controls 820+/-239 nmol/). In contrast with findings in other inflammatory diseases such as rheumatoid arthritis and polymyalgia rheumatica, the present data indicate that there is no apparent abnormality of the HPA axis activity in patients with AS.

Secondary hypoadrenalism

Secondary adrenal insufficiency (SAI) is a clinical disorder that results from hypothalamic or hypophyseal damage or from prolonged administration of supraphysiological doses of glucocorticoids. Since glucocorticoids are widely used for a variety of diseases, the prevalence of SAI is by far exceeding that of primary adrenal insufficiency. Although the presentation of adrenal insufficiency may be insidious and difficult to recognize, an appropriate adrenocortical hormone replacement could lead to a normal quality of life and longevity can be achieved. The spectrum of adrenal insufficiency ranges from overt adrenal crises to subtle dysfunctions in asymptomatic patients who may be at risk of developing acute adrenal insufficiency since their hypothalamic-pituitary-adrenal (HPA) axis cannot appropriately react to stress. Thus, identification of patients with subtle abnormalities of the HPA is mandatory for avoiding this life-threatening event in stressful conditions. The optimal tests and the optimal testing sequence for adrenal insufficiency are still matter of debate. Insulin tolerance test (ITT) could be the gold standard, as it tests the whole HPA axis, but there are some patients who pass the ITT failing the ACTH test. Various alternatives to the ITT, including the standard cosyntropin stimulation test (SST) and low-dose SST, have been proposed since the adrenal gland in SAI loses the capacity for a prompt response to ACTH stimulation. The standard ACTH dose, but not the 1 microg dose, increases adrenal blood flow and this may contribute to produce an early cortisol response of greater magnitude. Moreover, the loss of the early cortisol response to ACTH stimulation could be a specific property of adrenal insufficiency, thus being a sensitive and early marker of failing adrenal function. While the results of the SSTs are often positive in patients with long-standing and severe disease, in patients with mild or recent-onset SAI these tests, using either 250 microg or 1 microg ACTH, tend to give normal results; thus, a negative cosyntropin test result does not rule out the possibility of SAI. Further studies with a systematic comparison of the different tests in large series of patients submitted to a prolonged follow-up are needed to solve the controversy of the optimal diagnostic strategy of SAI.

Effect of growth hormone deficiency and recombinant hGH (rhGH) replacement on the hypothalamic–pituitary–adrenal axis in children with idiopathic isolated GH deficiency

Recombinant hGH (rhGH) therapy may unmask central hypoadrenalism in adults with organic GH deficiency (GHD), likely by normalizing 11beta-hydroxysteroid dehydrogenase type 1 isoenzyme (11betaHSD1) activity and reducing cortisone to cortisol conversion. The aim of the present study was to evaluate the hypothalamic-pituitary-adrenal (HPA) axis in children with idiopathic isolated GHD and normal pituitary magnetic resonance imaging (MRI) both before and during rhGH therapy. This was a single-centre study of 10 consecutive children [five males and five females, mean age: 12.2 +/- 1.0 year]. Evaluation was performed at baseline and on rhGH (mean duration: 10.9 +/- 2.9 months, mean dose: 0.030 +/- 0.002 mg/kg bw/day). HPA function was assessed by serum cortisol levels before and after appropriate provocative stimuli, that is, 1 microg ACTH test (N = 5 patients) or insulin tolerance test (ITT, N = 5 patients), evaluating all children with the same stimulation test both before and during rhGH therapy. Central hypoadrenalism was excluded by the presence of either a peak of > 500 nmol/l or a rise in cortisol levels of > 200 nmol/l, after both tests. On rhGH therapy, serum IGF-I levels normalized, while serum cortisol and ACTH levels did not significantly differ from those recorded at baseline. The mean serum cortisol peak after both provocative tests was not significantly different on rhGH therapy and at baseline (498 +/- 41 vs. 580 +/- 35 nmol/l, respectively, P = 0.06), the mean cortisol rise being 280 +/- 45 and 270 +/- 36 nmol/l on rhGH and at baseline, respectively. According to the diagnostic criteria, no child became hypoadrenal on rhGH, contrary to what observed in patients with organic GHD, further supporting the view that only in patients with organic multiple pituitary hormone deficiency GHD masks the presence of a hidden central hypoadrenalism.

