Postdexamethasone Cortisol Levels Research Articles

Susceptibility and characteristics of infections in patients with glucocorticoid excess or insufficiency: the ICARO tool.

Registry data show that Cushing's syndrome (CS) and adrenal insufficiency (AI) increase mortality rates associated with infectious diseases. Little information is available on susceptibility to milder forms of infections, especially those not requiring hospitalization. This study aimed to investigate infectious diseases in patients with glucocorticoid disorders through the development of a specific tool. We developed and administered the InfeCtions in pAtients with endocRinOpathies (ICARO) questionnaire, addressing infectious events over a 12-month observation period, to 1017 outpatients referred to 4 University Hospitals. The ICARO questionnaire showed good test-retest reliability. The odds of infection (OR (95% CI)) were estimated after adjustment for confounders and collated into the ICARO score, reflecting the frequency and duration of infections. In total, 780 patients met the inclusion criteria: 43 with CS, 32 with adrenal incidentaloma and mild autonomous cortisol secretion (MACS), and 135 with AI, plus 570 controls. Compared to controls, CS was associated with higher odds of urinary tract infections (UTIs) (5.1 (2.3-9.9)), mycoses (4.4 (2.1-8.8)), and flu (2.9 (1.4-5.8)). Patients with adrenal incidentaloma and MACS also showed an increased risk of UTIs (3.7 (1.7-8.0)) and flu (3.2 (1.5-6.9)). Post-dexamethasone cortisol levels correlated with the ICARO score in patients with CS. AI was associated with higher odds of UTIs (2.5 (1.6-3.9)), mycoses (2.3 (1.4-3.8)), and gastrointestinal infections (2.2 (1.5-3.3)), independently of any glucocorticoid replacement dose. The ICARO tool revealed a high prevalence of self-reported infections in patients with glucocorticoid disorders. ICARO is the first of its kind questionnaire, which could be a valuable tool for monitoring infections in various clinical settings.

Concomitant alterations of metabolic parameters, cardiovascular risk factors and altered cortisol secretion in patients with adrenal incidentalomas during prolonged follow-up.

Adrenal incidentalomas (AI) are associated with metabolic and hormonal abnormalities, most commonly autonomous cortisol secretion (ACS). Data regarding alterations of insulin resistance (IR) and ACS after prolonged follow-up are limited. We investigated the evolution of IR, cortisol secretion and ACS development in patients with AI during prolonged follow-up. Prospective study in a tertiary hospital. Seventy-one patients with AI [51 nonfunctioning (NFAI) and 20 ACS] and 5·54±1·7years follow-up underwent testing for ACS and oral glucose tolerance test to determine IR indices and adrenal imaging. At follow-up, 16/51 (31%) NFAI patients converted to ACS, while two with previous ACS reverted to NFAI; 21% (7/33) of patients who did not covert to ACS exhibited high urinary-free cortisol (H-UFC) levels. All AI patients developed deterioration of IR irrespective of their cortisol secretory status. Eight patients developed newly diagnosed type 2 diabetes (9·8% NFAI and 15% ACS, respectively) and 14 IR (17·6% NFAI and 25% ACS, respectively). Adenoma size increased from 2·1±0·8 to 2·3±0·8cm, whereas IR correlated with postdexamethasone cortisol level and adenoma size increase. IR showed an incremental continuum trend from normal UFC (Ν-UFC), to H-UFC, C-ACS and ACS patients. New-onset ACS developed in 31% patients with NFAI, whereas 21% of NFAI patients had H-UFC levels. All AI patients as a group and the subgroups of N-UFC, H-UFC, C-ACS and ACS patients developed deterioration of metabolic parameters during follow-up that was more prominent in ACS patients.

