The conundrum of differentiating Cushing's syndrome from non-neoplastic hypercortisolism: a systematic review and meta-analysis.

CONTEXT: Once hypercortisolemia is confirmed, differential diagnosis between Cushing's syndrome (CS) due to neoplastic endogenous hypercortisolism and non-neoplastic hypercortisolism (NNH, pseudo-Cushing's syndrome) is crucial. Due to worldwide corticotropin-releasing hormone (CRH) unavailability, accuracy of alternative tests to dexamethasone (Dex)-CRH, is clearly needed. OBJECTIVE: Assess the diagnostic accuracy of Dex-CRH test, desmopressin stimulation test, midnight serum cortisol (MSC), and late-night salivary cortisol (LNSC) levels to distinguish CS from NNH. METHODS: Articles through March 2022 were identified from Scopus, Web of Science, MEDLINE, EMBASE, and PubMed. All steps through the systematic review were performed independently and in duplicate and strictly adhered to the updated PRISMA-DTA checklist. DATA SYNTHESIS: A total of 24 articles (1900 patients) were included. Dex-CRH had a pooled sensitivity and specificity of 91% (95%CI 87-94%; I2 0%) and 82% (73-88%; I2 50%), desmopressin test 86% (81-90%; I2 28%) and 90% (84-94%; I2 15%), MSC 91% (85-94%; I2 66%) and 81% (70-89%; I2 71%), and LNSC 80% (67-89%; I2 57%) and 90% (84-93%; I2 21%), respectively. Summary receiver operating characteristics areas under the curve were Dex-CRH 0.949, desmopressin test 0.936, MSC 0.942, and LNSC 0.950 without visual or statistical significance. The overall risk of studies bias was moderate. CONCLUSION: Dex-CRH, the desmopressin stimulation test, and MSC have similar diagnostic accuracy, with Dex-CRH and MSC having slightly higher sensitivity, and the desmopressin test being more specific. LNSC was the least accurate, probably due to high heterogeneity, intrinsic variability, different assays, and lack of consistent reported cutoffs. When facing this challenging differential diagnosis, the results presented here should increase clinicians' confidence when deciding which test to perform.

Establishing Reference Intervals for Serum and Salivary Cortisol in a Selected Population in Kano, Nigeria.

OBJECTIVE: Serum cortisol has long been used in the assessment of disorders of the hypothalamic-pituitary-adrenal axis. The reference interval for cortisol in both serum and saliva depends on the analytical methodology and the population studied; hence, a locally derived population-based reference interval is recommended. To our knowledge, there are no studies on reference interval determination in the study area, raising concerns about the use of reference intervals established in European and North American populations. This work aimed to establish reference intervals for baseline serum and salivary cortisol levels among healthy adults in Kano, Nigeria, using methods available in our laboratory. METHODS: A cross-section of 148 apparently healthy reference individuals aged 16 to 67 years were recruited from a local community in Kano, Nigeria, using a systematic sampling technique. Baseline serum cortisol was analyzed using highly sensitive and specific electrochemiluminescence quantitative measurements on an automated immunology analyzer. Salivary cortisol levels were measured using Salimetrics' competitive enzyme-linked immunosorbent assay test kits. Parametric methods with a 95% confidence interval were used to calculate reference intervals. RESULTS: The reference intervals for cortisol in serum and saliva were 72.0 nmo/L to 554.0 nmol/L and 0.40 nmol/L to 18.0 nmol/L, respectively. There was a weak positive correlation between serum and salivary cortisol values, but this association was not statistically significant. CONCLUSION: The development of locally derived adult reference intervals can improve the diagnostic utility of serum and salivary cortisol assessment and strengthen the reliability of adrenal insufficiency diagnoses in our population.

Changes of serum cortisol during pregnancy and labor initiation: an onsite cross-sectional study.

