Postdexamethasone Plasma Cortisol Levels Research Articles

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.

Effects of Carbamazepine on Dexamethasone Suppression and Sleep Electroencephalography in Borderline Personality Disorder

The pathophysiology of borderline personality disorder (BPD) remains obscure, but there is mounting evidence of brain dysfunction without focal abnormality. The dexamethasone suppression test (DST) and sleep electroencephalography (sleep EEG) have been studied in BPD, but the findings seem to be related to a concomitant axis I diagnosis of major depression (MD) rather than to BPD itself. There is no effective treatment for BPD. Carbamazepine (CBZ) has shown contradictory results and in a previous study, our results were negative. In this study, we investigated the effects of CBZ versus placebo on the DST and sleep EEG in a sample of 20 BPD patients without concomitant MD. CBZ given at doses that are therapeutic for epilepsy and affective disorders may have an effect on the DST and sleep EEG in BPD. CBZ significantly increased the postdexamethasone plasma cortisol values. This did not parallel MD or an increase in the Hamilton depression rating scores. CBZ also increased slow wave sleep (SWS). The mechanisms by which CBZ increased postdexamethasone plasma cortisol levels and SWS in BPD are discussed.

Acute administration of buspirone increases the escape of hypothalamic-pituitary-adrenal-axis hormones from suppression by dexamethasone in depression

Recently, our laboratory found a significant enhancing effect of L-5-hydroxy-tryptophan (L-5-HTP) on post-dexamethasone (DST) plasma adrenocorticotropic hormone (ACTH) and cortisol levels in major-but not in minor-depression. To further elucidate the effects of central serotonin (5-HT) activity on the negative feedback of glucocorticoids on hypothalamic-pituitary-adrenal (HPA)-axis function in depression, this study investigates the effects of buspirone, a 5-HT1A receptor agonist, on post-DST ACTH and cortisol levels in 75 depressed subjects. Plasma post-DST ACTH and cortisol concentrations were significantly increased by the acute administration of buspirone (30 mg PO) compared to placebo. There were no differences in buspirone-induced post-DST ACTH or cortisol responses between minor and major depression. There were significant correlations between post-DST ACTH and cortisol, and between post-DST-buspirone ACTH and cortisol. The buspirone-induced post-DST cortisol responses were significantly higher in depressed women than men. It is concluded that buspirone may augment ACTH and, consequently, cortisol escape from suppression by dexamethasone in major as well as in minor depression.

Seasonal variation in the dexamethasone suppression test: a longitudinal study in chronic schizophrenics and in healthy subjects.

To evaluate seasonal influences on the dexamethasone suppression test (DST), cortisol and melatonin responses to dexamethasone were assessed in drug-treated chronic schizophrenics and in drug-free healthy volunteers in different seasons of the year, according to a longitudinal study design. In schizophrenic patients, there was a greater rate of cortisol non-suppression to DST in February as compared to November and May (chi 2 = 4.5, p = 0.03) with no significant differences in pre- and post-dexamethasone plasma cortisol levels. In healthy volunteers, in contrast, no seasonal variation in DST results was observed. Moreover, dexamethasone administration did not significantly affect morning plasma melatonin levels in either patients or healthy controls. These findings suggest that seasonality may be of critical importance in evaluating DST results in schizophrenic patients, but not in healthy subjects.

Hypothalamic-pituitary-adrenal axis function and suicidal behavior in depression

Hypothalamic-pituitary-adrenal (HPA) axis function was examined in relation to suicidal behavior in depression. There were no significant differences between depressed patients who had or had not attempted suicide for either cerebrospinal fluid concentrations of corticotropin-releasing hormone, plasma cortisol levels predexamethasone or postdexamethasone, or for urinary-free cortisol outputs. However, depressed patients who had made a violent suicide attempt had significantly higher 4 pm and maximum postdexamethasone plasma cortisol levels, and significantly more of them were cortisol nonsuppressors than patients who had made nonviolent suicide attempts. A 5-year follow-up was carried out. There were no significant differences on indices of HPA function between depressed patients who did or did not reattempt suicide during the follow-up or who had never attempted suicide. These results suggest the possibility that dysregulation of the HPA axis may be a determinant of violent suicidal behavior in depression.

Low amounts of the α subunit of GTP-binding protein Go in orbital frontal cortex of schizophrenic brain: Biochemical evidence of the hypofrontality hypothesis of schizophrenia

The hypothalamic-pituitary-adrenal (HPA) axis is dysregulated in many patients with major depressive disorder (MDD). To determine whether or not a past history of depressive episodes is associated with this dysregulation, we studied the relationships among number of past depressive episodes, number of previous hospitalizations for depression, and number of years since first depressive episode and biological markers of depression (postdexamethasone plasma cortisol levels and dexamethasone suppressor/nonsuppressor status). No significant relationships were detected.

