Plasma beta-endorphin levels in silent myocardial ischemia induced by exercise

Although silent myocardial ischemia is a well recognized phenomenon, the reasons for the lack of symptoms in patients with coronary artery disease (CAD) is unclear. Because the endogenous opioid beta-endorphin has been related to pain modulation, plasma beta-endorphin levels were studied before, during and after exercise-induced ischemia in symptomatic and asymptomatic men. Because beta-endorphin responses have been closely linked to adrenocorticotropic hormone (ACTH) and cortisol responses, these hormones also were measured. Nine symptomatic and 12 asymptomatic patients with a high probability (at least 95%) of CAD and 8 apparently healthy men completed a Bruce protocol treadmill test. Blood samples were drawn before, during and 10 minutes after exercise. During exercise the measured hormones showed no significant increases from basal levels. However, plasma beta-endorphin, ACTH and cortisol levels were significantly elevated (p less than or equal to 0.01) 10 minutes after exercise in all 3 groups. There was no significant difference in plasma beta-endorphin levels during or after exercise between the symptomatic and asymptomatic patients with CAD. Thus, differences in circulating levels of beta-endorphin, ACTH and cortisol are not associated with the presence or absence of pain during exercise-induced myocardial ischemia.     

Behavior of ACTH and cortisol in acute myocardial infarct

In 30 patients with acute myocardial infarction in 4-hour intervals the temporary course of the ACTH and cortisol in the plasma was pursued up to the 60th hour. Here 3 different patterns of behaviour were found. In group 1 (11 patients) normal ACTH and cortisol values are present during the period of examination. In group 2 (13 patients) ACTH in increased at admission to hospital, and a decrease of the values to the normal takes place after the beginning of the infarction within 4 to 8 hours, whereas the plasma cortisol remains clearly increased. Increased ACTH and cortisol values during the whole period were measured in group 3 (6 patients). The different hormone constellations found are possibly the expression of a different reaction behaviour of the adrenocortical system in acute myocardial infarction. There is a weak positive correlation between the creatine kinase and the plasma cortisol. The size and the duration of the increase of ACTH and cortisol seems to be connected with the degree of severity of the acute myocardial infarction. An increase of ACTH and cortisol for a longer time is to be regarded as unfavourable for the course of the acute myocardial infarction, while uncomplicated courses are connected with normal ACTH and cortisol in the plasma.     

Evaluation of the hypothalamic-pituitary-adrenal axis in untreated patients with polymyalgia rheumatica and healthy controls

OBJECTIVE: To explore the hypothalamic-pituitary-adrenal (HPA) axis in polymyalgia rheumatica (PMR). SUBJECTS AND METHODS: This study was carried out on 13 female patients with PMR who were diagnosed according to the criteria of Chuang et al (Ann Intern Med 1982;97:672-80) and 10 healthy female subjects in the Department of Physical Medicine and Rehabilitation, Erciyes University Medical School. In the patient and control groups, basal cortisol, adrenocorticotrophic hormone (ACTH), 17alpha-hydroxyprogesterone (17-OHP), 11-deoxycortisol (11-S), dehydroepiandrosterone sulfate (DHEAS), androstenedione (A), prolactin (PRL), and thyroid stimulating hormone (TSH) levels were measured. Cortisol, 17-OHP, 11-S and A responses after the low-dose (1 microg) ACTH stimulation test and cortisol and DHEAS responses after the dexamethasone suppression test were detected. We also measured acute phase reactants including C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR). RESULTS: Age and sex characteristics were similar in both patient and control groups. The levels of basal hormones including cortisol, ACTH, 17-OHP, 11-S, DHEAS, A, prolactin and TSH and cortisol and DHEAS levels after the low-dose dexamethasone suppression test were not significantly different between the patient and control groups. However, cortisol/CRP and ACTH/CRP ratios were significantly lower in the patient group. Cortisol and DHEAS responses after the low-dose dexamethasone suppression test were not significantly different between the patient and control groups. Cortisol response after the 1 microg ACTH stimulation test was significantly lower in the patients than in the control group, but there were no significant differences in 17-OHP, 11-S and A responses between the patients and controls. Correlation analysis showed that there was a negative correlation between peak cortisol levels after the ACTH stimulation test and disease duration, and also a positive correlation between cortisol levels after the low-dose dexamethasone suppression test and acute phase reactants including CRP and ESR. CONCLUSION: A significant low cortisol response to ACTH stimulation was detected in the patients with PMR. In addition, a negative correlation after the 1 microg ACTH stimulation test between peak cortisol levels and disease duration was detected. These findings may indicate hypoactivation in the HPA axis.     

