A simple radioimmunoassay for plasma cortisol: comparison with the fluorimetric method of determination

A quick and simple method for the radioimmunoassay of plasma cortisol is described. The mean morning plasma cortisol concentration in 43 normal subjects was 9.8 +/- 3.1 (S.D.) microgram/100 ml with a range of 5.0-19.5 microgram/100 ml. Mean midnight concentration in 24 normal subjects was 4.3 +/- 2.3 (S.D.) microgram/100 ml with a range of 1.4-9.6 microgram/100 ml. When compared with the fluorimetric method the mean results by radioimmunoassay of 154 routine specimens were 23% lower. In samples from unstimulated patients, regression analysis of results obtained by the two methods gave a correlation coefficient (r) of 0.93, regression line slope of 1.1, and intercept of 1.4 microgram. Mean radioimmunoassay results were 15% lower. When plasma cortisol concentration was above the normal range (greater than 30 microgram/100 ml) the regression line slope was 0.87, the intercept 17.9 microgram, r = 0.87 and mean radio immunoassay results were 37% lower. Plasma cortisol concentration in patients after insulin or Synacthen stimulation exhibited similar responses when measured by either method. Plasma cortisol concentration in normal subjects given metyrapone was lower when measured by radioimmunoassay (mean +/- S.D. = 8.7 +/- 2.7 microgram/100 ml) than when measured by fluorimetry (18.5 +/- 10.8 microgram/100 ml). The diagnostic usefulness of the two methods, ease of assay, and costs are compared.     

Effect of somatostatin-octreotide on secretion of adrenocorticotropin, cortisol and neuro-hypophyseal hormones in acromegaly

The present work was aimed at studying the combined effects of somatostatin and corticotropin releasing hormone on the activities of the pituitary-adrenocortical axis and neurohypophysis. Patients with active acromegaly were intravenously injected with a 100 micrograms human corticotropin releasing hormone bolus before and after a 3-month subcutaneous treatment with somatostatin-octreotide (SMS 201 995; Sandostatin; 200 micrograms t. i. d.). When the Sandostatin effect was investigated, corticotropin releasing hormone test was started 2 hrs after its first daily dose. Peripheral venous blood samples were taken before and 20, 60, 90 and 120 min after the corticotropin releasing hormone load. Plasma corticotropin, arginine-8-vasopressin and oxytocin were measured by radioimmunoassay, and serum cortisol by fluorimetry. In healthy subjects, corticotropin releasing hormone stimulus elicited increases of plasma corticotropin, serum cortisol, plasma arginine-8-vasopressin and oxytocin levels by 186, 41, 178 and 58 per cent, respectively. Untreated acromegalics exhibited missing arginine-8-vasopressin, blunted corticotropin, and normal oxytocin and cortisol responses. Sandostatin therapy improved the arginine-8-vasopressin reaction, suppressed the basal levels of corticotropin and cortisol with the maintenance of cortisol stimulability; the peak-reaction of corticotropin became normal in two patients, however, with a shortened duration of response. Diuresis of the patients increased under the treatment. Sandostatin markedly alleviated the clinical symptoms and suppressed the growth hormone secretion, but did not influence the size of the pituitary adenomas. Among other factors, the alterations of growth hormone and cortisol may be hypothesized to take part in the changes of the corticotroph and neurohypophysial functions.     

Solitary vertebral plasmacytoma

This study compares fetal corticoid response from conventional dose (12.0 mg) intramuscular betamethasone to large dose (1,000 mg) intravenous cortisol administered to women in premature labor for acceleration of fetal lung maturity. To compare these two regimens, 14 women selected at random were treated in groups of seven with either cortisol or betamethasone. Peripheral levels of unconjugated estriol were measured by specific radioimmunoassay prior to the cortisol dose and at 1, 4, 8, and 12 hours following the dose. The rate of corticoid delivery to the fetal hypothalamic-adrenal axis was estimated by the per cent suppression of unconjugated estriol at each post-treatment interval. Least-squares regression lines fitted (P less than 0.01) for each regimen were compared for time saved (delta t) when cortisol was used. Mean delta t (1, 4, 8, and 12 hours) was 9.0 +/- 0.2 S.E.M. hours. It is concluded that: (1) Intravenous cortisol delivers a fetal corticoid effect that is significantly more rapid in onset and more profound in magnitude than does intramuscular betamethasone and that (2) the cortisol regimen is probably better suited to the acceleration of fetal lung maturation in premature labor when time is short and rapid action is essential.     

