Cortisol Response In Patients Research Articles

Physiological responses to the virtual reality-based Trier social stress test in patients with psychosis

ObjectivesThe Trier social stress test (TSST) is one of the most reliable and widely used laboratory tests for evaluating the physiological stress response. We developed a virtual reality-based TSST (VR-TSST) and investigated the physiological responses to this test in patients with psychosis and healthy controls (HCs).MethodsThe participants comprised 60 patients with psychosis and 66 HCs. The VR-TSST consisted of three scenarios: a resting phase (baseline; 2 min), a job interview (5 min), and a mental arithmetic task (5 min). Blood cortisol levels were measured at baseline, during the test, and at 5–10 min and 30 min after the test. The skin conductance level, heart rate, and RR intervals were measured at baseline, during the job interview, and during the arithmetic task.ResultsThe VR-TSST produced no discernible cortisol response in patients with psychosis compared to the HCs. However, a higher skin conductance level and heart rate and shorter RR intervals were found in the patients than in the HCs at baseline, during the job interview, and during the arithmetic task.ConclusionThese findings suggest that the current version of the VR-TSST induces stronger autonomic and cardiovascular, but not endocrine, responses in patients with psychosis than in HCs. The VR-TSST could be a valuable tool to evaluate or train the stress response in patients with psychosis.

Variations in cortisol response in patients with known and suspected adrenal insufficiency.

Adrenal insufficiency (AI) is a relatively rare disease. While the adrenocorticotropic hormone (ACTH) stimulation test remains as one of the commonly used diagnostic test for AI, to date there is no consensus on the cortisol cutoff value post-ACTH stimulation test. This study aimed to investigate and characterize the cortisol response after the standard ACTH stimulation test in a group of Saudi Arabian patients. A single center retrospective study was conducted on Saudi Arabian adult patients who underwent ACTH stimulation test at the endocrinology clinics of King Abdulaziz Medical City in Riyadh, Saudi Arabia between 2015 and 2018. Demographic, clinical and biochemical variables were collected and analyzed. A total of 154 medical records of patients (44 males, 110 females, mean age 44.4 ± 17.0 years) were included in the study. All patients underwent ACTH stimulation test. Fatigue was the most common symptom of participants. Type 1 diabetes was the most frequent comorbidity. Cortisol levels were significantly lower in patients who received corticosteroid replacement therapy, and, within the context of ACTH stimulation tests, were useful in diagnosing AI in patients with vague symptoms and signs. For basal cortisol, the cutoff of ≤258.5 has a sensitivity and specificity of 69.2% and 58.6%, respectively. For 30-minute, the cutoff of ≤386 sensitivity and specificity are 61.5% and 69.0%. For 60-minute, the cutoff of ≤491.5 has a sensitivity and specificity of 61.5% and 65.5%, respectively. Higher cortisol cutoff values have better sensitivity. Patients with AI present with mostly nonspecific symptoms, with type 1 diabetes as the most common comorbidity. The cortisol level cutoffs obtained from Arab patients who underwent ACTH stimulation tests showed wide variability for its utility in AI diagnosis. Further studies to evaluate the optimal cortisol cutoff values for AI diagnosis in this population are needed.

Posttraumatic stress disorder (PTSD) and depression severity in sexually assaulted women: hypothalamic-pituitary-adrenal (HPA) axis alterations

BackgroundSexual assault is implicated in several adverse psychological and physical health outcomes, including posttraumatic stress disorder (PTSD) and depression. Neurobiological research has shown variations related to the hypothalamic-pituitary-adrenal (HPA) axis, immune alterations, metabolic function, and brain circuitry. Although these mechanisms have been extensively studied, the results have demonstrated different outcomes in PTSD.MethodsWe compared the plasma adrenocorticotropin (ACTH) and salivary cortisol levels of fifty-eight women with PTSD developed after sexual assault to those of forty-four female controls with no history of trauma. We also evaluated the psychiatric diagnosis and symptom severity of PTSD and depression. The participants’ clinical conditions were associated with their hormonal levels to assess whether symptom severity was related to hormonal imbalance.ResultsA large percentage of sexually assaulted women had PTSD and comorbid depression. The ACTH levels were higher in the PTSD group than the control group and increased as PTSD severity increased, considering depressive symptoms, measured by the Beck Depression Inventory (BDI) (p < 0.0001), as well as PTSD symptoms, measured by subscale D of the Clinician-Administered PTSD Scale (CAPS-5) (p = 0.045) and the CAPS-5 total scale (p = 0.026). Cortisol levels measured at 10 pm were higher for the PTSD group than the control group (p = 0.045, p = 0.037, respectively), and the cortisol awakening response showed elevated cortisol levels for the PTSD group.ConclusionsThese results show a correlation between symptom severity and HPA axis imbalance in patients with PTSD. Elevated ACTH and an elevated cortisol response in patients with comorbid depressive symptoms were the opposite of the expected response for patients with PTSD only. This association leads to the hypothesis that the neurobiological alterations of PTSD are related to the type of symptoms presented and their severity. These manifestations likely influence the disease course, prognosis and response to treatment. These outcomes highlight the need to discuss particular neurobiological alterations in patients with PTSD developed after sexual assault, mainly those with severe depressive symptoms.