Serial assessment of right ventricular function in the acute and convalescent stages after successful reperfusion: relationship to infarct-related coronary artery

OBJECTIVES: To elucidate the relationship between the infarct-related coronary artery and the right ventricular function before and after successful recanalization. METHODS: Hemodynamics and right ventricular function were measured using a REF-1 thermodilution catheter before and shortly after recanalization and during the convalescent stage in 35 patients, 17 with anteroseptal and 18 with inferior acute myocardial infarction. RESULTS: Pulmonary arterial pressure significantly decreased in both anteroseptal and inferior myocardial infarction patients after recanalization. Right ventricular volume index in patients with anteroseptal myocardial infarction increased after recanalization, but again decreased during convalescence. The right ventricle became enlarged in patients with inferior myocardial infarction to maintain the right ventricular stroke volume constant. Right ventricular ejection fraction (RVEF) did not significantly change in patients with inferior myocardial infarction during convalescence (38 +/- 13%, 38 +/- 13%, 46 +/- 9%), whereas RVEF in patients with anteroseptal myocardial infarction temporarily decreased after recanalization, and then increased during convalescence (37 +/- 10%, 31 +/- 12%, 41 +/- 7%). Patients with inferior myocardial infarction were divided into two groups, patients with increased RVEF (n = 6) and decreased RVEF (n = 12) shortly after recanalization. Patients with increased RVEF showed significantly improved RVEF during convalescence (49 +/- 7% vs 37 +/- 6%, p < 0.05). The increase in RVEF shortly after recanalization in patients with inferior myocardial infarction was an independent factor for predicting RVEF during convalescence. CONCLUSIONS: Patients with anteroseptal myocardial infarction showed a different pattern of change in the right ventricular function during the acute and convalescent stages. An early change in RVEF in patients with inferior myocardial infarction can predict RVEF in the convalescent stage.     

Effect of long-term androgen treatment on the function of hypothalamo-hypophysial and -adrenal axes in transsexual agonadal women

The study was aimed at assessing the influence of prolonged (18-24 months) androgen treatment of 11 agonadal transsexual women on basal concentrations of LH, FSH, testosterone (T), estradiol (E2), progesterone (P) and SHBG, on the hypothalamic-hypophysial (GH, PRL, ACTH) and hypothalamic-adrenal (cortisol) response in insulin test and TSH and PRL response after TRH administration. Fifteen healthy women in follicular phase of menstrual cycle and 15 men served as controls. In TS women basal concentrations of E2 were comparable with those in healthy women in follicular phase and the lowered T value showed negative correlation with SHBG. In most TS women the stimulated secretion of GH, PRL, ACTH and cortisol in insulin test was diminished. Basal values of these hormones oscillated within normal range except ACTH levels which were higher as compared with control values. In most cases the PRL response to TRH was diminished, but in three patients excessive secretion of PRL was found. Long-term priming with androgen was found to produce a dramatic change in the patterns of hormonal response to post-insulin hypoglycaemia and TRH in female-to-male transsexuals. It was concluded that in prolonged treatment of agonadal transsexual women the doses of testosterone preparations should be adjusted to individual patients in order to monitor steroid and gonadotropin hormone values, as well as the response of pituitary hormones, particularly that of PRL, to stimuli.     

Sex-related responses of beta-endorphin, ACTH, GH and PRL to cold exposure in humans.