Background: Increased maternal cortisol secretion has been observed during pregnancy and labor. However, due to the limitations in diagnostic methods, the dynamic change of cortisol during the short period between threatened labor and labor is unknown. In this study, we aim to evaluate the changes in serum cortisol during late pregnancy and full-term labor initiation, verifying if cortisol could serve as a biomarker for the diagnosis of labor initiation from threatened labor. Methods: This cross-sectional onsite study involved 564 participants of 6 different gestational stages (C: Control; T1: Trimester 1; T3: Trimester 3; E: expectant; TL: threatened labor; L: labor), all patients in the E, TL, and L groups were at full term. The serum cortisol concentration was quantified with a point-of-care test (POCT), and the gestation, age, parity, and BMI of participants were documented. Morning serum cortisol was collected between 8:00 and 10:00 a.m., except for the TL and L group women who were tested upon arrival or during latent labor. With cortisol levels or all five variables, L was distinguished from TL using machine learning algorithms. Results: Significant elevation of cortisol concentration was observed between T1 and T3, or TL and L group (P< 0.001). Women belonging to the E and TL group showed similar gestation week and cortisol levels. Diagnosis of labor initiation using cortisol levels (cutoff = 21.46 µg/dL) yielded sensitivity, specificity, and AUC of 86.50%, 88.60%, and 0.934. With additional variables, a higher specificity (89.29%) was achieved. The diagnostic accuracy of all methods ranged from 85.93% to 87.90%. Conclusion: Serum cortisol could serve as a potential biomarker for diagnosis of L form TL. The rapid onsite detection of serum cortisol with POCT could facilitate medical decision-making for admission and special treatments, either as an additional parameter or when other technical platforms are not available.

Plasma aldosterone response to ACTH stimulation test for diagnosis of primary aldosteronism: a cross-sectional study.

BACKGROUND: The diagnosis of primary aldosteronism (PA) requires screening and confirmation testing. The present study examined whether the 1 µg ACTH stimulation test for plasma aldosterone concentration (PAC) can accurately diagnose PA by bypassing the regular confirmatory steps of PA diagnosis. METHODS: A cross-sectional study with a total of 36 patients with an aldosterone-renin ratio (ARR) > 20 ng/dL per ng/m/hr were included. The confirmation test for PA was performed by saline infusion and the patients were categorized into PA and non-PA. PAC was collected at 20 and 40 min after 1 µg ACTH stimulation test. Multivariable logistic regression analysis was performed, and the associations are presented as odds ratios (OR) and 95% confidence intervals (CI). Diagnostic accuracy is presented as AuROC. RESULTS: Multivariable analysis found only PAC at 20 min after ACTH stimulation showed significant association with a diagnosis of PA (OR 1.18, 95%CI (0.99, 1.31), p = 0.040). AuROC for this value was 0.95 and the proposed cut-off was 52 ng/dL with a sensitivity of 71.4% and a specificity of 96.6%. CONCLUSIONS: Diagnosing PA may be aided by PAC at 20 min following 1 µg ACTH stimulation. This value may be used with patients for whom the confirmation test for PA cannot be conducted.

Long-acting porcine ACTH stimulated salivary cortisol reduces the overdiagnosis of adrenal insufficiency compared to serum cortisol in cirrhosis liver.

BACKGROUND: There are no reliable methods in clinical practice to diagnose adrenal insufficiency (AI) in patients with cirrhosis owing to variable cortisol-binding protein levels. This leads to unreliable results in ACTH stimulated serum cortisol test. We aimed to estimate the long-acting porcine (LA)ACTH-stimulated serum and salivary cortisol levels of patients at different stages of cirrhosis using second generation electrochemiluminescence and to determine the prevalence of true adrenal insufficiency in these patients. DESIGN, PATIENTS AND MEASUREMENTS: We included 135 noncritical patients with cirrhosis (45 each from CHILD A, B and C) and 45 healthy controls. Serum and salivary samples were collected at baseline in the morning and at 1 and 2 h after LA-ACTH injection. RESULTS: In healthy subjects, the 2.5th centile of 2 h ACTH stimulated serum and salivary cortisol were 19.8 and 0.97 µg/dL, which were used as cut-offs for defining AI based on serum and saliva respectively. The median (interquartile-range) 2-h stimulated salivary cortisol in Child A, B, C categories and controls were 1.36(1.23-2.38), 1.46(1.18-2.22), 1.72(1.2-2.2) and 2.12(1.42-2.72) µg/dL respectively. Six subjects (4.4%) were diagnosed to have AI based on stimulated salivary cortisol cut-off, whereas 39 (28.9%) cirrhosis subjects had inadequately stimulated serum cortisol. Three patients (symptomatic) required steroid replacement therapy. Hypoalbuminemia was identified as a major risk factor for the misdiagnosis of adrenal insufficiency by serum cortisol-based testing. CONCLUSIONS: Long-acting porcine ACTH stimulated salivary cortisol reduces the overdiagnosis of adrenal insufficiency compared to serum cortisol in cirrhosis liver. Stimulated salivary cortisol is a promising investigation for evaluation of adrenal function in cirrhosis and more studies are required for its further validation before clinical use.