Relationship between diabetes mellitus and hypothalamic-pituitary-adrenal axis: A systematic review

Objective To provide objective evidences for early screening of the hypothalamic-pituitary-adrenal(HPA)axis function in diabetic patients, the relationship between HPA axis function and diabetes mellitus was systematically reviewed. Methods PubMed, Ovid, Embase, Web of science Databases were retrieved from articles reporting the relationship between HPA axis function and diabetes mellitus. Meta-analysis were carried out by Stata 12.0 software for heterogeneity test and data merged among articles for the inclusion and exclusion criteria. Results Our meta-analysis showed the following results: Compared with control group, the basal plasma cortisol level in total diabetes group, T1DM group, T2DM group, diabetes patients(with or without chronic complications)combined with hypertension was significantly higher. Compared with control group, postdexamethasone cortisol level was markedly higher in diabetes group. There was no significant difference in 24 h urinary free cortisol(24h UFC)and ACTH levels between diabetes group and control group. Our qualitative evaluation shows the following results: the differences of awaking salivary cortisol and cortisol awakening response(CAR)between the two groups were inconsistent among all included studies. Most studies showed that CAR was lower in diabetic patients. Conclusion The present analysis has demonstrated that HPA axis dysfunction exists along with diabetes mellitus, and diabetic comorbidity may further worsen the HPA axis dysfunction. (Chin J Endocrinol Metab, 2016, 32: 668-673) Key words: Diabetes mellitus; Hypothalamic-pituitary-adrenal axis; Cortisol; 24 h urinary cortisol; Cortisol awakening response

"Nonfunctional" Adrenal Tumors and the Risk for Incident Diabetes and Cardiovascular Outcomes: A Cohort Study.

Benign adrenal tumors are commonly discovered on abdominal imaging. Most are classified as nonfunctional and are considered to pose no health risk, but some are considered functional because they secrete hormones that increase risk for metabolic and cardiovascular diseases. To evaluate the hypothesis that nonfunctional adrenal tumors (NFATs) increase risk for cardiometabolic outcomes compared with absence of adrenal tumors. Cohort study. Integrated hospital system. Participants with benign NFATs ("exposed"; n= 166) and those with no adrenal tumor ("unexposed"; n= 740), with at least 3 years of follow-up. Medical records were reviewed from the time of abdominal imaging for development of incident outcomes (hypertension, composite diabetes [prediabetes or type 2 diabetes], hyperlipidemia, cardiovascular events, and chronic kidney disease) (mean, 7.7 years). Primary analyses evaluated independent associations between exposure status and incident outcomes by using adjusted generalized linear models. Secondary analyses evaluated relationships between NFATs and cortisol physiology. Participants with NFATs had significantly higher risk for incident composite diabetes than those without adrenal tumors (30 of 110 [27.3%] vs. 72 of 615 [11.7%] participants; absolute risk, 15.6% [95% CI, 6.9% to 24.3%]; adjusted risk ratio, 1.87 [CI, 1.17 to 2.98]). No significant associations between NFATs and other outcomes were observed. Higher "normal" postdexamethasone cortisol levels (≤50 nmol/L) were associated with larger NFAT size and higher prevalence of type 2 diabetes. Potential bias in the selection of participants and ascertainment of outcomes. Participants with NFATs had a significantly higher risk for diabetes than those without adrenal tumors. These results should prompt a reassessment of whether the classification of benign adrenal tumors as "nonfunctional" adequately reflects the continuum of hormone secretion and metabolic risk they may harbor. National Institutes of Health and Doris Duke Charitable Foundation.

Predicting the neurobehavioral side effects of dexamethasone in pediatric acute lymphoblastic leukemia

