The diurnal patterns of the adrenal steroids cortisol and dehydroepiandrosterone (DHEA) in relation to awakening

The steroid hormones, cortisol and dehydroepiandrosterone (DHEA) are the two main peripheral secretory products of the hypothalamic-pituitary-adrenal stress-neuroendocrine axis. The diurnal pattern of cortisol secretory activity has been well characterised. Various aspects of this pattern have been related to time of awakening, light exposure, psychological dimensions of affect, immune function and systemic health and well-being. DHEA is also an important adrenocortical steroid whose secretory activity has been related to immune function, psychological and health variables. The most pronounced feature of the diurnal cortisol cycle is a burst of secretory activity following awakening with a diurnal decline thereafter. We mapped DHEA secretory activity onto this cycle by measuring both steroids in saliva samples collected at distinct time points over the diurnal cycle, synchronised to awakening. Both steroids, particularly DHEA, showed stability across days of sample collection. A main distinction between cortisol and DHEA was that although DHEA was elevated in post-awakening samples compared with later in the day there was no evidence of an awakening stimulatory burst of DHEA secretory activity. Although DHEA in many respects paralleled cortisol secretory activity there was some dissociation; mean levels were positively but not tightly correlated. The secretory pattern of DHEA is very stable whereas cortisol secretory activity seems more sensitive to day-to-day variability.     

Association between time of awakening and diurnal cortisol secretory activity

A 12-hour diurnal profile of salivary free cortisol was measured in healthy adults (n=40) on two consecutive days. Samples were collected at timed intervals synchronised to awakening. The mean profile is characterised by a marked increase in cortisol concentration following awakening, peaking after about 30 min, and a subsequent decline over the remainder of the day. Thus two components of the diurnal cycle were examined: a) the first 45 min post-awakening (the awakening cortisol response) and b) the underlying 12 h profile from immediately until 12 h post awakening (but without the awakening response). Both of these components were analysed in two ways such as to provide an indication of overall cortisol concentration and the degree of change in cortisol concentration, i.e. the rise for the awakening response and the diurnal decline. Both components of the cortisol diurnal profile were negatively correlated with awakening time. Thus, those subjects who awoke earliest had higher levels of cortisol over the 45 min following awakening as well as throughout the rest of the day. They also displayed a more marked diurnal decline to be convergent with late awakeners at the end of diurnal measurement, 12 h following awakening. Hence the diurnal cortisol cycle, which is synchronised to awakening, is significantly related to awakening time. These findings support the notion of a close association between suprachiasmatic nucleus (SCN) control of both awakening and cortisol secretory activity.     

The association between long-term accumulation of temporary employment, the cortisol awakening response and circadian cortisol levels

Temporary employment is an increasingly common contract type, which has not been investigated in a psychoneuroendocrinological context despite previous observations of associations between adverse work and employment conditions and hypothalamic-pituitary-adrenal (HPA) axis dysregulations. The present study aims to examine whether the 12-year accumulation of temporary employment is related to circadian cortisol levels, and if any association is independent of current employment conditions. Participants were drawn from the prospective Northern Swedish Cohort (n=791, 74% of the original cohort). At age 43 years, retrospective reports of employments over the last 12 years and of current social conditions were collected by questionnaire, and one-day salivary cortisol profile was measured (at awakening, +15 min post-awakening, pre-lunch, bedtime). Results indicated a gradually higher magnitude of the cortisol awakening response (CAR) in subjects with no (0 months in temporary employment; mean CAR=34%), moderate (1-25 months in temporary employment; mean CAR=41%) and heavy (>25 months in temporary employment; mean CAR=51%) exposure (p=.020), remaining after adjustment for potential confounders and for current employment conditions (p=.028). The higher CAR was explained by lower awakening rather than higher post-awakening cortisol levels. Cortisol levels at all times of the day except post-awakening displayed tendencies to negative relations to temporary employment; as indicated by a lower Area Under of Curve (regression coefficient=5.0%, p=.038 after adjustment). This study thus suggests that the long-term exposure to temporary employment might confer HPA dysregulations in the form of increased dynamics of the CAR and circadian suppression.     

