Morning Cortisol Concentrations Research Articles

SUN-307 Partial Secondary Adrenal Insufficiency and Growth Hormone Deficiency in Fibromyalgia

Introduction: Low or borderline cortisol concentrations and impaired response to dynamic testing have been reported in patients with fibromyalgia, potentially related to hypothalamus-pituitary dysfunction.1,2 Superimposed adrenal insufficiency (AI) may contribute to some fibromyalgia symptoms or delay improvement in patients enrolled in fibromyalgia treatment programs. We hypothesized that a subset of patients with fibromyalgia have: 1) partial secondary AI and concomitant growth hormone (GH) deficiency 2) a discordance in Cosyntropin stimulation test and 3) improvement in fibromyalgia symptoms with initiation of glucocorticoid and/or GH replacement. Design: This was a retrospective study of patients with fibromyalgia diagnosed with partial secondary AI based on abnormal insulin tolerance test (peak cortisol < 18 mcg/dL) at our institution from June 2002 to August 2019. Patients were excluded if they had other reasons for adrenal insufficiency, including steroid exposure and opioid use. Results: We identified 22 patients (18 women, 82%) diagnosed with partial AI at a median age of 38 years (range 19-65). The fibromyalgia symptoms included fatigue (n=22, 100%), pain (n=22, 100%), sleep disturbance (n=15, 68%), and bowel changes (n=13, 59%). The median morning cortisol concentration was 8.6 mcg/dL (range 1.1-11); 9 patients (41%) had a morning cortisol concentration below the normal range (7 mcg/dL). The median ACTH level was 15.5 pg/mL (range 7.7-54). Nineteen patients had baseline IGF1 levels, with a median z-score of -0.94 (range -1.96 to 1.70). MRI pituitary imaging was performed in 20 patients and showed no significant pituitary pathology.All patients achieved hypoglycemia <=40 mg/dL during the insulin tolerance test. Peak median cortisol level was 11 mcg/dL (range 5.4-17). Nineteen patients (86%) also had partial GH deficiency (defined as a peak GH < 4 ng/mL) with a median GH level of 0.36 ng/mL (range 0.03-3.83). Cosyntropin stimulation test was performed in 13 patients (59%) with a 1 mcg dose in 2 patients and 250 mcg dose in 11 patients. The peak cortisol was >=18 mcg/dL in 10 (77%) patients. All patients were started on physiologic glucocorticoid replacement, and 12 patients were started on GH replacement. Endocrinology follow-up information was available for 13 patients, and 8 (62%) reported symptom improvement after starting treatment. Conclusions: Patients with fibromyalgia can have co-existing partial secondary AI and GH deficiency as defined by insulin-induced hypoglycemia. Cosyntropin stimulation test can be used in patients with fibromyalgia, but a normal test does not rule out partial secondary AI. Replacing the underlying deficiency improved symptoms in some patients demonstrating certain fibromyalgia symptoms may overlap with AI and GH deficiency. 1Gur et al. Ann Rheum Dis. 2004. 63(11):1504-1506. 2Kirnap et al. Clin Endocrinol (Oxf). 2001. 55(4):455-459.

SUN-189 A Case of Delayed Hypoaldosteronism Following Unilateral Adrenalectomy for Primary Aldosteronism