Although dexamethasone is an effective treatment for acute lymphoblastic leukemia (ALL), it can induce a variety of serious neurobehavioral side effects. We hypothesized that these side effects are influenced by glucocorticoid sensitivity at the tissue level. We therefore prospectively studied whether we could predict the occurrence of these side effects using the very low-dose dexamethasone suppression test (DST) or by measuring trough levels of dexamethasone. Fifty pediatric patients (3–16 years of age) with acute lymphoblastic leukemia (ALL) were initially included during the maintenance phase (with dexamethasone) of the Dutch ALL treatment protocol. As a marker of glucocorticoid sensitivity, the salivary very low-dose DST was used. A post-dexamethasone cortisol level <2.0nmol/L was considered a hypersensitive response. The neurobehavioral endpoints consisted of questionnaires regarding psychosocial and sleeping problems administered before and during the course of dexamethasone (6mg/m2), and dexamethasone trough levels were measured during dexamethasone treatment. Patients with a hypersensitive response to dexamethasone had more behavioral problems (N=11), sleeping problems, and/or somnolence (N=12) (P<0.05 for all three endpoints). The positive predictive values of the DST for psychosocial problems and sleeping problems were 50% and 30%, respectively. Dexamethasone levels were not associated with neurobehavioral side effects. We conclude that neither the very low-dose DST nor measuring dexamethasone trough levels can accurately predict dexamethasone-induced neurobehavioral side effects. However, patients with glucocorticoid hypersensitivity experienced significantly more symptoms associated with dexamethasone-induced depression. Future studies should elucidate further the mechanisms by which neurobehavioral side effects are influenced by glucocorticoid sensitivity.

Hypothalamic-pituitary-adrenal axis dysfunction and illness progression in bipolar disorder.

Background:Impaired stress resilience and a dysfunctional hypothalamic-pituitary-adrenal (HPA) axis are suggested to play key roles in the pathophysiology of illness progression in bipolar disorder (BD), but the mechanisms leading to this dysfunction have never been elucidated. This study aimed to examine HPA axis activity and underlying molecular mechanisms in patients with BD and unaffected siblings of BD patients.Methods:Twenty-four euthymic patients with BD, 18 siblings of BD patients, and 26 healthy controls were recruited for this study. All subjects underwent a dexamethasone suppression test followed by analyses associated with the HPA axis and the glucocorticoid receptor (GR).Results:Patients with BD, particularly those at a late stage of illness, presented increased salivary post-dexamethasone cortisol levels when compared to controls (p = 0.015). Accordingly, these patients presented reduced ex vivo GR responsiveness (p = 0.008) and increased basal protein levels of FK506-binding protein 51 (FKBP51, p = 0.012), a co-chaperone known to desensitize GR, in peripheral blood mononuclear cells. Moreover, BD patients presented increased methylation at the FK506-binding protein 5 (FKBP5) gene. BD siblings presented significantly lower FKBP51 protein levels than BD patients, even though no differences were found in FKBP5 basal mRNA levels.Conclusions:Our data suggest that the epigenetic modulation of the FKBP5 gene, along with increased FKBP51 levels, is associated with the GR hyporesponsiveness seen in BD patients. Our findings are consistent with the notion that unaffected first-degree relatives of BD patients share biological factors that influence the disorder, and that such changes are more pronounced in the late stages of the illness.

HPA axis and aging in depression: Systematic review and meta-analysis

One of the most consistent findings in the biology of depression is an altered activity of the hypothalamic-pituitary-adrenal (HPA) axis. However, data concerning this issue have never been examined with a focus on the older population. Here we present a systematic review and meta-analysis, based on studies investigating levels of cortisol, adrenocorticotropic hormone (ACTH) and corticotropin-releasing hormone (CRH) in depressed participants older than 60 and compared with healthy controls. We found 20 studies, for a total of 43 comparisons on different indices of HPA axis functioning. Depression had a significant effect (Hedges' g) on basal cortisol levels measured in the morning (0.89), afternoon (0.83) and night (1.39), but a smaller effect on cortisol measured continuously (0.51). The effect of depression was even higher on post-dexamethasone cortisol levels (3.22), whereas it was non-significant on morning ACTH and CRH levels. Subgroup analyses indicated that various methodological and clinical factors can influence the study results. Overall, older participants suffering from depression show a high degree of dysregulation of HPA axis activity, with differences compared with younger adults. This might depend on several mechanisms, including physical illnesses, alterations in the CNS and immune-endocrinological alterations. Further studies are needed to clarify the implications of altered HPA axis activity in older patients suffering from depression. Novel pharmacological approaches might be effective in targeting this pathophysiological feature, thus improving the clinical outcomes.

