Diurnal Rhythm Of Cortisol Secretion Research Articles

Salivary Cortisol and Anxiety in Canadian Dentists over 1 Year of COVID-19

The dental profession has endured unprecedented disruption amid COVID-19. Novel stressors have included a high risk of occupational exposure to COVID-19, financial losses, and stricter infection prevention and control requirements. The present study investigated the longitudinal impact of COVID-19 on the stress and anxiety levels of a cohort of Canadian dentists (N = 222) between September 2020 and October 2021. Salivary cortisol was selected as a biomarker of mental stress, and 10 sets of monthly saliva samples (2,131 in total) were self-collected, sent to our laboratory in prepaid courier envelopes, and analyzed by enzyme-linked immunosorbent assay. To assess COVID-19 anxiety, 9 monthly online questionnaires were administered, comprising a general COVID-19 anxiety instrument and 3 items regarding the impact of dentistry-related factors. Bayesian log-normal mixed effect models were fitted to estimate the longitudinal trajectory of salivary cortisol levels and their association with the disease burden of COVID-19 in Canada. After accounting for age, sex, vaccination status, and the diurnal rhythm of cortisol secretion, a modest positive association was found between dentists’ salivary cortisol levels and the count of COVID-19 cases in Canada (96% posterior probability). Similarly, the self-reported impact of dentistry-related factors, such as fear of getting COVID-19 from a patient or coworker, was greatest during peaks of COVID-19 waves in Canada; however, general COVID-19 anxiety decreased consistently throughout the study period. Interestingly, at all collection points, the majority of participants were not concerned about personal protective equipment. Overall, participants reported relatively low rates of psychological distress symptoms in relation to COVID-19, a result that should be reassuring for the dental community. Our findings strongly suggest a link between self-reported and biochemical measurements of stress and anxiety in Canadian dentists during the COVID-19 pandemic.

Emerging treatment for congenital adrenal hyperplasia.

Although the basic treatment of congenital adrenal hyperplasia (CAH) is well established, there are active clinical research projects to more closely mimic the normal diurnal rhythm of cortisol secretion and to reduce total glucocorticoid doses to minimize adverse metabolic effects. We review clinical studies on CAH treatment published in the last 18 months or currently underway according to ClinicalTrials.gov listings. These can be grouped into several broad themes: alternative dosing forms of hydrocortisone with altered pharmacokinetics or easier dose titration; corticotropin-releasing hormone receptor antagonists that reduce corticotropin (ACTH) secretion and thereby reduce adrenal androgen secretion; androgen biosynthesis inhibitors; a first clinical trial of a gene therapy vector. Alternative dosing forms of hydrocortisone are, or will shortly be, marketed, but cost may be a barrier to utilization, at least in the US market. Trials of corticotropin releasing hormone receptor antagonists and androgen biosynthesis inhibitors are currently underway. The author believes that trials of gene therapy for CAH are premature.

Use of Salivary Diurnal Cortisol as an Outcome Measure in Randomised Controlled Trials: a Systematic Review.

BackgroundDysregulation of the hypothalamic-pituitary-adrenal (HPA) axis is associated with diverse adverse health outcomes, making it an important therapeutic target. Measurement of the diurnal rhythm of cortisol secretion provides a window into this system. At present, no guidelines exist for the optimal use of this biomarker within randomised controlled trials (RCTs).PurposeThe aim of this study is to describe the ways in which salivary diurnal cortisol has been measured within RCTs of health or behavioural interventions in adults.MethodsSix electronic databases (up to May 21, 2015) were systematically searched for RCTs which used salivary diurnal cortisol as an outcome measure to evaluate health or behavioural interventions in adults. A narrative synthesis was undertaken of the findings in relation to salivary cortisol methodology and outcomes.ResultsFrom 78 studies that fulfilled the inclusion criteria, 30 included healthy participants (38.5 %), 27 included patients with physical disease (34.6 %) and 21 included patients with psychiatric disease (26.9 %). Psychological therapies were most commonly evaluated (n = 33, 42.3 %). There was substantial heterogeneity across studies in relation to saliva collection protocols and reported cortisol parameters. Only 39 studies (50 %) calculated a rhythm parameter such as the diurnal slope or the cortisol awakening response (CAR). Patterns of change in cortisol parameters were inconsistent both within and across studies and there was low agreement with clinical findings.ConclusionsSalivary diurnal cortisol is measured inconsistently across RCTs, which is limiting the interpretation of findings within and across studies. This indicates a need for more validation work, along with consensus guidelines.Electronic supplementary materialThe online version of this article (doi:10.1007/s12160-015-9753-9) contains supplementary material, which is available to authorized users.

