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.     

The dexamethasone suppression test for Japanese with eating disorders

A one-mg oral overnight dexamethasone suppression test (DST) was conducted on 22 inpatients with eating disorders. To confirm that the dexamethasone tablets had been ingested, we measured the plasma concentrations of dexamethasone the next morning (at 0900 hr after DST). The diagnosis of anorexia nervosa and bulimia was made according to the criteria for DSM-III, respectively. Of the 22 patients with eating disorders, 16 satisfied the criteria for anorexia nervosa and 6 for bulimia. The DST was carried out within 2 weeks of hospitalization on each patient. The subjects were given 1 mg of dexamethasone in the evening (at 2300 hr) and blood samples were collected the following day (at 0900, 1600 and 2100 hr, respectively). The plasma cortisol and dexamethasone levels were concurrently determined by RIA. The criterion for non-suppression was a failure to suppress the plasma cortisol levels below 5.0 micrograms/dl in any one of the three samples. All but one patient with bulimia had ingested the dexamethasone. Thirteen (62%) of 21 patients with eating disorders were nonsuppressors. We found a significant positive correlation between the plasma cortisol levels at 1600 hr or 2100 hr and a decrease in ideal body weight (n = 16, r = 0.613, p less than 0.05; r = 0.75, p less than 0.01, respectively) and a significant inverse relationship between the plasma dexamethasone levels at 0900 hr and the plasma cortisol levels at 1600 hr was recognized (n = 21, r = 0.631, p less than 0.01). These results suggest that the blood dexamethasone levels as well as body weight might contribute to the abnormalities of DST seen in patients with eating disorders.     

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.     

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.     

Altered plasma dexamethasone and cortisol suppressibility in patients with panic disorders

Some abnormalities in the hypothalamic-pituitary-adrenal (HPA) axis in patients with panic disorders were recently reported. The possibility that the disposition of dexamethasone, which has been reported to influence the Dexamethasone Suppression Test (DST), might be altered in this subgroup of patients has not, as yet, been reported. We report that 4:00 PM dexamethasone plasma concentrations following a 1-mg oral DST were significantly (p less than 0.01) lower in 23 patients with panic disorders (0.49 +/- 0.44 ng/ml) compared to 52 normal control subjects (1.09 +/- 0.64 ng/ml). This is in addition to the significantly higher (p less than 0.05) 4:00 PM postdexamethasone cortisol values per nanogram per milliliter of dexamethasone in the panic disorder patients compared to normal controls (17.7 +/- 29.6 versus 5.0 +/- 11.2 micrograms/dl). The mean percent suppression of cortisol from baseline in panic disorder was normal despite one-half the dexamethasone concentrations in these subjects. The cortisol suppression versus dexamethasone concentration curve was also shifted lower (greater fraction of cortisol suppression) and to the left (toward lower dexamethasone concentrations). These results further suggest that the HPA system is indeed altered in panic disorders, but in a manner that is not readily apparent from the DST alone.     

4 p.m. baseline cortisol level as a predictor of DST results in depression

To assess the relationship of baseline cortisol to the 1 mg dexamethasone suppression test (DST), 4 p.m. baseline and 4 p.m. postdexamethasone blood samples were drawn on 52 consecutive depressed outpatients. Baseline cortisol correlated significantly with post-DST values, and baseline levels above 15 micrograms/dl predicted DST nonsuppression with 90.4% accuracy. These data lend some support to the usefulness of baseline cortisol determination in depressed outpatients in whom a full DST may be difficult.     

