A comparison of the cortisol suppression index and the dexamethasone suppression test in prepubertal children

Results of the dexamethasone suppression test (DST) and the cortisol suppression index (CSI) were compared in 50 depressed prepubertal children and 36 control subjects. The 4:00 p.m. DST, the two-point DST, and the 8:00 a.m. revised criterion CSI yielded the best results and had similar clinical utility and diagnostic confidence values.     

A comparison of the cortisol suppression index and the dexamethasone suppression test

The cortisol suppression index (CSI) (the ratio of pre- to postdexamethasone serum cortisol concentrations) was compared to the dexamethasone suppression test (DST) in endogenously depressed DST suppressors (N = 20) and nonsuppressors (N = 21) and in normal controls (N = 23). The 8 a.m. CSI detected 17.1% and 31.7% of endogenous depressives at the 4.0 and 6.0 thresholds; for the 4 p.m. CSI, rates were 48.8% and 65.9%. The 4 p.m. CSI produced 17.4% and 39.1% false positives in normal controls at the two thresholds, whereas the false positive rate for the DST was 4.3%. These data suggest that the CSI is not as specific as the standard DST for the detection of endogenous depression.     

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 less than 0.03) than suppressors; similar trends were observed when the population was divided into depressed and nondepressed patients; (2) mg/m2 dose of dexamethasone was directly correlated with plasma dexamethasone (p less than 0.003) and inversely correlated with postdexamethasone plasma cortisol levels (p less than 0.04); and (3) a statistically significant inverse correlation between plasma dexamethasone levels and postdexamethasone cortisol levels (p less than 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.     

The effect of serum dexamethasone concentrations in the dexamethasone suppression test

Serum dexamethasone and cortisol concentrations were measured in a sample of 98 psychiatric inpatients during the course of the 1-mg oral overnight Dexamethasone Suppression Test (DST). Suppressors were found to have significantly higher serum dexamethasone concentrations than nonsuppressors at each time of sampling (8:00 AM, 4:00 PM, and 11:00 PM). There was a significant inverse curvilinear relationship between serum dexamethasone and cortisol concentrations at each sample time. Although serum dexamethasone concentration was a potent determinant of postdexamethasone serum cortisol concentration, there were still significantly higher serum concentrations of cortisol in patients with major depression compared with patients with other disorders when dexamethasone concentrations were statistically controlled. By taking serum dexamethasone concentrations into account in defining DST suppression status, a modest increase in diagnostic specificity was achieved, but no substantial change in sensitivity.     

Urinary free cortisol levels and dexamethasone suppression testing in organic affective disorder associated with hyperthyroidism

Eleven of 32 newly diagnosed untreated patients with hyperthyroidism met DSM-III criteria for organic affective syndrome. Thirty of these patients submitted 24-hour urine specimens for measurement of urinary free cortisol levels, and 31 were given a 1-mg dexamethasone suppression test (DST) before antihyperthyroidism therapy was started. There was no difference in the mean +/- SD urinary free cortisol excretion levels between depressed and nondepressed hyperthyroid patients. One nondepressed patient demonstrated nonsuppression (greater than 5 micrograms/dl) at 8:00 a.m. These results suggest that cortisol abnormalities as reflected by urinary free cortisol levels and DST findings are uncommon in patients with hyperthyroidism whether they are depressed or nondepressed.     

Cortisol and Alzheimer's disease, I: Basal studies

Patients with Alzheimer's disease and nondemented elderly control subjects participated in studies of cortisol secretion during sleep and at 9:00 a.m. and were given dexamethasone suppression tests (DSTs) and lumbar punctures. Nocturnal and 9:00 a.m. cortisol concentrations were significantly higher in the demented patients. CSF MHPG negatively correlated with mean nocturnal cortisol. The most severely demented patients had the highest 9:00 a.m. and mean nocturnal cortisol concentrations. DST results did not distinguish samples with substantially different nocturnal cortisol concentrations. These results suggest that measurements of basal plasma cortisol concentrations and dexamethasone suppression provide different information but support the notion of somewhat higher than normal cortisol concentrations in Alzheimer's disease patients.     