BACKGROUND: Hypoaldosteronism occurs in 6–30% of patients following unilateral adrenalectomy for primary aldosteronism. The Endocrine Society guidelines recommend discontinuing potassium supplementation and spironolactone postoperatively with repeat renin and aldosterone after surgery to monitor for cure. Clinical Case: A 69-year-old male with a 15-year history of hypertension on amlodipine 10 mg daily, atenolol 100 mg daily, terazosin 5 mg daily, valsartan 160 mg daily, spironolactone 50 mg three times daily, with longstanding hypokalemia on potassium chloride 20 mEq four times daily presented with an ischemic stroke and persistent hypertension (BP 182/79). Following discontinuation of spironolactone, evaluation revealed aldosterone concentration of 214 ng/dL (normal 4.0 - 31) and plasma renin activity of 0.1 ng/mL/hr (normal 0.5 - 4.0), giving an aldosterone-to-renin ratio of 2,140. CT of the abdomen showed a 3 cm right adrenal mass. He underwent uncomplicated right adrenalectomy for primary aldosteronism. Postoperative potassium was 3.4 mEq/L (normal 3.5–5.0) and hypertension persisted, so he was discharged on potassium chloride 10 mEq, losartan 100 mg daily, amlodipine 10 mg daily, and labetalol 200 mg twice daily. Two weeks later potassium level was 5.1 mEq/L and potassium chloride supplement was discontinued. Six months postoperatively, potassium was 5.7 mEq/L with well-controlled blood pressure, so losartan was discontinued. Labs over the subsequent several weeks showed persistent hyperkalemia up to 6.2 mEq/L and new hyponatremia to 128 mEq/L (normal 134 - 150). Repeat plasma renin activity was 0.51 ng/mL/hr and aldosterone concentration <1.0 ng/dL. Morning cortisol concentration was 18.3 ug/dL (normal 6.7 - 22.6) and ACTH 38 pg/mL (normal 6.0 - 50 pg/mL). He was diagnosed with postsurgical hypoaldosteronism. Potassium stabilized at 5.1 mEq/L and sodium stabilized at 134 mEq/L, so he was monitored without treatment for hypoaldosteronism. One year postoperatively his labs showed: potassium 5.1 mEq/L, sodium 135 mEq/L, renin 1.0 ng/mL/hr, and aldosterone 5.7 ng/dL. Conclusion: This patient had primary aldosteronism leading to suppression of aldosterone secretion from the contralateral healthy adrenal gland. This resulted in postoperative hypoaldosteronism once the affected adrenal gland was resected. This case demonstrates the need for continued monitoring of potassium, sodium, renin, and aldosterone following unilateral adrenalectomy for primary aldosteronism, especially in the setting of postoperative angiotensin receptor blocker use or other medications which can affect the renin-angiotensin-aldosterone system.

Latino early adolescents' psychological and physiological responses during the 2016 U.S. presidential election.

Research has documented increased psychological distress among adults during the 2016 U.S. presidential election; however, little is known about how major political events affect adolescents. Despite not actively participating in the election process (e.g., voting), adolescents generally, and Latino youth specifically, may experience a unique stress response during elections, particularly when perceived policy changes center on issues related to their own families' stability and well-being. We examined 42 Latino early adolescents (Mage = 12.50 years, SD = .88; 58% male; 94% immigrant background) living in Arizona and explored their psychological and physiological responses during the 2016 U.S. presidential election. Adolescents self-reported their mood and behaviors for 5 consecutive days across election week (November 6-10, 2016): 2 days before the election, election day, and 2 days after the election. They also completed a saliva sampling protocol at waking and bedtime each day, to capture diurnal cortisol concentrations. Multilevel growth models were utilized to examine intraindividual changes in positive affect, negative affect, and diurnal cortisol patterns across election week. Only 2 of the participants reported supporting the winning candidate. Changes in adolescents' stress hormone concentrations were evident; increases in evening cortisol levels and flatter diurnal cortisol slopes emerged across election week. Negative affect, positive affect, and morning cortisol concentrations did not change. This study provides preliminary evidence that macrolevel factors, such as the recent presidential election, may relate to adolescents' daily stress physiology. Further research is needed to better understand adolescents' responses to sociopolitical change. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Salivary Aldosterone, Cortisol, and Their Morning to Evening Slopes in Patients with Depressive Disorder and Healthy Subjects: Acute Episode and Follow-Up 6 Months after Reaching Remission

Background/Objective: Cortisol is thought to be involved in the pathophysiology of affective disorders. Less attention has been given to other neuroendocrine factors. The aim of the present study was to test the hypothesis that adrenocortical steroids aldosterone and cortisol show different dynamic changes in the course of clinical depression with the assumption that aldosterone is a state marker of depression. Methods: A total of 78 adult subjects (39 patients with depressive disorder and 39 healthy controls) participated in a prospective non-interventional clinical study. Patients were investigated at the time of an acute episode and 6 months after reaching remission. The clinical and personal characteristics, and morning and evening salivary concentrations of aldosterone and cortisol were evaluated. Results: Patients with an acute depressive episode exhibited higher evening aldosterone and lower morning cortisol concentrations compared to healthy subjects. In these patients, both hormone concentrations showed flatter morning to evening slopes. Salivary aldosterone, but not cortisol concentrations, were lower in patients 6 months after reaching remission compared to those in the acute state. Similarly, 6 months of remission resulted in a steeper morning to evening slope of salivary aldosterone compared to the acute state. The cortisol rhythm remained dysregulated. A significant negative correlation between trait anxiety scores and morning cortisol concentrations in patients at 6 months of clinical remission was observed. Conclusion: Diurnal changes in salivary aldosterone concentrations appear to be a state marker, whilst those of cortisol a trait marker of depression.

Diurnal cortisol and obesity in adolescents with and without Down syndrome.