Low-dose (0.5 mg) DST in manic and major depressive episodes: in relation to the severity of symptoms]

BACKGROUND: Results of previous studies and our own preliminary study suggest that the dexamethasone suppression test (DST) using 1 mg of dexamethasone might result in lower sensitivity in Japanese and Asian people with major depressive episodes, when compared to Caucasian people. We investigated the clinical utility of low-dose (0.5 mg) DST in Japanese patients with manic or major depressive episodes. METHODS: Low-dose (0.5 mg) DST was performed 276 times in 122 patients with bipolar disorder (manic or depressed) or major depressive disorder who visited the Department of Psychiatry of Osaka Prefectural General Hospital. After strict exclusion criteria were applied, the remaining 225 test results in 98 patients were analyzed. The severity of symptoms was estimated in accordance with the DSM-IV, namely, severe, moderate, mild, or in remission. A 0.5 mg dose of dexamethasone was administered orally at 20:30, and blood samples were taken the following day at 8:00 (9:00 in outpatients) and 13:00. Serum cortisol levels were measured by radioimmunoassay. Nonsuppression was considered to have occurred when at least one of the postdexamethasone cortisol values was 4.0 micrograms/dl or over. RESULTS: In manic episodes, the postdexamethasone cortisol levels were significantly correlated with the severity of the symptoms, and the postdexamethasone cortisol levels in patients with severe symptoms were significantly higher than in those in remission. The rates of nonsuppression in manic episodes with severe, moderate, mild symptoms, and in remission, were 7/8 (88%), 1/4 (25%), 1/3 (33%) and 2/7 (29%), respectively. In major depressive episodes, the postdexamethasone cortisol levels were significantly correlated with the severity of the symptoms. The rates of nonsuppression in major depressive episodes with each grading of severity were 47/58 (81%), 28/52 (54%), 14/40 (35%), 10/53 (19%), respectively. In major depressive episodes, patients aged 50 or over showed significantly higher postdexamethasone cortisol levels than patients aged under 50. In particular, patients aged between 30 and 49 showed significantly lower postdexamethasone cortisol levels than those in the other age groups. There was no significant difference between male and female patients (two-way ANOVA), but female patients with severe depressive symptoms showed significantly higher postdexamethasone cortisol levels than male patients with severe symptoms. There was no significant difference between bipolar and unipolar patients with major depressive episodes (two-way ANOVA), with the exception that the rate of nonsuppression in remission in bipolar patients was significantly different than that in unipolar patients (9/33 (27%), 1/20 (5%), respectively). Among major depressive disorders, the rate of nonsuppression was highest in those with psychotic features, followed by those with melancholia, and then by those without melancholia. Re-evaluating the cut-off point discriminating nonsuppression from suppression, it was suggested that the optimal cut-off point might differ according to age and gender, but a fixed cut-off point at 4.0 micrograms/dl was considered to be appropriate. The postdexamethasone cortisol levels of samples obtained at 13:00 were more sensitive than those obtained at 8:00 or 9:00. The exclusion criteria and the clinical meanings of DST were discussed. CONCLUSIONS: Along with the previous studies indicating a low rate of nonsuppression in Japanese and other Asians using a standard 1 mg DST, our results suggest that low-dose (0.5 mg) DST is better in Japanese, and probably in most Asian patients, than 1 mg DST.     

Cortisol suppression per nanogram per milliliter of plasma dexamethasone in depressive and normal subjects

It has been suggested that dexamethasone pharmacokinetics may affect cortisol suppression during the Dexamethasone Suppression Test (DST). In depressed patients the cortisol response has been shown to negatively correlate with dexamethasone plasma concentrations, which also influence the sensitivity and specificity of the DST. These findings have been interpreted as weakening the utility of the DST. However, the analysis of pre- and post-1 mg DST cortisol concentrations corrected for plasma dexamethasone concentrations suggest that compared with normals (n = 52), patients with major depressive disorder (MDD) as a group (n = 71) had less suppressibility of cortisol to the same plasma dexamethasone concentrations. Moreover, when the MDD patients were evaluated based on DST status, the suppressors had cortisol/dexamethasone ratios (micrograms/dl of cortisol per ng/ml of plasma dexamethasone) similar to the normal controls, whereas the nonsuppressors had ratios that were significantly higher. These data suggest that DST non-suppression, as well as sensitivity and specificity of the DST in depression, is not only attributable to altered dexamethasone disposition, but indeed, there is a genuine reduced sensitivity of cortisol to dexamethasone that still points to an abnormality of the delayed feedback mechanism of the hypothalamic-pituitary-adrenal system in some depressed patients.     