Cortisol, DHEA and DHEA-S during exposure therapy in patients with obsessive-compulsive disorder – secretion patterns and prediction of treatment response

The cortisol response in patients with obsessive-compulsive disorder (OCD) during exposure with response prevention (ERP), a stressful but very effective psychotherapeutic treatment, has shown contradictory findings in three prior studies with low sample sizes. In a larger cohort of 51 patients with OCD we repeatedly measured subjective units of distress (SUD) and the adrenocortical stress hormones cortisol, dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEA-S) in saliva during the very first session of ERP and on the day before. Expectedly, SUD were increased on the ERP day before the session and further rose during ERP, but salivary cortisol and DHEA were statistically indistinguishable from the comparison condition. Interestingly, DHEA-S was significantly elevated throughout the ERP versus the comparison day, but did not further increase in acute response to ERP. According to an explorative analysis in a subsample, hormone levels on the comparison or the ERP day did not predict anti-OCD treatment response one month later. These results corroborate our prior findings of cortisol non-response despite considerable subjective stress in ERP. The role of DHEA-S in anticipatory anxiety and the effects of augmentative cortisol therapy in ERP need further study.

The effect of distress on the balance between goal-directed and habit networks in obsessive-compulsive disorder

The classical cognitive-behavioral theory of obsessive-compulsive disorder (OCD) holds that compulsions are performed to reduce distress that is evoked by obsessions, whereas a recent neuroscience-inspired theory suggests that compulsivity results from a disbalance between goal-directed and habit-related neural networks. To bridge these theories, we investigated whether the balance between goal-directed and habit networks in patients with OCD was affected during psychological distress. Twenty-three OCD patients and twenty-three healthy controls participated in a controlled stress induction paradigm using the socially evaluated cold-pressor test in a crossover design. Stress responses were evaluated through cortisol levels, blood pressure, and anxiety ratings. Functional connectivity of the caudate nucleus and posterior putamen was assessed using seed region analysis of resting-state functional magnetic resonance imaging data, which are hubs of the goal-directed and habit network, respectively. Stress induction increased blood pressure and psychological stress measures across groups and resulted in blunted cortisol responses in patients. Furthermore, patients showed a blunted reduction in connectivity between the caudate nucleus and precuneus during psychological distress, which was positively correlated with compulsivity but not obsession severity. The posterior putamen showed no significant group differences in distress-induced connectivity. These results suggest that compulsivity in OCD is associated with altered connectivity between the goal-directed and default mode networks during psychological distress.

P2669Enhanced interleukin-6 expression and impaired cortisol response in patients with coronary artery disease

P2669Enhanced interleukin-6 expression and impaired cortisol response in patients with coronary artery disease

Management of Suboptimal Cortisol Response in patients with Structural Heart Disease-Two Case Reports

1. Abstract Sub optimal Cortisol Response (SCR) is an inadequate cortisol response in relation to the severity of illness. Also known as critical illness induced corticosteroid insufficiency, it is frequently observed in patients with septic shock. We describe two patients presented to us with sign and symptoms of heart failure. Up titration of diuretics dose was a big challenge to us due to the concomitant severe electrolyte imbalance likely due to altered hypothalamic pituitary axis leading to relative adrenal insufficiency. Random serum cortisol level was checked which was relatively low. Cortisol was replaced which helped us in normalizing serum electrolytes by correcting the SCR. Purpose of writing these two cases is to highlight the importance of SCR in decompensated heart failure, as the early diagnosis and treatment of this condition will help physicians in the better management of patients with heart failure. 2. Keywords <span style=font-size:10.0pt;font-family: times= new= roman,serif=>: <span style=font-size:10.0pt; font-family: times= new= roman,serif=>Electrolyte Imbalance; Heart Failure; Suboptimal Cortisol Response (SCR); Structural Heart Disease

Prolonged hypothalamic-pituitary-adrenal axis activation after acute coronary syndrome in the GENESIS-PRAXY cohort.