The prevalence of obesity in adolescents with Down syndrome (DS) far exceeds that in the general population. Cortisol, an adrenal hormone, can be obesogenic when dysregulated. However, the diurnal patterns of this hormone have not been examined among individuals with DS. Variations in adiposity may also mediate cortisol regulation. This study sought to examine diurnal cortisol patterns in adolescents with DS as well as associations between cortisol function and obesity. A total of 32 adolescents, including 16 with DS and 16 controls with typical development (TD) of similar sex, age and Tanner pubertal stage (P>0.05), participated in this preliminary study. Participants completed a dual-energy X-ray absorptiometry scan to measure body composition and collected saliva samples for cortisol measurements in the morning, afternoon and night. Linear mixed models with random intercepts and repeated measures were used to examine the daily trajectory of log-transformed cortisol concentrations between adolescents with and without DS. A second model examined the interaction between DS and presence of elevated body fatness. Adolescents with DS had higher morning cortisol concentrations (intercept=0.37μg/dL), but this was not significantly different than in TD (0.35μg/dL, P=0.16). Cortisol significantly declined across hours (b=-0.026μg/dL/h, P<0.001), but this decline also did not differ from that observed in TD (b=-0.024μg/dL/h, P=0.43). While cortisol levels were slightly higher among adolescents with elevated body fatness, this difference was not statistically significant (P>0.05; d=0.30). This study is the first to examine diurnal cortisol in DS but is limited in sample size. These preliminary findings suggest that diurnal cortisol patterns are not significantly different between adolescents with DS and TD and that cortisol levels are not associated with adiposity in this population. Despite these non-significant differences, youth with DS continue to be an 'at-risk' population for paediatric obesity in need of clinical intervention.

MON-LB007 Incidence and Characteristics of Thyroid and Pituitary Dysfunction in Patients Treated with Immunotherapy

Background Endocrinopathies are well recognised immune-related adverse events associated with immunotherapy. Incidence rates of hypophysitis and thyroid dysfunction are widely variable in the literature. Hypophysitis has been reported in between 0.4% and 27% in patients treated with CTLA-4 inhibitors such as ipilimumab (1) while the incidence of thyroid dysfunction varies between 8% and 20% in patients treated with PD-1 inhibitors such as nivolumab and pembrolizumab (1). Aims Our aim was to determine real world rates of thyroid and pituitary dysfunction in patients treated with immunotherapy. We also sought to evaluate the characteristics of same-e.g. time to onset of adverse events and presence of autoantibodies. Methods A retrospective cohort study was performed in 347 patients who received treatment with PD-1 inhibitors nivolumab and pembrolizumab, anti-CD52 antibody alemtuzumab and CTLA-4 inhibitor ipilimumab between January 2013 and December 2017 at a tertiary referral metropolitan hospital in Melbourne, Australia. Patients were identified from pharmacy records and assessment of the clinical and biochemical records pertaining to thyroid function (TFT) and serum cortisol was performed. Results 45 patients (12.9%) had evidence of thyroid or pituitary dysfunction from the therapies. 34 of the 267 (12.7%) patients on PD-1 inhibitors developed thyroid dysfunction, 15 (5.6%) of whom had a clear thyroiditis picture-i.e. thyrotoxic phase with subsequent hypothyroidism. 3 of the 34 (8.8%) patients who received CTLA-4 inhibitor ipilimumab developed hypophysitis, all of whom were on combined treatment with a PD-1 inhibitor. Median time to onset of adverse effects was 30days. 12 out of 27 patients with thyroid dysfunction had positive anti-thyroid peroxidase antibodies. 25 of the 45 (55.6%) patients were reviewed in endocrine outpatient clinics. Only 2 of the 45 endocrinopathies were recorded in the hospital’s adverse drug reactions database. Conclusions In our tertiary centre, endocrinopathies are common in patients treated with immunotherapies; however reportage to the adverse drug reaction database is low and endocrinology services appear underutilised. Current guidelines suggest TFT monitoring every 4-6weeks on therapy (2) with baseline monitoring of early morning ACTH and cortisol concentrations to be considered in patients treated with CTLA-4 inhibitors. Greater clinician awareness and adherence to guidelines is needed for optimal patient care.