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.     

Depression, natural killer cell activity, and cortisol secretion

Natural killer (NK) cell activity was evaluated in 34 ambulatory patients with Major Depressive Disorder (MDD) and 21 healthy controls. No mean differences between the groups were found. However, female depressives (n = 19) exhibited higher NK activity than female controls (n = 14). The relationship between cortisol secretion and NK activity was examined using an integrated cortisol value derived from multiple blood samples taken between 1:00 and 4:00 PM. This comprehensive assessment of cortisol secretion circumvents spurious "single stick" cortisol values and provides a more accurate determination of hypercortisolemia than the dexamethasone suppression test. NK activity in depressives with cortisol hypersecretion (greater than 11 micrograms/dl) (n = 7) was no different than NK activity in depressives and controls with normal cortisol secretion. Furthermore, there was no correlation between cortisol secretion and NK activity in any of the groups. These results indicate that decreased NK activity is not a consistent finding in MDD and cannot be predicted by the presence of hypercortisolemia in these patients.     

Baseline plasma cortisol and dexamethasone test in unselected psychiatric inpatients

The plasma cortisol (PC) level at 08.00 a.m. was assessed in 250 unselected psychiatric inpatients suffering from various disorders, assorted in 8 diagnostic groups. Endogenously depressive patients showed a significantly higher rate of cortisol hypersecretion (PC greater than 560 nmol/l = 20 micrograms/dl) than the neurotically or reactively depressed patients and than schizophrenics or paranoid psychotics. The PC level after the midnight dose of 1 mg dexamethasone was examined in 125 patients at 08.00 a.m. (group I) and in 125 patients at 04.00 p.m. (group II). There was no statistical difference in the rate of dexamethasone test (DST) nonsuppressors (PC greater than 140 nmol/l = 5 micrograms/dl) in the separate diagnostic groups between group I and II, but in the postdexamethasone blood samples at 04.00 p.m., significantly more DST nonsuppressors were detected than in the samples at 08.00 a.m. in the total number of all patients, regardless of their diagnosis. DST nonsuppressors were found in all of our diagnostic groups with the exception of manic syndrome, and their various rates will be discussed and compared with the results of previous studies. The DST shows a high sensitivity in endogenous depression, but its diagnostic value is limited as a result of its relative lack of specificity.     

Plasma dexamethasone concentrations and differential suppression response of cortisol and corticosterone in depressives and controls

After a dexamethasone suppression test (DST), cortisol, corticosterone, and the test substance were determined by a direct radioimmunoassay in 42 samples obtained from 22 depressed patients and 8 controls. The DST results of both glucocorticoids agreed in most of the tests. In all seven cases with elevated but not definitely abnormal post-DST (1600 hr) cortisol levels (transitional range 30-50 ng/ml) the concurrent determination of corticosterone indicated that this corticosteroid may serve as a potent additional discriminator. Dexamethasone plasma concentrations at 1600 hr after a 1-mg test dose of dexamethasone at 2300 hr were significantly (p less than 0.01) lower in cortisol and corticosterone nonsuppressors than in suppressors. Since these data were obtained 17 hr after ingestion of dexamethasone (half-life 3.5-5 hr) any conclusions about an inverse correlation between dexamethasone and corticosteroid plasma concentrations would be speculative. However, the dexamethasone pharmacokinetics might be an important variable and may contribute to some of the recent uncertainty about the DST.     

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%).     