Background Glucocorticoid excess has been linked with cardiovascular disease. Little is known about the long-term cortisol response in patients after acute coronary syndrome. Design The objective of this study was to describe the distribution of salivary cortisol in the post-acute phase of acute coronary syndrome and to describe the association of late-night salivary cortisol with cardiovascular risk factors. Methods We used late-night salivary cortisol measurements post-discharge to estimate hypothalamic-pituitary-adrenal axis activity in 309 patients aged 18-55 years enrolled in the GENESIS-PRAXY study from January 2009-April 2013. We evaluated hypothalamic-pituitary-adrenal axis activity and its association with hypertension, dyslipidemia, diabetes, smoking, family history, prior acute coronary syndrome, psychiatric diseases, acute coronary syndrome severity, as well as mortality and rate of rehospitalization at 12 months. Results Persistently elevated late-night salivary cortisol>2.92 nmol/l was seen in 99 (32.0%) patients: within the range of what may be seen in Cushing's disease. Elevated late-night salivary cortisol was associated with previous acute coronary syndrome (13.3% vs 24.2%, p = 0.02), peripheral vascular disease (3.8% vs 13.1%, p = 0.002), and smoking (32.9% vs 46.5% p = 0.02). Elevated late-night salivary cortisol was associated with higher hemoglobin A1c values (5.6 ± 3.0 vs 6.1 ± 2.9, p = 0.008) and lower high density lipoprotein values (0.94 ± 0.53 vs 0.86 ± 0.50, p = 0.01). There were no differences in psychiatric symptom scores, acute coronary syndrome severity or mortality, and rate of rehospitalization at 12 months. Conclusions Many patients post-acute coronary syndrome have prolonged, marked activation of the hypothalamic-pituitary-adrenal axis. Late-night salivary cortisol co-associates with several cardiovascular risk factors. Further studies are needed to confirm the exact role of hypothalamic-pituitary-adrenal axis activity in the pathophysiology of cardiovascular disease.

Stress-induced release of matrix metalloproteinase-9 in patients with coronary artery disease: The possible influence of cortisol

Stress and inflammation are both important risk factors for coronary artery disease (CAD). However, the susceptibility to stress-induced inflammation and its determinants have been little explored in patients with CAD. Here, our aim was to study the stress-induced inflammatory response, more precisely the early release of matrix metalloproteinase (MMP)-9, and its association with cortisol response in patients with CAD. Sixty-four patients underwent a standardized laboratory stress test. The stress-induced release of MMP-9 was closely associated with the release of other neutrophil-associated proteins, MMP-8 and myeloperoxidase (MPO). It also showed a large variation among patients, as did cortisol. Twenty minutes after stress, a negative association between changes in MMP-9 and cortisol was seen (p<0.01). In vitro, dexamethasone reduced the IL-8-mediated release of MMP-9 from neutrophils, indicating that glucocorticoids may exert rapid effects on neutrophil activation. Further characterization of patients revealed that stress-induced release of MMP-9 was related to leukocyte telomere shortening and increased ultrasound-assessed plaque occurrence in the carotid arteries, but not to other characteristics such as age, gender or psychological background factors. The susceptibility to stress-induced release of MMP-9 may thus have impact on disease phenotype. Stress tests can be useful to identify CAD patients in need of novel prevention and treatment strategies.