Dynamics of the cortisol suppression index in depression

The cortisol suppression index (CSI), a ratio of predexamethasone to postdexamethasone plasma cortisol levels, has been suggested as an alternate approach to the use of the DST in the diagnosis of depression. Forty-eight psychiatric inpatients were prospectively studied to compare the utility of the CSI to results obtained using Carroll's fixed values at 4 p.m. and 11 p.m. Eighty-eight percent (22/25) of depressed patients had an 8 a.m. CSI below 7.0; 73% (16/22) had a 4 p.m. CSI less than 2.5. This compared to a 76% detection rate using Carroll's criteria for nonsuppression. In this study the CSI provided a sensitive and specific interpretation of the dexamethasone suppression test in depression.     

Plasma dexamethasone concentrations and the dexamethasone suppression test

Altered bioavailability or altered pharmacokinetics of dexamethasone (dex) may contribute to a positive Dexamethasone Suppression Test (DST) in psychiatric patients. We measured plasma dex and plasma cortisol concentrations in 32 patients with primary major depressive disorder (MDD), 14 patients with other psychiatric disorders, and 16 normal controls. Cortisol was measured by the competitive protein binding (CPB) assay and dex by RIA (IgG Corp.). Additionally, cortisol was measured by a fluorescent polarization immunoassay (FPIA) available on the Abbott TDx analyzer in an attempt to validate this method for use in the DST. The agreement between FPIA and CPB cortisol results was excellent. Depressed nonsuppressors, by definition, had significantly higher mean plasma cortisol concentrations than depressed suppressors, psychiatric controls, and normal volunteers at 8:00 AM, 3:00 PM, and 10:00 PM postdex. When DST nonsuppressors and suppressors were compared regardless of diagnostic group, plasma dex concentrations were significantly lower (p less than 0.01) in the DST nonsuppressors. There was a significant negative correlation between plasma cortisol levels and plasma dex levels across all subjects at 8:00 AM (r = -0.365, n = 44, p less than 0.05). When the subjects were sorted by diagnostic category, there was a strong, but not statistically significant, trend toward lower plasma dex concentrations in the melancholic nonsuppressors versus the melancholic suppressors and between the psychiatric control non-suppressors and the corresponding suppressor group. These relationships disappeared when we restricted our analyses to an empirically derived middle range of plasma dex concentrations within which the DST results were considered to be valid. We conclude that bioavailability or pharmacokinetics of dex may significantly contribute to DST results. Further investigation is needed to determine whether or not the quantification of dex and its metabolites and their determination at which specific timepoints during the DST will enhance the predictive or interpretive value of the DST in psychiatric patients.     

The plasma dexamethasone window: evidence supporting its usefulness to validate dexamethasone suppression test results

Two doses of dexamethasone (DEX) (0.5 and 1.0 mg) were administered in a randomized crossover design to 31 patients with major depression, 9 healthy controls, and 14 nondepressed psychiatric patients. Using this modified Dexamethasone Suppression Test (DST), minimum DEX levels of 6 nmol/liter at 8:00 AM and 2.0 nmol/liter at 4:00 PM were required to achieve reliable suppression of cortisol in healthy controls and nondepressed psychiatric patients. Failure to achieve these minimum plasma DEX levels was associated with similar rates of nonsuppression in both depressed and nondepressed patients, thereby reducing the specificity of the DST. Conversely, high DEX levels greater than 13 nmol/liter at 8:00 AM or 4.0 nmol/liter at 4:00 PM were associated with abnormal "suppressibility" in depressed patients, thereby reducing the sensitivity of the test. Controlling for plasma DEX concentrations by selecting a test result that fell within a plasma DEX window at 8:00 AM and 4:00 PM increased the sensitivity and specificity of the DST. Significant differences in plasma DEX between suppressors and nonsuppressors were no longer evident when comparing patients with adequate DEX levels, thus ensuring that cortisol escape reflected HPA axis changes associated with depression and not peripheral mechanisms responsible for the availability of DEX. These results suggest that the clinical utility of the DST would be significantly enhanced by extending the standard 1.0-mg DST and retesting those patients with levels outside the DEX window with a higher or lower dose. The data also indicate that the measurement of plasma DEX is essential to validly interpret DST status and highlight the need to standardize DEX assays to compare DST results between research centers.     