A prospective study on adrenal cortex responses and outcome prediction in acute critical illness: results from a large cohort of 203 mixed ICU patients

To assess whether adrenal cortex hormones predict ICU mortality in acute, mixed, critically ill patients. Prospective study in consecutive intensive care patients in the general ICU of a teaching hospital. 203 severely ill patients with multiple trauma (n = 93), medical (n = 57), or surgical (n = 53) critical states. Within 24 h of admission in the ICU a morning blood sample was obtained to measure baseline cortisol, corticotropin (ACTH), and dehydropiandrosterone sulfate (DHEAS). Subsequently a low-dose (1 microg) ACTH test was performed to determine stimulated cortisol. The incremental rise in cortisol was defined as stimulated minus baseline cortisol. Overall, 149 patients survived and 54 died. Nonsurvivors were older and in a more severe critical state, as reflected by higher SOFA and APACHE II scores. Nonsurvivors had a lower incremental rise in cortisol (5.0 vs. 8.3 microg/dl and lower DHEAS (1065 vs. 1642 ng/ml) than survivors. The two groups had similar baseline and stimulated cortisol. Multivariate logistic regression analysis revealed that age (odds ratio 1.02), SOFA score (1.36), and the incremental rise in cortisol (0.88) were independent predictors for poor outcome. In general ICU patients a blunted cortisol response to ACTH within 24 h of admission is an independent predictor for poor outcome. In contrast, baseline cortisol or adrenal androgens are not of prognostic significance.

Relative adrenal insufficiency: an identifiable entity in nonseptic critically ill patients?

To determine whether relative adrenal insufficiency (RAI) can be identified in nonseptic hypotensive patients in the intensive care unit (ICU). Retrospective study in a medical-surgical ICU of a university hospital. One hundred and seventy-two nonseptic ICU patients (51% after trauma or surgery), who underwent a short 250 microg ACTH test because of > 6 h hypotension or vasopressor/inotropic therapy. On the test day, the Simplified Acute Physiology Score II (SAPS II) and Sequential Organ Failure Assessment (SOFA) score were calculated to estimate disease severity. The ICU mortality until day 28 was recorded. Best discriminative levels of baseline cortisol, increases and peaks were established using receiver operating characteristic curves. These and corticosteroid treatment (in n = 112, 65%), among other variables, were examined by multiple logistic regression and Cox proportional hazard regression analyses to find independent predictors of ICU mortality until day 28. ICU mortality until day 28 was 23%. Nonsurvivors had higher SAPS II and SOFA scores. Baseline cortisol levels correlated directly with albumin levels and SAPS II. In the multivariate analyses, a cortisol baseline > 475 nmol/l and cortisol increase < 200 nmol/l predicted mortality, largely dependent on disease severity but independent of albumin levels. Corticosteroid (hydrocortisone) treatment was not associated with an improved outcome, regardless of the ACTH test results. In nonseptic hypotensive ICU patients, a low cortisol/ACTH response and treatment with corticosteroids do not contribute to mortality prediction by severity of disease. The data thus argue against RAI identifiable by cortisol/ACTH testing and necessitating corticosteroid substitution treatment in these patients.

Salivary cortisol in low dose (1 µg) ACTH test in healthy women: comparison with serum cortisol

To date, a single report has appeared on the use of salivary cortisol for adrenal function testing with a low dose ACTH, although 1 microg has become preferred as a more physiological stimulus than the commonly used 250 microg ACTH test. Our present study was aimed to obtain physiological data on changes of free salivary cortisol after 1 microg ACTH stimulation. This approach was compared with the common method based on the changes of total serum cortisol. Intravenous, low-dose ACTH test was performed in 15 healthy women (aged 22-40 years) with normal body weight, not using hormonal contraceptives, in the follicular phase of the menstrual cycle. Blood and saliva for determination of cortisol were collected before ACTH administration and 30 and 60 min after ACTH administration. Basal concentration of salivary cortisol (mean +/- S.E.M., 15.9+/-1.96 nmol/l) increased after 1 microg ACTH to 29.1+/-2.01 nmol/l after 30 min, and to 27.4+/-2.15 nmol/l after 60 min. The differences between basal and stimulated values were highly significant (p<0.0001). The values of salivary cortisol displayed very little interindividual variability (p<0.04) in contrast to total serum cortisol values (p<0.0001) A comparison of areas under the curve (AUC) related to initial values indicated significantly higher AUC values for salivary cortisol than for total serum cortisol (1.89+/-0.88 vs. 1.22+/-0.19, p<0.01). Correlation analysis of serum and salivary cortisol levels showed a borderline relationship between basal levels (r=0.5183, p=0.0525); correlations after stimulation were not significant. Low-dose ACTH administration appeared as a sufficient stimulus for increasing salivary cortisol to a range considered as a normal adrenal functional reserve.