Pitfalls in the diagnosis and management of Cushing's syndrome.

Despite many recent advances, the management of patients with Cushing's disease continues to be challenging. Cushing's syndrome is a complex metabolic disorder that is a result of excess glucocorticoids. Excluding the exogenous causes, adrenocorticotropic hormone-secreting pituitary adenomas account for nearly 70% of all cases of Cushing's syndrome. The suspicion, diagnosis, and differential diagnosis require a logical systematic approach with attention paid to key details at each investigational step. A diagnosis of endogenous Cushing's syndrome is usually suspected in patients with clinical symptoms and confirmed by using multiple biochemical tests. Each of the biochemical tests used to establish the diagnosis has limitations that need to be considered for proper interpretation. Although some tests determine the total daily urinary excretion of cortisol, many others rely on measurements of serum cortisol at baseline and after stimulation (e.g., after corticotropin-releasing hormone) or suppression (e.g., dexamethasone) with agents that influence the hypothalamic-pituitary-adrenal axis. Other tests (e.g., measurements of late-night salivary cortisol concentration) rely on alterations in the diurnal rhythm of cortisol secretion. Because more than 90% of the cortisol in the circulation is protein bound, any alteration in the binding proteins (transcortin and albumin) will automatically influence the measured level and confound the interpretation of stimulation and suppression data, which are the basis for establishing the diagnosis of Cushing's syndrome. Although measuring late-night salivary cortisol seems to be an excellent initial test for hypercortisolism, it may be confounded by poor sampling methods and contamination. Measurements of 24-hour urinary free-cortisol excretion could be misleading in the presence of some pathological and physiological conditions. Dexamethasone suppression tests can be affected by illnesses that alter the absorption of the drug (e.g., malabsorption, celiac disease) and by the concurrent use of medications that interfere with its metabolism (e.g., inducers and inhibitors of the P450 enzyme system). In this review, the authors aim to review the pitfalls commonly encountered in the workup of patients suspected to have hypercortisolism. The optimal diagnosis and therapy for patients with Cushing's disease require the thorough and close coordination and involvement of all members of the management team.

Salivary Stress Markers, Depression, Mood State and Back Pain in Healthy Men in Two Bed Rest Conditions: Validation of Two Models for Human Space Flight

The NASA promise to long-duration space flight includes astronauts who will be returning to the moon as well as those who will take part in human missions to Mars. Successful exploration will require a better understanding of the effects that extended missions pose for the behavioral health of astronauts, not just during flight but also pre and post-flight. The potential for psychiatric disorders developing in long-duration crews during or after missions requires that consideration be given to prevention and treatment .The objective of this study was to validate a ground-based models (Two bed rest conditions such as 6° head-down tilt (HDT) and bed rest position (HB) for microgravity and zero gravity and to study the effects of simulated condition on depression, mood state, back pain and biochemical stress markers. The aim of the present study was to determine the effects of 20-day HDT & HB on psychic stress, depression, mood-state, backache and headache in 10 healthy male volunteers. Psychological state was assessed by a stress test, mood state and cortisol was measured in saliva. During HDT and HB, all volunteers developed psychic stress, and the diurnal rhythm of cortisol secretion was significantly increased in simulated conditions. In addition, urine excretion of dopamine, epinephrine and norepinephrine were significantly increased. Thus 6° HDT & HB appears to be a valid model to induce psychic stress and neuroendocrine-related changes that could also be encountered by astronauts and marsonaunts during long-duration spaceflights.