Genetic Polymorphisms in 11β-Hydroxysteroid Dehydrogenase Type 1 Correlate With the Postdexamethasone Cortisol Levels and Bone Mineral Density in Patients Evaluated for Osteoporosis

Higher physiological cortisol levels may increase the risk of age-related osteoporosis. We hypothesized that common polymorphisms in the cortisol synthesis enzyme 11β-hydroxysteroid dehydrogenase (HSD11B) may cause interindividual variations in cortisol levels and age-related bone loss. We performed a retrospective study in a cohort of 452 ambulatory patients under evaluation for osteoporosis. We investigated the associations of 16 single-nucleotide polymorphisms (in the HSD11B1 and HSD11B2 genes with a postdexamethasone cortisol (PDC) level and bone mineral density (BMD; primary end points) and fracture risk (secondary end point) in a subgroup of 304 patients. The observed associations with BMD were validated in a subgroup of 148 patients. The PDC level increased with age (R = 0.274, P < 10(-5), n = 287) and was negatively correlated with BMD at the femoral neck (R = -0.278, P < 10(-5), n = 258). Three genetically linked single-nucleotide polymorphisms (in intron 5 of HSD11B1), rs1000283, rs932335, and rs11811440, were significantly associated with BMD, with rs11811440 having the strongest association. The presence of the minor rs11811440 A allele was correlated with a lower PDC level (R = -0.128, P = .03, n = 304). The A allele was also consistently correlated with a higher spinal BMD in both patient subgroups (R = 0.17, Bonferroni corrected P = .006, n = 452). The correlation with BMD remained significant after adjustment for age, gender, body mass index, and type of osteoporosis and was stronger in patients older than 65 years. Genetic variations in HSD11B1 may affect the physiological cortisol levels and the severity of age-related osteoporosis. Underlying functional mechanisms remain to be elucidated.

Dexamethasone suppression test in early- and late-stage patients with bipolar disorder type I and first-degree relatives: a preliminary analysis

Evidence suggests that Bipolar Disorder (BD) type I present a progressive feature, in which patients become less responsive to medications and less resilient to stress over time. Therefore, this study aimed to assess the hypothalamus-pituitary-adrenal (HPA) axis in patients with BD at early and late stages of disease and in first-degree relatives. Thirteen euthymic patients with BD type I were recruited and divided into early-stage (n = 6) and late-stage (n = 7) groups. Moreover, 9 age- and sex-matched first-degree relatives and 12 healthy controls were also recruited. Participants performed a dexamethasone suppression test (1 mg), collecting saliva at 8 pm two days in a row, before and after the administration of dexamethasone at 11 pm. All groups significantly suppressed cortisol levels, even though basal cortisol levels did not differ between groups. However, postdexamethasone cortisol levels were significantly increased in late-stage patients when compared to controls. No further differences were found in relatives or early-stage patients. In addition, postdexamethasone cortisol significantly correlated with mood symptoms scores. No significant correlations were found between cortisol and number of mood episodes, hospitalizations and suicide attempts. Our results suggest that patients with BD at a late stage of illness present an impaired negative feedback of the HPA axis, which may be related to clinical parameters reported in patients along with illness progression. This study was supported by INCT for Translational Medicine, CNPq, Brazil

Cortisol, obesity, and the metabolic syndrome: A cross‐sectional study of obese subjects and review of the literature

Circulating cortisol and psychosocial stress may contribute to the pathogenesis of obesity and metabolic syndrome. To evaluate these relationships, we performed a cross-sectional study of 369 overweight and obese subjects and 60 healthy volunteers and reviewed the previous literature.Overweight and obese subjects had at least two other features of Cushing’s syndrome. They underwent measurements representing cortisol dynamics (24h urine cortisol excretion (UFC), bedtime salivary cortisol, 1 mg dexamethasone suppression test) and metabolic parameters (BMI, blood pressure (BP); fasting serum triglycerides, HDL, insulin, and glucose). Subjects also completed the Perceived Stress Scale (PSS). UFC, salivary cortisol and weight from 60 healthy volunteers were analyzed.No subject had Cushing’s syndrome. UFC and dexamethasone responses were not associated with BMI or weight. However, salivary cortisol showed a trend to increase as BMI increased (P< 0.0001), and correlated with waist circumference (WC) in men (rs=0.28, P=0.02) and systolic BP in women (rs=0.24, P =0.0008). Post-dexamethasone cortisol levels were weak to moderately correlated with fasting insulin (rs=− 0.31, P=0.01) and HOMA-IR (rs=−0.31, P=0.01) in men and systolic (rs=0.18, P= 0.02) and diastolic BP (rs=0.20, P=0.009) in women. PSS results were higher in obese subjects than controls, but were not associated with cortisol or metabolic parameters. As expected, WC correlated with fasting insulin, HOMA-IR and systolic BP (adjusted for BMI and gender; P < 0.01). Literature showed inconsistent relationships between cortisol and metabolic parameters.Taken together, these data do not support a strong relationship between systemic cortisol or stress and obesity or metabolic syndrome.