Hypothalamic-pituitary-adrenal axis function in patients with active rheumatoid arthritis: a controlled study using insulin hypoglycemia stress test and prolactin stimulation

OBJECTIVE: To study the response of cortisol and of prolactin (PRL) to specific stimuli in rheumatoid arthritis (RA). METHODS: We measured the response of cortisol to insulin induced hypoglycemia and of PRL to thyrotropin releasing hormone (TRH) in 10 patients with active RA and in 10 paired control subjects. All were women with regular menstrual cycles. They had never received corticosteroids before the study. The PRL concentration was assessed by chemiluminescence immune assay and the cortisol concentration by radioimmunoassay. RESULTS: The basal serum levels of cortisol (14.47+/-2.5 microg/dl) and PRL (10.1+/-1.3 ng/ml) in the RA group were not significantly different from those of the control group (12.3+/-1.1 microg/dl and 13.7+/-2.4 ng/ml, respectively). The peak value of cortisol after hypoglycemia was comparable in both groups (25.5+/-2.4 microg/dl in RA vs. 26.0+/-1.5 ng/ml in controls). The integrated cortisol response to hypoglycemia expressed as area under the response curve (AUC) did not differ significantly in either group (1927+/-196 in RA vs. 1828+/-84 in controls). The interval-specific "delta" cortisol response was significantly higher for the 30 to 45 min interval in controls compared to patients with RA (9.8+/-0.9 microg/dl vs. 6.1+/-1.1 microg/dl; p = 0.02). The peak of PRL after TRH did not differ significantly in both groups (56.4+/-6.4 ng/ml in RA vs. 66.3+/-7.7 ng/ml in controls) and the AUC of PRL secretion after TRH was comparable in both groups (3245+/-321 vs. 4128+/-541). CONCLUSION: Our findings suggest that active RA is associated with subtle dysfunction of the hypothalamic-pituitary-adrenal glucocorticoid function and normal PRL secretion.     

Impaired cortisol binding to glucocorticoid receptors in hypertensive patients

We compared glucocorticoid receptor binding characteristics and glucocorticoid responsiveness of human mononuclear leukocytes (HML) from hypertensive patients and matched normotensive volunteers. We also considered associations of these variables with plasma renin activity, aldosterone, cortisol, corticotropin, and electrolyte concentrations. We calculated binding affinity (Kd; nmol/L) and capacity (Bmax; sites/cell) for dexamethasone and cortisol from homologous and heterologous competition curves for specific [3H]dexamethasone binding sites on HML isolated from the blood of normotensive volunteers and subjects with essential hypertension. Glucocorticoid responsiveness of HML was evaluated as IC50 values (nmol/L) for dexamethasone and cortisol for the inhibition of lysozyme release. We measured plasma hormones by radioimmunoassay. Kd values (mean+/-SE) for cortisol in HML of hypertensive patients were higher than in control subjects (24.6+/-2.4 versus 17.5+/-1.7 nmol/L, P<.04). Binding capacity (4978+/-391 versus 4131+/-321 sites/cell), Kd values for dexamethasone (6.7+/-0.5 versus 5.7+/-0.3 nmol/L), and IC50 values for dexamethasone (3.4+/-0.3 versus 3.1+/-0.2 nmol/L) and cortisol (12.2+/-1.6 versus 9.5+/-0.3 nmol/L) were not significantly different. Patients with renin values less than 0.13 ng angiotensin I/L per second were markedly less sensitive to cortisol than those with higher values. Both Kd (30.3+/-2.5 versus 19.2+/-2.4 nmol/L) and IC50 values (15.5+/-1.8 versus 8.9+/-1.2 nmol/L) for cortisol were significantly higher in patients with lower renin values (P<.03). Other variables, including plasma hormone and electrolyte values and binding characteristics for dexamethasone, were not different. These data suggest that cortisol binding to glucocorticoid receptor is slightly impaired in patients with essential hypertension. In vivo, this could lead to inappropriate binding of cortisol to mineralocorticoid receptors. Hence, decreased sensitivity to cortisol is associated with renin suppression. This hypothesis is supported by evidence of hypertension and low renin activity, which others have described in patients with primary glucocorticoid resistance due to mutations of the glucocorticoid receptor.     