Alpha-1-acid glycoprotein in major depressive and eating disorders

Plasma α 1-acid glycoprotein (AGP) levels were measured in 49 subjects with major depressive disorder, 15 subjects with anorexia nervosa and 18 subjects with bulimia nervosa, together with age- and sex-matched controls. AGP levels were elevated in depression and bulimia compared to controls. They were particularly elevated in depressed subjects who proved unresponsive to treatment with a standard course of antidepressants. In the depressed subjects, elevated AGP levels returned to control levels after treatment whether or not treatment was successful. There was a correlation between AGP and post-dexamethasone plasma cortisol levels in depression but not in bulimia and a correlation with age in depressed subjects only. There was no correlation between AGP values and tritiated imipramine binding parameters. Further studies are suggested to explore the issue of whether variations in AGP level are responsible for the abnormalities in platelet 5HT uptake and tritiated imipramine binding that have been reported in depression or for treatment non-response.

Suicidal behavior and hypothalamic-pituitary-adrenocortical axis indices in child psychiatric inpatients

Studies of adults have reported associations between suicidal behavior and hypothalamic-pituitary-adrenocortical (HPA) axis functioning, but these associations were inconsistent. Very few studies of prepubertal children evaluating these relations exist. This study of 49 prepubertal psychiatric inpatients evaluates associations between suicidal behavior and predexamethasone and postdexamethasone plasma cortisol levels shortly after hospital admission and 7 weeks later. Results suggest that associations between suicidal behavior and plasma cortisol levels are independent of diagnosis. Covariation of predexamethasone and postdexamethasone plasma cortisol levels with major depression was associated with severity of suicidal behavior. Implications of these results for childhood suicidal risk are discussed.

Dexamethasone suppression test in schizophrenia: Relationship to symptomatology, ventricular enlargement, and outcome

To relieve confusion about the clinical correlates and prognostic implications of the dexamethasone suppression test (DST) in schizophrenia, we conducted a DST in 44 schizophrenic inpatients at drug-free baseline and approximately 4 weeks after neuroleptic treatment. Patients were rated on positive, negative, and depressive symptoms at both times. A head computed tomography (CT) scan was performed and measures of ventricle-brain ratio (VBR) obtained. Clinical improvement was monitored at four weeks, and longer-term outcome assessed at 1 year. Seventeen of the 44 patients were DST nonsuppressors at baseline, and five of these remained nonsuppressors at 4 weeks posttreatment. Postdexamethasone plasma cortisol levels were correlated with negative symptoms at baseline (r = 0.45; p less than 0.01), but not after 4 weeks of neuroleptic treatment. Postdexamethasone plasma cortisols were not related to global severity, positive, or depressive symptoms at either timepoint or to VBR. Persistent nonsuppression was associated with poor outcome, but baseline postdexamethasone cortisol levels were unrelated to outcome at 4 weeks and 1 year. The literature on DST in schizophrenia is reviewed and attempts are made to reconcile discrepant findings and to discuss pathophysiological implications.

Severity of depression and hypothalamic‐pituitary‐adrenal axis dysregulation: identification of contributing factors

Severity of depression, as reflected by total scores on depression rating scales, has been established as one of several major sources of variance associated with hypothalamic-pituitary-adrenal axis dysregulation in patients with major depressive disorder. To determine which of the symptoms comprising clinically defined severity of illness contribute most to this relationship, we studied the associations between postdexamethasone plasma cortisol levels and components of the Hamilton Rating Scale for Depression (HRSD) in 114 patients with major depressive disorder. At pretreatment baseline, severity of depression was modestly but significantly correlated with postdexamethasone plasma cortisol; a large part of this relationship was associated with the anxiety components of the HRSD. When relationships between postdexamethasone plasma cortisol and severity measures were studied longitudinally during treatment, this contribution of the anxiety items persisted. The anxiety associated with depression appears to be a major clinical factor associated with the hypothalamic-pituitary-adrenal axis dysregulation in major depressive disorder.