The cortisol awakening response: a pilot study on the effects of shift work, morningness and sleep duration

This study concerned the possible influence of experimental shift work, morningness and sleep length on the cortisol awakening response (CAR). Eight morning-oriented (MT) and eight evening-oriented (ET) healthy young men (19-27 years) slept after three consecutive day shifts during the night and after three consecutive night shifts during the day in the laboratory. Salivary cortisol concentrations were ascertained after each sleep period upon awakening and half an hour later, half-hourly during work shifts, and hourly during two 24-h periods, after the three day shift/night sleep sequences and after the three night shift/day sleep sequences. Statistical analyses considered the temporal position of sleep (night, day), the succession of sleep periods, the diurnal type and the polysomnographically verified total sleep time. The CAR was significantly smaller after day than after night sleep and increased significantly with total sleep time in ET. MT had moderately higher cortisol concentrations upon awakening than ET probably because they wake up at a later time of their circadian rhythm. But neither the CARs nor the cortisol concentrations during the following work shifts or during the 24h profiles were different in both diurnal types. The cortisol concentrations during work shifts correlated significantly with the previous post-awakening concentrations in MT but not in ET. Due to the small samples further studies are needed.     

The cortisol awakening response: More than a measure of HPA axis function

In most healthy people morning awakening is associated with a burst of cortisol secretion: the cortisol awakening response (CAR). It is argued that the CAR is subject to a range physiological regulatory influences that facilitate this rapid increase in cortisol secretion. Evidence is presented for reduced adrenal sensitivity to rising levels of ACTH in the pre-awakening period, mediated by an extra-pituitary pathway to the adrenal from the suprachiasmatic nucleus (SCN). A role for the hippocampus in this pre-awakening regulation of cortisol secretion is considered. Attainment of consciousness is associated with ‘flip-flop’ switching of regional brain activation, which, it is argued, initiates a combination of processes: (1) activation of the hypothalamic pituitary adrenal (HPA) axis; (2) release of pre-awakening reduced adrenal sensitivity to ACTH; (3) increased post-awakening adrenal sensitivity to ACTH in response to light, mediated by a SCN extra-pituitary pathway. An association between the CAR and the ending of sleep inertia is discussed.     

Seasonal differences in the diurnal pattern of cortisol secretion in healthy participants and those with self-assessed seasonal affective disorder

This study compared the daily pattern of free salivary cortisol secretion in winter and in summer between two groups; participants with self-assessed seasonal affective disorder (SAD) and age- and sex-matched healthy controls. Fifty-two participants completed the study with an equal number in each group. The diurnal pattern of cortisol secretion was assessed across two consecutive weekdays in summer, and two in winter, with conditions being counterbalanced. On each study day participants collected multiple saliva samples in the domestic setting to capture the cortisol awakening response (CAR) and declining levels across the day. In addition, perceived stress, anxiety, depression, state stress and state arousal were assessed using validated questionnaires. There was no evidence for any seasonal changes in psychological data or cortisol pattern for the healthy control population. In summer, self-assessed SAD and control participants had similar psychological and cortisol profiles. In winter however, SAD participants reported greater depression, stress and anxiety, and lower levels of arousal. Furthermore, the CAR was significantly attenuated in SAD participants during winter months. There was no difference in cortisol levels during the rest of the day between controls and SAD participants in winter. In line with the above findings and previous research, there was an inverse relationship between the increase in cortisol following awakening and a measure of seasonality in winter. Furthermore in winter, a general dysphoria construct correlated inversely with the CAR, indicating that participants reporting greater depression, stress and anxiety and lower arousal, exhibited lower CARs. In conclusion, during the shortened photoperiod in winter, the cortisol response to awakening is attenuated in participants with self-assessed SAD in comparison to controls. These findings contribute to the understanding of the physiology of SAD.     

Abnormal diurnal patterns of salivary α-amylase and cortisol secretion in acute patients with anorexia nervosa

Abstract

Objectives. The evidence that the activity of the sympathetic nervous system (SNS) is decreased in acute anorexia nervosa (AN) is not consistent. Therefore, we aimed to assess the SNS basal activity in malnourished AN patients through the measurement of diurnal salivary levels of α-amylase, whose secretion is regulated by the SNS. As secondary aim, we measured also salivary cortisol. Methods. Eight symptomatic female patients with restrictive AN and eight age-matched healthy women underwent saliva sample collection at awakening and over the day. α-amylase and cortisol were assayed by ELISA method. Results. In both patients and controls, saliva α-amylase levels significantly decreased during 60 min after awakening and then progressively rose towards the afternoon/evening. AN patients exhibited significantly reduced levels of the salivary enzyme with a significant decrease in its overall diurnal secretion and a dysregulated secretory pattern. As compared to control women, AN patients exhibited significantly enhanced levels of salivary cortisol at awakening, an enhanced and advanced cortisol secretion after awakening but no significant change in the overall diurnal secretion of the salivary hormone. Conclusions. These results suggest that the activity of the SNS, evaluated through the assessment of the diurnal secretion of salivary α-amylase, is impaired in the acute phase of AN whereas the cortisol awakening response is enhanced.     