Update on the biologic effects of macrophage colony-stimulating factor

OBJECTIVE: The aims of this investigation were to measure corticotropin-releasing hormone (CRH), corticotropin (ACTH) and cortisol before, during and after delivery searching for an endocrine intercorrelation of the hypothalamic-pituitary-adrenal (HPA) axis and to correlate these findings with obstetrical variables. METHODS: Blood was sampled from 50 women with singleton pregnancies at term without uterine contractions, during delivery (after full cervical dilatation) and on the 4th postnatal day. Hormones were measured by radioimmunoassay (RIA). The correlation between obstetric variables, sociodemographic and endocrine data were evaluated using the Spearman rank coefficient. Group comparisons for continuous variables were calculated using the Mann-Whitney U test and Kruskal-Wallis test. RESULTS: Maternal plasma ACTH and cortisol increased significantly during labor, declining toward the 4th postnatal day (p < 0.001) and showing a significant intercorrelation (p < 0.01). Compared to women without uterine contractions CRH rose during labor (p < 0.05) and decreased rapidly to the 4th postnatal day (p < 0.001). No correlations between CRH and ACTH or cortisol were observed. None of the obstetrical variables (parity, newborn's weight, duration of delivery) revealed any significant correlation with ACTH. Analgetic medication (pethidine hydrochloride) was not able to influence the endocrine response to labor stress. CONCLUSIONS: Stressful experience during childbirth has an impact on endocrine response. However, this is not fully evident along the HPA axis in a simple biological model with monocausal dependencies. This 'biological stress model' is not sensitive enough to detect different childbirth conditions and the hormones in the maternal compartment have partially fetal (placental) origin.     

Dysregulation of the hypothalamo-pituitary axis in rheumatoid arthritis

OBJECTIVE: To study the dynamic response of the hypothalamo-pituitary- adrenal axis and of prolactin (PRL) pituitary secretion in rheumatoid arthritis (RA). METHODS: We performed a cortisol releasing hormone (CRH) provocation test followed by determination of adrenocorticotropin hormone (ACTH), beta-endorphin, and cortisol concentration, and then a thyrotropin releasing hormone (TRH) provocation test followed by assessment of PRL pituitary secretion in 10 patients with RA and 5 control subjects. All were women under 40 years of age. Hormone concentrations were assessed by radioimmunoassay. RESULTS: Basal PRL cortisol, and ACTH concentrations were similar in patients with RA and controls. We observed a dissociation between the pituitary secretion of beta-endorphin and of ACTH in response to CRH in RA. The ACTH peak and total ACTH production (area under the curve, AUC) were similar in the 2 groups. In contrast, basal beta-endorphin was increased in RA (12.6 +/- 1.41 vs 8.29 +/- 0.144 pg/ml), and the response upregulated (AUC: 83,080 +/- 12,000 vs 54,200 +/- 2400) after CRH compared to controls (p < 0.05). Cortisol adrenal response curve was blunted, but did not reach statistical significance. In contrast, the PRL response to TRH was increased at 120 and 150 min (3461 +/- 303 vs 1897 +/- 520 muIU/ml)(p < 0.01) in patients with RA, independent of disease activity. CONCLUSION: We observed upregulated pituitary PRL secretion in RA, and a dissociation of ACTH stress. The implication concerning the neuroendocrine system in the chronic immune response in RA is discussed.     