Glucocorticoid Receptor and Molecular Chaperones in the Pathogenesis of Adrenal Incidentalomas: Potential Role of Reduced Sensitivity to Glucocorticoids

Glucocorticoid (GC) sensitivity depends on glucocorticoid receptor (GR) and heat shock proteins (Hsps). We investigated whether common GR genes (ER22/23EK, N363S, Bcl I, and 9β) and adrenocorticotropin receptor promoter polymorphisms influence susceptibility for unilateral adrenal incidentaloma (AI), plus GR and Hsp expression in tumorous (n = 19), peritumorous (n = 13) and normal adrenocortical (n = 11) tissues. Patients (n = 112), population-matched controls (n = 100) and tumor tissues (n = 32) were genotyped for these polymorphisms. Postdexamethasone serum cortisol was higher in patients (p < 0.001). GR gene variants, larger allele of Bcl I (odds ratio [OR] 2.9; 95% confidence interval [CI] 1.7-5.1; p < 0.001] and minor allele of 9β (OR 3.0; 95% CI 1.6-5.7; p < 0.001) were independent predictors of AI. In patients, the first allele is linked with larger tumors (p = 0.002) and the latter with higher postdexamethasone cortisol levels (p = 0.025). Both allele carriers had lesser waist circumference (p = 0.02), similar adrenocorticotropin and higher basal (p = 0.024) and postdexamethasone cortisol concentrations (p < 0.001). Tumorous and constitutional genotypes were similar. GR-D is the major receptor isoform in normal adrenal cortex by Western blotting. Loss of other receptor isoforms, decrease in immunostaining for GR (p < 0.0001), underexpression of chaperones (p ≤ 0.01) and the presence of inducible Hsp70 were found in adenomas. In conclusion, GR gene variants, C allele of Bcl I and minor allele of 9β, are associated with AIs. Their concurrent presence in patients reduces GC sensitivity. Normal adrenal cortex preferentially expresses GR-D. In adenomas, the lack of other GR isoforms and underexpression of heat shock proteins perhaps permanently impair GC signaling, which could promote dysregulated cortisol production and tumor growth. The innate GC sensitivity probably modifies these effects.

The effect of a 4-week treatment with reboxetine on metabolic parameters of depressed inpatients

In the present study, we examined several metabolic parameters in a group of 19 acutely depressed inpatients with major depression (DSM-IV) at baseline and investigated their development after 4 weeks of antidepressant treatment with reboxetine (8-12 mg per day). We performed oral glucose tolerance tests and additionally assessed free saliva cortisol and post-dexamethasone cortisol levels, as well as whole cholesterol, HDL- and LDL-cholesterol, triglycerides, free fatty acids, waist and hip circumference, heart rate, systolic and diastolic blood pressure. Furthermore, we evaluated the incidence of a metabolic syndrome and investigated the metabolic changes in depressed patients with and without a metabolic syndrome. We found 42.1% of patients to fulfil the criteria for a metabolic syndrome. Overall, reboxetine was well tolerated with essentially no side effects during the observation period. A 4-week treatment with reboxetine showed a beneficial effect on several metabolic parameters that was independent from treatment outcome and could therefore theoretically be attributed to the pharmacological profile of the drug. Due to the preliminary character of the present investigation, no conclusions about the clinical efficacy of reboxetine can be drawn.

