Further neuroendocrine evidence of enhanced vasopressin V3 receptor responses in melancholic depression

BACKGROUND: In situations of chronic stress vasopressin plays an important role in regulating the hypothalamic-pituitary adrenal axis. The aim of the current study was to investigate the role of anterior pituitary vasopressin V3 receptors in maintaining the hypercortisolism seen in melancholic depression. METHOD: Fourteen patients with major depression and 14 age- and sex-matched healthy comparison subjects were recruited. Desmopressin (ddAVP) 10 microg was given intravenously and ACTH and cortisol release was monitored for 120 min. RESULTS: The mean +/- S.E.M. ACTH response in the depressives was 28.4 +/- 4.3 ng/l and in the healthy subjects was 18.8 +/- 4.9 ng/l (P = 0.04). The mean +/- S.E.M. cortisol response in the depressives was 261.8 +/- 46.5 nmol/l and in the healthy subjects was 107.3 +/- 26.1 nmol/l (P < 0.01). CONCLUSIONS: Patients with major depression have augmented ACTH and cortisol responses to desmopressin indicating enhanced V3 responsivity.     

Hyperprolactinemia does not influence hypothalamic-pituitary-adrenocortical function during hypoglycemia in women

Elevated plasma prolactin and mild hypocortisolemia have been observed in patients with rheumatic disorders. This study was designed to assess the potential inhibitory effect of hyperprolactinemia on hypothalamic-pituitary-adrenocortical function. Hypoglycemia was induced by intravenous insulin injection (0.1 IU/kg) in 10 female volunteers of fertile age during their follicular phase twice: 60 min after either domperidone (10 mg orally) or placebo administration. Blood samples were collected from an indwelling catheter inserted into the cubital vein at -60, 0, 30, 45, 60 and 90 min. The concentrations of prolactin, adrenocorticotropic hormone (ACTH), cortisol, epinephrine, norepinephrine and glucose were measured in plasma. Domperidone administration significantly increased plasma prolactin concentrations (71 +/- 11 ng/ml vs. 14 +/- 6 ng/ml; p <0.001), while basal plasma concentrations of ACTH, cortisol, norepinephrine and epinephrine were unaffected. Insulin-induced hypoglycemia resulted in a significant rise in the mean plasma ACTH levels from 10 +/- 1 pg/ml (domperidone) and 11 +/- 1 pg/ml (controls) to 148 +/- 19 pg/ml (domperidone) and 139 +/- 12 pg/ml (controls) at 45 min (p < 0.001), in plasma cortisol from 407 +/- 62 nmol/l (domperidone) and 391 +/- 42 nmol/l (controls) to 925 +/- 60 nmol/l (domperidone) and 810 +/- 52 nmol/l (controls) at 60 min (p < 0.001), and in plasma epinephrine from 40 +/- 26 pg/ml (domperidone) and 16 +/- 3 pg/ml (controls) to 274 +/- 55 pg/ml (domperidone) and 352 +/- 61 pg/ml (controls) at 30 min; (p < 0.001). The significant increase in ACTH, cortisol and epinephrine responses to hypoglycemia was similar in both groups. We observed mild norepinephrine response to hypoglycemia but this was irrespective of the medication. In conclusion, pharmacologically-induced hyperprolactinemia did not induce significant changes of hypothalamic-pituitary-adrenocortical function and did not influence sympathoadrenal activity in healthy young women.     

Blood glucose concentration dependent ACTH and cortisol responses to prolonged exercise

