Comparison of plasma cortisol and corticosterone in the dexamethasone suppression test for melancholia

The suppression of plasma corticosterone (B), measured by radioimmunoassay (RIA), was compared to simultaneous suppression of plasma cortisol (F), measured as total corticoids by a competitive protein binding (CPB) assay, in the overnight dexamethasone suppression test (DST). Baseline plasma B concentrations in IO control subjects were 4.04 ± 1.07 ng/ml (X ± S.D.) at 0800 hr and 1.51 ± 0.68 ng/ml at 1600 hr. Post-dexamethasone 1600 hr B levels in the controls were 0.46 ± 0.29 ng/ml. An early escape of plasma B (> 1.2 ng/ml), like that of F (> 5 μg/dl), during the overnight 24 hr 1.0 mg dose DST was noted in patients with melancholia (endogenous depression).Half-hourly catheter samples in a normal subject stimulated to escape from dexamethasone suppression showed that in general, plasma B concentrations parallel plasma F concentrations over a 12 hr period. Repeated weekly DSTs on two patients with different psychiatric diagnoses resulted in B: F correlations of 0.74 and 0.60. Overall agreement between B- and F-DST outcomes in all categories tested at 1600 and 2300 hr was 93%; the agreement in the melancholic and non-endogenous depressed groups was 100%.Post-dexamethasone, both B and F were suppressed 55–60% below the criterion level in controls. In those patients who escaped from dexamethasone suppression, the percentage increase in plasma B above the criterion level was significantly greater (+ 55%) than the corresponding percentage change in plasma F. Most patients with borderline abnormal F-DSTs (3.5–4.9 μg/dl) exhibited clearly abnormal B-DSTs (> 1.2 ng/ml). We conclude that the use of dexamethasone suppression of plasma B (using 1.2 ng/ml as the abnormal criterion value) is an additional indicator of an abnormal DST in depressed patients.     

Use of the dexamethasone suppression test in an inpatient setting: a replication and new findings

The dexamethasone suppression test (DST) was administered to 131 depressed and 109 nondepressed psychiatric inpatients. The depressed patients were categorized according to DSM-III as minor depression, major depression without melancholia, and major depression with melancholia and/or with psychotic features. The nondepressed patients were stratified over several DSM-III subcategories. DST nonsuppression was nonspecific for major depression: the mean post-dexamethasone cortisol value and the number of nonsuppressors were not significantly different between the major depressives and the nondepressed psychiatric controls. Within the depressive sample the DST was a significant (p less than 0.01) discriminator between major and minor depression. Postdexamethasone plasma greater than or equal to 3.5 micrograms/dl at 0800h was the most sensitive (39%) and specific (94%) criterion; cortisol values at 1600h and 2300h showed no significant discriminating power for major vs. minor depression. The diagnostic utility of the DST thus appears to be limited to confirming the diagnosis of major depression, once the clinical diagnosis of depression is made. There was no significant influence of age or gender on postdexamethasone cortisol values.     

Consistency of pituitary-adrenocortical function across multiple psychiatric hospitalizations

The dexamethasone suppression test (DST) was done in 53 psychiatric patients during at least two separate hospital admissions. The agreement between DST results on both admissions exceeded chance expectations: 69.8% of all patients and 72.3% of those with major depression had consistent DST results.     

Evening urine cortisol excretion and DST results in depression and anorexia nervosa

Cortisol determination in a single one-hour urine sample collected between 2200 h and 2300 h has been shown to identify accurately patients with Cushing's disease. To examine the usefulness of this procedure for identifying psychiatric patients with a pituitary-adrenal disturbance, we studied 17 drug-free depressed patients, 6 euthymic anorectic patients and 10 healthy volunteers. We found that there was good agreement between DST results and evening urine cortisol excretion in this sample (when cortisol levels were expressed as ng of cortisol per mg of creatinine), and that adopting as a criterion a urine cortisol value two standard deviations above the mean cortisol value of the controls predicts 74% of the dexamethasone suppression test (DST) results. We would like to suggest that this measure deserves further study as a potentially useful and simple alternative to the DST for identifying psychiatric patients with a pituitary-adrenal disturbance.     