Plasma dexamethasone levels in children given the dexamethasone suppression test

To determine whether children who demonstrate dexamethasone suppression test (DST) nonsuppression have lower plasma dexamethasone levels than DST suppressors, we administered the DST to 73 patients ranging in age from 5–14 years. Plasma dexamethasone levels and postdexamethasone cortisol levels were measured at 4:00 pm on day 2. We found: (1) DST nonsuppressors had significantly lower plasma dexamethasone levels ( p < 0.03) than suppressors; similar trends were observed when the population was divided into depressed and nondepressed patients; (2) mg/m 2 dose of dexamethasone was directly correlated with plasma dexamethasone ( p < 0.003) and inversely correlated with postdexamethasone plasma cortisol levels ( p < 0.04); and (3) a statistically significant inverse correlation between plasma dexamethasone levels and postdexamethasone cortisol levels ( p < 0.04). Our findings show that plasma dexamethasone levels are important in evaluating DST results in psychiatrically disturbed children and suggest that dexamethasone dosage for use in the DST in children might be better calculated in terms of body surface area.

Psychopathology and plasma cortisol responses to dexamethasone in prepubertal psychiatric inpatients

This study of 51 prepubertal psychiatric inpatients evaluates plasma cortisol measurements at 8 am, 4 pm, and 11 pm before and after dexamethasone was administered in counterbalanced order at does of 0.5 mg and 1.0 mg. Approximately 76.5% of the children had an affective disorder. Major depressive disorder was associated with higher plasma cortisol levels than other disorders. Pre- and postdexamethasone plasma cortisol levels using 0.5 mg dexamethasone exhibited a circadian variation. The optimal criterion for cortisol nonsuppression was 5 μgldl measured at 8 am after administration of 0.5 mg dexamethasone.

The effect of in or outpatient status on EEG sleep data and postdex controls levels in depressed patients

In a sample of inpatients with major depressive disorder (MDD), we reported that patients with short REM latency (RL) had higher postdexamethasone (postdex) plasma cortisol levels. We now report on the general association of EEG sleep measures and postdex cortisol levels in the above sample, with comparison to a group of 36 outpatients. EEG sleep data averaged over two nights were compared to data for the 1 .O mg DST. After a two-week drug wash-out period, all patients had a SADS/RDC diagnosis of definite MDD and had a HRS > 14. Clinical and demographic data showed the 52 inpatients did not differ from the 36 outpatients with respect to mean age or HRS. Concerning a comparison of EEG sleep measures, however, the inpatient group showed significantly more impaired sleep efficiency (77.4 ? 14.0% vs 83.0 & 11.77%, p < .05) and other measures of sleep continuity, and had greater abnormalities of REM sleep, including a shorter RL (35.0 ? 25.3 minutes vs 56.3 + 27.5 minutes, p < .OOl), and greater REM time (25.1 ? 13.8 vs 18.5 ? 9.3, p < .05) and REM activity (55.2 + 47.5 vs 29.9 + 24.0, p < .Ol) in the first REM period. A significant correlation between sleep measures and cortisol existed only within the inpatient group, in which the maximum postdex cortisol level was correlated positively with%awake(+0.40,p<.01),%stage1(+0.36,pC.01)andnumberof~ousals (+0.32, p < .05), and negatively with time spent asleep (-0.28, p < .05) and sleep efficiency (-0.44, p < .Ol). Cortisol was negatively correlated with REM latency minus awake (-0.44, p C .OOl) but not with REM activity or REM density. These data suggest that the relationship between sleep and postdex cortisol secretion may hold only in a more severely ill (i.e. inpatient) group.

Cognitive impairment and cortisol resistance to Dexamethasone Suppression in elderly depression

The present study evaluates the relationship between cognitive impairment and the Dexamethasone Suppression Test (DST) in elderly persons suffering from depression. Twentynine subjects meeting DSM-III criteria for major depressive disorder (MDD) were assessed using the Global Deterioration Scale (GDS) and the DST. Plasma cortisol levels before and after receiving 0.5 mg dexamethasone were compared, and correlations were determined between GDS and postdexamethasone plasma cortisol levels. The results show that there is a positive correlation between the GDS scores andpost-DEX cortisol levels ( r = 0.57, p < 0.005). It is suggested that increased activity of the HPA axis, seen in depression, could contribute to the cognitive impairments observed in this disorder.

Family history of psychosis, obstetric complications, premorbid functioning, and CT scan findings in schizophrenia patients

To relieve confusion about the clinical correlates and prognostic implications of the dexamethasone suppression test (DST) in schizophrenia, we conducted a DST in 44 schizophrenic inpatients at drug-free baseline and approximately 4 weeks after neuroleptic treatment. Patients were rated on positive, negative, and depressive symptoms at both times. A head computed tomography (CT) scan was performed and measures of ventricle-brain ratio (VBR) obtained. Clinical improvement was monitored at four weeks, and longer-term outcome assessed at 1 year. Seventeen of the 44 patients were DST nonsuppressors at baseline, and five of these remained nonsuppressors at 4 weeks posttreatment. Postdexamethasone plasma cortisol levels were correlated with negative symptoms at baseline (r = 0.45; p < 0.01), but not after 4 weeks of neuroleptic treatment. Postdexamethasone plasma cortisols were not related to global severity, positive, or depressive symptoms at either timepoint or to VBR. Persistent nonsuppression was assocciated with poor outcome, but baseline postdexamethasone cortisol levels were unrelated to outcome at 4 weeks and 1 year. The literature on DST in schizophrenia is reviewed and attempts are made to reconcile discrepant findings and to discuss pathophysiological implications.