To establish a possible different reaction between the male and the female to short-term exposure to cold, thermal, cardiovascular and pituitary hormonal responses to cold stress were measured in eight normal men and eight women (ages 19-24). The women were eumenorrheic and were tested in the follicular phase. Each subject, lightly clad, was required to remain for 30 min in a room at an ambient temperature of 25 degrees C followed by a 30 min period in a cold room at 4 degrees C. A month later, control tests were carried out at a constant 25 degrees C temperature for 1 h in the same subjects. Skin temperature, heart rate, blood pressure and plasma levels of beta-endorphin, ACTH, cortisol, GH and PRL were measured before and after cold exposure in the two groups. Before the test, all examined parameters were similar in the two groups. During cooling, blood pressure rose and pulse rate decreased significantly in the men, but not in the women, whereas skin temperature dropped in both groups. However, after cold exposure skin temperature was significantly lower in the women than in the men. A slight, but not significant increase in beta-endorphin, ACTH, cortisol and GH levels was observed after cooling in the men, whereas the women showed significant increments of these hormones. When values of skin temperature were combined with the differential (after minus before cold test) hormonal values, significant negative correlations were found for beta-endorphin, ACTH, cortisol and GH.(ABSTRACT TRUNCATED AT 250 WORDS)     

Gonadal and adrenocortical hormone changes in myocardial infarct

On a male group of patients investigations of the behaviour of the testosterone, LH, cortisol and ACTH serum concentrations in the hospital phase of the acute myocardial infarction were carried out. Apart from an early activation of the adreno-cortico-pituitary axis a decrease of the testosterone concentrations at consistent LH levels was observed. On healthy test persons in the ACTH and hydrocortisone tolerance test possible interactions between adrenocortical and gonadal hormone system were controlled.     

Hormonal and metabolic disturbances during acute and subacute myocardial infarction in man

Summary To investigate the cause of glucose intolerance (GIT), frequently seen during acute myocardial infarction (AMI), seventeen males without history of diabetes were studied with intravenous glucose tolerance tests within seventy-two hours after uncomplicated myocardial infarction and again three weeks later. Seventy percent (12/17) of the patients showed GIT during AMI. In 7 of these patients (41%) glucose tolerance (GT) remained abnormal after 3 weeks. In addition, all 7 showed markedly diminished insulin responses to glucose during both the acute and subacute phase. Therefore, their GIT was considered to be due to newly-recognized chemical diabetes. In the remaining patients in whom the initially depressed GT improved during SMI elevated serum levels of FF A, insulin, HGH and cortisol suggested the temporary presence of insulin antagonism. Increased adrenal medullary activity was not found to be a major factor inhibiting glucose tolerance.Supported in part by the Genesee Valley Heart Association, Rochester, New York and PHS Research Grant No. 5 MOI RR349.     

Ketanserin without effects on basal anterior pituitary hormone secretion in healthy subjects

The effect of ketanserin, a selective serotonin-2 (5-HT2) receptor blocking agent, on the secretion of anterior pituitary hormones was studied in 4 healthy volunteers. Ketanserin (10 mg) was administered as a slow iv injection and its effect was compared with that of saline. Ketanserin influenced neither the basal plasma levels of HGH, ACTH, TSH, LH or prolactin, nor the plasma levels of T4, T3, cortisol or glucose. Even if a single dose of ketanserin had no hormonal effects, this must also be studied after long term use.     

Adrenocorticotropin and cortisol responsiveness to thyrotropin-releasing hormone and luteinizing hormone-releasing hormone discloses two subsets of patients with Cushing's disease