The dexamethasone suppression test in depressed retarded adults: preliminary findings

This study was undertaken to determine the utility of the Dexamethasone Suppression Test (DST) for diagnosing depression in institutionalized mentally retarded persons. Depressed and nondepressed institutionalized mentally retarded persons were given 1 mg dexamethasone for an overnight DST. Serum cortisol concentrations greater than 4 micrograms/dl at both 8:00 AM and 4:00 PM provided discrimination of depressed from nondepressed groups. Also, using the criteria of serum cortisol concentrations greater than 4 micrograms/dl at 8:00 AM and 4:00 PM, at 4:00 PM and 10:00 PM, or at 8:00 AM, 4:00 PM, and 10:00 PM differentiated these groups. These results suggest that the DST may be useful for detecting melancholia among institutionalized retarded persons.     

Dexamethasone suppression test: use of two different dexamethasone doses

The endocrinologic methods used in the dexamethasone suppression test (DST) for depression were examined, by employing two different doses of dexamethasone (0.5 or 1.0 mg) at 11 p.m. Nonsuppression to the 1.0 mg DST (plasma cortisol criterion value of 5 micrograms/dl) was seen in 33% of major depressives and in 15% of schizophrenics. A similar result was obtained with the 0.5 mg DST when 12 micrograms/dl was employed as the plasma cortisol criterion value. Plasma cortisol levels 33 hours postdexamethasone did not distinguish between major depressives and schizophrenics.     

Enhanced cortisol suppression following dexamethasone administration in domestic violence survivors

OBJECTIVE: The authors compared responses of female domestic violence survivors and a matched group of nontraumatized participants to a low-dose (0.5 mg) dexamethasone suppression test (DST). METHOD: Seventy female domestic violence survivors and 14 nontraumatized women matched for age and race were recruited. Participants were assessed for trauma severity, severity of PTSD and depressive symptoms, and DST cortisol response. Of the domestic violence survivors who were DST-compliant, comparisons were made among those with PTSD (N=15), those with PTSD plus depression (N=27), and those with no PTSD or depression diagnosis (N=8) along with the nontraumatized comparison subjects (N=14). RESULTS: Domestic violence survivors with PTSD, regardless of whether or not they had comorbid depression, had significantly lower baseline cortisol levels at 9:00 a.m. than the healthy subjects and trauma survivors with no diagnosis. Survivors with a sole diagnosis of PTSD showed significantly greater cortisol suppression to dexamethasone than did healthy subjects or the group diagnosed with PTSD plus depression. CONCLUSIONS: These findings agree with previous studies showing hypothalamic-pituitary-adrenal (HPA) axis abnormalities in PTSD. The findings suggest that the chronic nature of domestic violence leads to a severe dysregulation of the HPA axis.     

Effects of trauma exposure on the cortisol response to dexamethasone administration in PTSD and major depressive disorder

OBJECTIVE: To evaluate cortisol suppression following 0.5 mg of dexamethasone (DEX) in trauma survivors (N=52) with posttraumatic stress disorder (PTSD), major depressive disorder (MDD), both, or neither disorder, and in subjects never exposed to trauma (N=10), in order to examine interactions between diagnosis and trauma history on cortisol negative feedback inhibition. METHOD: Lifetime trauma exposure and psychiatric diagnoses were assessed and blood samples were obtained at 8:00 a.m. for the determination of baseline cortisol. Participants ingested 0.5 mg of DEX at 11:00 p.m. and blood samples for determination of cortisol and DEX were obtained at 8:00 a.m. the following day. RESULTS: PTSD was associated with enhanced cortisol suppression in response to DEX. Among trauma survivors, the presence of a traumatic event prior to the "focal" trauma had a substantial impact on cortisol suppression in subjects with MDD. Such subjects were more likely to show cortisol alterations similar to those associated with PTSD, whereas subjects with MDD with no prior trauma were more likely to show alterations in the opposite direction, i.e. relative non-suppression. CONCLUSIONS: Cortisol hypersuppression in PTSD appears not to be dependent on the presence of traumatic events prior to the focal trauma. However, prior trauma exposure may affect cortisol suppression in MDD. This finding may have implications for understanding why only some depressed patients show non-suppression on the DST.     

Cortisol suppression index: a further evaluation

The cortisol suppression index (CSI) is the ratio of pre- to postdexamethasone plasma cortisol concentrations. The 8 a.m. CSI was previously found to identify 66% of a sample of psychiatric inpatients with major depression. In the present study, a 4 p.m. CSI identified 71% of psychiatric inpatients with major depression, in contrast to 53% when using DST criteria alone. This finding adds further validation to the CSI. Further studies of the utility of the CSI are suggested to help improve the detection of major depression.     