Cortisol Reactivity to Acute Psychosocial Stress in Physician Burnout.

BACKGROUND: Physician burnout, characterized by chronic job-related stress leading to emotional exhaustion, depersonalization, and reduced personal accomplishment. This cross-sectional study investigates cortisol reactivity in male physicians with burnout compared to healthy controls during an acute psychosocial stress test. METHODS: Sixty male physicians (30 burnout, 30 healthy controls) participated between September 2019 and December 2021 to investigate the impact of burnout on cardiovascular health. Salivary cortisol levels were measured before and after a Trier Social Stress Test (TSST). Burnout was assessed with the Maslach Burnout Inventory-Human Services Survey (MBI-HSS). Covariates included age, BMI, and physical activity. Data were analyzed using repeated measures analysis and area under the curve analysis. RESULTS: Male physicians with burnout exhibited significantly greater cortisol reactivity during the TSST, notably post-stress to 15 min post-stress. Emotional exhaustion correlated with reduced cortisol increase from pre-stress and smaller post-stress to 15- and 45-min declines. DISCUSSION: Findings suggest heightened cortisol reactivity in male physicians with burnout, possibly reflecting initial chronic stress stages. This study highlights the necessity for long-term research on cortisol's influence on cardiovascular health and stress responses across diverse groups. CONCLUSIONS: The findings contribute to comprehending physiological responses in burnout-afflicted physicians, emphasizing cortisol reactivity's pivotal role in stress-related research and its potential health implications, particularly within the burnout context.

Salivary cortisol as a biomarker of stress in surgical patients.

Background: Surgical stress and pain result in activation of hypothalamus-pituitary-adrenal axis. The aim of this study was to establish the effects of postoperative pain and various modalities of analgesic administration on salivary and serum cortisol levels, as well as to establish the validity of salivary cortisol as a stress indicator in surgical patients. Methods: A randomized controlled trial involved 60 patients scheduled for elective abdominal aortic aneurysm surgery. Patients were randomly divided into two groups depending on the model of postoperative analgesia. The first group (MI - morphine intermittently) included patients given morphine doses 0.1 mg/kg/6h s.c. intermittently. The second group (MPCA - morphine patient-controlled analgesia) included patients who received morphine via the PCA system - intravenous administration of morphine adjusted to a dose of 1 mg per shot and a lockout interval of 6 minutes.

Revisiting the cortisol reference ranges in humans: the role of demographics.

The current study explores the effect of demographics on serum cortisol expression in a study group of 52 individuals to improve the current serum reference ranges to produce personalized expression profiles consequently increasing clinical confidence in the diagnosis. The serum cortisol concentration was inspected against demographical data like age, sex, and body mass index and showed an association with age and sex. The serum cortisol values also indicated a positive association with chronic illnesses however this finding requires a more focused study for establishment. Additionally, saliva samples are also collected from the same study group at the same time through drool and an absorbent sponge and correlated with serum values to draw an alternative route of serological testing. Salivary cortisol from drool showed a linear correlation with Pearson's correlation coefficients of 0.71 and 0.72 with serum cortisol and with saliva samples collected using a porous sponge respectively. Overall, the study shows the role of demographics in shaping the reference ranges for cortisol, suggesting a path for developing personalized diagnostics. The study also highlights the efficacy of saliva as an alternative to serum cortisol to facilitate cortisol measurement for efficient stress management.

Biochemical and Radiological Factors for Prognostication of Traumatic Brain Injury: An Institutional Experience.