The cortisol awakening response: More than a measure of HPA axis function

In most healthy people morning awakening is associated with a burst of cortisol secretion: the cortisol awakening response (CAR). It is argued that the CAR is subject to a range physiological regulatory influences that facilitate this rapid increase in cortisol secretion. Evidence is presented for reduced adrenal sensitivity to rising levels of ACTH in the pre-awakening period, mediated by an extra-pituitary pathway to the adrenal from the suprachiasmatic nucleus (SCN). A role for the hippocampus in this pre-awakening regulation of cortisol secretion is considered. Attainment of consciousness is associated with ‘flip-flop’ switching of regional brain activation, which, it is argued, initiates a combination of processes: (1) activation of the hypothalamic pituitary adrenal (HPA) axis; (2) release of pre-awakening reduced adrenal sensitivity to ACTH; (3) increased post-awakening adrenal sensitivity to ACTH in response to light, mediated by a SCN extra-pituitary pathway. An association between the CAR and the ending of sleep inertia is discussed.     

Salivary cortisol profiles in patients remitted from recurrent depression: one-year follow-up of a mindfulness-based cognitive therapy trial

Few studies have examined changes of diurnal cortisol profiles prospectively, in relation to non-pharmacological interventions such as mindfulness-based cognitive therapy (MBCT). Fifty-six patients remitted from recurrent depression (≥3 episodes) were included in an 8-week randomized controlled trial comparing MBCT plus treatment as usual (TAU) with TAU for depression relapse prophylaxis. Saliva samples (0, 15, 30, 45, 60 min post-awakening, 3 PM, 8 PM) were collected on six occasions (pre- and post-intervention, 3-, 6-, 9-, 12-month follow-up). Cortisol awakening response (CAR), average day exposure (AUCday) and diurnal slope were analyzed with mixed effects models (248 profiles, 1-6 per patient). MBCT (n = 28) and TAU groups (n = 28) did not significantly differ with respect to baseline variables. Intra-individual variability exceeded inter-individual variability for the CAR (62.2% vs. 32.5%), AUC(day) (30.9% vs. 23.6%) and diurnal slope (51.0% vs. 34.2%). No time, group and time by group effect was observed for the CAR and diurnal slope. A significant time effect (p = 0.003) was detected for AUCday, which was explained by seasonal variations (p = 0.012). Later wake-up was associated with lower CAR (-11.7% per 1-hour later awakening, p < 0.001) and lower AUCday (-4.5%, p = 0.014). Longer depression history was associated with dampened CAR (-15.2% per 10-year longer illness, p = 0.003) and lower AUCday (-8.8%, p = 0.011). Unchanged cortisol secretion patterns following participation in MBCT should be interpreted with regard to large unexplained variability, similar relapse rates in both groups and study limitations. Further research is needed to address the scar hypothesis of diminished HPA activity with a longer, chronic course of depression.     

Impact of exogenous glucocorticoid use on salivary cortisol measurements among adults with asthma and rhinitis

The diurnal rhythm of cortisol secretion in chronic disease can reflect the interactions between exogenous and endogenous factors. Exogenous glucocorticoid use may impact salivary cortisol measurements, but this has not been well-studied in ambulatory settings. In this report salivary cortisol levels were used to evaluate aspects of the diurnal rhythm of cortisol secretion within an ambulatory population of patients with asthma and allergic rhinitis. 183 persons with asthma with or without concomitant rhinitis and 34 persons with rhinitis alone were asked to collect at home, two saliva samples, 30 min after awakening and 12h later. The salivary cortisol levels were quantified by enzyme immunoassay. The recent use of glucocorticoids in the study group was determined by interview and direct examination of medications. We report that the median salivary cortisol levels 30 min post-awakening significantly differed by exogenous steroid status: no glucocorticoid use (n = 91), 10.1 nmol/l; nasal gluco-corticoid use alone (n = 25), 11.4 nmol/l; inhaled glucocorticoids (with or without concomitant nasal glucocorticoids; n = 76), 9.0 nmol/l; systemic glucocorticoids (n = 17), 4.0 nmol/l; (P = 0.02). 12-h post-awakening salivary cortisol values among the groups were similar (P = 0.85). The median 30-min post-awakening cortisol differed significantly by type and amount of inhaled steroid used: non-fluticasone users (n = 21), 11.5 nmol/l; lower dose fluticasone (<800 microg per day, n = 35); 9.2 nmol/l; and higher dose fluticasone (> or =800 microg, n=20), 5 nmol/l; (P=0.01). We conclude that in an ambulatory setting, exogenous glucocorticoid use can decrease the 30 min post-awakening but not the 12-h post-awakening salivary cortisol levels, an effect that should be taken into account in assessing the effects of other potential determinants on cortisol secretion.     