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.     

Dexamethasone suppression test in schizophrenic patients before and during neuroleptic treatment

The dexamethasone suppression test (DST) was performed in 21 drug-free schizophrenic patients. The patients satisfied DSM-III and Research Diagnostic Criteria for schizophrenia and were in an acute phase of the disease. In 15 of the patients the DST was repeated after about 5 weeks of treatment with neuroleptics. DST compliance was checked by analysis of dexamethasone concentrations in plasma. In the acute phase 71% (at 04 p.m.) of the patients were nonsuppressors. After neuroleptic treatment the frequency of abnormal responders had decreased to 20%. The decrease in nonsuppressors was not due to alteration of the dexamethasone concentration between the two test occasions. Prolactin levels were markedly increased at the second test occasion compared with the first. There were no significant relationships between cortisol levels, cortisol suppression and prolactin levels. The high frequency of nonsuppressors among schizophrenic patients in the acute phase of the disease indicates that acute stress may be a confounding factor in the outcome of DST.     

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.     

Use of saliva cortisol in the dexamethasone suppression test

In a sample of 26 inpatients (15 primary endogenous depressives and a heterogeneous comparison group of 11 psychiatric patients), results of the dexamethasone suppression test (DST) for endogenous depression were compared when cortisol was measured in plasma (total and free) and in saliva. Results showed a close linear relationship among plasma total and free cortisol, plasma total cortisol, and saliva cortisol, and between free plasma and saliva cortisol. A saliva cortisol cutoff point of 70 ng/dl achieved the same sensitivity (67%), specificity (91%), and diagnostic confidence (91%) as the best cutoff scores of plasma total cortisol (5 μ/dl) and plasma free cortisol (0.15 μ/dl). These results suggest that saliva cortisol, which directly reflects the biologically active fraction of cortisol, can be used as a reliable and more practical index in the DST, especially in outpatients.     

Anxiety and the dexamethasone suppression test monitored with saliva

To assess the effect of anxiety on response to the Dexamethasone Suppression Test (DST), cortisol concentrations were determined in patients who had various diagnoses, with anxiety as a secondary characteristic. Saliva was collected before and after venepuncture at 4:05 PM following completion of the Leeds Questionnaire at 3:00 PM. Matrix effects, which caused an initial artefactual decrease in cortisol levels in some saliva samples in patients with high anxiety, could be eliminated by repeated freezing/thawing. There was no significant difference between salivary cortisol concentrations before and after venepuncture, indicating that variability in response to the DST is not a correlate of anxiety and stressful venepuncture. There was no association between anxiety scores and plasma or salivary cortisol values: thus, anxiety is unlikely to be a major contributory cause of nonsuppression of hypercortisolemia in the DST.     

A modified dexamethasone suppression test for endogenous depression

In order to simplify the dexamethasone suppression test (DST), we have administered a lower dosage of dexamethasone (DEX) and shortened the sampling time to a single morning blood sample. DEX (in dosage increments from 0.125 to 1.0 mg, p.o.) was administered at 2300 h to normal volunteers in a double-blind randomized fashion, and blood samples were taken at 0700 h the following morning. While significant cortisol suppression occurred after the 0.375 mg, 0.5 mg, and 1.0 mg doses of DEX, the 0.5 mg dose was the smallest that clearly suppressed cortisol in all eight subjects. This dose then was used to test the feedback sensitivity of the central nervous system (CNS)-pituitary-adrenal axis in endogenously depressed patients. Twenty endogenously depressed patients and 20 normal volunteers were given both the standard 1.0 mg DST, with post-DEX serum cortisol determined at 1500 h, and the simplified 0.5 mg DST, with post-DEX serum cortisol determined at 0700 h. Four patients (20%) and one control (5%) were nonsuppressors after the 1.0 mg DST, and nine patients (45%) and one control (5%) were nonsuppressors after the 0.5 mg DST. In addition, nine patients with major depression (nonendogenous subtype) and 15 patients with panic attacks also were studied using the 0.5 mg DST. Only 2 of these 24 patients (8%) were nonsuppressors. The results suggest that the single-sample 0.5 mg DST is more sensitive than the standard 1.0 mg DST, and the specificity of the modified test appears comparable to the standard form of the test.