L-5-hydroxytryptophan stimulated cortisol escape from dexamethasone suppression in melancholic patients

The dexamethasone suppression test (DST) was carried out in 62 depressed patients. At 0800 the postdexamethasone cortisol values were determined and 125 mg L-5-hydroxytryptophan (L-5-HTP) was administered. The second cortisol sample at 0930 revealed a significant enhancing effect for L-5-HTP on the postdexamethasone cortisol values in melancholic patients, whereas no effects were detected in minor depressives. Our results show that L-5-HTP converts some DST suppressors into nonsuppressors, whereas the escape from dexamethasone in some nonsuppressors is markedly stimulated. The L-5-HTP-stimulated 0930 postdexamethasone cortisol values performed markedly better than the 0800 DST results: at a cut-off value of greater than or equal to 5 micrograms/dl the sensitivity for melancholia increased from 46% to 68%, and the specificity remained unchanged (96%).     

Effect of hospital admission on DST results

The authors examined the dexamethasone suppression test (DST) responses of 41 patients with primary major depressive disorder and 40 patients with other psychiatric disorders who were tested within 2-6 days of hospital admission. Significantly more patients with primary depression who were tested on day 2 demonstrated abnormal cortisol suppression than those who were tested on days 3, 4, or 3-6 and than patients with other psychiatric disorders regardless of test day. These results suggest that patients with primary depression may be sensitive to psychophysiologic stresses associated with hospital admission and that the utility of the DST may require further evaluation vis-à-vis the day of DST administration.     

Dexamethasone suppression test in severe schizophrenic illness: effects of plasma dexamethasone and caffeine levels

A dexamethasone suppression test (DST) was administered to 31 inpatients with a severe acute schizophrenic exacerbation 4 or 5 days following admission and repeated after 4 weeks or prior to discharge. We identified 15 patients (48%) who were nonsuppressors on the DST at the first test. To exclude major confounders of DST results we monitored weight constancy and plasma concentrations of dexamethasone. In a subgroup of patients also plasma caffeine contents were determined. Our results indicate that DST nonsuppression occurs frequently among patients with schizophrenic crisis. Since caffeine plasma levels were indistinguishable between suppressors and nonsuppressors we reject that excessive caffeine intake accounts for DST nonsuppression among individuals with schizophrenia. Nonsuppressors had lower plasma dexamethasone levels than suppressors and reversal of the DST status from nonsuppression to suppression was associated with an increase of plasma concentrations of the test drug.     

The dexamethasone suppression test: its relationship to diagnoses, severity of depression and response to treatment

1. The dexamethasone suppression test (DST) was applied to 40 depressed patients, 40 healthy volunteers and 40 patients with other psychiatric disorders. 2. The post-dexamethasone cortisol level, adopted as the non-suppression criterion and established locally, was 3.0 micrograms/dl. 3. The DST sensitivity in depression was 45%, with a specificity of 95% and a positive predictive value of 90%. 4. There was a significant correlation (r = 0.38, p less than 0.05) between HDRS scores of depressed patients and their post-dexamethasone cortisol levels. 5. A prospective study of the depressed group, which was assessed with three depression rating scales, showed differences between non-suppressors and suppressors regarding to the symptoms severity and response to the treatment. It suggests that an abnormal DST result could have a prognostic value to antidepressant drugs and ECT. 6. The DST specificity in depression was also calculated from its performance in the group with other psychiatric disorders, and their diagnoses as well as the abnormal DST results were critically discussed.     

Abnormal dexamethasone suppression test in daily chronic headache sufferers

The dexamethasone suppression test (DST) was administered in 48 daily chronic headache (DCH) sufferers, 37 of whom also suffered from mild to severe depression. In 14 of 48 subjects (29.2%), cortisol values at 1600h were greater than 50 ng/ml, despite normal suppression at 0800h. The escapers showed basal cortisol values and (Depression scale) scores on the Minnesota Multiphasic Personality Inventory higher than suppressors. Thus, a group of DCH sufferers appeared to share a biochemical defect often seen in endogenous depression. The escape from dexamethasone suppression could be a psychobiological indicator of vulnerability to develop depressive disorder and/or chronic pain complaints.     

