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Dexamethasone concentrations and the dexamethasone suppression test in psychiatric disorders.

The dexamethasone suppression test (DST) has been widely used in psychiatry as a laboratory aid for the diagnosis of endogenous depression; failure to suppress serum cortisol levels is interpreted as confirming a clinical diagnosis of endogenous depression. We found that serum dexamethasone concentrations in this test vary widely and are determinants of the DST response: non-suppression of serum cortisol levels is associated with low serum dexamethasone concentrations, and suppression is associated with high concentrations.

Adjustment Disorders↗

The clinical diagnostic value of dexamethasone suppression test in depressive illness.

Dexamethasone suppression test (DST) was done for Chinese melancholics. The overall sensitivity of DST is 41.0%, and its specificity is 85%. The prevalence of abnormal DST is higher in inpatient melancholics (66.7%) than in outpatient melancholics (7.1%). Three schizophrenic patients who had abnormal DST were found to have severe degree of depression and impaired social function. The clinical diagnostic value of DST for severely impaired inpatient was tested. 35.7% of primary depressives (28 cases) had abnormal DST. 50% of secondary depressives (26 cases) had abnormal DST. 11 cases (50%) of 22 initially admitted, undiagnosed cases were found to have abnormal DST. 5 (45.5%) of these 11 cases were of primary depressives. 6 (54.5%) of these were of secondary depressives. DST was found to be of limited value in differential diagnosis for inpatient undiagnosed cases. Yet, DST could be a powerful research tool in psychopathology.

Asia↗

The dexamethasone suppression test in psychotic disorders.

Dexamethasone suppression tests were given to 69 consecutively admitted psychiatric patients. Nonsuppression rates for depression with or without melancholia and for schizophrenia were similar to those previously reported, but for mania and other psychoses the frequencies were higher than expected.

Adolescent↗

The dexamethasone suppression test during bereavement.

The dexamethasone suppression test (DST) was given to 13 elderly grieving subjects having a major depressive disorder. Forty-six per cent had some predisposition for depression. All had a post-DST, 4:00 p.m. serum cortisol below 5 micrograms/dl, but these cortisols correlated with Hamilton Depression scores (r = .59, p less than .05).

Depressive Disorder↗

Seasonal variations in the dexamethasone suppression test.

One hundred and fifty-six patients from Epsom (U.K.) and Brussels, all suffering from major depressive disorder, were tested on the dexamethasone suppression test. Post-dexamethasone cortisol concentration in the plasma was found to be much lower in the winter months (November to February) than in the rest of the year.

Adult↗

[Dexamethasone suppression test in psychiatric pathology].

The dexamethasone suppression test (DST) has been used in psychiatric pathology for about 10 years. Carroll et al. consider this test to be specific of endogenous depression. According to these, and many other authors, approximately 55% of patients with endogenous depression show a positive response to the test, whereas a positive response is observed in only 4% of normal subjects or patients with psychiatric disorders other than major depressive disorders. The DST was performed in 162 psychiatric inpatients (5 with organic disease, 28 with schizophrenic disorders, 17 with major affective disorders, 5 with obsessive compulsive disorders, 103 with dysthymic disorders and 4 unclassified). Dexamethasone (1 mg) was administered orally at 11 p.m., and plasma cortisol concentration was measured the following day at 16 p.m. Response to the test was positive in 53% of patients with major affective disorders, 25% of those with schizophrenic disorders, 60% with obsessive compulsive disorders and 18% with dysthymic disorders. There was no statistical difference in the results according to age, sex ratio, family history of depression or duration of the disorders. Only two variables were close to the P less than 0.05 level of statistical significance: severity of the disorders and early morning awakening. DST sensitivity, therefore, would appear to be about 50% in major affective disorders, but this test is not specific as it may also be positive in other psychiatric disorders. A positive dexamethasone suppression test may be regarded as a sign of severity of psychiatric disorders.

Depressive Disorder↗

How to evaluate a diagnostic marker test. Lessons from the rise and fall of dexamethasone suppression test.

To understand why the dexamethasone suppression test (DST) for the diagnosis of depression became widely accepted and later rejected, we reviewed the sequence of publications in the DST literature. To evaluate the events, we developed and applied concepts of a five-phase process that can be used to assess the clinical utility of diagnostic marker tests. The review showed that when the DST was introduced into the clinical arena, the initial and final two phases of testing (I, IV, and V) had not been adequately conducted. When these phases of testing were suitably checked many years later, the Phase I studies (exploring basic mechanics of test procedures) showed that dexamethasone had variable bioavailability and that the cortisol assay procedure was unreliable. The Phase IV and V studies (examining test results in groups with suitably broad spectrums of cases and controls) showed that the test did not differentiate depression from most pertinent comorbid conditions. Beyond application to the specific problems of the DST, the proposed five phases of development and evaluation for diagnostic marker tests can be used to plan suitable research and avoid similar problems in the future.

Depression↗

The dexamethasone suppression test and depression. Approaches to the use of a laboratory test in psychiatry.