Introduction Traumatic brain injury (TBI) necessitates identifying patients at risk of fatal outcomes. Classic biomarkers used clinically today in other organ systems are quantitative in nature. This aspect largely restricts the prognostic ability of a theoretical quantitative brain biomarker. This study aimed to explore biochemical markers and imaging findings reflecting the severity of cerebral damage to predict outcomes. Methodology In this study, 61 TBI cases with moderate to severe brain injury were prospectively observed, and various indices including random blood sugar (RBS), hemoglobin, international normalized ratio (INR), lactate dehydrogenase (LDH), cortisol, and CT findings were assessed. Glasgow Outcome Scores (GOS) determined the outcomes. Statistical analysis was carried out to assess correlations.  Results The mean RBS level of those who did not survive was 259.58 mg/dL, whereas in those who survived the value was 158.48 mg/dL. Analysis indicated that patients with high RBS value on admission had a higher risk of mortality (p=0.000). We noted that the mean serum cortisol levesl on both Days 1 and 5 were higher in patients who died and were able to establish a statistically significant correlation between both the values and outcome. A statistically significant negative correlation between Day 1 and Day 5 serum LDH levels and outcomes was evident from our study (p=0.000 for both). Among the components of the Rotterdam score, the presence of intraventricular hemorrhage (IVH) in the CT scan had a significant association with unfavorable outcomes (p=0.01) while midline shift was significantly associated with a low GCS (p=0.04). Conclusion Biochemical markers such as INR, RBS, serum cortisol, and LDH at admission can serve as valuable indicators of prognosis in TBI patients. Furthermore, a persistent increase in LDH and cortisol levels between Days 1 and 5, along with the Glasgow Coma Scale and Rotterdam Scoring system, are good predictors of mortality.

Comparison of salivary cortisol levels between women with functional hypothalamic amenorrhea and healthy women: a pilot study.

INTRODUCTION: Functional Hypothalamic Amenorrhea (FHA) has been associated with excessive-chronic stress, eating disorders, and weight loss. A common feature is the increased serum cortisol, but its measurement has many limitations. Currently, salivary cortisol (SC) has been proposed as a more sensitive and adequate index. AIM: To investigate the SC alterations through a 24-h period and the possible correlation with the severity of stress in women with FHA. METHODS: Between July 2019 and March 2021, 12 FHA women and 12 healthy controls of comparable age were included. Psychological, eating, and physical abnormalities were evaluated by applying equivalent validated self-questionnaires. RESULTS: No significant differences were found between FHA women and healthy individuals with respect to morning (8:00 am) serum cortisol and ACTH (522.5 ± 162.2 vs 442 ± 138.5 nmol/l; p = 0.204 and 37 ± 44.8 vs 17.4 ± 10.8 pg/ml; p = 0.186, respectively). Women with FHA had statistically significant higher morning SC compared to control subjects (21.8 ± 5.9 nmol/l vs 12.8 ± 3.8 nmol/l; p < 0.001), while no significant differences were found regarding the afternoon (4:00 pm) and midnight (12:00 am) SC. A significant positive correlation was found between morning SC and morning serum cortisol (rho = 0.532; p = 0.007), EAT-26 (rho = 0.527; p = 0.008) and HADS-Anxiety score (rho = 0.471; p = 0.02). Additionally, a significant negative correlation between morning SC and BMI was observed (rho = -0.53; p = 0.009). CONCLUSION: Compared to serum cortisol, SC seems to express better the hypercortisolemic state of women with FHA and correlates well with the underlying contributing factors. Larger studies are needed in order to confirm these results and validate the optimal SC cut-off value associated with the development of FHA.

To evaluate serum cortisol levels in patients with alcohol withdrawal delirium v/s patients with delirium due to any other disorder.