SAT-612 An Anti-Idiotype Antibody to T3 Measurements: A Misleading Cause of Inappropriate TSH Secretion

Background: Measurements of thyrotropin (TSH), total and free thyroxine (TT4,FT4), triiodothyronine (TT3,FT3) are widely used diagnostic methods for thyroid function evaluation. However, some serum samples demonstrate a nonspecific binding with assay reagents that can interfere with the measurement of these hormones. Several steps can be taken to identify results that may reflect the presence of interfering factors including: 1) discrepancies between current values and previous results using the same methods; 2) clues from the clinical setting; 3) the pattern of discrepant and non-discrepant thyroid profile results (1,2) Clinical case: A 67-year-old woman admitted with generalized muscle weakness for one week. On physical examination she had left facial palsy (LMN), dysarthria, motor power grade 1 in her lower extremities and grade 3 in her upper extremities, her deep tendon reflex was diminished and her peripheral sensation was decreased as glove and stocking pattern. She was also experiencing normal anal sphincter tone and perianal sensation. She was diagnosed with hypertension and she was prescribed atenolol for treatment. She was clinically euthyroid. Provisional clinical diagnosis was Guillain-Barre syndrome. Because her laboratory profile showed hyponatremia, the following thyroid function tests were ordered: TSH 7.090 mIU/L (0.27-4.20 normal range [NR]); FT3 13.33 pg/ml (2.00-4.40 NR); FT4 1.37 ng/dl (0.93-1.70 NR) tested by one-step electrochemiluminescent immunoassay (ECLIA,Roche platform,Cobas®);anti-thyroid peroxidase antibody (16.25 IU/ml, normal); anti-thyroglobulin antibody (<10 IU/ml); serum morning cortisol concentration, normal. The thyroid profile was repeated on new samples from the same patient 3 and 7 days later. The results confirmed mildly elevated TSH with high FT3 concentration but normal FT4. Then, the thyroid profile also was processed in a different laboratory using a different technique (Abbott® platform). Using this platform, the FT3, FT4 and TSH were all within reference ranges. To confirm that the sample contained an interfering, an aliquot also was sent to Roche for further analysis. The results showed that the patient had antibodies to anti-idiotype of both the T3 and FT3 assays. Conclusion To avoid misdiagnosis or inappropriate treatment decisions, when there are discrepancies between the clinical setting and the thyroid function tests, the clinician should always consider that there is a substance interfering with the assay.

Adrenal function of extremely premature infants in the first 5 days after birth.

Background There is limited data on adrenal function in the early days after birth in extremely premature infants. The relationship between plasma adrenocorticotrophic (ACTH) and cortisol hormone is central to the integrity of the hypothalamic-pituitary-adrenal (HPA) axis yet there are no studies examining this relationship in prematurity. Methods The aim of this study was to examine the relationship between early morning plasma cortisol and ACTH concentrations during the first 5 days after birth in infants born at less than 28 weeks' gestation and to identify any independent factors that determine plasma cortisol levels in these infants during extreme prematurity. We prospectively studied early morning plasma ACTH and cortisol concentrations in infants born below 28 weeks' gestation during the first 5 days of birth. Plasma cortisol was measured without extraction, using DPC Immulite® 2000 using a solid phase 2 site chemiluminescent immunometric assay. ACTH was measured using a radioimmunoassay. Spearman's correlation was used to examine the relationship between cortisol and ACTH. Multiple regression analysis was used to examine the relationship between plasma cortisol and clinical risk index for babies (CRIB) score, antenatal dexamethasone, mode of delivery and gestation. Results There were 95 infants (53 males) of mean gestation 25.3 ± 1.3 standard deviation (SD) (range 23-27 + 6) weeks. The mean birth weight was 809 ± 17.0 g. The mean plasma cortisol was 400.5 ± 42.6 nmol/L and the mean plasma ACTH was 4.5 ± 0.9 pmol/L. Early morning plasma cortisol correlated significantly with gestation (R = 0.4, p = 0.005). Early morning plasma ACTH did not correlate with early morning plasma cortisol (R = -0.12, p = 0.7). Multiple regression analysis showed that gestation was the only independent determinant of early morning plasma cortisol concentration (beta coefficient = -0.4, p = 0.04). Conclusions The relationship between early morning plasma ACTH and plasma cortisol is either not established or is impaired in infants of less than 28 weeks' gestation in the first 5 days after birth. The plasma cortisol level is mainly determined by gestation and is not directly related to illness severity, antenatal steroids or plasma ACTH in these infants in the first 5 days after birth.