The purpose of this study is to investigate responses of serum ACTH and cortisol concentration to low intensity prolonged exercise. In experiment 1, 10 subjects fasted for 12 h and performed bicycle exercise at 49.3% VO2max (+/- 4.3%) until exhaustion or up to 3 h. During the early part of the exercise, serum ACTH and cortisol concentrations did not increase from the pre-exercise values (ACTH: 44 +/- 5 micrograms/l, cortisol: 139 +/- 52 micrograms/l). Whilst the time to serum ACTH concentration increasing varied among the subjects (60-180 min), the increases of this hormone occurred for all subjects (175 +/- 85 ng/l, P less than 0.05) when blood glucose concentration decreased to a critical level of 3.3 mmol/l. At the end of the exercise, blood glucose concentration decreased to 2.60 +/- 0.21 mmol/l, and serum ACTH and cortisol concentrations increased to 313 +/- 159 ng/l and 371 +/- 151 micrograms/l, respectively. In experiment 2, four subjects performed the same intensity exercise until exhaustion, and were then given 600 ml of 20 g glucose solution, and immediately afterwards, they were asked to repeat the same exercise. The subjects continued the exercise for between 30 to 90 min until again reaching exhaustion. During the second exercise, blood glucose concentration increased to the pre-exercise value (2.72 +/- 0.58 to 4.00 +/- 0.22 mmol/l, P less than 0.05) and simultaneously, serum ACTH concentration decreased considerably (354 +/- 22 to 119 +/- 54 ng/l, P less than 0.05). The results of the present study suggest that serum ACTH and cortisol concentration during low intensity prolonged exercise may be dependent on blood glucose concentration.     

Plasma cortisol and β-endorphin concentrations in trained and over-trained standardbred racehorses

The effects of training and over-training on plasma cortisol and beta-endorphin (betaEP) concentrations at rest and after standardised exercise tests and the cortisol responses to adrenocorticotropin (ACTH) administration were investigated in standardbred horses. Twelve horses were divided randomly into control and over-trained (OT) groups after 17 weeks slow- and moderate-intensity treadmill training. The standardised treadmill exercise test consisted of 2 min at velocities corresponding to 30, 50, 70 and 100% of maximum O2 consumption. Over-training, defined as a significant decrease in body weight and treadmill run-time-to-fatigue in an incremental velocity test, occurred in the OT group after 32 weeks of training exercise. Peak cortisol concentrations after exercise decreased significantly in the OT group from 320+/-15.6 at week 8 to 245+/-17.0 nmol l(-1) at week 32, and mean cortisol concentrations over a 120-min period after exercise decreased from 258+/-11.7 to 192+/-16.6 nmol l(-1) (P<0.05). Mean and total cortisol and betaEP concentrations in resting horses were not significantly different after over-training. Peak cortisol concentrations after adrenocorticotropin (ACTH) administration were not significantly different in the over-trained group. Dysfunction of the hypothalamo-pituitary-adrenocortical axis occurs in over-trained horses, but this adaptation is not associated with a change in the adrenocortical responsiveness to ACTH.     

Hormone replacement therapy increases ACTH/dehydroepiandrosterone sulfate in menopause.

OBJECTIVE: To demonstrate that hypoestrogenism in menopause is in part responsible for the decrease in circulating dehydroepiandrosterone sulfate (DHEA-S) and ACTH levels. To test this hypothesis, 25 postmenopausal women aged 47-60 years, were given orally conjugated equine estrogen (CEE) to study the effect on circulating DHEA-S, cortisol and ACTH. DESIGN: A prospective, non-blinded study was performed. Hormonal levels were analyzed before and after three cycles of CEE 0.625 mg/day for 21 days followed each by chlormadinone acetate for 5 days. RESULTS: Low baseline levels of DHEA-S increased significantly after HRT (1.71+/-0.75 to 3.3+/-1.5 micromol/l, (P<0.001). ACTH levels augmented moderately from 3.26+/-1.4 to 4.7+/-1.8 pmol/l (P<0.05) and cortisol from 350.4+/-118 to 450.8+/-144 nmol/l (P<0.01). A positive correlation was obtained between 17 beta-estradiol and ACTH (r=0.48), estradiol and cortisol (r=0.52) as well as estradiol and DHEA-S (r=0.60). In addition, the correlation was highly significant (P<0.001) between ACTH and DHEA-S at the term of HRT. CONCLUSION: HRT increased DHEA-S, ACTH and cortisol concentrations, which may suggest that this therapy may exert a stimulatory effect on the pituitary gland when baseline hypoestrogenism is present, but further studies are required to clarify the mechanism underlying this process.     