Effects of metyrapone on hepatic cortisone-cortisol conversion in the rat

In previous studies in human subjects metyrapone has been found to exert significant extra-adrenal effects, consistent with an effect on the 11-reductase activity of 11beta-hydroxysteroid dehydrogenase (11beta-HSD). In the present study the effects of metyrapone on cortisone metabolism by rat liver microsomes were investigated. Aliquots of microsomal preparations were incubated with NADPH cofactor and different concentrations of cortisone for a range of time intervals up to 30 min. The products of the reaction were extracted with ethyl acetate and separated using thin-layer chromatograph. Cortisol was estimated by radioimmunoassay. There was a linear increase in cortisol formation over the first 150 sec of the reaction. Over this time period metyrapone had no effect on the rate of the reaction. When the reaction was allowed to proceed for 30 min, however, metyrapone caused a 50% decrease in the amount of cortisol formed. These data suggest that metyrapone may alter cortisone-cortisol conversion by directly interacting with 11beta-HSD but in this system metyrapone does not appear to have the characteristics of a conventional enzyme inhibitor.     

Regulation of 18-oxocortisol and 18-hydroxycortisol by the renin-angiotensin system and ACTH in man

Based on urinary excretion studies the secretion of the cortisol derivatives, 18-oxocortisol and 18-hydroxycortisol are believed to be regulated by ACTH and to a lesser degree by the renin-angiotensin system. Plasma concentrations of 18-oxocortisol and 18-hydroxycortisol were measured during the simultaneous activation of the renin-angiotensin system and inhibition of ACTH secretion. Five healthy male subjects consuming a sodium diet ad libitum were studied. Blood was drawn at 0800 h after 1 h in the supine position. In the first set of experiments, the subjects remained in the supine position from 0800 to 1000 h with or without the oral administration of 2 mg dexamethasone at 0800 h. In the second set of experiments the subjects were placed in the upright position after drawing the 0800 h sample. The subjects were studied with and without dexamethasone administered at 0800 h. Blood was drawn again at 1000 h. Plasma levels of 18-oxocortisol, 18-hydroxycortisol, ACTH, plasma renin activity (PRA), cortisol, aldosterone and 18-hydroxycorticosterone were measured by radioimmunoassay. None of these parameters changed during the 2 h in the supine position. 18-Oxocortisol, 18-hydroxycortisol, aldosterone, 18-hydroxycorticosterone and PRA increased, but ACTH and cortisol did not change when the subjects were placed in the upright position. After dexamethasone administration, 18-oxocortisol, 18-hydroxycortisol, cortisol, aldosterone and 18-hydroxycorticosterone decreased in the supine position and no increase occurred in 18-oxocortisol, 18-hydroxycortisol and 18-hydroxycorticosterone in the upright position. PRA and aldosterone increased and ACTH and cortisol decreased in these subjects. 18-Oxocortisol and 18-hydroxycortisol were more dependent on ACTH regulation and less on the renin-angiotensin system than aldosterone.     

Relationship between endocrine, immune, and clinical variables in patients with systemic lupus erythematosus

OBJECTIVE: To assess the frequency of increased plasma prolactin (PRL) in patients with systemic lupus erythematosus (SLE) and to evaluate its relationship to other hormonal and immune variables. METHODS: Thirty-five patients with SLE with various levels of disease activity were studied. Plasma PRL, cortisol, growth hormone (GH) were determined by radioimmunoassay and interleukin 6 (IL-6) by ELISA: SLE activity was evaluated using the European Consensus Lupus Activity Measurement (ECLAM). RESULTS: Increased plasma PRL concentration (> 20 ng/ml) was recorded in 11 patients (31%). No correlation was found between plasma PRL and GH, IL-6, cortisol, or C-reactive protein, nor was any significant correlation observed between plasma PRL and the ECLAM score. Patients with hyperprolactinemia were, however, found to have been treated with higher doses of prednisone therapy than patients with normal plasma PRL. Further analysis of the relationship of plasma PRL and therapy showed that patients with SLE selected by the attending physician for prednisone therapy in doses > or = 10 mg/day were more frequently hyperprolactinemic. CONCLUSION: Our findings that patients with SLE with a more active form of the disease and who are less responsive to therapy had increased plasma PRL levels more frequently may be indicative of a potential relationship of hyperprolactinemia to severity of disease.     