Background: Delirium is an acute confusional state characterized by changes in the mental status, level of consciousness, impaired cognition, and inattention. It can develop within hours or days. Cortisol release from the hypothalamic-pituitary-adrenal axis (HPA) is vital for the host survival in stress. Biomarkers are used as an indicator of pathogenic processes or to assess the responses to a therapeutic intervention. To improve delirium recognition and care, investigators have identified possible biomarkers that may help in diagnosing individuals with delirium, assessing the severity of delirium. Cortisol has been suggested as biomarker for the diagnosis of delirium. Aims and Objectives: To evaluate and compare levels of serum cortisol in patients with alcohol withdrawal delirium with delirium due to other disorders. Materials and Methods: It was a cross-sectional prospective observational study. A total of 30 patients in Group A and 32 in Group B were included. The participants were evaluated based on delirium rating scale (DRS). Results: It was seen that in alcohol withdrawal delirium group, there was significant positive correlation between DRS score and serum cortisol level, i.e., with increase in DRS score, there was increase in serum cortisol levels and vice versa. Conclusion: Serum cortisol levels are associated and directly correlate with the occurrence and severity of delirium. Further studies are needed to elucidate the implications of this association for diagnosis and treatment.

Comparative Assessment of the Stress Response of Cattle to Common Dairy Management Practices.

While studies have been conducted examining the stress response of dairy cattle to individual acute and chronic stressors, the results are difficult to compare due to differences in study design and analysis methods. The aim of the present study was to conduct a comparative assessment of the impact of eight common stimuli: artificial insemination (AI), embryo transfer (ET), morning milking (MM), evening milking (EM), veterinary examination (VE), ultrasound examination (US), hoof trimming (HT), and natural breeding (NB) on the hypothalamic-pituitary-adrenal axis and milk production of 24 Holstein-Friesian cattle. After random allocation into control and treatment groups, a total of five blood samples were collected 40 min (Ba1) and 20 min (Ba2) prior to stimulus application, immediately following the stimulus (St), as well as 20 min (Re1) and 40 min (Re2) post-stimulus. A comparison between the overall serum cortisol concentrations in the treatment groups showed a significant difference between HT to AI (p = 0.006), ET (p = 0.010), MM (p = 0.021), VE (p = 0.009), EM (p = 0.007), and US (p = 0.010), except for NB (p = 0.542). There is no significant difference between the control groups (p > 0.05). The stimuli HT (p < 0.001) and NB (p < 0.001) showed significant increases in cortisol following stimulus application, and the levels failed to decrease significantly by sample Re2. No significant differences in daily milk yield (kg) were measured amongst the tested stimuli (p = 0.472) nor amongst the groups 'Control', 'Treatment' and 'no stimulus' (p = 0.350). In conclusion, when factors such as increased physical activity, novel social interaction, sexual arousal, and a more intense restriction of movement are present, the animal's perceived controllability and predictability might decrease, affecting the animal's response to stress. Treatments carried out while animals are restrained in a headlock while remaining within their regular group likely result in a less intense activation of the HPA axis.

Association of high cortisol levels in pregnancy and altered fetal growth. Results from the MAASTHI, a prospective cohort study, Bengaluru.

Background: The role of maternal stress levels on mothers' mental health and fetal growth has been previously studied. However, the evidence linking cortisol exposure during pregnancy to growth outcomes in infants is sparsely available from lower and middle-income countries. We aim to investigate the association of serum cortisol levels in pregnancy with infant birth outcomes and postpartum depressive symptoms in a public health facility in India. Methods: The current study is a part of the maternal antecedents of adiposity and studying the transgenerational role of hyperglycemia and insulin (MAASTHI) prospective cohort. We assessed the relationship between maternal exposure to serum cortisol and adverse neonatal outcomes and postpartum depressive symptoms. Serum cortisol levels in stored blood samples were measured in 230 pregnant women as a biomarker for stress during pregnancy. Pregnant women between 18 and 45 years of age were recruited for the study, presenting at ≥14 weeks of gestation and providing voluntary written informed consent. The Edinburgh Postnatal Depression Scale assessed postpartum depressive symptoms, and detailed infant anthropometric measurements were carried out at birth. Findings: We found that higher levels (>17.66 µg/L) are significantly associated with low birth weight (OR = 2.28; 95% CI 1.21-4.32) and lower weight for length (OR = 2.16; 95% CI 1.07-4.35). The odds of developing postpartum depressive symptoms in pregnant women with higher mean cortisol cut-off levels is 2.3-fold [OR: 2.33, 95% CI (1.17, 4.64)] compared than women with lower cortisol levels. No significant association was found between serum cortisol and infants' birth weight for gestational age, head circumference, the sum of skinfold thickness, and crown-rump length. Interpretation: Our results support the hypothesis that higher maternal cortisol levels may adversely impact birth weight, weight for length in newborns, and postpartum depressive symptoms in mothers. Funding: This study was supported by the India Alliance Senior Fellowship [Grant No. IA/CPHS/20/1/505278] awarded to Giridhara R. Babu.