In 23 consecutive patients with Cushing's disease and 52 control subjects, the responses of ACTH and cortisol to TRH and LRH were investigated. From the pattern of cortisol levels after the administration of the releasing hormone in the controls, a criterion for paradoxical responsiveness could be derived (maximum cortisol increase, greater than 6.0 micrograms/100 ml). According to this criterion, 9 patients with Cushing's disease showed a paradoxical responsiveness to one or both releasing hormones (3 to both TRH and LRH, 3 to TRH alone, and 3 to LRH alone; group I). In all patients tested, paradoxical responses of cortisol were preceded by paradoxical increments in ACTH. The remaining 15 patients showed no paradoxical increments in ACTH or cortisol after TRH or LRH (group II). ACTH levels in group I (89 +/- 28 pg/ml) were significantly lower than those in group II (185 +/- 164 pg/ml; P less than 0.02). Nevertheless, in both groups, a similar plasma cortisol level was found, suggesting a relatively higher bioactivity of ACTH in group I. A second difference between both groups was a lower amplitude of cortisol variability during the day in group I. The 2 groups did not differ in clinical data, such as age, sex distribution, sellar volume, and duration of disease, or dexamethasone suppressibility, bromocriptine sensitivity, and basal PRL levels. These latter findings do not favor an intermediate lobe origin of Cushing's disease in patients with paradoxical responses to TRH/LRH. To conclude, TRH/LRH responsiveness of ACTH/cortisol discloses two subsets of patients with Cushing's disease.     

Hypothalamo-pituitary-adrenal axis in acute myocardial infarction treated by percutaneous transluminal coronary angioplasty: effect of time of presentation

Acute myocardial infarction (AMI) is associated with a stimulation of cortisol which lasts 24 hours in patients treated by thrombolysis. Percutaneous transluminal coronary angioplasty (PTCA) is an alternative treatment for AMI which reduces the length of myocardial ischemia. Our objective was the determination of the amplitude and duration of cortisol and other hormones of the hypothalamo-pituitary-adrenal (HPA) axis release in patients undergoing PTCA. These responses were also analyzed in relation with the time of onset of AMI. The effect of coronarography with or without angioplasty in patients without AMI was also studied. Plasma ACTH, cortisol, corticotropin-releasing hormone and arginine vasopressin levels were determined during the first 48 hours in 20 patients with first AMI, treated by PTCA and in 10 patients without AMI undergoing coronarography (and angioplasty in five of them). A strong stimulation of the HPA axis was observed in AMI patients, but the duration of cortisol secretion was significantly reduced (less than 8 hours) as compared with previous studies in patients treated with thrombolysis. A clear-cut ACTH-cortisol dissociation was also observed after the third hour. ACTH and cortisol stimulation was higher in patients admitted between 04:00 h and 16:00 h than in patients admitted between 16:00 h and 04:00 h In patients without AMI, coronarography induced a moderate, but significant short-lasting ACTH and cortisol stimulation. In conclusion, our data suggest that the degree of stimulation of the HPA axis may depend upon the type of treatment and the circadian rhythm of this axis.     

Different regulation of adrenocorticotropin and cortisol secretion in young, mentally healthy elderly and patients with senile dementia of Alzheimer's type.

Previous studies suggest that an alteration of the neuroendocrine system may particularly occur in senile dementia of Alzheimer's type (SDAT). In the present study the reactivity of the hypophyseal-adrenocortical axis (HPA) in the elderly was assessed by hormonal stimulation of the hypophysis. Twelve young men (aged 21-24 yr), 15 mentally healthy elderly (aged 65-90 yr), and 12 patients with SDAT (aged 60-84 yr) received an iv bolus injection containing 50 micrograms CRH and 0.5 IU lysine vasopressin after a baseline period of 2 h. ACTH, cortisol, and dehydroepiandrosterone secretion was monitored over a period of 2 h before and after the injection. The baseline ACTH concentrations were increased in both groups of elderly, the baseline cortisol levels were not different in either group. The peak ACTH and cortisol levels were significantly elevated in the mentally healthy elderly, whereas senile demented patients showed a rise comparable with that in the young subjects. Moreover, in the demented patients the post-stimulus decline in plasma ACTH levels seemed to be delayed. Dehydroepiandrosterone was significantly lowered in subjects of all ages. Our results demonstrate an enhanced reactivity of the HPA in mentally healthy elderly. This is possibly due to a diminished sensitivity of the feedback regulation to glucocorticoids. However, SDAT patients had, compared to healthy elderly subjects, an attenuated response to CRH/lysine vasopressin and a prolonged ACTH secretion, indicating alterations of the HPA in this disease.     