High Perceived Stress Is Linked to Afternoon Cortisol Levels and Greater Symptom Distress in Patients With Localized Prostate Cancer

Patients treated with radical prostatectomy (RP) or radiation therapy (RT) for prostate cancer can experience stress and symptoms that impact quality of life. The objectives of this study were to describe cortisol levels, perceived stress, symptoms, and symptom distress; compare differences in variables measured between RP and RT; and identify associations among cortisol levels, perceived stress, symptoms, and symptom distress in patients treated for localized prostate cancer. A descriptive, cross-sectional study was conducted with 53 patients (RP n = 24, RT n = 29). Data from saliva, questionnaires, and interviews were collected within 3 months of treatment. Saliva samples were collected at 4 times over 2 consecutive days. Data were analyzed using descriptive statistics, correlations, and regressions. A robust diurnal rhythm of cortisol secretion with heightened levels in the early morning and lowered levels late in the day was found. On average, the entire sample had moderate symptoms and symptom distress for urinary, bowel, and sexual dysfunction. The RP group reported significantly more urinary and sexual dysfunction symptoms and fewer bowel symptoms than did the RT group. Perceived stress was positively correlated with higher afternoon cortisol levels and greater symptom distress. Moderate symptoms and symptom distress found in our sample indicate the need for interventions to address these outcomes in men treated for prostate cancer. Self-reported perceived stress can be used to assess the stress level and symptom distress in clinic setting. Patients treated for prostate cancer with RP or RT should be assessed for symptoms and symptom distress and targeted for early symptom management interventions.

Psychophysiological Stress Response during Competition between Elite and Non-elite Korean Junior Golfers

The purpose of this study was to investigate the effects of stress hormone and competition state anxiety response between elite and non-elite junior golfers in competition. Six elite (Handicap: 2.67+/-0.82; 16.2+/-1.38 yrs) and six non-elite (Handicap: 7.83+/-1.17; 15.8+/-0.75 yrs) Korean junior golfers participated in this study. Physiological stress and psychological stress responses were measured on four occasions (at rest, prior to, during, after competition) by salivary cortisol and Competitive State Anxiety Inventory-2 (CSAI-2) respectively. In salivary cortisol, no interaction was found between groups and the test occasions. However, both groups showed significantly increased levels between rest and all other occasions and between prior to and after competition. The interpretation of this finding is limited by the interaction with the diurnal rhythm of cortisol secretion. In cognitive state anxiety, significant interaction was found. Elite golfers had significantly lower cognitive state anxiety scores than non-elite golfers at rest, prior to and during competition. No interaction was shown in somatic state anxiety. However, there was significant difference among occasions. Both groups had higher somatic state anxiety scores prior to and during competition than after competition. No interaction was shown in self-confidence, but elite group had significantly higher scores than non-elite group at all occasions. This study demonstrates the differences of psychophysiological response in competition between elite golfers and non-elite golfers.

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.

Alterations in diurnal cortisol rhythm and acoustic startle response in nonhuman primates with adverse rearing

Early adverse experiences represent risk factors for the development of anxiety and mood disorders. Studies in nonhuman primates have largely focused on the impact of protracted maternal and social deprivation, but such intense manipulations also result in severe social and emotional deficits very difficult to remediate. This study attempts to model more subtle developmental perturbations that may increase the vulnerability for anxiety/mood disorders but lack the severe deficits associated with motherless rearing. We investigated the consequences of repeated maternal separations between 3 to 6 months of age on rhesus monkeys' hypothalamic-pituitary-adrenal (HPA) axis function and acoustic startle reactivity. Repetitive maternal separation led to increased cortisol reactivity to the separation protocol in female infants and alterations in mother-infant interaction. It also resulted in a flattened diurnal rhythm of cortisol secretion and increased acoustic startle reactivity at later ages. Macaques with adverse rearing exhibited short-term and long-term alterations in HPA axis function and increased acoustic startle response comparable with changes associated with mood/anxiety disorders. The magnitude of HPA axis reactivity to the separations and the alterations in mother-infant relationship detected during the separation protocol predicted some of the alterations in HPA axis and emotionality exhibited later in life.

Effects of confinement (110 and 240 days) on neuroendocrine stress response and changes of immune cells in men.

