The dexamethasone suppression test: importance of dexamethasone concentrations

Plasma dexamethasone concentrations and cortisol response to dexamethasone were measured in 29 normal healthy volunteers, 23 depressed patients, and 10 patients with anorexia nervosa at 4:00 PM postdexamethasone. In each of the 3 groups, nonsuppressors had lower dexamethasone concentrations than suppressors. Of the subjects with plasma dexamethasone at or below 0.7 ng/ml, a significantly higher proportion (48%) were nonsuppressors compared to the proportion above 0.7 ng/ml (14%), all of whom were patients. Plasma dexamethasone concentrations in a subgroup of depressed nonsuppressors were high (mean 1.35 ng/ml), whereas the remainder were low (0.42 ng/ml) and were similar to the normal nonsuppressors (0.35 ng/ml), suggesting different mechanisms for nonsuppression in the subgroups. Plasma dexamethasone concentrations were similar in nonendogenous and endogenous depressives, in men and women, and in medicated and drug-free patients. None of the variables of age, weight, history of weight loss, Hamilton depression rating score, predexamethasone cortisol, or postdexamethasone cortisol were significantly correlated with plasma dexamethasone, except for body weight and a history of weight loss in the depressed group only. Mean plasma dexamethasone concentrations increased significantly from week 1 to week 2 in 7 depressed patients, whereas plasma cortisol decreased; however, the relationship between dexamethasone and cortisol varied considerably for individual patients.     

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 dexamethasone suppression test in relation to symptomatology: preliminary findings controlling for serum dexamethasone concentrations

A diagnostically heterogeneous sample of psychiatric inpatients (n = 52) was administered the 1 mg dexamethasone suppression test (DST) shortly after hospital admission. Each was also assessed using the Hamilton Rating Scale for Depression (HRSD) and selected items of the Present State Examination (PSE) representing psychomotor retardation and anxiety. A potent determinant of postdexamethasone serum cortisol concentrations was found to be the level of serum dexamethasone concentration achieved following the oral dose. No relationship was found between postdexamethasone cortisol concentration and the scores on either the HRSD or an anxiety scale derived from selected PSE items. However, symptoms of psychomotor retardation were significantly related to postdexamethasone serum cortisol concentration, particularly when the serum dexamethasone concentrations were taken into account. It may be that DST nonsuppression in psychiatric patients is in part a reflection of the presence of psychomotor retardation, a phenomenon that cuts across diagnostic categories.     

The effect of stress on the dexamethasone suppression test

The dexamethasone suppression test (DST) was studied in 40 presurgical subjects and 20 controls. Cortisol plasma concentrations were measured before and after a nocturnal dose of 1 mg dexamethasone. Nineteen of the 40 patients (47.5%) failed to show a suppression of plasma cortisol after dexamethasone. Nonsuppression on the DST was associated with a significantly higher baseline plasma cortisol concentration. Another putative indicator of emotional stress, the level of acute anxiety, was also studied. There was a significant difference in the level of acute anxiety among suppressors, nonsuppressors, and controls--the level of anxiety in nonsuppressors being significantly higher than in controls. It is concluded that stress associated with a physical danger can be a cause of nonsuppression on the DST.     

The effect of anticonvulsants on the dexamethasone suppression test

Rates of non-suppression on the DST were compared in 19 psychiatric inpatients and anticonvulsants and 38 psychiatric inpatients not on anticonvulsants who were matched for age, sex, and diagnosis. Patients on anticonvulsants had a significantly higher rate of nonsuppression.     

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.     

The dexamethasone suppression test in the puerperium

A consecutive series of 45 women admitted to an obstetric unit were given the dexamethasone suppression test (DST) on days three to five post-partum, 82% being abnormal. The likelihood of an abnormal DST on one or both occasions increased linearly across the days of testing. Subjects completed the Beck self-report depression measure and the General Health Questionnaire at baseline and at six weeks. Baseline cortisol levels were not associated with baseline morbidity as assessed on the questionnaires and were not predictive of morbidity assessed at the six-week follow-up. It is concluded that the immediate post-partum period be included as a false-positive influence on the DST.     

The dexamethasone suppression test in bulimia

Nineteen (35%) of 55 women with bulimia failed to exhibit cortisol suppression after dexamethasone administration. Although there was no statistically significant difference between suppressors and nonsuppressors on any clinical variable, there was a higher frequency of major depression among nonsuppressors.     

The dexamethasone suppression test in depression

The DST does appear to be abnormal in a sizable subgroup of patients with major depressive disorder, particularly those characterized as "endogenomorphic" or "melancholic." At present the available data seem clear in indicating this abnormality is significantly less common in normal controls and patients without affective illness. The test holds considerable promise in helping to define new subgroups of depressed individuals for further study. In terms of its ability to predict treatment response to an adequate course of somatic therapy, the test does not appear to be of value, and the clinician should still be guided by the clinical presentation and history in initiating or choosing between various somatic treatments. With further attention to issues of diagnosis and DST methodology this strategy could help in addressing questions of differential diagnosis in potential "variants" of affective illness and providing a better understanding of the pathophysiology of depression.     