Psychopathological correlates of plasma cortisol after dexamethasone suppression: A polydiagnostic approach

Seventy-seven consecutively admitted inpatients with depressive syndromes were examined with the Present State Examination and classified according to eight different operational diagnoses of endogenous depression. All patients received a 1.5 mg dexamethasone suppression test (DST). Sensitivity, specificity and the corrected predictive values of DST nonsuppression (50 or more ng/ml at 0800 hr, 1600 hr, or 2300 hr), adjusted to a 50% prevalence of endogenous and nonendogenous depression, varied considerably depending on the diagnostic definition used. The highest predictive value (89.9%) was found with the Taylor-Abrams criteria (sensitivity = 43.9%, specificity = 95.0%), and the lowest predictive value (53.3%) with DSM-III (sensitivity = 37.7%, specificity = 68.1%). Eliminating the patients with dexamethasone levels of less than 2000 pg/ml improved the diagnostic specificity of the DST for most of the eight definitions of endogenous depression. This further indicates that plasma dexamethasone levels should be analyzed in studies designed to explore the diagnostic utility of the DST. A significant, chance-corrected association between DST nonsuppression and the diagnosis of endogenous depression was found with clinical diagnosis (according to the International Classification of Diseases), and for four out of eight operational diagnoses (Newcastle Scale 1, Newcastle Scale II, Taylor-Abrams Criteria, and Vienna Research Criteria). For the other diagnoses (Research Diagnostic Criteria, DSM-III, Michigan Discriminant Index, and Hamilton Endogenomorphy Index), no significant association was found. The RDC criterion “early or intermittent awakening” was the only one out of 28 diagnostic criteria tested which was significantly associated with DST nonsuppression.     

Dexamethasone suppression test and plasma dexamethasone levels in bulimia

A 1-mg dexamethasone suppression test (DST) was carried out in 66 women with bulimia and in 26 age- and sex-matched controls. Blood samples were obtained at 4 PM on the day following dexamethasone ingestion, and levels of cortisol and of dexamethasone in the plasma were measured. Thirty-two percent of the patients vs only 7% of the controls had plasma cortisol levels of 140 nmol/L (5 micrograms/dL) or greater following the DST (a positive DST). The plasma levels of dexamethasone varied substantially, and there was a significant inverse relationship between the plasma level of cortisol and that of dexamethasone. Patients with positive DST results had lower levels of plasma dexamethasone than did those with negative DST results, and the mean plasma level of dexamethasone was lower in the bulimic group than in the control group. These results suggest that factors other than a disturbance of hypothalamic-pituitary-adrenal activity may contribute to positive DST results in bulimia.     

Dexamethasone suppresion test (DST) and plasma dexamethasone levels in depressed patients

The dexamethasone suppression test (DST) was evaluated in newly hospitalized patients with a DSM-III diagnosis of major depression. Patients with other psychiatric disorders and a normal control group were also studied. Plasma dexamethasone levels were obtained in all patients, and the relationship between plasma cortisol and plasma dexamethasone was examined. Rates of non-suppression in patients with major depression (39%) were not significantly different from those in patients with minor depression (25%), mania (38%), or other psychiatric illnesses (17%). The ranges of dexamethasone levels at 8 a.m. and 4 p.m. were similar between patient groups and controls. However, there was a significant difference in dexamethasone levels between suppressors and nonsuppressors, irrespective of diagnosis, which could not be explained by differences in weight or plasma dexamethasone half-life. Inappropriately high dexamethasone levels were found in some patients with a 1 mg test, a problem that critically affects the sensitivity of the test procedure.     

The dexamethasone suppression test in prepubertal depressed children

The dexamethasone suppression test (DST) was performed in 50 hospitalized prepubertal children who met DSM-III criteria for major depressive episode, 18 hospitalized controls with a psychiatric disorder, and 18 nonhospitalized normal controls. Baseline and post-DST cortisol levels were measured at 8 a.m. and 4 p.m. The depressed children had consistently higher cortisol levels than the controls at baseline and post-DST. The DST was positive in 82% of depressed children, 28% of psychiatric controls, and 11% of normal controls. The results indicate that prepubertal depressed children may have abnormalities in the hypothalamic-pituitary-adrenal axis similar to those in adults with a major depressive illness.     