DNA methylation differences at the glucocorticoid receptor gene in depression are related to functional alterations in hypothalamic–pituitary–adrenal axis activity and to early life emotional abuse

Depression is associated with alterations in hypothalamic–pituitary–adrenal (HPA) axis activity. A proposed mechanism to explain these alterations are changes in DNA methylation levels, secondary to early life adversity (ELA), at stress-related genes. Two gene regions that have been implicated in the literature, the glucocorticoid receptor gene (NR3C1) exon 1F and the FKBP5 gene intron 7 were examined in 67 individuals (33 depressed patients and 34 controls). We investigated whether cortisol concentrations, evaluated in 25 depressed patients and 20 controls, and measures of ELA were associated with the degree of methylation at these candidate gene regions. Mean NR3C1 exon 1F DNA methylation levels were significantly increased in the depressed cohort and the degree of methylation was found to be positively associated with morning cortisol concentrations. DNA methylation levels at specific CG sites within the NR3C1 exon 1F were related to childhood emotional abuse severity. DNA methylation at CG38 was related to both HPA axis and childhood emotional abuse measures in the depressed group. No FKBP5 differences were revealed. Our findings suggest that hypermethylation at the NR3C1 exon 1F may occur in depression. This locus-specific epigenetic change is associated with higher basal HPA axis activity, possibly reflecting acquired glucocorticoid receptor resistance.

Morning cortisol and fasting glucose are elevated in women with chronic widespread pain independent of comorbid restless legs syndrome.

Chronic widespread pain (CWP) is associated with poor quality of sleep, but the detailed underlying mechanisms are still not fully understood. In this study we investigated the influence of CWP on morning cortisol and fasting glucose concentrations as well as sleep disordered breathing. In this case-control study, subjects with CWP (n=31) and a control group without CWP (n=23) were randomly selected from a population-based cohort of women. Current pain intensity, sleep quality, excessive daytime sleepiness [Epworth sleepiness scale (ESS)], psychiatric comorbidity and occurrence of restless legs syndrome (RLS) were assessed. Overnight polygraphy was applied to quantify sleep apnoea, airflow limitation and attenuations of finger pulse wave amplitude (>50%) as a surrogate marker for increased skin sympathetic activity. Morning cortisol and fasting glucose concentrations were determined. Generalised linear models were used for multivariate analyses. CWP was associated with higher cortisol (464±141 vs. 366±111 nmol/L, p=0.011) and fasting glucose (6.0±0.8 vs. 5.4±0.7 mmol/L, p=0.007) compared with controls. The significance remained after adjustment for age, body mass index, RLS and anxiety status (β=122±47 nmol/L and 0.89±0.28 mmol/L, p=0.009 and 0.001, respectively). The duration of flow limitation in sleep was longer (35±22 vs. 21±34 min, p=0.022), and pulse wave attenuation was more frequent (11±8 vs. 6±2 events/h, p=0.048) in CWP subjects compared with controls. RLS was associated with higher ESS independent of CWP (β=3.1±1.3, p=0.018). Elevated morning cortisol, impaired fasting glucose concentration and increased skin sympathetic activity during sleep suggested an activated adrenal medullary system in subjects with CWP, which was not influenced by comorbid RLS. CWP is associated with activated stress markers that may deteriorate sleep.

Corrigendum: Budesonide Multimatrix Is Efficacious for Mesalamine-refractory, Mild to Moderate Ulcerative Colitis: A Randomised, Placebo-controlled Trial.

Background and aims Safety and efficacy of budesonide multimatrix, an oral extended-release second-generation corticosteroid designed for targeted delivery throughout the colon, were examined for induction of remission in patients with mild to moderate ulcerative colitis refractory to baseline mesalamine therapy. Methods A randomised, double-blind, placebo-controlled, multicentre trial evaluated efficacy and safety of budesonide multimatrix for induction of remission [ulcerative colitis disease activity index score ≥ 4 and ≤ 10] in 510 adults randomised to once-daily oral budesonide multimatrix 9 mg or placebo for 8 weeks. Patients continued baseline treatment with oral mesalamine ≥ 2.4 g/day. Results Combined clinical and endoscopic remission at Week 8 was achieved by 13.0% and 7.5% of patients receiving budesonide multimatrix [n = 230] or placebo [n = 228], respectively, in the modified intention-to-treat population [p = 0.049]. Clinical remission [ulcerative colitis disease activity index rectal bleeding and stool frequency subscale scores of 0] was similar in both groups [p = 0.70]. More patients receiving budesonide multimatrix vs placebo achieved endoscopic remission [ulcerative colitis disease activity index mucosal appearance subscale score of 0; 20.0% vs 12.3%; p = 0.02] and histological healing [27.0% vs 17.5%; p = 0.02]. Adverse event rates were similar [budesonide multimatrix, 31.8%; placebo, 27.1%]. Mean morning cortisol concentrations decreased at Weeks 2, 4, and 8 with budesonide multimatrix but remained within the normal range. Conclusion Budesonide multimatrix was safe and efficacious for inducing clinical and endoscopic remission for mild to moderate ulcerative colitis refractory to oral mesalamine therapy.