Single Serum Cortisol Value as a Prognostic Marker in Acute Ischemic Stroke.

BACKGROUND: Stroke is a major global burden with significant morbidity, mortality, and long-term disability. Acute ischemic stroke (AIS) is a stressful condition causing stimulation of the hypothalamic-pituitary-adrenal (HPA) axis resulting in numerous endocrinal alterations in the body. We evaluated the serum cortisol as a prognostic marker in AIS. METHODS: This was a prospective observational study comprising 100 cases suffering from AIS, and serum cortisol at the baseline was measured. Severity was evaluated using the National Institutes of Health Stroke Scale (NIHSS) during admission, and functional outcome was assessed at 1, 4, and 24 weeks using a modified Rankins score (mRS). Statistical analysis was performed to find the relationship between serum cortisol and the severity of stroke, outcome, and mortality at 1, 4, and 24 weeks of stroke. RESULTS: In our study, we found positive correlations between random blood sugar and serum cortisol (r = 0.273, p = 0.006); stroke severity (NIHSS) and serum cortisol (r = 0.785, p < 0.001); stroke outcome (mRS) at 1, 4, and 24 weeks; and serum cortisol (p < 0.001 and r = 0.676, 0.654, 0.650 for all three intervals, respectively). We also found higher serum cortisol among patients who died at 1, 4, and 24 weeks compared to those who survived with a p-value being <0.001 for all three intervals. CONCLUSIONS: A stress response causing an increase in serum cortisol occurs in AIS. This response is detrimental to the patient. The serum cortisol at baseline can be considered a marker of severity, short- and long-term prognosis, and mortality after AIS.

Effect of aerobic exercise, slow deep breathing and mindfulness meditation on cortisol and glucose levels in women with type 2 diabetes mellitus: a randomized controlled trial.

Background: Aerobic exercise combined with breathing exercise can be an integral part of diabetes mellitus treatment. This single-center, randomized, parallel-group study investigated the effect of the combination of aerobic exercise with slow deep breathing and mindfulness meditation on the glucose and cortisol levels of women with type 2 diabetes mellitus (T2DM). Materials and Methods: Fifty-eight middle-aged women with T2DM (mean age: 45.67 ± 2.92 years) were randomly assigned to either the aerobic training group (AT: n = 29; mean age [46.1 ± 2.7 years]) or the aerobic exercise combined with slow deep breathing and mindfulness meditation (AT + DMM: n = 29; mean age [45.24 ± 3.14 years]). Aerobic exercise was performed at 60%-75% of the maximum heart rate. The women in each group were asked to perform the training three times weekly over a 6-week period. The duration of each session was 40 min for the AT group and 60 min for the AT + DMM group. The two groups were asked to perform aerobic exercise at 60%-75% of the maximum heart rate. Their fasting blood glucose (FBG) and serum cortisol levels were measured at the baseline and after the 6 weeks. Results: Compared with the AT group, the group undertaking 6 weeks of aerobic training combined with slow, deep breathing exercises and mindfulness meditation showed significantly lower levels of FBG (p = 0.001) and cortisol levels (p = 0.01) than the AT group. Conclusion: The addition of slow deep breathing and mindfulness meditation to aerobic exercise can better control the glucose and cortisol levels of women with T2DM and thereby improve their outcomes and decrease their cardiometabolic risk.

Osteopathic Manipulation as a Method of Cortisol Modification: A Systematic Review.