A Low Dose Adrenocorticotropin Test (1 μg ACTH) for the Evaluation of Adrenal Function in Children with ß-Thalassemia Receiving Hypertransfusion with Suboptimal Iron-chelating Therapy

A cross-sectional study of adrenal function was carried out in 48 patients with beta-thalassemia who were receiving hypertransfusion with suboptimal desferoxamine. A low dose adrenocorticotropic hormone (1 microg ACTH) stimulation test was performed using the cut-off criteria of peak cortisol for adrenal sufficiency >18 microg/dl. Adrenal impairment was diagnosed in 22 patients, giving a prevalence of 45.8%. The peak cortisol concentrations in normal and impaired adrenal function groups were 26.22 +/- 2.84 and 14.03 +/- 3.12 microg/dl, respectively, and the mean basal morning cortisol was 8.93 +/- 2.97 and 6.52 +/- 2.45 microg/dl, respectively. There was no significant difference in any clinical characteristic between the patients with impaired adrenal function and those with normal adrenal function.

Low‐dose ACTH (1 µg) salivary test: a potential alternative to the classical blood test

Salivary cortisol is unaffected by cortisol binding globulin (CBG) and hence allows CBG-related variations in serum total cortisol to be bypassed. We assessed whether or not salivary cortisol can be used for the low-dose (1 microg) ACTH test in subjects with presumed normal and elevated levels of CBG. We measured serum and salivary cortisol responses to intravenous administration of 1 microg ACTH in 14 healthy volunteers, 14 'hyperoestrogenic' women [in their first or early second trimester of pregnancy, using oral contraceptives (OC) or on hormone replacement therapy (HRT)] and 10 patients with secondary hypoadrenalism. Cortisol levels were recorded before as well as 30 and 60 min (+30; +60 min) after ACTH administration. Baseline salivary cortisol did not differ significantly between the hypoadrenal and healthy patients (7.11+/-1.4 and 12.13+/-1.59 nmol/l; P=0.48) but there was a significant difference between hypoadrenal and hyperoestrogenic patients (18.94+/- 3.44 nmol/l; P=0.01). The largest difference between hypoadrenal patients and healthy individuals was observed at+30 min (9.16+/-2.8, 52.65+/-8.78 and 48.81+/- 6.9 nmol/l, in the hypoadrenal, healthy and hyperoestrogenic patients, respectively; P< 0.05). At this time-point values< 24.28 nmol/l were found in all hypoadrenal patients and cortisol levels >or= 27.6 nmol/l were found in 26 out of 28 healthy volunteers. ACTH-stimulated serum cortisol but not salivary cortisol was significantly higher in hyperoestrogenic women than in the healthy volunteers at either+30 or+60 min. The salivary low-dose ACTH test yields results that parallel the response of circulating cortisol to ACTH and may provide an alternative to the blood test, particularly in situations where increased CBG levels complicate the changes in serum cortisol levels.

Adrenal Hyperandrogenism Is Induced by Fetal Androgen Excess in a Rhesus Monkey Model of Polycystic Ovary Syndrome

Adrenal androgen excess is found in approximately 25-60% of women with polycystic ovary syndrome (PCOS), but the mechanisms underlying PCOS-related adrenal androgen excess are unclear. The objective of this study was to determine whether adrenal androgen excess is manifest in a nonhuman primate model for PCOS. Six prenatally androgenized (PA) and six control female rhesus monkeys of similar age, body weight, and body mass index were studied during d 2-6 of two menstrual cycles or anovulatory 30-d periods. Predexamethasone adrenal steroid levels were assessed in the first cycle (cycle 1). In a subsequent cycle (cycle 2), occurring one to three cycles after cycle 1, adrenal steroids were determined 14.5-16.0 h after an i.m. injection of 0.5 mg/kg dexamethasone (postdexamethasone levels) and after an i.v. injection of 50 microg ACTH-(1-39). Both before and after dexamethasone, serum levels of dehydroepiandrosterone (DHEA) in PA females exceeded those in controls. After ACTH injection, PA females exhibited higher circulating levels of DHEA, androstenedione, and corticosterone but comparable levels of 17alpha-hydroxyprogesterone, cortisol, the sulfoconjugate of DHEA, and testosterone compared with controls. Enhanced basal and ACTH-stimulated adrenal androgen levels in PA female monkeys may reflect up-regulation of 17,20 lyase activity in the adrenal zona reticularis, causing adrenal androgen excess comparable with that found in PCOS women with adrenal androgen excess. These findings open the possibility that PCOS adrenal hyperandrogenism may have its origins in fetal androgen excess reprogramming of adrenocortical function.