Lower early morning plasma cortisol levels are associated with thyroid autoimmunity in the elderly

Thyroid autoimmunity decreases in the very old. We investigated whether glucocorticoid (GC) activity, which increases in old age, is involved in this process. A total of 321 ambulatory subjects (age 51-95 years, median 71, 207 female) were studied. Thyroid function tests, cortisol, glucose, insulin and biochemical parameters were measured. A modified overnight dexamethasone suppression test (0.25 mg) was performed as an index of GC sensitivity. Forty subjects had positive anti-thyroid peroxidase antibodies and 36 had positive anti-thyroglobulin antibodies, while 57 had either one or the other or both thyroid autoantibodies (ThAbs) positive. Mean basal cortisol levels were significantly lower in the ThAbs (+) groups (320+/-125 vs 378+/-128 nmol/l, P=0.002). Triiodothyronine, free thyroxine, post-dexamethasone cortisol levels, C-reactive protein, homeostasis model assessment-insulin-resistance-index and body mass index did not differ between these two groups. Mean age of ThAbs (+) subjects was lower compared to the ThAbs (-) group (67.38+/-7.38 vs 71.64+/-8.57 years, P=0.001). Reduced GC activity is associated with an increased prevalence of ThAbs positivity in older ambulatory subjects. Subjects without ThAbs in this population sample are relatively older. It is not known whether this is related to increasing GC activity with age.

Hippocampus, glucocorticoids and neurocognitive functions in patients with first-episode major depressive disorders

The aim of this study was to determine whether there was any relationship between hippocampal volume, and glucocorticoid regulation, and cognitive dysfunctions in drug-naïve major depressive disorder (MDD) patients during their first episode. Twenty drug-free female MDD patients in their first episode and 15 healthy females as control subjects were included in the study. All subjects underwent 3.0 Tesla (T) magnetic resonance imaging (MRI), comprehensive neuropsychological testing and dexamethasone suppression tests (DST). The volumes of the right and left hippocampus of the patients were found to be significantly smaller than those of the controls. Patients were found to have significantly lower scores on measures of attention, working memory, psychomotor speed, executive functions, and visual and verbal memory fields. The performance of the patients only in the recollection memory and memory of reward-associated rules were positively correlated with hippocampal volumes. The volumes of the left and right hippocampus did not correlate with basal or post-dexamethasone cortisol levels. Our findings indicate that depressed patients have smaller hippocampi even in the earlier phase of their illness. Further research efforts are needed to explain the mechanisms that are responsible for the small hippocampus in depressed patients.

Major Depressive Disorder and Hypothalamic-Pituitary-Adrenal Axis Activity

There is a central belief that depression is associated with hyperactivity of the hypothalamic-pituitary-adrenal axis, resulting in higher cortisol levels. However, results are inconsistent. To examine whether there is an association between depression and various cortisol indicators in a large cohort study. Data are from 1588 participants of the Netherlands Study of Depression and Anxiety who were recruited from the community, general practice care, and specialized mental health care. Three groups were compared: 308 control subjects without psychiatric disorders, 579 persons with remitted (no current) major depressive disorder (MDD), and 701 persons with a current MDD diagnosis, as assessed using the DSM-IV Composite International Diagnostic Interview. Cortisol levels were measured in 7 saliva samples to determine the 1-hour cortisol awakening response, evening cortisol levels, and cortisol suppression after a 0.5-mg dexamethasone suppression test. Both the remitted and current MDD groups showed a significantly higher cortisol awakening response compared with control subjects (effect size [Cohen d] range, 0.15-0.25). Evening cortisol levels were higher among the current MDD group at 10 pm but not at 11 pm. The postdexamethasone cortisol level did not differ between the MDD groups. Most depression characteristics (severity, chronicity, symptom profile, prior childhood trauma) were not associated with hypothalamic-pituitary-adrenal axis activity except for comorbid anxiety, which tended to be associated with a higher cortisol awakening response. The use of psychoactive medication was generally associated with lower cortisol levels and less cortisol suppression after dexamethasone ingestion. This large cohort study shows significant, although modest, associations between MDD and specific hypothalamic-pituitary-adrenal axis indicators. Because a higher cortisol awakening response was observed among both subjects with current MDD and subjects with remitted MDD, this may be indicative of an increased biological vulnerability for depression.