The effectiveness of osteopathic manipulative treatment (OMT) in the modification of various hormones has been studied; however, there is still a need for quantitative measurements to determine how large of an influence exists. The goal of this meta-analysis is to investigate the implications OMT has on cortisol levels. A systematic literature search restricted to English was performed from October 2022 to November 2022 using Google Scholar, OSTMED.DR, and PubMed and included articles from 2000 onward. Articles were excluded if they did not include a measurement for the control group in their study. We identified 4120 studies for potential inclusion. Of these, a total of four studies met the inclusion criteria, with a total of 135 participants (N= 68 OMT, N= 67 control). Out of the 135 participants, 126 participants (N= 62 OMT, N= 64 control) made up the salivary cortisol studies, and the remaining nine participants made up the serum cortisol studies (OMT N= 6, control N= 3). The National Institutes of Health (NIH) bias assessment tool was utilized to measure the risk of bias. Standard mean differences were calculated for effect size. A mean difference in cortisol of 0.10µg/dl (-10µg/dl, 95%CI -0.15, -0.04) was found when comparing all pre- versus post-cortisol levels with OMT versus sham control groups. OMT demonstrated a 0.10µg/dl larger decrease in cortisol than sham control treatments. The standard mean difference was found to be -0.46 (95%CI -1.40, 0.48) making this finding a medium effect size without significance. Heterogeneity for the salivary analysis measured by I2 was 0% indicating no significant heterogeneity across studies. When serum cortisol was included, heterogeneity stayed at 0%. A larger number of high-quality studies, especially those specific to serum cortisol, are recommended, to elucidate the relationship between OMT and cortisol. This research suggests OMT reduces cortisol more than sham treatment before versus after OMT treatment, and though the change is small when comparing after one treatment, it may have clinical usage if multiple OMT sessions are performed.

Assessment and correlation of anxiety, depression and serum cortisol levels in patients with oral submucous fibrosis and leukoplakia: A clinicohematological study.

Context: Potentially malignant disorders (PMDs) of the oral cavity like oral submucous fibrosis (OSMF) and leukoplakia are known to be caused due to addictive habits, while serum cortisol is accepted to be a stress hormone. Aim: The present study was aimed to assess and correlate the anxiety, depression and serum cortisol levels in habit-associated PMDs such as OSMF and leukoplakia and compare it with healthy subjects. Materials and Methods: Ninety patients were included in the study and were divided into three Groups, namely Group I (OSMF), Group II (leukoplakia) and Group III (control group). Serum cortisol levels and severity of anxiety and depression using the Hamilton Anxiety Rating Scale (HAM-A) and Hamilton Depression Rating Scale (HAM-D) were recorded and correlated. Results: A significant correlation existed between serum cortisol level and levels of both anxiety and depression between Group I and II as compared to the control group. Conclusion: There exists a definite correlation between serum cortisol levels and the levels of anxiety and depression in patients with leukoplakia and OSMF, with increasing levels of serum cortisol and higher values in both the HAM-A and HAM-D scales in patients with both OSMF and leukoplakia. PMDs such as leukoplakia and OSMF have an established cancer-causing potential. Anxiety and depression although prevalent are underdiagnosed and poorly understood. Hence, a holistic approach in the treatment of such pathologies including hematological investigations and psychological evaluation should be mandatorily made a part of the workup and treatment plan.

The Utility of Salivary Cortisone in the Overnight Dexamethasone Suppression Test in Adrenal Incidentalomas.

CONTEXT: Guidelines recommend the assessment of cortisol secretion in patients with adrenal incidentalomas (AI) using the overnight dexamethasone suppression test (ONDST). This requires attendance at a health care facility and venepuncture. Alternatively, the ONDST can be done by measuring salivary cortisol and cortisone, which can be collected at home. OBJECTIVE: We aimed to assess the utility of these measurements in patients with AI. METHODS: A retrospective analysis of data from 173 patients with AI who underwent an ONDST and salivary cortisol/cortisone diurnal studies. Serum and salivary cortisol and salivary cortisone were collected at 09:00, late night, and at 09:00 the following morning after dexamethasone. Dexamethasone levels were measured in the postdexamethasone samples. Serum and salivary samples were analyzed with liquid chromatography-tandem mass spectrometry. RESULTS: We identified a strong correlation between salivary cortisone and serum cortisol after 1 mg of dexamethasone (r = 0.95). Stepwise multivariate regression showed that postdexamethasone salivary cortisone, baseline serum cortisol, salivary cortisone suppression (predexamethasone/postdexamethasone ratio), and sex were the only significant or near-significant independent variables. Performance of predictive indices using these 4 parameters (sensitivity = 88.5%, specificity = 91.2%; kappa 0.80) and postdexamethasone salivary cortisone alone (sensitivity = 85.3%, specificity = 91.7%; kappa 0.77) were comparable when used to predict an ONDST serum cortisol of ≤50 nmol/L. No correlation was observed with any of the other measured parameters. CONCLUSION: In AI patients, after dexamethasone, salivary cortisone correlates very strongly with serum cortisol in the ONDST and could therefore be used as an alternative sampling method which does not require venepuncture or attendance at hospital.