Budesonide Multimatrix Is Efficacious for Mesalamine-refractory, Mild to Moderate Ulcerative Colitis: A Randomised, Placebo-controlled Trial.

Background and Aims:Safety and efficacy of budesonide multimatrix, an oral extended-release second-generation corticosteroid designed for targeted delivery throughout the colon, were examined for induction of remission in patients with mild to moderate ulcerative colitis refractory to baseline mesalamine therapy.Methods:A randomised, double-blind, placebo-controlled, multicentre trial evaluated efficacy and safety of budesonide multimatrix for induction of remission [ulcerative colitis disease activity index score ≥ 4 and ≤ 10] in 510 adults randomised to once-daily oral budesonide multimatrix 9 mg or placebo for 8 weeks. Patients continued baseline treatment with oral mesalamine ≥ 2.4 g/day.Results:Combined clinical and endoscopic remission at Week 8 was achieved by 13.0% and 7.5% of patients receiving budesonide multimatrix [n = 230] or placebo [n = 228], respectively, in the modified intention-to-treat population [p = 0.049]. Clinical remission [ulcerative colitis disease activity index rectal bleeding and stool frequency subscale scores of 0] was similar in both groups [p = 0.70]. More patients receiving budesonide multimatrix vs placebo achieved endoscopic remission [ulcerative colitis disease activity index mucosal appearance subscale score of 0; 20.0% vs 12.3%; p = 0.02] and histological healing [27.0% vs 17.5%; p = 0.02]. Adverse event rates were similar [budesonide multimatrix, 31.8%; placebo, 27.1%]. Mean morning cortisol concentrations decreased at Weeks 2, 4, and 8 with budesonide multimatrix but remained within the normal range.Conclusion:Budesonide multimatrix was safe and efficacious for inducing clinical and endoscopic remission for mild to moderate ulcerative colitis refractory to oral mesalamine therapy.

Sleep Alterations in Non-demented Older Individuals: The Role of Cortisol.

Sleep alterations can impair quality of life and contribute to disease progression but they, and their features and contributing factors, are rarely analysed in institutionalised older individuals. In this study, we investigated sleep alterations, the factors involved, and the role of cortisol in sleep-related problems in institutionalised individuals. We conducted a descriptive cross-sectional study in participants living in nursing homes in Valencia (Spain); sleep alterations were determined based on two validated tools: the Athens insomnia scale and Oviedo sleep questionnaire. Plasma cortisol was measured in the morning and determined by high performance liquid chromatography-mass spectroscopy, along with other blood analytical parameters. We also analysed any confounding factors (sleep duration, morning awakening time, intake of hypnotic and psychotropic medication, and cognitive function). The mean age was 82.5 years (range: 65-99); approximately 80% were women and sleep alterations were present in 25-60% of the population, depending on the scale used or type of sleep disorder considered. There was no significant correlation between morning cortisol concentrations and sleep disorders, sex, age, or psychotropic drug ingestion (including hypnotic drugs). However, there was a significant correlation between cortisol and an Oviedo questionnaire subscale for evaluating insomniarelated adverse events, which remained significant after adjusting for multiple potentially confounding factors. Sleep disorders are common in institutionalised older individuals and are not related to sleep duration or decreased by ingestion of hypnotic medications. There is a significant relationship between morning cortisol levels in blood and insomnia-related sleep disorders (e.g. snoring with awakenings, nightmares, restless legs syndrome, etc.) but not directly with insomnia or hypersomnia.

Are neuroticism and extraversion related to morning cortisol release in healthy older people?

The cortisol awakening response (CAR) is a discrete component of the hypothalamic-pituitary-adrenal axis (HPA-axis) function that has been widely related to both health and some personality traits. There is evidence that neuroticism and extraversion affect health and well-being and play a damaging or protective role, respectively. In this study, we aimed to explore the relationship between these personality dimensions and morning cortisol concentrations in people aged 55 or older. To do so, morning saliva samples were collected on two consecutive weekdays from a total of 160 older men and women. Neuroticism and extraversion were assessed using the Eysenck Personality Questionnaire-Revised, short form (EPQ-RS). Our results showed that neuroticism was negatively related to overall morning cortisol concentrations (AUCG) (i.e., area under the curve with respect to the ground in cortisol levels), but not to the CAR. When we explored sex as a moderator, neuroticism was related to a CAR of increased magnitude in women, although this relationship was not significant in men. No significant relationships were found between extraversion and CAR or AUCG, regardless of sex. In conclusion, neuroticism – but not extraversion – was related to HPA-axis function in older adults, highlighting its potential relevance in health alterations associated with HPA-axis functioning.