Efeito de exercícios físicos e de lazer sobre os níveis de cortisol plasmático em pacientes com Aids

The advent of antiretroviral drugs for the treatment of AIDS individuals provided an increase in survival time, however, despite having the patient is often asymptomatic, can present significant disturbances in psychosocial sphere, among them, the weakening of social relations, which are lose with the discovery of the contamination. Regular physical exercise can be an interesting strategy to combat the psychological problems associated with HIV infection. Individuals engaged in a physical training program may have improved well ‐being, increased self‐esteem, decrease in symptoms of depression and anxiety, but also provide greater social interaction. Patients infected with HIV generally have higher baseline serum cortisol and some studies suggest that high levels of cortisol can impair the function of the immune system, acting as accelerators of viral progression and development of AIDS. The objective of this study was to evaluate the effect of physical exercise and leisure on plasma cortisol levels in patients with AIDS. Selected patients were divided into two groups: Group I participated in physical activity and exercise Group II participated in leisure activities, both for a period of 16 weeks. The evaluation consisted of measurement of plasma cortisol before the start of activities and after 16 weeks. 57% of patients showed improvement in the levels of plasma cortisol after the program applied. This work suggests that physical exercise and leisure induce a physiological improvement cortisol response in patients with AIDS.

Modified-release prednisone in rheumatoid arthritis: Rationale for chronotherapy, mechanistic considerations, and clinical implications

Pain, stiffness of joints, and functional disability of rheumatoid arthritis (RA) are maximum in the morning. Cytokines, especially interleukin (IL)-6, demonstrate a circadian variation in patients with RA and contribute to the severity of aforementioned symptoms. Perturbed cortisol response in patients with RA is not effectively able to negate the effects of interleukin 6 rise in the early morning. Modified-release (MR) prednisone is a polymer-based drug delivery system which releases the drug 4 h after the ingestion of tablet closely simulating the cortisol rise and peak in patients with RA. In this review, we focus on the rationale for chronotherapy, mechanistic considerations, and clinical implications of MR prednisone.

Evidence for a normal HPA axis response to psychosocial stress in patients remitted from depression

The purpose of this study was to investigate subjective mood and the effect of a psychosocial stress challenge on cortisol response in patients remitted from depression in comparison to healthy controls. Only few studies on small samples have been conducted on the influence of psychosocial stress on HPA system responsivity in this group. Results regarding patients who have achieved clinical remission from depression remain inconclusive so far. In comparison to healthy controls, some studies found blunted cortisol responses to a psychological stressor in patients with remitted depression. However, others found no differences. This discrepancy may be due to use of heterogeneous stress measures or dissimilar sample sizes and characteristics, e.g. including patients with comorbid generalized anxiety or patients with an unknown duration of remission. The present study included 77 healthy controls and 70 unipolar depressed patients who had achieved stable, full remission for at least 6 months (average 31 months) with no further Axis I disorder. Participants underwent the Trier Social Stress Test and salivary cortisol levels and mood were assessed repeatedly during the experimental procedure. For both groups, we observed a marked cortisol response and worsening of mood after the stress challenge. However, no differences between formerly depressed patients and healthy participants were observed. Assuming a disturbed HPA system regulation in acute depression, we interpret these findings as evidence for a restored HPA axis function in fully remitted patients.

Blunted salivary and plasma cortisol response in patients with panic disorder under psychosocial stress

BackgroundPanic disorder (PD) has been associated with an altered activity of the hypothalamic–pituitary–adrenal–cortical (HPA) axis. Recent findings from a patient sample with PD with secondary depression on psychotropic medication using salivary cortisol as outcome measure suggest a non-responsiveness of the HPA-axis under acute psychosocial stress. Salivary cortisol does not necessarily reflect the total plasma cortisol due to interfering variables. Whether the present findings can be replicated on a patient sample with pure PD using both salivary cortisol and total plasma cortisol as outcome variables remains to be elucidated. MethodsFor this study, the Trier Social Stress Test (TSST) was implemented to assess the HPA-axis reactivity indicated by the plasma adreno-corticotropin-hormone (ACTH), plasma cortisol, and salivary cortisol release. The sample included 32 patients diagnosed with PD in a Structured Clinical Interview (SCID). Twelve male and fifteen female patients [mean age=32.87years, SD=11.23] were matched with 32 healthy controls by age and gender. ResultsThe plasma ACTH, total plasma cortisol and salivary cortisol release increased significantly in both groups due to the psychosocial stress test. The patients with PD showed a decreased plasma and salivary cortisol response as compared to the healthy controls. Plasma cortisol and salivary cortisol were highly correlated in both groups. ConclusionThese findings provide strong evidence for a hypo-responsiveness of the HPA-axis as measured in both blood and saliva. Salivary and total plasma cortisol showed a strong concordance of results. Thus, future investigations could consider salivary cortisol as reliable marker of the HPA-axis under psychosocial stress.