A simple and rapid method to measure non-protein-bound fractions of cortisol, testosterone and oestradiol by equilibrium dialysis: comparison with centrifugal filtration.

A simple method for measuring the free, non-protein-bound steroid fraction in plasma by equilibrium dialysis is described. The alteration occurring in the volume of the inner phase (undiluted plasma) is corrected by the difference in weight before and after dialysis. Total cortisol was determined by radioimmunoassay. Although it is not possible to differentiate between values for total cortisol after ACTH stimulation (242.2+/-shing's syndrome (n: 15)), and women treated with oestrogens (211.8+/-42.0 ng/ml (n: 20)), there were significant differences for free cortisol (ACTH stimulation: 29.3+/-5.6 ng/ml; Cushing's syndrome: 31.5+/-8.6 ng/ml; women under increased oestrogenic activity: 10.0+/-2.1 ng/ml; pregnant women: 13.7+/-5.1 ng/ml plasma). Compared with normal values for healthy women and men (9.3+/-1.4 ng/ml), women with increased oestrogenic activity showed slight elevations of free cortisol. Compared to cortisol, the percentage of dialysable testosterone and oestradiol was lower in women than in men (1.57 vs. 2.08% for testosterone and 1.68 vs. 2.15% for oestradiol). In healthy men the concentration of free steroid was 13.1+/-1.0 ng free testosterone/100 ml plasma (0.44+/-0.045 pg free oestradiol/ml plasma), in healthy women 0.64+/-0.07 ng/100 ml (0.98+/-0.10 pg/ml) and in women receiving oestrogens 0.37+/-0.04 ng/100 ml (0.01+/-0.015 pg/ml). When the method described here for determing the free fractions of cortisol (n: 45), oestradiol (n: 18) and testosterone (n: 18) at 37 degrees C is compared with the method of centrifugal filtration, the correlation was r: 0.80 r: 0.86 and r: 0.91, respectively. In practice, equilibrium dialysis with undiluted plasma is simple, fast and can be applied to all steroid hormones. It allows direct measurements of non-protein-bound steroids under nearly physiological conditions.     

Assessment of hemodynamic changes in the early phase of uncomplicated acute myocardial infarction

The purpose of our study was to evaluate the early phase hemodynamic changes in patients with clinically uncomplicated acute myocardial infarction. Detailed sequential hemodynamic evaluation is hardly available in the early phase of acute myocardial infarction in this group of patients as opposed to patients with complicated acute myocardial infarction. We evaluated sequentially the hemodynamics of 17 patients with uncomplicated acute myocardial infarction (Kilip class I). Cardiac output and ventricular ejection period were determined by impedance cardiography. All patients had an uneventful recovery, without clinical evidence of derangement of myocardial function as assessed by physical examination, chest X-ray and blood gases. Despite the uniformly uncomplicated convalescence, different hemodynamic patterns were found. Based on the hemodynamic data, patients were divided into two groups. In 10 patients no significant change in hemodynamic parameters was observed, while in 7 patients a significant decrease in cardiac output was found during the early post myocardial infarction period. Total peripheral resistance was significantly elevated in the group with decreased cardiac output. No relationship was found among location of infarction, creatine phosphokinase levels and hemodynamic outcome. A considerable proportion of patients with asymptomatic and uneventful convalescence after acute myocardial infarction have a decrease in cardiac output and a significant increase in total peripheral resistance which is not detected by routine clinical evaluation.     