Tolerance, safety, and kinetics of the new antineoplastic compound dexniguldipine-HCl after oral administration: a phase I dose-escalation trial

Hormonal changes during exercise is of growing interest because of their role in adaptation, and performance. The production of amino acids (AA) due to the degradation of muscle protein increases during exercise and some AA may be utilized for energy expenditure or as hormonal secretagogues. Thus, one can propose a strategy to reduce muscle protein breakdown and regulate hormones involved in energy metabolism by dietary AA supplementation. We assessed the effects of glutamate-arginine salt (AGs) ingestion on exercise-induced hormonal alterations in highly trained cyclists (age 18-22 yrs). Using an indwelling catheter, we collected multiple blood samples at rest, during warm up, during and after an intense exercise session. Plasma growth hormone (hGH), insulin and cortisol were measured by radioimmunoassay. As reported in previous studies, we observed a marked increase in plasma hGH and cortisol levels during and after exercise in the placebo (Pl) condition as well as a slight decrease in insulin concentration. In addition, we found that the ingestion of AGs had significant effects on some dynamic hormonal changes. AGs had no effect on resting plasma levels of hGH, insulin or cortisol. However, the marked elevation in cortisol and hGH during and after exercise in the placebo condition, was greatly diminished when subjects ingested AGs. Our results show that AGs can modify exercise-induced hormonal changes and raise the possibility that it may be used to alter energy metabolism during endurance exercise.     

Effects of the Transcendental Meditation program on adaptive mechanisms: changes in hormone levels and responses to stress after 4 months of practice

Stress has been implicated in both somatic and mental disorders. The mechanisms by which stress leads to poor health are largely unknown. However, studies in animals suggest that chronic stress causes high basal cortisol and low cortisol response to acute stressors and that such changes may contribute to disease. Previous studies of the Transcendental Meditation (TM) technique as a possible means of countering effects of stress have reported altered levels of several hormones both during the practice and longitudinally after regular practice of this technique. In this prospective, random assignment study, changes in baseline levels and acute responses to laboratory stressors were examined for four hormones-cortisol, growth hormone, thyroid-stimulating hormone and testosterone-before and after 4 months of either the TM technique or a stress education control condition. At pre- and post-test, blood was withdrawn continuously through an indwelling catheter, and plasma or serum samples were frozen for later analysis by radioimmunoassay. The results showed significantly different changes for the two groups, or trends toward significance, for each hormone over the 4 months. In the TM group, but not in the controls, basal cortisol level and average cortisol across the stress session decreased from pre- to post-test. Cortisol responsiveness to stressors, however, increased in the TM group compared to controls. The baselines and/or stress responsiveness for TSH and GH changed in opposite directions for the groups, as did the testosterone baseline. Overall, the cortisol and testosterone results appear to support previous data suggesting that repeated practice of the TM technique reverses effects of chronic stress significant for health. The observed group difference in the change of GH regulation may derive from the cortisol differences, while the TSH results are not related easily to earlier findings on the effects of chronic stress.     

Human leukocyte antigens associated with hyperthyroid Graves ophthalmology in Japanese patients

PURPOSE: Leptin is a recently discovered hormone that appears as a regulator of energy balance. It is important to know whether leptin concentrations are changed under conditions of altered energy homeostasis. Consequently, we examined the effects of exercise with fasting and exercise with feeding on circulating leptin concentrations in healthy men and in type 1 diabetic patients with normal body weight and well controlled diabetes. METHODS: Leptin concentrations were determined with radioimmunoassay. RESULTS: During a 3-h cycle ergometer exercise with fasting, leptin decreased by 42% (P < 0.01) in nine healthy men and by 23% (P = 0.05) in eight male type 1 diabetic patients. Leptin fell equally by 12% (P < 0.03) both in nine healthy men and in eight male type 1 diabetic patients who were studied as a resting control group. The absolute fall in leptin in healthy men was similar in the exercise and resting control groups (0.8 +/- 0.1 microgram.L-1 vs 0.8 +/- 0.2 microgram.L-1). However, due to lower leptin concentration before the exercise, the relative decrease (42%) was greater than during the resting control study (12%, P < 0.005). This difference was not seen in the diabetic patients. Fasting leptin concentration correlated positively with BMI (r = 0.75, P < 0.001) and fasting insulin (r = 0.71, P < 0.01) in healthy men as well as with insulin level (r = 0.54, p < 0.05) in type 1 diabetic patients. When exercise was performed with feeding, and this was associated with a significant rise in serum cortisol level (marathon run, 14 healthy men and 7 type 1 diabetic patients), leptin concentration did not change significantly. CONCLUSIONS: 1) During morning hours, leptin decreases both in healthy men and in type 1 diabetic patients, reflecting a diurnal variation of leptin concentration and the effect of fasting on leptin concentration. 2) The fall in leptin during morning hours is augmented by physical exercise in healthy men. 3) If exercise is performed with feeding and associated with a rise in serum cortisol level, leptin concentration remains unchanged. These data suggest that although exercise may reduce circulating leptin levels, the effect is small and can be counterbalanced by feeding or a rise in serum cortisol concentration.     