Reduced morning cortisol concentration in saliva was associated with obesity: Evidence from community-dwelling adults in papua new guinea.

This study investigated morning salivary cortisol concentration in relation to total body fat composition among community-dwelling Papua New Guinean adults. In addition to demographic and anthropometric measurements, saliva was collected in a single morning from 478 residents in Eastern Highlands Province and Madang Province. After adjusting for age, region, and occupation, the morning salivary cortisol concentration was significantly negatively correlated with body mass index among men (B = -0.01, P < 0.05) and women (B = -0.013, P < 0.05), and waist circumference (B = -0.007, P < 0.05), waist-to-hip-ratio (B = -1.214, P < 0.05), and subscapular-to-triceps skinfold-thickness ratio (B = -0.045, P < 0.05) among men. Men with total or abdominal body fat mass known for elevated risk of non-communicable diseases displayed lower cortisol compared to men without such risk. Papua New Guinean adults with increased accumulation of body fat showed reduced cortisol concentration in morning saliva. Am. J. Hum. Biol. 28:587-590, 2016. © 2016 Wiley Periodicals, Inc.

Preclinical laboratory assessments of predictors of social rank in female cynomolgus monkeys.

Physiological and behavioral differences between dominant and subordinate monkeys have been useful in preclinical models investigating numerous disease states. In captivity, it has been inferred that subordinate monkeys live in a context of chronic social stress and may be at risk for a variety of dysfunctions; however, the factors that influence eventual rank are not entirely known. The goal of the present study was to first evaluate several phenotypic characteristics as potential trait markers for eventual social rank and then to determine the consequences of social hierarchy on these measures (i.e., state markers). Baseline estradiol, progesterone, cortisol and testosterone concentrations were obtained from 16 pair-housed female cynomolgus monkeys before and after introduction into new social groups (n = 4/group). Furthermore, effects of the initial week of social rank establishment on outcome measures of cognitive performance and homecage activity were examined. Baseline body weight and mean serum estradiol concentrations were the only statistically significant predictors of eventual rank, with future subordinate monkeys weighing less and having higher estradiol concentrations. During initial hierarchy establishment, future subordinate monkeys had increased morning and afternoon cortisol concentrations, increased locomotor activity and impaired cognitive performance on a working memory task. After 3 months of social housing, subordinate monkeys had blunted circulating estradiol and progesterone concentrations. These findings demonstrate differential effects on gonadal hormones and cortisol as a function of social context in normally cycling female monkeys. Furthermore, disruptions in cognitive performance were associated with subordinate status, suggesting strong face validity of this model to the study of factors related to the etiology and treatment of human diseases associated with chronic stress. Am. J. Primatol. 78:402-417, 2016. © 2015 Wiley Periodicals, Inc.

Are changes in workplace bullying status related to changes in salivary cortisol? A longitudinal study among Danish employees

ObjectivesThis study aims to investigate whether incident workplace bullying and its dicontinuance is related to subsequent change in morning and evening saliva cortisol concentrations. MethodsParticipants came from two Danish cohort studies, the PRISME cohort (n=4489) and the Workplace Bullying and Harassment Cohort (n=3707). At baseline and follow-up exposure to bullying was measured by a single question on bullying (preceded by a definition). Two saliva samples to measure cortisol were collected during a work-day (30min after awakening and at 8p.m.). All participants responding to the item on workplace bullying, giving saliva samples and participated at both baseline and follow-up were included. The reference group consisted of non-bullied respondents at both baseline and follow-up. Multilevel mixed-effects linear regressions were used to test for changes in salivary cortisol after newly onset of and discontinuance of workplace bullying. All analyses were adjusted for the potentially confounding effect of differences from baseline to follow-up in education, smoking, alcohol consumption, body mass index, cohort, sampling waves, time of awakening, and time of sampling. ResultsWe found no indication of statistically significant difference in saliva cortisol, neither when participants changed their self-labelling from not bullied at baseline to being bullied at follow-up, nor when they at follow-up two years later reported discontinuance of bullying. ConclusionThis longitudinal study on the impact of changes in bullying status on change in cortisol levels showed consistent lack of associations with onset and discontinuance of workplace bullying.