The aim of the study was to evaluate the effects of long-term confinement on stress-permissive neuroendocrine and immune responses in humans. Two groups of four male subjects were confined 240 days (group 240) or 110 days (group 110) in two space modules of 100 or 200 m3, respectively. During confinement, none of the volunteers developed psychic stress as could be examined and verified by a current stress test. However, in group 240 but not in group 110, the diurnal rhythm of cortisol secretion was slightly depressed and the urine excretion of norepinephrine significantly increased. The innate part of the immune system became activated as seen by a rise in the number of circulating granulocytes and the enhanced expression of beta2-integrins. In contrast, the ratio of T-helper to T-suppressor cells decreased. All these effects, observed during confinement, were even more pronounced in both groups when values of endocrinological and immunological parameters were compared between before and 1 wk after the end of the confinement period. Hence, return to normal life exerts pronounced effects to a much higher degree, irrespective of how long or under which conditions individuals were confined. Because the delayed-type hypersensitivity skin reaction against recall antigens remained unaffected, it is to be presumed that confinement appears to induce distinct sympathoadrenergic activation and immunological changes but no clinically relevant immunosuppression.

Simulated microgravity, psychic stress, and immune cells in men: observations during 120-day 6 degrees HDT.

Because 6 degrees head-down tilt (HDT) is an established method to mimic low gravity on earth, the aim of the present study was to determine the effects of 120-day HDT on psychic stress and peripheral blood immune cells in six healthy male volunteers. Psychological state was assessed by a current stress test, and cortisol was measured in saliva. During HDT, all volunteers developed psychic stress, and the diurnal rhythm of cortisol secretion was significantly altered. In addition, urine excretion of dopamine and norepinephrine increased. The innate part of the immune response was activated, as evidenced by the increase in the expression of beta(2)-integrins on polymorphonuclear leukocytes and a rise in the number of circulating natural killer (NK) cell lymphocytes. The ratio of T-helper to T-cytotoxic and T-suppressor cells decreased, whereas no changes in T and B lymphocytes were observed. Plasma levels of interleukin-6 increased significantly and returned to basal levels after the end of the HDT period. Thus 6 degrees HDT appears to be a valid model to induce psychic stress and neuroendocrine-related changes in the immune system, changes that might also be encountered by astronauts and cosmonauts during long-duration spaceflights.

Preclinical Cushing's syndrome in adrenal "incidentalomas": comparison with adrenal Cushing's syndrome.

Adrenal tumors are usually diagnosed by clinical symptoms of hormone excess. The increasing use of ultrasound and computed tomography results in the detection of a substantial number of incidentally discovered adrenal tumors. Most of these tumors are nonfunctional adrenocortical adenomas, but a few cases of subclinical cortisol production in "incidentalomas" have been reported. We investigated prospectively the prevalence of autonomous cortisol production in 68 patients (44 females and 24 males, aged 25-90 yr) with adrenal incidentalomas at our institution. As a screening procedure all patients with incidentalomas underwent an overnight dexamethasone suppression test (1 mg). Patients who failed to suppress serum cortisol below 140 nmol/L (5 micrograms/dL) underwent more comprehensive studies (prolonged dexamethasone suppression test, determination of the diurnal rhythm of cortisol secretion in saliva, and CRH stimulation test). Eight patients (12% of all patients with incidentalomas; 5 females and 3 males, aged 25-71 yr) were finally identified as having cortisol-producing tumors, and the findings in these patients were compared with those of overt Cushing's syndrome in 8 patients (8 females, aged 26-50 yr) suffering from cortisol-producing adrenal adenomas. The tumor size of patients with cortisol-producing incidentalomas ranged from 2-5 cm. No specific signs and symptoms of hypercortisolism were present, but arterial hypertension (seven of eight subjects), diffuse obesity (four of eight subjects), and noninsulin-dependent diabetes mellitus (NIDDM; two of eight subjects) were frequently observed. Baseline cortisol levels were in the normal to upper normal range, whereas baseline ACTH levels were suppressed in five of the eight patients. In none of the patients was serum cortisol suppressible by low dose or high dose dexamethasone. The ACTH and cortisol responses to CRH were normal in two, blunted in one, and suppressed in four patients. Unilateral adrenalectomy was performed in seven patients and resulted in temporary adrenal insufficiency in four of them. After surgery, improvement of arterial hypertension, a permanent weight loss in obese subjects, and a better metabolic control of NIDDM were noted in the majority of patients. The following conclusions were reached. Incidentally diagnosed adrenal tumors with pathological cortisol secretion in otherwise clinically asymptomatic patients are more frequently observed than previously assumed. Adrenocortical insufficiency is a major risk in these patients after adrenalectomy. After surgery, hypertension, obesity, and NIDDM may improve. Patients with asymptomatic adrenal incidentalomas, therefore, should be screened for cortisol production by means of an overnight dexamethasone suppression test.