Physical, social, and spiritual depression in old age: our last identity crisis

A group of 138 B cell chronic lymphocytic leukaemia (B-CLL) patients, 83 with active disease and 53 having the indolent form of the disease, were evaluated. The aim of the study was to clarify whether indolent and active B-CLL differ in their immune and hormonal characteristics. Peripheral blood lymphocyte proliferation in response to phytohaemagglutinin, concanavalin A, recombinant interleukin-2, dextran sulphate, Pisum sativatum agglutinin and wheat germ agglutinin was investigated. Serum immunoglobulin and beta 2 microglobulin levels were determined. Adrenocorticotropic hormone (ACTH), cortisol, follicle-stimulating hormone luteinizing hormone, 17 beta-oestradiol, testosterone, triiodothyronine, thyroxine, thyroglobulin and thyrotropic hormone levels were determined by radioimmunoassay. Active and indolent CLL presented differences in immunological characteristics, as demonstrated by the more severe suppression of T lymphocyte function, reduced IgA level and considerably higher serum beta 2-microglobulin values in active disease. Immune disturbances were accompanied by hormonal imbalance, depending on disease status: lower ACTH, cortisol and triiodothyronine levels were established to occur in active CLL compared to indolent disease. Male patients demonstrated striking changes in sex hormones, which were more evident in active disease. The findings point to the complexity of immuno-hormonal disturbances in CLL with differences in the active and indolent state of the disease.     

Dexamethasone levels in treated pregnant women and newborn infants

Dexamethasone concentration was measured in plasma and amniotic fluid by radioimmunoassay using a rabbit antiserum raised against DX-hemisuccinate-albumin. Recoveries of added tracers averaged 70% after paper chromatography. The within- and between-assay coefficients of variation averaged 10%. The lower limit of detection was 0.2 mug/dl when 0.4 ml of plasma was assayed. Ten healthy pregnant women at term had cesarean sections 8 to 11 hours following administration of 8 mg of DX orally. DX levels in maternal vein, in umbilical vein and artery, and in amniotic fluid averaged 2.2, 2.9, 2.6, and 2.5 mug/dl, respectively. Although cortisol levels were markedly suppressed, the total relative glucocorticoid activity in blood of fetuses treated with DX far exceeded that of the untreated group.     

Increased urinary free cortisol: a potential intermediate phenotype of essential hypertension

We evaluated urinary cortisol excretion as a potential intermediate phenotype of essential hypertension in 153 white patients with essential hypertension and 18 normotensive white control subjects. Analyses were controlled for dietary sodium and gender to adjust for potential confounding effects of these variables on cortisol excretion. Urinary cortisol excretion measured on both high- and low-salt diets was significantly related to hypertension by repeated measures ANCOVA (P=.02). Additional determinants of urinary free cortisol included dietary sodium intake and gender; cortisol excretion was significantly higher in men (P=.0006) and during a high-sodium diet (P=.0001). Maximum likelihood analysis showed urinary cortisol to have a bimodal distribution on both 200-mmol (P<.01) and 10-mmol (P<.002) sodium diets in hypertensive subjects. On the low-salt diet, the mean urinary cortisol in normotensive subjects (108.7+/-44.7 nmol/d) was similar to the mean of hypertensive subjects in the low mode (127.2+/-43.0 nmol/d). The high mode comprised 31.2% of the hypertensive population and had a mean urinary cortisol of 224.3+/-93.8 nmol/d. Subjects with the highest urinary free cortisol showed the least sensitivity of blood pressure to dietary sodium loading (P<.05). These data suggest that there is an association between salt-resistant hypertension and high urine cortisol levels. This association may have a genetic basis.     