Effect of continuous positive airway pressure therapy on hypothalamic-pituitary-adrenal axis function and 24-h blood pressure profile in obese men with obstructive sleep apnea syndrome

Obstructive sleep apnea syndrome (OSAS) increases the risk of cardiovascular events. Sympathetic nervous system and hypothalamic-pituitary-adrenal (HPA) axis activation may be the mechanism of this relationship. The aim of this study was to evaluate HPA axis and ambulatory blood pressure monitoring in obese men with and without OSAS and to determine whether nasal continuous positive airway pressure therapy (nCPAP) influenced responses. Twenty-four-hour ambulatory blood pressure monitoring and overnight cortisol suppression test with 0.25 mg of dexamethasone were performed in 16 obese men with OSAS and 13 obese men controls. Nine men with severe apnea were reevaluated 3 mo after nCPAP therapy. Body mass index and blood pressure of OSAS patients and obese controls were similar. In OSAS patients, the percentage of fall in systolic blood pressure at night (P = 0.027) and salivary cortisol suppression postdexamethasone (P = 0.038) were lower, whereas heart rate (P = 0.022) was higher compared with obese controls. After nCPAP therapy, patients showed a reduction in heart rate (P = 0.036) and a greater cortisol suppression after dexamethasone (P = 0.001). No difference in arterial blood pressure (P = 0.183) was observed after 3 mo of nCPAP therapy. Improvement in cortisol suppression was positively correlated with an improvement in apnea-hypopnea index during nCPAP therapy (r = 0.799, P = 0.010). In conclusion, men with OSAS present increased postdexamethasone cortisol levels and heart rate, which were recovered by nCPAP.

Vasopressin–neurophysin and DST in major depression: Relationship with suicidal behavior

The purpose of the present study was to assess if AVP-neurophysin is associated with hypercortisolemia and suicidal behaviour in depressed patients. The study included 28 patients subgrouped into suicide attempters ( n = 13) and nonattempters ( n = 15). We assessed basal AVP-neurophysins concentrations and post-dexamethasone (DST) cortisol levels. Concentrations of AVP-neurophysins did not differ between DST suppressors and nonsuppressors: 0.29 ± 0.13 ng/ml vs 0.36 ± 0.21 ng/ml, ( F = 1.1, df = 1, 27, p = 0.30). Suicide attempters did not differ from nonattempters for AVP-neurophysins levels. Our results fail to support a role of AVP in the early cortisol escape.

Empty sella syndrome, hyperadrenocorticism and megaoesophagus in a dachshund

A five-year-old, entire, male dachshund was presented with a five day history of hypersalivation and regurgitation as well as polyuria and polydipsia for several months. Chest radiographs demonstrated megaoesophagus and aspiration pneumonia. Furthermore, hyperadrenocorticism was demonstrated by means of elevations in levels of serum alkaline phosphatase and cholesterol, decreased urinary specific gravity, increased response to adrenocorticotropic hormone stimulation, insufficient suppression of the post-dexamethasone plasma cortisol levels, an increased endogenous adrenocorticotropic hormone concentration and bilaterally enlarged adrenal glands on abdominal ultrasound. The dog became severely dyspnoeic and was euthanased after magnetic resonance imaging was performed. The magnetic resonance imaging and necropsy revealed the sellar region mainly filled with fluid, with only small tissue remnants, a condition defined as empty sella syndrome in human medicine. To the author's knowledge, this is the first dog described with empty sella syndrome and only the second dog described with hyperadrenocorticism secondary to ectopic adrenocorticotropic hormone production. However, the association between empty sella syndrome and hyperadrenocorticism may be no more than incidental.