93 PRESENCE OF DIURNAL VARIATION FOR IONIZED AND TOTAL Ca EXCRETION IN PREMATURE INFANTS

Diurnal variation in urinary calcium is observed in adult subjects, and is ascribed primarily to food intake, exercise habits, a day/night routine, and lastly an intrinsic rhythm. We wished to see whether premature infants showed diurnal variation in urinary Ca, and hypothesized that this would be largely an intrinsic rhythm since the infants were exposed to 24 h light and regular feeds around the clock.We studied 5 infants (3 male, 2 female) birth weight 1.17±0.20 kg (mean±SD), gestational age 28±0.7 wks at 34±5 days of life, who were being fed every 2-3 hours. Urine was collected each time the infant voided for a period of 24 hours. Each specimen was analyzed for ionized Ca (iCa), total Ca (tCa), and pH, and excretion rates for Ca were calculated. The mean three-hourly Ca excretion rate for each infant was expressed as a percentage above or below the mean 3-hourly rate for the 24 h from midnight to midnight, and the average patterns of the five subjects graphed. Urinary iCa and tCa showed a diurnal variation (p<0.05). The values between 04.00 and 09.00 h were 17% above the 24 h mean and between 16.00 and 24.00 h were 19% below the 24 h mean. This is very similar to the intrinsic rhythm for Ca excretion described in adults, which coincides with the diurnal rhythm of cortisol secretion by the adrenal cortex, and is possibly linked to a rhythm in bone resorptive mechanisms. Thus this intrinsic rhythm of Ca excretion is present even in premature infants, and should be remembered when timed urine collections are made.

Relationship between plasma cortisol concentrations and depression in chronic alcoholic patients

Plama cortisol levels were estimated by the competitive protein binding (CPB) method with radioactive selenium-75 in 32 male chronic alcoholics with depression. The degree of depression was rated by the Hamilton Depression Rating Scale (HDRS). Duration of drinking ranged from 5–25 years with an average daily amount of ethanol intake of 100–150 g (equivalent to half a bottle of spirits). Plasma cortisol levels were often raised in drinking chronic alcoholics and there was a strongly positive and statistically highly significant correlation between them and depression ratings ( r = + 0.56; P = 0.001). It is possible that the diurnal rhythm of cortisol secretion is disturbed or adreno-cortical activity is stimulated in these patients due to chronic ethanol ingestion. It is further suggested that brain serotonin deficiency known to occur in chronic alcoholics might lead to raised plasma cortisol levels in ethanol-induced depression.

A Complete Remission of Cushing''s Disease Following Therapy with Reserpine and Pituitary Irradiation

The clinical progress of a patient with Cushing's disease has been studied in detail for two years. Standard ests of pituitary-adrenal function revealed bilateral hyperplasia secondary to excessive ACTH. Reserpine therapy alone, administered for a month, resulted in marked clinical and biochemical improvement. Subsequent treatment consisted of pituitary irradiation in combination with reserpine therapy. Upon completion of irradiation, both plasma cortisol and base line urinary 17-OHCS decreased to normal levels. The patient has been treated for another 22 months with reserpine. Fourteen months after initiation of therapy, the patient was judged to be in complete remission as indicated by return of the diurnal rhythm of cortisol secretion to the normal pattern. On the basis of this study and earlier observations, we suggest that reserpine might be helpful in the therapy of Cushing's disease, especially in those patients who have no demonstrable pituitary adenoma.

Adrenocortical function in experimental protein malnutrition

Adrenocorticoid activity was investigated in experimentally induced protein malnutrition in Rhesus monkeys. Control studies were carried out in the same animals before inducing protein malnutrition. Plasma cortisol levels were elevated in the protein malnourished state. There was a total abolition of the diurnal rhythm of cortisol secretion. Fasting hypoglycemia was also observed in the protein malnourished state. It is concluded that increased adrenocorticoid activity and sustained steroidogenesis result from protein deficiency. Hypoglycemia may be an important stimulus, in addition to the metabolic stress imposed by the protein deprivation. The recognition of increased adrenocorticoid activity is important in a protein-deficient host, since the defense against infections might be impaired in such a situation.