Impact of gender, menstrual cycle phase, and oral contraceptives on the activity of the hypothalamus-pituitary-adrenal axis

OBJECTIVE: Results from animal and human studies suggest that disregulations of the hypothalamus-pituitary-adrenal (HPA) axis are involved in several behavioral, circulatory, endocrine, and immune disorders with clear-cut gender differences in disease prevalence. The aim of the present study was to investigate sex-specific HPA response patterns with a focus on the contribution of gonadal steroids as possible mediators. METHODS: A total of 81 healthy adults were investigated in the present study. Twenty men, 19 women in the follicular phase of the menstrual cycle, 21 women in the luteal phase, and 21 women using oral contraceptives (OC) were exposed to a brief psychosocial stress test (Trier Social Stress Test; TSST) and injected with 0.25 mg ACTH1-24 on consecutive days. Basal HPA activity was investigated by repeatedly measuring cortisol levels immediately after awakening, as well as in 30-minute intervals from 9:00 AM to 9:00 PM. Additionally, questionnaires were used to assess psychological state and trait parameters. RESULTS: Results show that the TSST induced significant increases in ACTH, salivary-free cortisol, total plasma cortisol, and heart rates, as well as increased wakefulness and reduced calmness in the total group. Significant group differences emerged for ACTH and salivary-free cortisol stress responses: Although men showed higher ACTH responses to the TSST compared with each of the three groups of women, salivary cortisol responses showed the following response pattern: Luteal = Men > Follicular = OC. The salivary cortisol responses to ACTH1-24 showed a similar response pattern: Luteal > Men > Follicular > OC. In contrast, total blood cortisol levels did not reveal any group difference between sexes or follicular versus luteal phase in either test. Although a similar salivary-free cortisol increase after awakening was found in the four groups, the circadian cortisol profile was significantly different throughout the first 4 hours of sampling. Questionnaire-derived psychological variables, as measured in the present study, could not explain the observed results. CONCLUSIONS: We conclude that gender, menstrual cycle phase, and OC use exert important effects on HPA responsiveness to psychosocial stress in healthy subjects. Although men seem to have a stronger hypothalamic drive in response to stressful stimulation than women, differences in salivary-free cortisol levels, at least in part, may be explained by estradiol-induced changes in corticosteroid-binding protein levels. ACTH and cortisol secretion is not affected by OC use per se but the amount of bioavailable unbound cortisol ("free") is greatly reduced in this group of women after stimulation. Inasmuch as none of these differences between the study groups emerged in total blood cortisol levels, we strongly advocate for the simultaneous measurement of free and total cortisol levels in future studies on HPA functioning.     

Personality, manual preference and neuroendocrine reactivity in hirsute subjects

Behavioral and neuroendocrine differences may be postulated in hirsute subjects since central effects of gonadal steroids are well established. We conducted a controlled clinical study with 25 consecutive young hirsute participants compared with 20 consecutive controls. Neuropsychological evaluation included the Minnesota Multiphasic Personality Inventory (MMPI) and the Edinburgh Inventory of Manual Preference (EIMP). Neuroendocrine reactivity was assessed by the adrenocorticotropic hormone (ACTH) and cortisol responses to corticotropin releasing hormone (CRH). Hirsute participants presented a flattened personality profile with lower neurotic triad scores--146 +/- 20 versus 166 +/- 28. Left-hand preference was more common in hirsute participants--4/21 versus 0/20. Decreased ACTH [area under the curve (AUC)--36 +/-2 8 vs. 72 +/- 63 pg/ml h] and cortisol (AUC--18 +/- 4 vs. 25 +/- 10 microg/dl h) responses to CRH were found in the hirsute group. In the hirsute group, higher manual preference scores were associated with lower ACTH responses to CRH, while the opposite association was found in the control group. In the hirsute group, the hyporeactive hypothalamic-pituitary-adrenal (HPA) axis was associated with lower behavior-deviant scores, while in the control group, the hyporeactive HPA axis was associated with more psychopathology. We conclude that personality and HPA axis reactivity are different in hirsute female participants when compared with controls, with a trend for differences regarding handedness. Personality and handedness are differently associated with HPA reactivity. Distinctive features in hirsute participants are probably established very early during ontogenic development.     