Abnormalities in sex hormones are a risk factor for premature manifestation of coronary artery disease in South African Indian men

The relation between sex hormone levels and myocardial infarction was studied in a case-control study among 117 Indian men with myocardial infarction aged 30-60 years and in 107 healthy Indian male controls. The patients and controls were further divided into subsets defined by age in decades. In the total patient population, testosterone concentration was significantly lower than in the controls (P less than 0.01), whilst oestradiol (P less than 0.0005) and the oestradiol to testosterone ratio (P less than 0.0005) were significantly higher. Multivariate stepwise logistic regression analyses demonstrated that free testosterone index, the free oestradiol index, and the oestradiol to testosterone ratio were significantly associated with myocardial infarction, and that this association was independent of age, body mass index, smoking and serum lipids. Further analyses according to age subsets revealed that compared to respective control groups, patients in the 4th decade had both significant hypotestosteronaemia and hyperoestrogenaemia, whereas in patients of the 5th decade significant differences in total and in the calculated free oestradiol index were noted, and in the 6th decade a significant difference was detected only in the free oestradiol index. Hence, we conclude that aberrations in endogenous sex hormones are significantly associated with myocardial infarction, and that this association appears to be strongest in young men and diminishes with age, suggesting that these disturbances in sex hormones may be associated with premature manifestation of coronary artery disease.     

Acute suppressive effect of ACTH-induced cortisol secretion on serum prolactin levels in healthy man

The effect of ACTH on serum prolactin concentrations was studied in 6 healthy women in the follicular phase of the menstrual cycle, in 5 healthy men and in 6 patients (5 males, 1 female) with adrenocortical insufficiency. In healthy women prolactin levels decreased from basal, 14.4 +/- 2.1 (SEM) microgram/l to 9.4 +/- 0.9 microgram/l after 30 min and to 8.1 +/- 0.7 micrograms/l after 60 min of iv administration of synthetic ACTH1-24 (0.25 mg). Upon continuous infusion of ACTH1-24 (0.25 mg for 8 h) prolactin fell to 4.4 +/- 0.6 microgram/l in healthy women and to 4.6 +/- 1.5 micrograms/l (basal: 10.6 +/- 1.8 micrograms/l) in healthy men. In patients with adrenocortical insufficiency prolactin concentrations remained unchanged following an 8 h infusion of ACTH1-24 (before ACTH: 14.5 +/- 2.3 micrograms/l, after ACTH: 16.3 +/- 3.1 micrograms/l). After treatment with dexamethasone (2 mg/day for 3 days) however, prolactin concentrations were suppressed both in healthy women (-52 +/- 7%) and men (-25 +/- 11%) and in patients with adrenocortical insufficiency (-21 +/- 10%). Thus the effect of ACTH on prolactin appeared to be mediated via enhanced cortisol secretion. It is suggested that an acute increase in cortisol levels within the physiological range may modulate prolactin secretion.     

Low serum levels of DHEAS in untreated polymyalgia rheumatica/giant cell arteritis

OBJECTIVE: To address a controversy regarding the existence of a relative adrenal hypofunction in patients with untreated polymyalgia rheumatica (PMR) and giant cell arteritis (GCA) we evaluated baseline serum levels of ACTH, cortisol, and DHEAS in a cohort of patients with recent onset PMR/GCA not previously treated with glucocorticoids, in comparison with healthy controls. Possible correlations between baseline DHEAS levels and laboratory measures of disease activity were also explored. METHODS: Basal serum levels of these hormones were prospectively investigated in 25 patients with active untreated disease and compared with those of 25 age- and sex-matched control subjects. RESULTS: Of the 25 patients, 19 had isolated PMR and 6 had biopsy-proven GCA + PMR. Basal levels of cortisol and ACTH in PMR/GCA patients did not differ from control subjects; in relation to inflammatory status, lower than expected basal production of cortisol was observed in active untreated PMR/GCA. Baseline serum DHEAS levels were significantly lower in all patients compared with controls. In these patients, a significant correlation was found between baseline DHEAS values and laboratory measures of disease activity. The percentage of DHEAS reduction and the severity of inflammatory response were higher in women than in men. CONCLUSION: Patients with PMR/GCA with new-onset active disease before steroid treatment have inappropriately normal cortisol levels regarding the ongoing inflammation, and significantly lower levels of DHEAS compared to the age- and sex-matched healthy control subjects. These data support the existence of a relative adrenal hypofunction in PMR and GCA.     