Comparison of the cortisol responses to testing with two doses of ACTH in patients with suspected adrenal insufficiency

To compare the cortisol response of the 1 μg and the 250 μg ACTH test in a large study of patients with suspected adrenal insufficiency. Retrospective cohort study. Single center study assessing patients tested for primary or secondary adrenal insufficiency between January 2004 and December 2007, who had both ACTH tests (1 μg and 250 μg; n=207) within a time interval of 6 weeks. Test results were compared with a Bland-Altman plot and McNemar's test. The mean difference between the cortisol responses in the two ACTH tests was 26 nmol/l (95% confidence interval (CI) 13, 40), showing a marginally higher response for the 250 μg test. The diagnostic performances of the two tests were similar (P=0.49) using a cut-off value for cortisol of 550 nmol/l. A normal cortisol response to the 1 μg ACTH test could be accompanied by an abnormal response to the 250 μg ACTH test, and vice versa. This study shows that the 1 μg and the 250 μg ACTH tests have comparable cortisol responses in patients with suspected adrenal insufficiency. However, in individual patients, the difference in cortisol response to the two tests can be substantial, and the response in the 250 μg test is not invariably higher than the response in a 1 μg test.

Mapping of hormones and cortisol responses in patients after Lyme neuroborreliosis

BackgroundPersistent symptoms after treatment for neuroborreliosis are common for reasons mainly unknown. These symptoms are often unspecific and could be caused by dysfunctions in endocrine systems, an issue that has not been previously addressed systematically. We therefore mapped hormone levels in patients with previous confirmed Lyme neuroborreliosis of different outcomes and compared them with a healthy control group.MethodsTwenty patients of a retrospective cohort of patients treated for definite Lyme neuroborreliosis were recruited 2.3 to 3.7 years (median 2.7) after diagnosis, together with 23 healthy controls. Lyme neuroborreliosis patients were stratified into two groups according to a symptom/sign score. All participants underwent anthropometric and physiological investigation as well as an extensive biochemical endocrine investigation including a short high-dose adrenocorticotropic hormone stimulation (Synacthen®) test. In addition to hormonal status, we also examined electrolytes, 25-hydroxy-vitamin D and interleukin-6.ResultsEight patients (40%) had pronounced symptoms 2-3 years after treatment. This group had a higher cortisol response to synacthen as compared with both controls and the Lyme neuroborreliosis patients without remaining symptoms (p < 0.001 for both comparisons). No other significant differences in the various baseline biochemical parameters, anthropometric or physiological data could be detected across groups.ConclusionsApart from a positive association between the occurrence of long-lasting complaints after Lyme neuroborreliosis and cortisol response to synacthen, no corticotropic insufficiency or other serious hormonal dysfunction was found to be associated with remaining symptoms after treatment for Lyme neuroborreliosis.

Lack of cortisol response in patients with posttraumatic stress disorder (PTSD) undergoing a diagnostic interview

BackgroundAccording to DSM-IV, the diagnosis of posttraumatic stress disorder (PTSD) requires the experience of a traumatic event during which the person's response involved intense fear, helplessness, or horror. In order to diagnose PTSD, clinicians must interview the person in depth about his/her previous experiences and determine whether the individual has been traumatized by a specific event or events. However, asking questions about traumatic experiences can be stressful for the traumatized individual and it has been cautioned that subsequent "re-traumatization" could occur. This study investigated the cortisol response in traumatized refugees with PTSD during a detailed and standardized interview about their personal war and torture experiences.MethodsParticipants were male refugees with severe PTSD who solicited an expert opinion in the Psychological Research Clinic for Refugees of the University of Konstanz. 17 patients were administered the Vivo Checklist of War, Detention, and Torture Events, a standardized interview about traumatic experiences, and 16 subjects were interviewed about absorption behavior. Self-reported measures of affect and arousal, as well as saliva cortisol were collected at four points. Before and after the experimental intervention, subjects performed a Delayed Matching-to-Sample (DMS) task for distraction. They also rated the severity of selected PTSD symptoms, as well as the level of intrusiveness of traumatic memories at that time.ResultsCortisol excretion diminished in the course of the interview and showed the same pattern for both groups. No specific response was detectable after the supposed stressor. Correspondingly, ratings of subjective well-being, memories of the most traumatic event(s) and PTSD symptoms did not show any significant difference between groups. Those in the presumed stress condition did not perform worse than persons in the control condition after the stressor. However, both groups performed poorly in the DMS task, which is consistent with memory and concentration problems demonstrated in patients with PTSD.ConclusionA comprehensive diagnostic interview including questions about traumatic events does not trigger an HPA-axis based alarm response or changes in psychological measures, even for persons with severe PTSD, such as survivors of torture. Thus, addressing traumatic experiences within a safe and empathic environment appears to impose no unacceptable additional load to the patient.