Low 11-deoxycortisol to cortisol conversion reflects extra-adrenal factors in the majority of women with normo-gonadotrophic normo-estrogenic infertility

BACKGROUND: Women with normogonadotrophic normo-estrogenic oligomenorrhoea often disclose a variety of clinical symptoms. Many of these individuals are obese with features of pseudo-hypercortisolism. In the current study, 11-deoxycortisol and cortisol concentrations were determined in this group and compared with ovulatory controls. METHODS AND RESULTS: Twenty-six women with clomiphene citrate-resistant infertility, 12 lean and 11 obese ovulatory controls were studied. Women with infertility had the highest 11-deoxycortisol concentrations (mean +/- SD: 4.1 +/- 1.5 ng/ml) compared with obese and lean controls (3.1 +/- 1.4 and 2.4 +/- 0.9 ng/ml) (P < 0.01), but similar morning cortisol concentrations (0.47 +/- 0.15, 0.45 +/- 0.16 and 0.47 +/- 0.18 nmol/l). Baseline 11-deoxycortisol/cortisol ratios (>90th percentile of ovulatory controls) were elevated in 23/26 infertile women (88%), and in 3/26 women (12%) after adrenocorticotrophic hormone (ACTH) stimulation. Three out of six lean infertile women had elevated baseline 11-deoxycortisol/cortisol ratios, but none of these women had elevated ratios after ACTH stimulation. Stepwise regression analysis, after exclusion of testosterone, revealed significant correlations between the groups (lean controls, obese controls, infertility) and ACTH-stimulated 11-deoxycortisol/cortisol ratio (P < 0.05), but not with fasting glucose, insulin, cortisol, 11-deoxycortisol and baseline 11-deoxycortisol/cortisol ratios. CONCLUSIONS: Congenital adrenal hyperplasia was not observed in the majority of infertile women. The data indicate that extra-adrenal factors were involved in most of the infertility syndromes that were studied.     

Cortisol and cortisone in human follicular fluid and serum and the outcome of IVF treatment

BACKGROUND: The glucocorticoid status of ovarian follicular fluid has been linked to oocyte quality. The aim of this study was to examine whether the concentrations of cortisone and cortisol and their calculated ratios in the follicular fluid and serum samples are predictive of IVF outcome. METHODS: In the prospective study of 387 patients (420 treatment cycles) undergoing IVF treatment the concentrations of cortisone and cortisol were measured with specific assays, and their calculated ratios in the follicular fluid and serum samples obtained after ovarian stimulation and induced ovulation were determined. RESULTS: In 75 patients, treatment resulted in clinical pregnancy and was associated with significantly lower follicular cortisone (24+/-12 versus 29+/-16 nmol/l, P<0.002) and higher cortisol/cortisone ratio (7.24+/-2.22 versus 6.45+/-2.17 nmol/l, P<0.007). In addition, the ratios of serum cortisone and cortisol to follicular cortisone and cortisol were significantly higher in those women who became pregnant. CONCLUSIONS: We propose that the follicular fluid glucocorticoid concentration resulting from the conditions in the circulation and the course of the intrafollicular cortisol-cortisone interconversion appear to play a role in the outcome of IVF.     

The effect of an inhaled steroid on the hypothalamic-pituitary-adrenal axis-which tests should be used?

Inhaled corticosteroids may produce systemic effects which include decreased hypothalamic-pituitary-adrenal (HPA) axis activity. Four tests of HPA axis function were assessed in 12 healthy volunteers, during inhalation of two actuations of beclomethasone dipropionate (250 micrograms) aerosol four times daily for 15 days, to determine the most appropriate test for this effect of inhaled corticosteroids. Measurement of basal adrenal activity showed that both 24-hr urinary free cortisol and 0900 hr plasma cortisol were decreased by the fourth day of steroid treatment. All 12 subjects had decreases in basal adrenal activity. Overall the 24-hr urinary free cortisol showed the greater change, with mean pre-steroid baseline values of 497 and 515 nmol/24 hr reduced to 167 nmol/24 hr on the ninth day of treatment (P less than 0.001). The single-dose metyrapone test showed marked changes in each of the six subjects tested. The mean 11-deoxycortisol response was 96 nmol/l on the eleventh day of treatment, compared to baseline and eight-day post-treatment values of 439 and 407 nmol/l respectively (P less than 0.001). In contrast, no consistent treatment-related changes were observed with the short tetracosactrin test. Only two out of six subjects had an abnormal short tetracosactrin test, although all showed a decrease in basal adrenal activity. From these results, the 24-hr urinary free cortisol and single-dose metyrapone test at 0600 hr are recommended to assess the effect of inhaled glucocorticoids on the HPA axis.(ABSTRACT TRUNCATED AT 250 WORDS)     