Gastrointestinal symptoms are associated with hypothalamic-pituitary-adrenal axis suppression in healthy individuals

Objective. The brain-gut axis has been proposed to influence symptoms in irritable bowel syndrome (IBS). In animal studies corticotropin-releasing hormone (CRH) challenge has been associated with decreased upper gastrointestinal motility and increased colonic motility. The purpose of this study was to investigate the association between gastrointestinal symptoms and the effect of CRH on the hypothalamic-pituitary-adrenal (HPA) axis using a weight-adjusted low-dose dexamethasone test in a group of healthy individuals (n=157). Material and methods. Pre- and post-dexamethasone morning serum cortisol was analysed. All participants completed questionnaires regarding symptoms of IBS (GSRS-IBS (Gastrointestinal Symptom Rating Scale-IBS) and symptoms of anxiety and depression (HADS (Hospital Anxiety and Depression Scale)). After exclusions, 124 subjects were available for analysis (F/M: 60/64, mean age 55.8 years, SD 15.4, range 21–80 years). Results. A positive correlation was found between the GSRS-IBS score and HADS score (rs=0.36; p<0.001). There was no linear correlation between either pre- (rs=0.145; p=0.11) or post-dexamethasone cortisol levels (rs=0.087; p=0.337) and GSRS-IBS scores. By subgrouping the subjects at the lower and higher 25th percentiles of their post-dexamethasone morning cortisol levels, we found a trend towards a higher GSRS-IBS score (median 7.0 versus 5.0; p=0.069) (multivariate adjusted OR 2.6; CI 0.80–8.3) and a significantly higher diarrhoea score (median 2 versus 0; p=0.021) (multivariate adjusted OR 5.7; CI 1.5–22), and a higher early satiety score (p=0.008) (multivariate adjusted OR 6.7; CI: 1.9–23) in the subjects with high post-dexamethasone cortisol levels (low HPA suppression) compared with the subjects with intermediate post-dexamethasone cortisol levels. Furthermore, individuals with low post-dexamethasone cortisol levels (high HPA suppression) showed a significant, higher score for diarrhoea (median 2.0 versus 0; p=0.010) (multivariate adjusted OR 6.1; CI 1.8–20) and early satiety (p=0.076) (multivariate adjusted OR 3.2; CI 1.0–10) compared with those with intermediate cortisol levels. Conclusions. A trend toward a non-linear relationship between IBS-like symptoms and post-dexamethasone cortisol levels was observed in healthy individuals, with significantly more symptoms of diarrhoea and early satiety in individuals with high or low post-dexamethasone cortisol levels in comparison with those with intermediate post-dexamethasone cortisol levels.

Hormonal differences between psychotic and non-psychotic melancholic depression

BackgroundThe dexamethasone suppression test (DST) is the main hormonal disturbance in psychotic depression compared to non-psychotic depression. However, although there have been many studies of individual hormonal axes in depression, few multi-axial studies have been reported. This study aims to examine hormonal differences between these groups of patients through three functional hormonal tests: DST, thyroid stimulating hormone response to thyroid releasing hormone (TSH–TRF) and growth hormone response to growth hormone releasing factor (GH–GRF). MethodsForty inpatients meeting DSM-III-R criteria for major depressive episode with melancholia (21 non-psychotic and 19 psychotic) were studied. Dexamethasone suppression test, TSH–TRF and GH–GRF tests were undertaken for all patients. ResultsIn the whole melancholic sample, 80.0% showed disturbances in at least one hormonal axis, 40.0% in two axes and 5.0% in all three axes. Basal and post-dexamethasone cortisol levels were significantly higher in psychotic than in non-psychotic patients. An association between post-dexamethasone cortisol and blunted GH–GRF response was demonstrated in those with psychotic depression. In the whole sample, GH blunting was found in 62.5% of patients, DST non-suppression in 37.5% and TSH blunting in 25.0% (no differences were found between psychotic and non-psychotic patients). LimitationsSample was restricted to melancholia and unknown factors may influence hormonal responses to stress. ConclusionsHormonal disturbances in depression are more evident when studying several axes, being the HPA and the GH axes the most prominents. Psychotic depression showed more HPA disturbance than non-psychotic depression. Influence of the HPA on the GH axis is discussed.