Comparison of solid-phase radioimmunoassay and competitive protein binding method for postdexamethasone cortisol levels in psychiatric patients

Results obtained by competitive protein binding assay (PBA) and a solid-phase radioimmunoassay (RIA) for cortisol were compared in 157 samples from 100 psychiatric patients given a dexamethasone suppression test (DST). Cortisol levels in plasma samples obtained at 8:00 a.m. or 4:00 p.m. the day following 1.0 mg dexamethasone orally at bedtime ranged from 0 to 30 micrograms/dl and correlated closely (r = 0.96). However, RIA gave values that were consistently and significantly lower (average = 8.9%) than those obtained by PBA. When samples were further assayed by a specific RIA for corticosterone, there was a strong correlation between cortisol and corticosterone RIA values (r = 0.79), and corticosterone (7.8% of cortisol levels) accounted for most of the difference between PBA and RIA for cortisol. The relationship between results of the two cortisol assay methods can be expressed (in micrograms/dl) by the equation: RIA = 0.92(PBA) - 0.10, based on findings obtained in a separate analysis of 127 samples with cortisol values in the 0-10 micrograms/dl range, critical to the valid interpretation of the DST in melancholia. A reported criterion of a "positive" DST in psychiatry, of plasma cortisol of greater than or equal to 5.0 micrograms/dl has been suggested by use of a PBA. Use of the present RIA required that this value be adjusted downward, at least to 4.5 micrograms/dl; application of this criterion increased the clinical sensitivity of the DST by 10%. We urge local, independent verification of criteria to define the DST as "positive" in each laboratory and with each method of assay.     

The dexamethasone suppression test for diagnosis and prognosis in psychiatry. Commentary and review

A modified dexamethasone suppression test (DST) has had unprecedented evaluation among biologic tests proposed for clinical use in psychiatry. It has not proved to reflect pathophysiologic changes at the level of the central nervous system or pituitary, and tissue availability of dexamethasone itself may contribute to test outcome. The sensitivity of the DST in major depression is limited (about 44% in over 5,000 cases) but is higher in psychotic affective disorders and mixed manic-depressive states (67% to 78%). The high specificity of the DST vs control subjects (over 90%) is not maintained vs other psychiatric disorders (77% specificity overall), and acute "distress" may contribute to nonsuppression of cortisol. The test may have power in differentiating severe melancholic depression, mania, or acute psychosis from chronic psychosis (87% specificity) or dysthymia (77% specificity). The DST status adds about 11% to the prediction of short-term antidepressant response. Suggestions that failure to maintain normal suppression of cortisol predicts poor outcome are not secure. Uncritical enthusiasm or excessive skepticism regarding the DST are unwarranted.     

Diagnostic heterogeneity and the DST in consecutive psychiatric admissions

There is uncertainty about the clinical usefulness of the dexamethasone suppression test (DST). It is also unclear whether there are advantages to a 1-mg or 2-mg DST. Eighty-three consecutive psychiatric inpatients were randomly given a 1-mg or 2-mg DST within the first week of admission. Sensitivity, specificity, and diagnostic confidence are reported for this group, and also in combination with those for 119 semi-consecutive psychiatric admissions. Although rates of nonsuppression were consistently higher in patients with affective disorders than in patients with other diagnoses, the diagnostic confidence of the DST for major depression in a diverse and unselected patient population was not greater than the prevalence of the disorder. The DST does not appear to be useful for clinical diagnostic decision-making. Nonetheless, the DST may still be an important biological marker in neuroendocrine psychiatric research.     

Age and cortisol suppression by dexamethasone in normal subjects

A study of 60 healthy volunteers ranging from 19-88 yr of age found nonsuppression rare (5%) and confirmed that the dexamethasone suppression test (DST) of the reactivity of the hypophyseal-pituitary-adrenal axis to negative feedback inhibition requires 0800 h plasma dexamethasone (DEX) levels in excess of 220 ng/dl. All of the subjects with inadequate DEX levels (N = 3) were older than 50 yr of age as were the nonsuppressors (N = 3); two of the three nonsuppressors had inadequate DEX concentrations. Thus, DST may be more often invalid in elders than in younger adults because of inadequate plasma dexamethasone (DEX) concentration, indicating that plasma DEX levels should be assayed concomitantly with DST in elders.     