Hypothalamic-pituitary-adrenocortical axis dysregulation in patients with major depression is influenced by the insertion/deletion polymorphism in the angiotensin I-converting enzyme gene

The Dex/CRH test is one of the most reliable neuroendocrine function tests for hypothalamic-pituitary-adrenocortical (HPA) system dysregulation in depression. Persistent overdrive of HPA system activity after successful antidepressant treatment predicts an enhanced risk for relapse of a depressive episode. As the renin-angiotensin system has been shown to play a role in HPA system activity, we investigated the impact of the angiotensin converting enzyme (ACE) gene insertion (I)/deletion (D) polymorphism, which determines ACE plasma concentrations, on HPA system dysregulation. We performed repeated combined Dex/CRH tests in 115 patients suffering from major depression. Dex/CRH test results were related to the I/D polymorphism within the ACE gene, which was assessed by PCR. Genotype frequencies were comparable to those in the general population (I/I 16.8%, I/D 59.3%, D/D 23.9%). D/D genotypes showed a higher cortisol stimulation during the first Dex/CRH test after admission than homozygous I-allele carriers (repeated measurement ANOVA: P=0.034). Cortisol area under the curve values were highest in those with the D/D genotype (mean+/-SEM [nmol/l*75 min]: 12700+/-2220), intermediate in those with the I/D genotype (9570+/-1000), and lowest in those with the I/I genotype (5160+/-1000; ANOVA: P=0.04). After successful antidepressive treatment and attenuation of HPA system overdrive these differences were no more detectable. The HPA axis stimulating properties of higher ACE and consecutively higher AT-II and/or lower substance P concentrations may be crucial factors for the HPA system hyperactivity during major depressive episodes.     

Cortisol and ACTH responses to severe asphyxia in preterm fetal sheep

It has been hypothesized that the hypothalamic-pituitary-adrenal (HPA) axis is immature in the preterm fetus and that this compromises their ability to adapt to hypoxic stress; however, there are few direct data. We therefore examined the effects of asphyxia on HPA responses in chronically instrumented preterm fetal sheep (104 days of gestation; term is 147 days), allocated to a sham control group (n = 7) or 25 min of complete umbilical cord occlusion (n = 8), followed by recovery for 72 h. During umbilical cord occlusion there was a rapid rise in ACTH levels (230.4 +/- 63.5 versus 14.1 +/- 1.8 ng ml(-1) in sham controls, 16-fold) and cortisol levels (7.4 +/- 4.9 versus 0.2 +/- 0.1 ng ml(-1), 31-fold), with further increases after release of cord occlusion. ACTH levels were normalized by 24 h, while plasma cortisol levels returned to sham control values 72 h after asphyxia. Fetal arterial blood pressure was elevated in the first 36 h, with a marked increase in femoral vascular resistance, and correlated positively with cortisol levels after asphyxia (P = 0.05). In conclusion, the preterm fetus shows a brisk, substantial HPA response to severe hypoxia.     

Comparison between the central effects of CRH and AVP in steers

In cattle, the in vivo effects of centrally administered corticotropin-releasing hormone (CRH) or arginine vasopressin (AVP) from the perspective of stress regulation have not been fully elucidated. We compared behavioral, adrenocorticotropic, and autonomic nervous responses to intracerebroventricularly infused bCRH or AVP in steers. Intracerebroventricular infusions of both bCRH and AVP (0.2, 2, 10 and 20 nmol/500 mul/30 min) evoked a dose-related increase in plasma concentrations of ACTH and cortisol. At 10 nmol, the AUC response of cortisol concentration to bCRH tended to be higher than that in response to AVP (p=0.075). There were significant differences among treatments in the total number of head shaking (Friedman's test, chi2=22.79, p=0.004), upright posture (chi2=16.80, p=0.032), head rubbing (chi2=23.93, p=0.002), tongue playing (chi2=27.18, p=6.58E(-4)), and bleating (chi2=26.84, p=7.54E(-4)). AVP 10 and 20 nmol treatments induced more head shaking and tongue playing than vehicle treatment (Nemenyi multiple comparisons: p<0.1). Ten nmol (32.8+/-40.2 times) and 20 nmol (34.8+/-19.9 times) of bCRH induced bleating, but no dosage of AVP induced bleating. These findings indicate that both bCRH and AVP could activate HPA axis in steers when infused intracerebroventricularly and that bCRH was more potent to stimulate HPA axis than AVP. As for the effects on behavioral function, high dosages of both peptides induced stereotyped behaviors and the types of stereotyped behaviors induced were different between bCRH and AVP.     