Enhanced psychosocial stress-induced IL-6 responses are associated with attenuated stress-induced cortisol responses in patients with major depression and increased early life stress

Enhanced psychosocial stress-induced IL-6 responses are associated with attenuated stress-induced cortisol responses in patients with major depression and increased early life stress

Tu-P10:428 Impaired cortisol response in patients with coronary artery disease — relation to inflammatory activity

Tu-P10:428 Impaired cortisol response in patients with coronary artery disease — relation to inflammatory activity

Male patients with paranoid schizophrenia have greater ACTH and cortisol secretion in response to metoclopramide-induced AVP release

Dynamic testing of the hypothalamic-pituitary-adrenal axis in schizophrenia has yielded conflicting results, which may be related to patient selection and previous exposure to psychotropic medication. The objective of this study was to determine the pattern of corticotropin (ACTH) and cortisol release in response to metoclopramide (a dopamine antagonist), which appears to be unique in its ability to release vasopressin (AVP), in drug naive patients with schizophrenia experiencing their first episode of psychosis. In this study, we examined AVP, ACTH and cortisol release in response to metoclopramide in 10 drug-naive, first-episode male patients with a DSM IV diagnosis of paranoid schizophrenia and compared them to healthy control subjects matched for age, sex and smoking status. Patients, as compared to controls had higher levels of baseline plasma cortisol (375.5+/-47.4/l vs. 273.8+/-42.2 nmol/l, respectively; t=2.48, df=9, p< 0.02) and plasma ACTH (14.9+/-0.85 vs. 11.3+/-0.57 pg/ml, respectively; t=4.29, df=9, p<0.001). AVP levels were lower in patients though this did not reach statistical significance (0.89+/-0.09 vs. 1.3+/-0.08 pmol/l, respectively; t=1.97, df=9, p<0.07). A repeated measures 2-way ANOVA to compare responses to metoclopramide over time between the two groups yielded a significant group by time interaction for cortisol (F=11.3, df=6, 108, p<0.001) and ACTH (F=15.65, df=6, 108, p<0.002). Post hoc Tukey's test revealed significant differences between the two groups at +30, +45, +60, +90 and +120 min for cortisol (p<0.01) and at +30, +45, +60 and +90 min for ACTH (p<0.01). The group by time interactions continued to remain significant when cortisol (F=10.9, df=6, 107, p<0.001) and ACTH (F=13.04, df=6, 108, p<0.002) were entered as co-variates. There was a significant positive correlation between AVP and cortisol responses in patients (r=0.65, df=8, p<0.01). Male patients with paranoid schizophrenia release greater amounts of ACTH and cortisol in responses to metoclopramide-induced AVP secretion than control subjects.

No morning cortisol response in patients with severe global amnesia

Activity of the hypothalamus pituitary adrenal (HPA) axis is characterized by a pronounced circadian rhythm. An acute increase in cortisol levels occurs after awakening in the morning with continuously declining levels over the course of the remaining day. The morning cortisol increase probably reflects an activational response of the HPA axis aimed at preparing the body for the day. Some studies found patterns of enhanced or blunted waking cortisol responses observed under chronic stress, burnout, or post traumatic stress disorder. The present study wanted to characterize the morning cortisol response and the circadian cortisol day profile in a sample of six male patients with severe amnesia due to hypoxia, herpes simplex encephalitis or closed head injury. Age and gender matched relatives or friends served as controls. Cortisol was measured from saliva samples collected at home on two consecutive days. The patients were woken up in the morning by their partners or caregivers. The morning cortisol increase typically observed in healthy subjects and also observed in the control group was absent in the amnesic patients. In contrast, a normal circadian day profile was found in the amnesic patients, with a pronounced circadian cortisol decrease. Further studies are needed to understand the neurological or psychological mechanisms leading to a missing morning cortisol response in amnesic patients.