The dexamethasone suppression test in dementia

The dexamethasone suppression test (DST) was performed on 13 patients with multi-infarct dementia (MID), 5 patients with primary degenerative dementia (PDD) and 18 elderly controls. Abnormal lack of suppression was found in 7 demented patients (3 with PDD, 1 mild and 2 severe, and 4 with MID, 1 mild and 3 severe), and in 2 of the controls. Only one demented patient was depressed. The value of DST in the differential diagnosis of dementia from the major depressive disorders is discussed.

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Sommario Il test di soppressione al desametazone (DST) è stato applicato a 13 pazienti con demenza multi-infartuale (MID), a 5 pazienti affetti da demenza degenerativa primaria (PDD), e a 18 controlli (anziani). Una nonsoppressione è stata ritrovata in 7 pazienti affetti da demenza (3 di tipo PDD, in 1 caso di grado moderato ed in 2 casi severo, e 4 di tipo MID, in 1 caso moderato ed in 3 casi severo). Solo uno dei pazienti affetti da demenza si presentava contemporaneamente affetto da depressione. Viene discussa l’utilità del DST nel giudizio diagnostico-differenziale tra la demenza ed il disturbo depressivo maggiore.

     

The dexamethasone suppression test in the clinical setting

The authors administered the dexamethasone suppression test (DST) to 47 inpatients on a clinical, nonresearch psychiatric unit who had been diagnosed according to DSM-III. Of the 30 patients with major depression, 23 (77%) exhibited nonsuppression (serum cortisol concentrations greater than 5 micrograms/dl); only 1 of the 17 patients with other diagnoses and depressive symptoms exhibited nonsuppression. There was no difference in the rate of nonsuppression between the patients with subgroups of major depression, but those with major depression and psychosis had significantly higher postdexamethasone cortisol levels than those with major depression with and without melancholia and those with diagnoses other than major depression.     

The dexamethasone suppression test in panic disorder

The dexamethasone suppression test (DST) was performed in 35 patients with panic disorder and 21 normal control subjects. Non-suppression of plasma cortisol was determined as 4 micrograms/dl and using this figure 29% of panic patients and 9.5% of controls were non-suppressors. There was no significant difference in the number of suppressors and non-suppressors between patient and control groups (chi 2 = 1.81; P greater than 0.05). Both pre- and postdexamethasone cortisol concentrations were significantly different between the two groups possible indicating a cortisol hypersecretion in some panic patients.     

The low-dose dexamethasone suppression test in fibromyalgia

OBJECTIVE: Fibromyalgia syndrome (FMS) has been associated with decreased cortisol secretion. Patients with posttraumatic stress disorder (PTSD) exhibit similar hypocortisolism in the context of increased negative feedback sensitivity of the hypothalamic-pituitary-adrenal (HPA) axis. Because trauma and PTSD have been associated with fibromyalgia, we evaluated whether patients with fibromyalgia demonstrate increased HPA feedback sensitivity. METHOD: Baseline blood samples were obtained at 0800 h, and 0.5 mg of dexamethasone was administered to 15 female patients with FMS and 20 normal controls at 2300 h. Adrenocorticotropin (ACTH), cortisol, and dexamethasone levels were measured at 0800 h after dexamethasone intake. RESULTS: There were no group differences in mean ACTH or cortisol levels or in ACTH/cortisol ratio at baseline. After dexamethasone intake, patients with FMS exhibited more pronounced suppression of cortisol but not of ACTH, as well as increased ACTH/cortisol ratios compared with controls. Percent cortisol suppression was associated with pain and fatigue, while ACTH/cortisol ratio and dexamethasone availability were associated with stress and anxiety measures. CONCLUSION: Our results suggest increased sensitivity to glucocorticoid feedback, manifested at the adrenal level, in FMS.     

The dexamethasone suppression test in healthy controls

We have summarized the results of 53 studies which examined the dexamethasone suppression test in normal controls. Only 3.6% of 687 0800 hr postdexamethasone cortisol levels were above 5 micrograms/dl. Corresponding figures for 1600 hr and 2300 hr cortisol levels were 7.4% (85/1144) and 6.3% (28/434), respectively. Neither the type of assay (competitive protein binding or radioimmunoassay) nor mean/median age of the subjects was associated with non-suppression rates.     

The dexamethasone suppression test in acute grief

Nineteen recently widowed women and men were given diagnostic interviews, psychometric evaluations, and dexamethasone suppression tests (DSTs). While 58% of the subjects (N = 11) met Research Diagnostic Criteria for depression, only 16% (N = 3) were nonsuppressors on the DST. In this population, nonsuppression was related more to levels of anxiety than to depression.