The dexamethasone suppression test has undergone unprecedented study among the biologic tests proposed for clinical use in psychiatry. Since the 1970s, its study has involved hundreds of reports and thousands of patients. Although important technical aspects of the test appear to be well accepted and validated, additional information is needed regarding the pharmacokinetics of dexamethasone. Marked interindividual differences in plasma dexamethasone suggest that performance of the test might be improved by factoring dexamethasone levels into test interpretations. There also may be advantages to the development of a modified test involving other exogenous and index steroids, such as monitoring corticosterone levels. Although it is too early to determine how ROC analysis will alter the clinical application of the test, some implications for methodology and data presentation are already clear. First, because the test is a diagnostic system with nonbinary outcomes, ROC analysis can augment traditional performance indices such as sensitivity, specificity, and positive predictive power. Second, ROC analysis will improve comparisons between the studies of different research groups and will help assess innovations in the application of the test. Third, ROC analytic techniques permit appropriate planning of sample size given estimates of the expected values of AUC that would be obtained from the studies. ROC theory thus promises to play an increasingly important role in the evaluation and future improvement of the dexamethasone suppression test and other biologic markers in clinical psychiatry. In conclusion, neither uncritical enthusiasm nor excessive skepticism is warranted about the use of the dexamethasone suppression test in clinical psychiatry. Evidence to date should encourage investigators to pursue refinement of the test or other tests of hypothalemic-pituitary-adrenal functioning to increase their accuracy and clinical utility.

Adrenocorticotropic Hormone↗

The dexamethasone suppression test and depression. Approaches to the use of a laboratory test in psychiatry.

The dexamethasone suppression test has undergone unprecedented study among the biologic tests proposed for clinical use in psychiatry. Since the 1970s, its study has involved hundreds of reports and thousands of patients. Although important technical aspects of the test appear to be well accepted and validated, additional information is needed regarding the pharmacokinetics of dexamethasone. Marked interindividual differences in plasma dexamethasone suggest that performance of the test might be improved by factoring dexamethasone levels into test interpretations. There also may be advantages to the development of a modified test involving other exogenous and index steroids, such as monitoring corticosterone levels. Although it is too early to determine how ROC analysis will alter the clinical application of the test, some implications for methodology and data presentation are already clear. First, because the test is a diagnostic system with nonbinary outcomes, ROC analysis can augment traditional performance indices such as sensitivity, specificity, and positive predictive power. Second, ROC analysis will improve comparisons between the studies of different research groups and will help assess innovations in the application of the test. Third, ROC analytic techniques permit appropriate planning of sample size given estimates of the expected values of AUC that would be obtained from the studies. ROC theory thus promises to play an increasingly important role in the evaluation and future improvement of the dexamethasone suppression test and other biologic markers in clinical psychiatry. In conclusion, neither uncritical enthusiasm nor excessive skepticism is warranted about the use of the dexamethasone suppression test in clinical psychiatry. Evidence to date should encourage investigators to pursue refinement of the test or other tests of hypothalamic-pituitary-adrenal functioning to increase their accuracy and clinical utility.

Adrenocorticotropic Hormone↗

[The relation between results of thyrotropin-releasing hormone stimulation tests (TRH-ST), dexamethasone suppression test (DST) and urinary MHPG. SO4 excretion in depressive patients].

Thyrotropin-releasing hormone stimulation test (TRH-ST) was performed in 68 depressive patients, 25 normal subjects and 4 schizophrenics. Dexamethasone suppression test (DST) and urinary MHPG. SO4 determination was also administered in part of this depressive patients. Our data show that some of depressive patients suffered from the dysfunction of hypothalamic-pituitary-thyroid axis, and this dysfunction was not related to the dysfunction of hypothalamic-pituitary-adrenal axis and urinary MHPG. SO4 excretion. A blunted TSH response to TRH was a "STATE MARKER" for some of depressive patients.

Adult↗

Low level of glucocorticoid receptor messenger ribonucleic acid in pituitary adenomas manifesting Cushing's disease with resistance to a high dose-dexamethasone suppression test.

OBJECTIVES: The overnight 8-mg dexamethasone suppression test is often used to differentiate Cushing's disease, due to an oversecretion of ACTH from the pituitary gland, from other kinds of Cushing's syndrome. However, a few patients with ACTH-producing pituitary adenoma show no suppression of plasma cortisol after the administration of 8 mg of dexamethasone. To clarify the relationship between the level of glucocorticoid receptor (GR) in the pituitary adenoma and the sensitivity to dexamethasone in Cushing's disease, we thus examined the levels of GR alpha and GR beta mRNAs in the pituitary adenomas in six patients who were proven at surgery to have pituitary ACTH-producing adenomas. MATERIALS: Total RNA was extracted from six pituitary adenomas and pituitary tissue adjacent to one of the adenomas, and the mRNA levels of GR alpha, GR beta, pro-opiomelanocortin (POMC) and beta-actin in these samples were sampled by quantitative RT-PCR. RESULTS: The GR alpha mRNA levels in the adenomas from the two patients who showed no response to the 8-mg dexamethasone suppression test were significantly lower than those in the adenomas of four patients who showed suppression. The GR beta mRNA level was much lower than that of GR alpha mRNA but not significantly different among the six adenomas. CONCLUSIONS: These results suggest strongly that decreased expression of GR alpha in pituitary adenomas may be the major reason for the marked insensitivity to the 8-mg dexamethasone suppression test observed in two patients with Cushing's disease.