Comparison of Midazolam and Propofol Infusion to Suppress Stress Response in Patients With Severe Traumatic Brain Injury: A Prospective, Randomized Controlled Trial.

Objective: The stress response following traumatic brain injury (TBI) is a preventable cause of secondary brain injury. This can be prevented using sedation in the intensive care unit (ICU). To date, the choice of sedative agent for preventing stress response is not well-studied in literature. Methods: This prospective randomized controlled trial included 60 patients with severe TBI admitted to ICU. The patients were randomized into 2 study groups according to the choice of sedation: propofol (group I) and midazolam infusion (group II). The serum cortisol was measured as the primary outcome at admission to ICU and 48 hours following sedation infusion. The baseline Glasgow coma scale, hemodynamic, optic nerve sheath diameter (ONSD), and computed tomography scan findings were noted at admission. Glasgow outcome scale (GOS) was measured as a neurological outcome at discharge from ICU. Results: There was a statistically significant reduction in serum cortisol level in both the study groups (Δ cortisol, p-value=134.91 (50.5,208.2), 0.00 and 118.8 (42.6,160.4), 0.00, in group I and II, respectively). Serum cortisol levels were comparable among both groups at baseline and 48 hours. Similarly, there was a statistically significant difference in ONSD in both groups, but there was no difference in ONSD value between the groups at 48 hours. The GOS was also similar in both groups at discharge from ICU. Conclusion: The study demonstrated a similar reduction in serum cortisol levels following 48 hours of propofol or midazolam infusion in patients with severe TBI.

Morning Serum Cortisol Is Uniquely Associated with Cardiometabolic Risk Independent of Body Composition in Latino Adolescents.

Background: Alterations in morning serum cortisol (MSC) have been associated with higher cardiometabolic risk. This finding has been documented primarily in populations with overweight or obesity; however, it has not been clearly established if obesity plays a requisite role in this relationship. This study seeks to extend earlier findings by examining whether body composition measures alter the relationship between MSC with glucose and insulin markers, blood pressure, and lipid parameters in Latino youth in middle adolescence. Methods: This cross-sectional study included 196 healthy adolescents (130F/66M; mean age: 16.4 ± 0.6 years; 95% Latino; mean body mass index, BMI: 24.3 ± 5.7) from Los Angeles, California. Morning cortisol, glucose, insulin, glycated hemoglobin, and lipids (triglycerides and high-density lipoprotein cholesterol) were assessed from a fasting blood sample. Sitting systolic and diastolic blood pressure was averaged from duplicate measures. Body composition measures included BMI and waist circumference, which were used as proxies for total body and abdominal adiposity, respectively. Triplicate measurements of weight and height were averaged for calculation of BMI; age- and sex-specific BMI z-score was used to classify into normal BMI or overweight/obese BMI status. Waist circumference was measured in duplicate and the average was used to classify participants into two strata: normal/healthy waist circumference (<90th percentile for age, sex, and ethnicity) and high waist circumference (≥90th percentile). Results: The primary findings were that higher MSC was associated with higher fasting glucose and systolic blood pressure after adjusting for age, sex, and BMI z-score (and/or waist circumference). BMI status or waist circumference status did not alter these relationships. Main Conclusion: Our results suggest that the relationships between hypothalamic-pituitary-adrenal axis function and certain cardiometabolic risk factors may be independent of adiposity. Future research is warranted to discover the contributors and underlying mechanisms of these relationships in adolescent populations. ClinicalTrials.gov identifier: NCT02088294.