Hypothalamic-pituitary-adrenal axis functioning in Huntington's disease mutation carriers compared with mutation-negative first-degree controls

Neurodegeneration in Huntington's disease (HD) occurs in various brain regions including the hypothalamus. In this cross-sectional study, hypothalamic-pituitary-adrenal (HPA) axis functioning was studied in 26 presymptomatic and 58 symptomatic HD mutation carriers, and 28 controls. HPA axis functioning was measured through salivary cortisol in the day curve, the cortisol awakening response (CAR), the area under the curve (AUC), the morning rise, and the dexamethasone suppression test (DST). Only the CAR was statistically different between the three groups, being explained by higher cortisol concentrations at 45 and 60 min post-awakening for presymptomatic mutation carriers compared to both symptomatic mutation carriers and controls. No differences were found for the AUC, evening and post-DST cortisol concentrations. Our study indicates a mild disturbance in morning cortisol secretion in HD mutation carriers that precedes the onset of motor symptoms.     

Several daily measurements are necessary to reliably assess the cortisol rise after awakening: state- and trait components

The cortisol rise after awakening (CAR) is a frequently applied measure of pituitary-adrenal activity. This measure seems to reflect the acrophase of the diurnal cycle and can easily be assessed in saliva samples, collected by the proband or patient under real life conditions. Since different state and trait factors affect the CAR, we here address the questions (a) to which extent state and trait factors affect the CAR, and (b) how often cortisol measures after awakening have to be taken to obtain reliable results. In this study, we assessed the CAR on 6 consecutive days. After applying structural equation models and correlation analyses, we conclude that (a) the CAR of a single day is determined to a great extent by situational factors and only for a small proportion by trait factors and (b) from two (AUC(t)) to six (AUC(i)) days are necessary to achieve reliable trait measures, since state factors bias data from a single day.     

Cortisol and severe fatigue: a longitudinal study in adolescent girls

Fatigue is a common complaint among adolescents, especially in girls, and is associated with high rates of school absenteeism. Severe fatigue is often accompanied by psychological and physical symptoms. In the chronic fatigue syndrome (CFS) functioning of the hypothalamic-pituitary-adrenal (HPA)-axis has previously been found to be altered. The aim of the present study was to investigate whether cortisol production is deviant in fatigued adolescent girls from the general population and to study longitudinal changes in fatigue in association with possible changes in HPA-axis functioning. In the cross-sectional part of the study the cortisol response to awakening (CAR) and to a low-dose oral dexamethasone were examined in a group of fatigued adolescent girls (n=87) in comparison to a non-fatigued control group (n=77). Questionnaires regarding fatigue, depression, anxiety, sleep quality, somatic symptoms and CFS-related symptoms were filled out. Follow up measurements were performed after 6 and 12 months. While the fatigued and non-fatigued group differed remarkably on all symptom self-reports, no differences between groups in CAR and response to dexamethasone were observed. Girls in the fatigued group remained fatigued over time and reported high levels of other psychological and physical symptoms during the whole year of the study. The CAR varied between time points but correlated non-systematically with situational characteristics or symptom reports. We conclude that trait-like fatigue, as measured in a sample of adolescent girls from a high school population, is not reflected in a dysregulation as assessed on the level of salivary cortisol after awakening.     