Plasma postdexamethasone cortisol levels in schizoaffective disorder

The degree of hypothalamic-pituitary-adrenal (HPA) axis dysregulation in depressed patients with schizoaffective disorder was compared to that seen in patients with major depressive disorder with and without delusional features. The frequency of nonsuppression to dexamethasone was similar for all three diagnostic groups. Maximum postdexamethasone plasma cortisol was greater for delusional depressives, but did not differ between patients with major depressive and schizoaffective disorders. Modest correlations were found between postdexamethasone plasma cortisol levels, severity of illness, age, and recent weight loss, for patients with both major depressive disorder and delusional depression. For schizoaffective patients, associations between postdexamethasone plasma cortisol levels and various measures of severity of illness, but not age and recent weight loss, were found. Although HPA axis dysregulation occurs more frequently in all three of the studied diagnostic groups than in normal individuals, factors contributing to this dysregulation may be qualitatively different for schizoaffective patients.

Cortisol nonsuppression in depression: relationship to clinical variables

The dexamethasone suppression test was performed in 63 depressed patients and 43 normal controls. Cortisol nonsuppression was found in 47.6% of the depressed patients and 4.6% of the controls. Among depressed patients both age and reported weight loss, but not severity of depression, were significantly related to postdexamethasone plasma cortisol levels. Patients who were cortisol suppressors had experienced significantly more life events before the onset of depression and had significantly higher hostility scores on a personality questionnaire than cortisol nonsuppressors.

Thyrotropin releasing hormone test in unipolar depressed patients and controls: Relationship to clinical and biologic variables

We compared unipolar depressed patients (n = 31) with controls (n = 38) for their responses to the thyrotropin releasing hormone (TRH) test. Depressed patients showed significantly smaller thyrotropin stimulating hormone (TSH) responses to TRH which correlated negatively with post-dexamethasone plasma cortisol levels. Depressed patients also showed significant negative correlations between delta max TSH and urinary outputs of norepinephrine and normetanephrine with similar trends with plasma levels of norepinephrine and 3-methoxy-4-hydroxyphenylglycol. Patients who showed a blunted TSH response, compared with those who did not, had significantly lower platelet serotonin uptake values. These results suggest that the blunted TSH response to TRH seen in depression may be associated with dysregulation of the cortisol, noradrenergic and serotonin systems.

Postdexamethasone plasma cortisol and β-endorphin levels in depression: Relationship to severity of illness

The hypothalamic-pituitary-adrenal (HPA) axis is dysregulated in many patients with depression, probably at all levels of the axis. To determine if HPA dysregulation is associated with severity of depression, we studied a group of 66 patients with major depressive disorder. Each patient underwent a pretreatment Dexamethasone Suppression Test, with plasma postdexamethasone cortisol determination at 8:00 AM, 4:00 PM, and 11:00 PM. All three postdexamethasone cortisol levels were significantly correlated with the Hamilton Rating Scale for Depression (HRSD) scores. We also examined the “profile” measures of mean, maximum, and minimum of the three cortisol values; again, all three were significantly correlated with HRSD scores. To evaluate associations between clinical severity and HPA dysregulation at the pituitary level, we studied a second group of 44 patients with major depressive disorder. Each had postdexamethasone cortisol determinations at 4:00 PM and 11:00 PM as well as pre- and postdexamethasone β-endorphin determinations at 4:00 PM. The cortisol data from this group followed the same pattern as in the first sample, and there was a significant relationship between HRSD score and degree of β-endorphin nonsuppression as well. These results suggest that severity of depression is one of the determinants of dysregulation at both adrenal and pituitary levels of the HPA axis, accounting for 10%–20% of the observed variance.

Multiple depressive episodes and plasma postdexamethasone cortisol levels

The hypothalamic-pituitary-adrenal (HPA) axis is dysregulated in many patients with major depressive disorder (MDD). To determine whether or not a past history of depressive episodes is associated with this dysregulation, we studied the relationships among number of past depressive episodes, number of previous hospitalizations for depression, and number of years since first depressive episode and biological markers of depression (postdexamethasone plasma cortisol levels and dexamethasone suppressor/nonsuppressor status). No significant relationships were detected.