Intranasal Administration of ACTH(1-24) Stimulates Catecholamine Secretion

Previously, we reported that intranasal (IN) ACTH(1-24) administration stimulates adrenocortical steroid secretion in normal subjects. To determine the efficiency of transmucosal absorption of ACTH into the adrenal medulla, we measured serum cortisol, aldosterone, epinephrine, norepinephrine and dopamine levels after IN vs. intravenous (IV) administration of 250 microg ACTH(1-24) in 7 healthy adult men (mean age 21.7 +/- 1.2 yr; range, 21 - 24 yr). Blood was collected at 0, 30, 60 and 120 min after administration of ACTH(1-24), and the levels of adrenocortical steroids and catecholamines were measured by specific RIA and HPLC methods, respectively. There were no side effects associated with IN or IV ACTH administration. Consistent with the previous study, serum cortisol and aldosterone increased after IN administration of ACTH(1-24), peaking 30 min after administration. Sixty minutes after IN and IV administration of ACTH, epinephrine levels increased by 41.9 +/- 13.1 % and 63.3 +/- 11.8 %, respectively, and remained elevated throughout the sampling period. Thirty minutes after IN or IV administration of ACTH(1-24), plasma norepinephrine levels increased by 55.9 +/- 13.4 % and 73.7 +/- 15.0 %, respectively, peaking 30 min after ACTH(1-24) administration, and decreasing to basal levels within 60 min. Plasma dopamine levels did not change after IN administration of ACTH(1-24). Adrenocortical steroid and catecholamine levels did not increase after IN administration of saline. These results demonstrate that IN administration of ACTH(1-24) not only stimulates adrenocortical steroids, but also epinephrine and norepinephrine.

Cortisol Response in Relation to the Severity of Stress and Illness

The aim of the study was to compare the adrenal response, the course of the ACTH/cortisol ratio, as well as the variance and the diagnostic performance of different cutoffs after 1 and 250 microg ACTH stimulation in different stress situations. We investigated three groups with increasing stress levels: ambulatory controls (group A; n = 20), hospitalized medical patients (group B; n = 25), and patients undergoing coronary artery bypass grafting (group C; n = 29). All subjects underwent four consecutive ACTH stimulation tests and were randomized to either a 1- or 250-microg dose. Stimulated cortisol levels in group A were similar to basal cortisol levels under maximal stress (C3; P = 0.8). Peak cortisol concentrations were higher after 250 microg compared with 1 microg ACTH in group B (P = 0.006) and under maximal stress after extubation (group C3; P = 0.027), whereas there were no differences in group A. The ACTH/cortisol ratio was lower in surgical patients after extubation compared with unstressed conditions (P < or = 0.03) The within-subject variance was similar in ambulatory controls and medical patients and after both ACTH doses (all 17-36% of total variance). Cutoff dependent, the diagnosis of relative adrenal insufficiency would have been made in 0-58.3%, respectively. In moderate and major stress situations, cortisol concentrations in patients without hypothalamic-pituitary-adrenal disease were higher after stimulation with 250 microg compared with 1 mug ACTH. Data from our study give insight into the physiological adaptations of the hypothalamic-pituitary-adrenal axis to stress.

Endocrine Alterations in Critically Ill Patients With Stroke During the Early Recovery Period

Endocrine abnormalities in critically ill patients with stroke during the early recovery period have not been well characterized. To investigate this issue, 33 consecutive mechanically ventilated patients (27 men) with hemorrhagic (n = 21) or ischemic (n = 12) stroke having a mean age of 57 +/- 12 years were studied. Glasgow Coma Scale score on admission in the hospital was 8 +/- 3. The following basal hormones were measured within 72 hours postextubation: cortisol, corticotropin (ACTH), free thyroxine, tri-iodothyronine, thyroid-stimulating hormone, testosterone, estradiol, follicle-stimulating hormone, luteinizing hormone, growth hormone, and insulin-like growth factor (IGF)-1. Subsequently, a low-dose (1 microg) ACTH stimulation test was performed. Twenty-six (79%) patients showed endocrine alterations. The most common change was low IGF-1 levels compatible with growth hormone deficiency (45%), followed by hypogonadism (39%), thyroid dysfunction (36%), and cortisol hyporesponsiveness (33%). Neuroendocrine changes occur with high frequency in critically ill patients with stroke during the early recovery period. It remains to be determined whether these changes have implications for functional and/or clinical outcome.

The adrenal sensitivity to ACTH stimulation is preserved in anorexia nervosa.