Cloning of the V-ATPase subunit G in plant: functional expression and sub-cellular localization

OBJECTIVE: To define the normal cortisol response to the Short Synacthen Test using four different cortisol immunoassays and to assess the implications for the investigation of hypothalamic-pituitary disorders. DESIGN AND PATIENTS: The cortisol response to 250 micrograms im ACTH1-24 (Synacthen, Ciba Geigy) in 100 healthy volunteers using four different cortisol immunoassays has been measured. In 44 newly diagnosed and untreated patients with pituitary disease, basal and 30 minute post-ACTH cortisol results were also determined using the four immunoassays. RESULTS: The distribution of cortisol results at all time points and for all methods were non-Gaussian and significant differences in the absolute values of the 5th-95th percentiles were found between methods (P < 0.01). At 30 min post-Synacthen in normals the 5th percentile of the cortisol response ranged from 510 to 626 nmol/l with the different methods. Similarly the relationship between assay results differed at different time points. No effect of age on the cortisol response was found but for stimulated cortisol values and the incremental responses females showed significantly higher responses than males (P < 0.05) for most methods. Although there was a significant positive linear correlation (P < 0.001) between stimulated and basal cortisol values for all methods, no significant relationship was found between the incremental response and basal cortisol values. In the pituitary disease patients basal and 30 minute post-ACTH cortisol results were significantly lower (P < 0.05 and < 0.001) than the control group using the same cortisol assay. When the results were compared to the 5th percentile of the gender and assay specific control group 33.3% of male and 17.4% of female patients failed the Synacthen test at 30 min. CONCLUSIONS: The definition of the 'normal' response to Synacthen should be both gender and method related at all time points. The data suggest that up to one-third of untreated patients with pituitary disease may have subtle defects in the hypothalamic-pituitary-adrenal axis.     

Steroid hormones, memory and mood in a healthy elderly population

Men (n = 31), women estrogen-users (n = 14), and women estrogen non-users (n = 41), whose average age was 72.1 +/- 5.6 years, were tested with a battery of psychological tests measuring verbal memory, visual memory, concentration and attention, language fluency and semantic memory, and mood. Plasma levels of testosterone (T), estradiol (E2), cortisol (CRT) and dehydroepiandrosterone-sulfate (DHEAS) were assessed by radioimmunoassay. The ratio of DHEAS to CRT was calculated to determine it's relationship to memory functioning. The men had higher T and DHEAS levels than both groups of women. Women estrogen-users had higher E2 levels than both men and estrogen non-users and the men had higher E2 levels and a higher DHEAS/CRT ratio than the estrogen non-users. There were no group differences in CRT levels. Men and estrogen-users had higher total (p < .01) and forward (p < .001) digit span scores compared with non-users. Women estrogen-users also had higher backward digit span scores than non-users (p < .05), while both groups of women performed better than men on category retrieval (p < .01). The implications of these findings with respect to hormonal influences on memory in elderly men and women are discussed.     

Neuroendocrine regulation and physical and relational aggression: The moderating roles of child maltreatment and gender.

The purpose of the present investigation was to examine the association between circadian rhythms of cortisol and physical and relational aggression. Morning arrival, prelunch, and afternoon predeparture salivary cortisol were assessed among 418 maltreated and nonmaltreated children (52% maltreated; 49% female) attending a summer day camp. Counselors and peers rated participants' involvement in physically and relationally aggressive behaviors. Results indicated that physical aggression was associated with heightened cortisol following morning arrival and relatively steep declines in cortisol over the day, whereas relational aggression was associated with low cortisol following morning arrival and blunted diurnal change in cortisol. Moreover, maltreatment was a significant moderator of this relationship such that aggression was related to greater cortisol dysregulation among nonmaltreated than among maltreated children. The findings suggest that physiological correlates of aggression may differ for physical and relational forms of aggression and among maltreated versus nonmaltreated populations. (PsycINFO Database Record (c) 2010 APA, all rights reserved)