Ageing, physical function, and the diurnal rhythms of cortisol and dehydroepiandrosterone

The present study examined the relationship between ageing, physical function and the diurnal rhythms of cortisol and dehydroepiandrosterone (DHEA). Participants were 36 community dwelling older adults aged between 65 and 86 years old. Salivary cortisol and DHEA were measured over the course of one day: immediately upon awakening, 30 min later, and then 3 h, 6 h, 9 h and 12 h post-awakening. Participants completed the Nottingham extended activities of daily living index, the Berg Balance Scale and their handgrip strength was assessed. Older participants had a significantly higher cortisol area under the curve (AUC), lower overall DHEA levels, lower DHEA AUC, a decreased diurnal slope of decline and increased cortisol:DHEA ratio. Lower diurnal cortisol levels were associated with poorer performance on the Berg Balance Scale and lower handgrip strength, and those with a flattened DHEA diurnal profile reported less independence in carrying out daily tasks. These associations withstood adjustment for age. In conclusion, this study suggests an association between cortisol, DHEA, ageing and physical function.     

Chronotype and diurnal cortisol profile in working women: differences between work and leisure days

The influence of chronotype on the diurnal profile of salivary cortisol was examined in a sample of 187 healthy women: 21 evening chronotype, 24 morning chronotype and 142 intermediate chronotype. Saliva samples were collected at waking, 30 min post-awakening, at 1000 h, 1200 h, 1500 h, 1700 h and at bedtime on one work and one leisure day. Several components of the diurnal profile were examined including the cortisol awakening response, the total cortisol output and the diurnal profile on both the work and the leisure day, a significant main effect of time emerged (both p<0.01). After adjustment for age, smoking status, self-rated health, time of waking, and sleep problems, no effect of chronotype was evident for cortisol in the evening, the cortisol awakening response, or total cortisol output over the working day. However, on the leisure day, total cortisol output was greater in evening-types than intermediate or morning-types, after adjustment for covariates (p=0.029). The present data indicate that chronotype has a limited impact on the diurnal cortisol profile of healthy women, and may be somewhat impervious to individual preferences for morning or evening activity.     

Circadian regulation of cortisol after hippocampal damage in humans.

BACKGROUND: There is substantial evidence that the hippocampus (HC) regulates the activity of the hypothalamic-pituitary-adrenocortical (HPA) axis. Damage to the HC in animals produces a transient alteration in diurnal and stress-related HPA activity. This study was designed to examine the effects of HC damage on basal cortisol secretion in humans. METHODS: Salivary cortisol was measured in 22 patients with HC damage (12 with bilateral damage and 10 with unilateral damage), 7 brain-damaged comparison participants, 10 healthy, age-matched comparison participants, and 6 of the patients' caregivers. Salivary cortisol samples were taken immediately after awakening, 30 min after awakening, at 8:00 am, 11:00 am, 3:00 pm, 6:00 pm, and at bedtime on a single day. Brain-injured patients underwent a structural magnetic resonance imaging scan to examine quantitative volumes of the HC. RESULTS: Both bilateral and unilateral HC damage abolished the cortisol response to awakening documented in the comparison groups. Caregivers of bilateral HC patients showed a reduced response to awakening. The remainder of the circadian pattern was not affected in the HC patients; all groups showed a significant diurnal variation. There was no association between HC volume and cortisol secretion. CONCLUSIONS: Hippocampal damage in humans abolishes the cortisol response to awakening, whereas the remainder of the diurnal cycle is unaffected in these patients. These data suggest a unique role of the HC in the control of basal cortisol secretion.     

Transactions among adolescent trait and state emotion and diurnal and momentary cortisol activity in naturalistic settings

In a community sample of 52 adolescents, multilevel growth curve modeling was utilized to examine whether within-person changes in momentary mood states, and individual differences in trait emotional functioning, were related to adolescent cortisol levels in naturalistic settings. Salivary cortisol levels were measured seven times a day on two typical weekdays in conjunction with diary reports of adolescent mood states. Questionnaire reports of trait emotional functioning (depression, anxiety, and anger) were obtained, as were reports of demographic, developmental, and health control variables. After accounting for the effects of time of day and a wide range of control variables, within-person increases in state negative mood (worry/stress and anger/frustration) were significantly associated with within-person increases in cortisol. When examining trait emotional functioning, adolescents with higher levels of depressive symptoms had slightly lower basal cortisol levels, and adolescents with higher levels of trait anger had a significantly stronger cortisol response to awakening. Several developmental effects were found-adolescents at higher stages of pubertal development had daytime basal cortisol curves that were more elevated, had a steeper diurnal decline, and showed a lesser cortisol awakening response, and cortisol responses to worry/stress increased with age. Cortisol levels were also higher at moments adolescents were alone rather than with others, an effect that declined significantly with age. Cortisol levels were also higher at moments adolescents were alone rather than with others, an effect that declined significantly with age. Results suggest that ongoing transactions occur between adolescents' everyday emotional experiences and their cortisol levels, and that adolescent cortisol activity is modified by age/pubertal stage and by trait emotional functioning.     