Comparison of CRH test and ACTH test in patients with bronchial asthma]

Although glucocorticoid is the most effective agent for bronchial asthma, its systemic administration leads to suppression of adrenocortical function. Rapid ACTH test has been performed for assessing the function of the hypothalamic-pituitary-adrenocortical (HPA) system of asthmatics. Recently human corticotropin-releasing hormone (CRH) has been chemically synthesized. In order to evaluate clinical usefulness of CRH, we compared CRH test with ACTH test in 17 patients with bronchial asthma (3 patients out of them concurrently receiving prednisolone 5-10 mg/day). Both tests were carried out within 2 weeks after 6 month treatment with fluticasone propionate (800 micrograms/day) inhaled via pMDI. There is no significant difference between results obtained from the both tests. Thus, dividing subjects into high and low responders based on an extent of increases in plasma ACTH levels after the CRH injection, we found a significant difference in maximal plasma concentrations of cortisol between after CRH and ACTH injections in the low responders. Therefore, in some patients, CRH test provides more accurate assessment of the function of HPA system than ACTH test.     

Effect of maternal nutrient restriction in early gestation on responses of the hypothalamic-pituitary-adrenal axis to acute isocapnic hypoxaemia in late gestation fetal sheep

Epidemiological and experimental evidence suggests that maternal undernutrition during pregnancy may alter development of fetal organ systems. We have demonstrated previously that fetal hypothalamic-pituitary-adrenal (HPA) axis responses to exogenous corticotropin-releasing hormone (CRH) + arginine vasopressin (AVP), or adrenocorticotrophin hormone (ACTH), are reduced in fetuses of mildly undernourished ewes. To examine these effects further we tested HPA axis responses to acute isocapnic hypoxaemia in fetal sheep at 114-129 days gestation (dGA), following 15% reduction in maternal nutritional intake between 0 and 70 dGA. Fetuses from control (C) and nutrient-restricted (R) ewes were chronically catheterised and plasma ACTH and cortisol responses were determined at 114-115, 120-123 and 126-129 dGA during hypoxaemia (1 h) induced by lowering the maternal inspired O2 fraction (FI,O2). Basal plasma cortisol concentrations and HPA axis responses at 114-115 and 120-123 dGA did not differ between C and R fetuses. At 126-129 dGA, both plasma ACTH (P < 0.01) and cortisol (P < 0.05) responses were smaller in R fetuses compared to C fetuses. Fetal blood gas status, fetal body weight, body proportions and organ weights did not differ between the groups. We conclude that mild maternal undernutrition alters development of the fetal HPA axis producing a reduction in pituitary and adrenal responsiveness to endogenous stimuli.     

Functional evaluation of the hypothalamic-pituitary-adrenal axis

The regulation of hypothalamic pituitary-adrenal (HPA) axis is controlled by three major factors: stress, circadian rhythm and negative feedback. Hypothalamic CRF binds to CRF receptor on ACTH cells and stimulates synthesis and secretion of ACTH. However, vasopressin binds to V1b receptor and enhances CRF induced ACTH secretion. ACTH stimulate secretion of cortisol and DHEA-S. Cortisol inhibits secretion of CRF and ACTH with negative feedback mechanism. To evaluate the ability of the hypothalamus to secrete CRF, insulin-induced hypoglycemia and metyrapone tests are used. For evaluation of the secretion of pituitary ACTH and adrenal cortisol, a CRF test is useful. Autonomic secretion of ACTH and/or cortisol is evaluated with a dexamethasone suppression test.     

Assessment of the one hour adrenocorticotrophic hormone test in the diagnosis of attenuated 21-hydroxylase deficiency.