Actins↗

Dexamethasone metabolism in dexamethasone suppression test suppressors and nonsuppressors.

BACKGROUND: Variable dexamethasone kinetics is a possible confound in the dexamethasone suppression test. Modifications to include dexamethasone plasma levels and specific dexamethasone "windows" have been proposed. Our study aims to validate our proposed dexamethasone windows in an independent sample of 121 subjects. METHODS: We performed dexamethasone suppression tests in 162 subjects with mixed psychiatric diagnoses. Dexamethasone levels and beta-phase half-life of dexamethasone were computed for suppressors and nonsuppressors. RESULTS: Dexamethasone levels were lower in nonsuppressors than in suppressors. Dexamethasone levels correlated inversely with cortisol levels in the total sample, but were nonsignificant or weakly associated in those samples restricted to the windows. The beta-phase half-life of dexamethasone was shorter in nonsuppressors. The dexamethasone windows were validated at 3:00 PM and 10:00 PM. We propose 4.0 ng/mL as a revised upper limit of the 8:00 AM dexamethasone window. CONCLUSIONS: The plasma dexamethasone level is confirmed as a confound in the dexamethasone suppression test through more rapid dexamethasone clearance in nonsuppressors. Application of dexamethasone windows will reduce this source of test variance.

Adrenal Cortex Function Tests↗

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.

Adult↗

Dexamethasone suppression test and TRH test in endogenous depression.

Dexamethasone suppression test (DST) and thyrotropin releasing hormone (TRH) stimulation test were performed in 34 patients with endogenous depression. Compared with 33 psychiatric controls (limit of discrimination for serum cortisol of 275 nmol/l = 10 micrograms/100 ml) the specificity of the DST was 91% and the sensitivity was 65%. Compared with 24 healthy subjects the sensitivity of the TRH test was 24%, and the combined sensitivity for the DST and the TRH test was 76%. In contrast to the TRH test the DST showed a significant relationship (r = 0.54, P less than 0.01) to the Hamilton Rating Score. Repeating the tests after clinical recovery parallel changes of the two tests were found in 14 of 19 patients with abnormal DST in the depressed phase. In the remaining five patients the DST normalized, while the TRH test remained unchanged. It is suggested that both the apparent higher diagnostic sensitivity and the higher rate of normalization after clinical recovery of the DST is due to the dependency of the severity of depression.

Adolescent↗

Circulating concentration of dexamethasone in healthy dogs, dogs with hyperadrenocorticism, and dogs with nonadrenal illness during dexamethasone suppression testing.

Concentration of dexamethasone was determined in plasma or serum samples from dogs after i.v. administration of a low dose (0.01 mg/kg of body weight) or high dose (0.1 mg/kg) of dexamethasone. On the basis of history, clinical signs of disease, and degree of cortisol suppression in response to dexamethasone, dogs were assigned to these groups: healthy dogs, dogs with nonadrenal illness, and dogs with hyperadrenocorticism. Four hours after administration of the low dose of dexamethasone, concentration of the steroid was reduced (P < 0.05) in dogs with hyperadrenocorticism, compared with healthy dogs, but not compared with values from dogs with nonadrenal illness. By 8 hours after dexamethasone administration, values were similar across groups. Dexamethasone concentration 4 and 8 hours after high-dose administration was similar between healthy dogs and dogs with hyperadrenocorticism. Concentration of dexamethasone 4 and 8 hours after its administration overlapped after the 2 doses. For example, in 11 of 66 dogs from all groups, concentration measured 4 hours after the low dose was greater than the minimal concentration determined in the 18 dogs given the high dose. These data indicate that dexamethasone metabolism may be altered in dogs with hyperadrenocorticism, and that individuals may have appreciable variability in dexamethasone clearance. Such variability provides a possible explanation for false-positive and false-negative results associated with dexamethasone suppression testing in dogs.

Adrenocortical Hyperfunction↗

The dexamethasone suppression test in acute mania.

The dexamethasone suppression test was administered to 40 newly admitted manic patients. Twenty-four patients (60%) had abnormal escape from suppression. There was no correlation of DST results with sex, age, age of onset, family history of affective disorder, psychosis during index episode, or duration of hospitalization. DST non-suppressors were significantly more likely than suppressors to be discharged on lithium alone.

Adult↗

The effect of benzodiazepine withdrawal on the dexamethasone suppression test.

Recent studies of the dexamethasone suppression test (DST) suggest lack of specificity for the diagnosis of melancholia. An earlier study showed that high doses of benzodiazepines lead to DST normalisation in depressed patients. This present study examines the effect of benzodiazepine withdrawal on the DST in a middle aged, non-depressed group. Forty-eight volunteers from a double blind placebo-controlled trial of triazolam 0.5 mg and lormetazepam 2 mg all suppressed normally when given the DST on the sixth day of withdrawal following 25 days of drug.

Adult↗

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 micrograms/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 micrograms/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.

Adult↗