Stress-mediated effect of metoclopramide on cortisol secretion in man

Five healthy adult men were given metoclopramide (10 and 20 mg) iv, and in repeated tests almost always developed transient restlessness lasting from 10-30 min. The effects of L-dopa and dexamethasone on metoclopramide-induced increases in cortisol concentration were determined. These response values were compared with those of a control. After an injection of 10 mg metoclopramide, the cortisol level increased significantly only at 40 min; the ACTH level did not change. The cortisol rise was suppressed by dexamethasone pretreatment. Pretreatment with 0.5 g L-dopa resulted in a decrease in the PRL level from -20 min to 20 min, and the increase in cortisol seen at 40 min was cancelled. The ACTH level did not change. After injecting 20 mg metoclopramide, the ACTH level increased significantly from 20 min to 60 min and the cortisol level showed a significant increase from 20 min to 120 min. Pretreatment with dexamethasone resulted in a decrease in these hormones. The L-dopa pretreatment did not reduce even the rise in the PRL level which resulted from the administration of 20 mg metoclopramide. These findings suggest that the ACTH and cortisol response to metoclopramide is a stress-mediated effect. Plasma cortisol responses to 20 mg metoclopramide and insulin-induced hypoglycemia were studied and compared in seven volunteers and found to be similar.     

The effect of naloxone on ATCH and beta-endorphin in patients with Cushing's disease

Endogenous opiates may be important in the control of ACTH secretion in men. The effect of opiate receptor blockade by naloxone on ACTH, beta-endorphin-like substance and cortisol release was studied in healthy women and in 9 patients with Cushing's disease. In the healthy subjects, ACTH, beta-endorphin and cortisol levels were increased in response to naloxone. However, in 3 our of the 9 patients with Cushing's disease, a paradoxical decrease in serum ACTH, cortisol and beta-endorphin concentrations was observed after naloxone administration. In the patients with a paradoxical response to naloxone, transsphenoidal microadenomectomy was ineffective.     

Circadian variations in plasma levels of hypophyseal, adrenocortical and testicular hormones in men infected with human immunodeficiency virus

Alterations in the circadian time structure of the secretion of several hormones were investigated in 13 male patients infected with human immunodeficiency virus (HIV). Seven were asymptomatic (classified CDC II, according to the criteria of the Atlanta Centers for Disease Control), and 6 had acquired immunodeficiency syndrome (CDC IV). Ten healthy males volunteered as controls. Plasma levels of dehydroepiandrosterone (DHEA) and its sulfate (DHEA-S), cortisol, testosterone, ACTH, and beta-endorphin were determined by RIA in blood samples obtained every 4 h from 0830-0830 h the next morning. Data were analyzed both by two-way analysis of variance and the cosinor method. Circadian rhythms were statistically validated for each of the six hormones in each of the three groups of subjects. Compared with the control subjects, mesors (24-h adjusted means) were significantly higher for cortisol and lower for DHEA, DHEA-S, and ACTH (P less than 0.001 for all four hormones) in all HIV-infected patients. Plasma testosterone mesors were similar in controls and CDC II patients, but decreased significantly in the CDC IV patient group (P less than 0.05). Analysis of the circadian rhythms of plasma hormone levels clearly indicated an altered adrenal hormonal state in HIV-infected male patients, even during the asymptomatic period of the infection. For instance, plasma cortisol at 0430 h was more than twice as high in HIV-infected patients as it was in time-qualified controls. Although patients already had elevated plasma cortisol and lowered adrenal androgen levels at this stage, hypogonadism was not observed, as gauged by plasma testosterone concentrations. We speculate that the primary hormonal defect in HIV-infected patients is increased cortisol secretion resulting from circadian-varying stimulation of the adrenal cortex by a factor other than pituitary ACTH. This factor might be a stimulating substance secreted primarily by infected immune cells. Excess cortisol would lower adrenal androgen secretion by shifting adrenal steroid biosynthesis toward glucocorticoids and decreasing pituitary ACTH secretion via a negative feedback mechanism.