Attenuated or partial 21-hydroxylase deficiency is one of several biochemical defects in steroid metabolism that can lead to hirsutism in young women after puberty. The diagnosis is made through the exaggerated response of 17 alpha-hydroxyprogesterone (17-OH) to adrenocorticotrophic hormone (ACTH). To provide reference data 72 mild to moderately hirsute patients aged 18 to 35 were studied (over two years) with the ACTH test. Four patients with an exaggerated response were found. The mean (+/- 1SD) for zero time was 2.4 (0.96) nmol/l and for the 60 minute time was 7.2 (2.04) nmol/l. A subpopulation was found with a significantly higher baseline at 6.2 (1.3) nmol/l but a blunted 60 minute response at 8.7 (2.5) nmol/l. This is important because of the potential confusion arising from the known variability in baseline values in previously reported patients with partial 21-hydroxylase deficiency. Extending the test to 90 minutes did not show further increase in the 17-OH response to ACTH, thus confirming the validity of the 60 minutes ACTH test. The cortisol response to ACTH was also studied. One patient with presumptive partial 21-hydroxylase deficiency overlapped in cortisol response with eight of the reference population. Theoretically, a blunted cortisol response would be expected because of the postulated enzyme block, and these results suggest that other steroid enzyme defects should also be considered when an exaggerated 17-OH response to ACTH is seen.     

Adrenocorticotropin responses to interpersonal stress: effects of overt anger expression style and defensiveness.

This study evaluated the influence of overt anger expression style and defensiveness on the hypothalamic-pituitary-adrenocortical (HPA) responses to acute psychological stress. These personality traits are thought to modulate the stress cardiovascular response and influence disease risk, however, little is known about their influence on HPA responses. Forty-six young, healthy male volunteers worked on counterbalanced extended public-speaking and mental arithmetic. The sample was dichotomitized into groups low vs. high in anger-out, using Spielberger's Anger-Expression Inventory, and in defensiveness, using the Marlowe-Crown Social Desirability Scale. Serum cortisol and adrenocorticotropic hormone (ACTH) concentrations were measured before and after performing each task. Heart rate (HR) and blood pressures (BP) were obtained continuously in 2-min intervals before, during and after the tasks. Public speaking produced greater adrenocortical and cardiovascular stress responses than mental arithmetic, and the greatest increases in ACTH occurred in subjects high in anger-out and defensiveness. These preliminary findings provide evidence that a mismatch between traits of preferred anger expression style and defensive style produces pronounced adrenocorticotropic responses during socially salient stress.     

The long-term effect of high-dose beclomethasone dipropionate on the pituitary-adrenal function]

The pituitary-adrenal function was studied in seven asthmatic subjects who had been received daily inhalations of 800 to 1,000 micrograms of beclomethasone dipropionate (BDP) over a year. None of the subjects had taken oral corticosteroids for at least six months prior to the study. As indices of pituitary-adrenal function, 1) circadian rhythm of plasma ACTH and cortisol, 2) urine 17-OHCS and 17-KS, and 3) the response of cortisol in rapid ACTH test were examined. All subjects showed normal circadian rhythms of plasma ACTH and cortisol levels. Urinary 17-OHCS and 17-KS excretions over a 24-hour period were also within the normal range. Plasma cortisol levels in the rapid ACTH test were significantly increased and judged as normal responses in all subjects. These results indicate that long-term treatment with BDP ranging from 800 to 1,000 micrograms/day induces no suppressive effect on the pituitary-adrenal function.     

Non-interaction of spironolactone medication and cortisol metabolism in man

Summary In 5 healthy subjects and in 5 patients with decompensated liver diseases, the concentrations of cortisol, canrenone and canrenoate-K were determined after single doses and after a long-term treatment with spironolactone. The concentrations of the metabolites of spironolactone were determined fluorimetrically, those of cortisol by a highly specific radioimmunoassay with previous chromatographic separation.As a result, non-interaction between spironolactone medication and cortisol metabolism, even at high dose and long-term treatment conditions, was established neither in normal test subjects nor in patients with liver failure.The study was supported by grants of the Deutsche Forschungsgemeinschaft to Dr. Abshagen (Ab 28/3) and Dr. L'age.