Hyperactivity of hypothalamus-pituitary-adrenal (HPA) axis in anorexia nervosa (AN) has been demonstrated and is likely to reflect a central nervous system (CNS)-mediated effect of starvation. Alterations in the adrenal response to ACTH in AN have also been reported by some authors. In order to define the adrenal sensitivity to ACTH in this condition, we studied cortisol (F), aldosterone (A) and DHEA responses to the sequential administration of low and supramaximal ACTH 1-24 doses (0.06 microg/m2 ACTH 1-24 iv at 0 min and 250 microg ACTH 1-24 iv at +60 min, respectively) in 10 young women with AN [ANW, age 21.2 +/- 0.9 yr, body mass index (BMI) 15.7 +/- 0.6 kg/m2]. The results in this group were compared with those recorded in 10 healthy normal women (HW, 23.4 +/- 1.1 yr, 21.9 +/- 0.9 kg/m2). In ANW urinary F levels were similar to those in HW. Basal serum F, A and DHEA levels in ANW were not significantly different from those in HW. In HW the lowest ACTH dose induced a significant (p<0.05) increase of F, A and DHEA. The maximal ACTH dose induced F, A and DHEA increases greater (p<0.05) than those induced by the lowest ACTH dose. In ANW both ACTH doses induced significant (p<0.05) F and DHEA increases which were not significantly different from those in HW, though a trend toward a lower cortisol response after ACTH 0.06 microg/m2 in ANW was present. Like in HW, in ANW the maximal ACTH dose induced F and DHEA increases greater (p<0.01) than those induced by the lowest dose. Unlike HW, in ANW A levels did not increase after the lowest ACTH dose while they increased after the maximal one overlapping the response in HW. In conclusion, the cortisol and DHEA responses to a very low and a supra-maximal ACTH dose in patients with AN were similar to those in healthy subjects, indicating that the sensitivity to ACTH of the fasciculata and reticularis adrenal zones is preserved in this condition. On the other hand, a reduced sensitivity to ACTH of the glomerularis adrenal zone in patients with AN is suggested by the lack of aldosterone response to the lowest corticotropin dose.

Common polymorphisms in the glucocorticoid receptor gene are associated with adrenocortical responses to psychosocial stress.

Chronic dysregulation of hypothalamus-pituitary-adrenal axis activity is related to several stress-related disorders. Evidence suggests that polymorphisms in the glucocorticoid receptor (GR) gene may have an impact on this neuroendocrine system. In the present investigation, 112 healthy males were studied to estimate the impact of three GR gene polymorphisms (BclI RFLP, N363S, ER22/23EK) on cortisol and ACTH responses to psychosocial stress (Trier Social Stress Test) and pharmacological stimulation (1 microg ACTH(1-24), 0.5 mg dexamethasone). Because only four ER22/23EK heterozygotes were identified, these subjects were not statistically analyzed. Compared with subjects with the wild-type GR genotype (n = 36), 363S allele carriers (n = 10) showed significantly increased salivary cortisol responses to stress, whereas the BclI genotype GG (n = 18) was associated with a diminished cortisol response. BclI heterozygotes and homozygotes (GG) exhibited a trend toward lower ACTH responses, compared with wild-type subjects and 363S carriers. The cortisol response to ACTH(1-24) administration was not significantly different between genotypes. After dexamethasone ingestion, 363S carriers showed a trend toward an enhanced cortisol suppression. This is the first report documenting an impact of GR gene polymorphisms on cortisol (and perhaps ACTH) responses to psychosocial stress. These variants may contribute to the individual vulnerability for hypothalamus-pituitary-adrenal-related disorders.

Prolonged psychological stress suppresses cortisol secretion

Response to acute psychological stress is characterized by activation of the hypothalamic-pituitary-adrenal (HPA) axis and the sympathetic nervous system. However, response to the prolonged psychological stress is less well known. This study was designed as a prospective assessment of cortisol secretion during prolonged psychological stress induced by continuous air raids and after elimination of the stress-inducing factor. The study group consisted of five healthy subjects (34-39 years). Psychological and endocrine (morning cortisol and 1 microg ACTH test) testing was done 2 months after the war had begun and 18 months after the end of it. Psychiatric assessment was done at the same periods, and 30 months after the start of the study. After 2.5 years of follow-up, there were no signs of endocrine or psychiatric disorders in any of the subjects. After the war, Beck Inventory of Depression and Hamilton Anxiety Rating Scale scores were significantly reduced. Suppression of the HPA axis was present during the war but not after. Prolonged psychological stress is associated with a transient suppression of the HPA axis, manifested by low morning cortisol and reduced cortisol response to ACTH. The reduction of cortisol response is sufficient to cause false diagnosis of HPA insufficiency.