Melatonin, cortisol and ACTH in patients with major depressive disorder and healthy humans with special reference to the outcome of the dexamethasone suppression test

The 24 hr profiles of melatonin and cortisol in serum, morning levels of ACTH in plasma, and the dexamethasone suppression test (DST) were investigated in 32 acutely ill patients with a RDC diagnosis of major depressive disorder, 24 patients with a history of longlasting unipolar or bipolar major depressive disorder studied in remission, and 33 healthy subjects. A significant decrease in maximum nocturnal melatonin level (MTmax) was found in the acutely ill depressed patients with abnormal DST compared to both those with normal DSTs and the healthy subjects. The MTmax levels were unaltered when these patients were reinvestigated in remission. A decrease of MTmax was also seen in the group of unipolar and bipolar patients studied in remission. Low nocturnal melatonin is proposed to be a trait marker for major depressive disorder and depressive states with abnormalities in the hypothalamic--pituitary--adrenal (HPA) axis. A significant decrease of ACTH levels at 0800 hr after dexamethasone administration the preceding evening was found in the healthy subjects, the unipolar--bipolar patients in remission, and the acutely ill depressed patients with normal DSTs, but was not found in the acutely ill depressed patients with abnormal DSTs. These findings support the hypothesis that pituitary ACTH regulation is altered in depressed patients with abnormal DST. Morning plasma ACTH before the administration of dexamethasone did not significantly differ between the acutely ill depressed patients with abnormal DSTs, normal DSTs, the patients with unipolar--bipolar disease in remission, or the healthy subjects. Thus, the abnormalities in the HPA axis in depresséd patients are proposed to be due to a hypersecretion of corticotrophin releasing factor (CRF) with a subsequent stimulus-induced pituitary desensitization. A significant decrease of melatonin after dexamethasone was seen at 0800 hr in the unipolar--bipolar patients in remission as well as in the healthy subjects, at 1600 hr and 2200 hr in the acutely ill depressed patients in remission, but not at 0800 hr in the acutely ill depressed patients in relapse. A significant regression was found between MTmax levels and the degree of non-suppression of cortisol at 0800 hr in the DST in the acutely ill depressed patients both in relapse and in remission. Melatonin thus is proposed to be an inhibiting factor for CRF during depression. A trend to a phase-advance of cortisol nadir and melatonin peak was seen in the acutely ill depressed patients with abnormal DST, possibly indicating an involvement of the suprachiasmatic nuclei in the hypothalamus.     

The dexamethasone suppression test and pituitary-adrenocortical function

The dexamethasone suppression test (DST) as now commonly carried out in psychiatric settings yields "abnormal" results in many conditions including the healthy state. To determine whether the DST accurately identifies patients with physiologically meaningful increases in pituitary-adrenocortical activity, we compared DST results to baseline urinary cortisol level. Thirty-four psychiatric inpatients underwent a 24-hour urine collection and then a DST using 1 or 2 mg of dexamethasone. With the common 1-mg DST, 24-hour urinary cortisol levels in nonsuppressors and suppressors did not differ. With the 2-mg DST, however, nonsuppressors had significantly higher urinary cortisol levels than suppressors, and all nonsuppressors had urinary cortisol levels above the normal range. Thus, the 1-mg DST may not identify the heuristically important subgroup of psychiatric patients who have a pathophysiologically meaningful alteration in pituitary-adrenal regulation.     

Diagnostic performance of the thirty-four hour dexamethasone suppression test

The performance of the dexamethasone suppression test (DST) in the diagnostic confirmation of endogenous depression was compared according to two times of blood collection—1600 hr on day 2 (usual sample) and 0800 hr on day 3 (34 hr after dexamethasone intake)—in 14 endogenous depressives and in a control group of 17 psychiatric inpatients with other diagnoses. For the day 2 (1600 hr) sample, a 5 μg/dl cortisol concentration represented the best cut-off score, with sensitivity of 57% specificity of 88%, and diagnostic confidence of 80%. For the day 3 (0800 hr) sample, the best cut-off score was 20 μg/dl, with the same sensitivity (57%) but there was a decrease of both specificity (to 76%) and diagnostic confidence (to 67%). The mean cortisol levels were much higher on day 3 than on day 2, suggesting that the inhibitory activity of dexamethasone was no longer present.