The relation between early life adversity, cortisol awakening response and diurnal salivary cortisol levels in postpartum women

Early life adversity has been associated with hypothalamic-pituitary-adrenal (HPA) axis dysfunction in both children and adults. However, in adulthood, most studies have focused on the effects of early adversity on HPA axis stress reactivity rather than the cortisol awakening response or diurnal cortisol profiles. The goal of this study was to examine the cumulative effects of early life adversity on the cortisol awakening response (CAR) and diurnal cortisol profiles in a sample of postpartum women. Ninety women between 2 and 6 months postpartum completed two retrospective reports assessing adverse early life experiences (maltreatment and consistency of care). Eighteen women reported having experienced both parental loss and some form of childhood maltreatment and 36 women reported having experienced one type of early life adversity, either parental loss or maltreatment. HPA axis function was assessed through salivary cortisol collections over two consecutive days for measurement of the cortisol awakening response (n=61) and diurnal cortisol rhythm (n=90). Women who reported experiencing adverse early life experiences exhibited a tendency towards higher levels of awakening cortisol compared to women who reported no adverse early life experiences (p=.07). These higher awakening cortisol levels were sustained throughout the morning in the groups who experienced early adversity, with all groups exhibiting the typical diurnal decline in the afternoon and evening (p<.05). Women reporting early adversity exhibited more heterogeneity in their diurnal cortisol levels across the two collection days (p<.01). Our findings suggest that in a community sample of postpartum women, early adversity is associated with current HPA axis function. These findings may have implications for the nature of mother-infant interactions.     

Familial influences on basal salivary cortisol in an adult population

To understand the underlying genetic and environmental sources of individual variation in basal cortisol levels, we collected salivary cortisol at awakening and at six fixed time points during the day in adult twins and their singleton siblings. Reported time of awakening was verified with heart rate and body movement recordings. Cortisol data were available for 199 MZ twins, 272 DZ twins and 229 singleton siblings from 309 twin families. No differences in cortisol means and variances were found between twins and singleton siblings. Additionally, the correlations for DZ twins and siblings were not significantly different, indicating generalizability of twin study results to the general population. Genetic model fitting showed heritability for cortisol levels during the awakening period (34% for cortisol level at awakening and 32% for cortisol level at 30 min after awakening) but not for cortisol levels later during the day. The current study shows that, while cortisol levels in the awakening period are influenced by genetic factors, cortisol levels throughout most of the day are not heritable, indicating that future gene finding studies for basal cortisol should focus on the first hour post-awakening.     

Evidence for altered hypothalamus-pituitary-adrenal axis functioning in systemic hypertension: blunted cortisol response to awakening and lower negative feedback sensitivity

BACKGROUND: Hypothalamus-pituitary-adrenal (HPA) axis functioning in systemic hypertension is not fully understood. We explored HPA axis activity and feedback sensitivity to oral administration of dexamethasone in systemic hypertension via assessment of the cortisol awakening response (CAR) and the circadian cortisol profile. METHODS: The CAR and circadian cortisol profile were assessed in 20 unmedicated and otherwise healthy middle-aged hypertensive men and in 22 normotensive male controls. Salivary free cortisol measures for the CAR were obtained immediately after awakening and 15, 30, 45, and 60 min thereafter. Circadian cortisol secretion was sampled at 08:00, 11:00, 15:00, and 20:00 h. Assessment of the CAR was repeated on the next day after administration of 0.5mg dexamethasone at 23:00 h on the previous night. RESULTS: Hypertensives had a significantly lower CAR (p<0.02) and significantly reduced suppression of the CAR after dexamethasone administration (p<0.01) than normotensive controls. There were no significant differences in cortisol levels at awakening and in circadian cortisol profiles between hypertensives and normotensives. CONCLUSION: We found evidence for altered HPA axis activity in men with systemic hypertension evident with the CAR. Hypertensives showed relative attenuation in the CAR and in the HPA axis feedback sensitivity following dexamethasone suppression. Such alterations in HPA axis regulation might contribute to the atherosclerotic risk in hypertensive individuals.