Budesonide Foam Has a Favorable Safety Profile for Inducing Remission in Mild-to-Moderate Ulcerative Proctitis or Proctosigmoiditis.

Background Budesonide foam, a rectally administered, second-generation corticosteroid with extensive hepatic first-pass metabolism, is efficacious for the treatment of mild-to-moderate ulcerative proctitis and ulcerative proctosigmoiditis.AimThe aim of this study was to comprehensively assess the safety and pharmacokinetic profile of budesonide foam.MethodsData from five phase III studies were pooled to further evaluate safety, including an open-label study (once-daily treatment for 8 weeks), an active-comparator study (once-daily treatment for 4 weeks), and two placebo-controlled studies and an open-label extension study (twice-daily treatment for 2 weeks, then once daily for 4 weeks). Data from the placebo-controlled studies and two phase I studies (i.e., patients with mild-to-moderate ulcerative colitis and healthy volunteers) were pooled to evaluate the pharmacokinetics of budesonide foam.ResultsA similar percentage of patients reported adverse events in the budesonide foam and placebo groups, with the majority of adverse events being mild or moderate in intensity (93.3 vs 96.0 %, respectively). Adverse events occurred in 41.4 and 36.3 % of patients receiving budesonide foam and placebo, respectively. Mean morning cortisol concentrations remained within the normal range for up to 8 weeks of treatment; there were no clinically relevant effects of budesonide foam on the hypothalamic–pituitary–adrenal axis. Population pharmacokinetic analysis demonstrated low systemic exposure after budesonide foam administration.ConclusionsThis integrated analysis demonstrated that budesonide foam for the induction of remission of distal ulcerative colitis is safe overall, with no clinically relevant effects on the hypothalamic–pituitary–adrenal axis.

Life satisfaction moderates the impact of socioeconomic status on diurnal cortisol slope

The association between SES and health is well established; however, only a handful of studies have investigated the relationship between SES and daily cortisol parameters. Further, within this small literature, virtually no studies have looked at psychological factors that might mitigate this relationship. In this study, we tested whether life satisfaction – the overall subjective affective assessment of one's own life – acts as a protective factor against cortisol dysregulation driven by low-SES. Among a large sample (N=1325) of individuals from the Midlife in the United States (MIDUS) survey, we found that low-SES individuals with high levels of life satisfaction had a cortisol circadian profile similar to those of high-SES individuals. In contrast, low-SES individuals reporting low life satisfaction experienced attenuated morning cortisol concentrations and a flatter (“less healthy”) diurnal cortisol slope. Although more studies are needed to investigate the constellation of psychological resources and processes through which life satisfaction exerts its effects, the current work shows that the general affective evaluation of one's own life acts as a buffer against the detrimental effect of low-SES on health-related physiological processes.

Factitious Cushing's syndrome masquerading as Cushing's disease

Factitious Cushing's syndrome is extremely rare. The diagnosis is challenging as cross-reactivity of synthetic corticosteroids or their metabolites in immunoassay measurements of plasma or urinary cortisol can make distinguishing between true and factitious Cushing's syndrome difficult. Adrenocorticotropin (ACTH) is usually suppressed in factitious Cushing's syndrome. A 54-year-old woman presented with clinical and biochemical features of Cushing's syndrome and an unsuppressed ACTH concentration. She denied recent exogenous corticosteroid use. Initial investigations revealed a markedly elevated urinary free cortisol, mildly elevated midnight salivary cortisol and normal morning cortisol concentration. Plasma ACTH was not suppressed at 13 ng/l (RR 10-60 ng/l). A pituitary MRI was normal, but inferior petrosal sinus sampling (IPSS) revealed a post corticotrophin releasing hormone ACTH ratio >20:1 in the left petrosal sinus. Ketoconazole therapy amplified discordance between the urinary free and morning plasma cortisol concentrations. Further investigation of this discordance using high-pressure liquid chromatography tandem mass spectrometry (HPLC-MS/MS) revealed a urinary free cortisol excretion of only 20 nmol/24 h, but prednisolone excretion of 16,200 nmol/24 h. Factitious Cushing's syndrome can mimic endogenous ACTH-dependent hypercortisolism during initial investigations and IPSS. This case highlights the importance of (i) recognizing the significance of discordant results; (ii) using an ACTH assay capable of reliably differentiating ACTH-dependent from ACTH-independent Cushing's syndrome; and (iii) appreciating that IPSS is only useful to localize the source of ACTH in confirmed ACTH-dependent Cushing's syndrome. In this case, measurement of corticosteroids by HPLC-MS/MS was essential in reaching the correct diagnosis.