Plasma cortisol determination for the dexamethasone suppression test. Comparison of competitive protein-binding and commercial radioimmunoassay methods

Quality control serum samples and postdexamethasone plasma pools were used to compare 16 commercial cortisol radioimmunoassay kits with the competitive protein-binding assay for plasma glucocorticoids that we used to standardize the dexamethasone suppression test (DST). Thirteen radioimmunoassays gave higher criterion values for the DST than those established using the competitive protein-binding assay. The range of radioimmunoassay criterion values was 4.34 to 8.70 mu mg/dL. Possible explanations are given for these findings, and their importance to the clinical utility of the DST are emphasized. Each laboratory should validate its own criterion cortisol value for depression based on local data, including appropriate control groups.     

Results of the 8 a.m. dexamethasone suppression test constitute a suitable tool for confirming the diagnosis of melancholia. A test unaffected by the variations in the bioavailability of dexamethasone

This prospective study was conducted in order (1) to examine which postdexamethasone cortisol value i.e., 8 a.m., 4 p.m. or peak cortisol - is most suitable as a laboratory test to help confirm the diagnosis of melancholia and (2) to investigate the influence of the dexamethasone levels in the results of the dexamethasone suppression test (DST). To this end we administered the DST to 48 controls and 115 depressed inpatients categorized according to DSM-III. The 8 a.m. and 4 p.m. dexamethasone levels were determined in 100 subjects. We found that an 8 a.m. postdexamethasone cortisol value greater than or equal to 3.5 micrograms/dl was of the most significant diagnostic value in order to separate melancholia from normal controls and/or minor depressives. The 8 a.m. and 4 p.m. dexamethasone values did not differ between healthy controls, minor and severely depressed patients. Although cortisol nonsuppressors exhibited significantly lower dexamethasone values, the predictive value of the DST for melancholia was not affected by the large variation in the bioavailability of dexamethasone.     

Occurrence of high concentrations of postdexamethasone cortisol in elderly psychiatric inpatients

The authors retrospectively studied 161 psychiatric inpatients who had received a dexamethasone suppression test (DST). The majority of the patients were over 60 years old, female, and had concurrent chronic medical illnesses. Age was significantly correlated with log-transformed postdexamethasone cortisol concentrations in the 118 nondemented patients with major depression. Four p.m. cortisol concentrations greater than 15 micrograms/dl occurred in 15 patients. All were over 60 years old; all but one had major depressive disorder (MDD); and five had dementia plus MDD. In the same population, a 5 micrograms/dl criterion did not distinguish MDD from non-MDD patients. The results support the existence of a clinically relevant age effect on the DST in patients with MDD. Elderly depressed patients with markedly elevated cortisol concentrations occur frequently, and warrant further clinical and pathophysiological study.     

The Dexamethasone Suppression Test for Japanese with Eating Disorders

Abstract: A one-mg oral overnight dexamethasone suppression test (DST) was conducted on 22 inpatients with eating disorders. To confirm that the dexamethasone tablets had been ingested, we measumd the plasma concentrations of dexamethasone the next morning (at 0900 hr after DST). The diagnosis of anorexia nervosa and bulimia was made according to the criteria for DSM-III, respectively. Of the 22 patients with eating disorders, 16 satisfied the criteria for anorexia nervosa and 6 for bulimia. The DST was carried out within 2 weeks of hospitalization on each patient. The subjects were given 1 mg of dexamethasone in the evening (at 2300 hr) and blood samples were collected the following day (at 0900, 1600 and 2100 hr, respectively). The plasma cortisol and dexamethasone levels were concurrently determined by RIA. The criterion for non-suppression was a failure to suppress the plasma cortisol levels below 5.0 μg/dl in any one of the three samples. All but one patient with bulimia had ingested the dexamethasone. Thirteen (62%) of 21 patients with eating disorders were nonsuppressors. We found a significant positive correlation between the plasma cortisol levels at 1600 hr or 2100 hr and a decrease in ideal body weight (n = 16, r = 0.613, p < 0.05; r = 0.75, p < 0.01, respectively) and a significant inverse relationship between the plasma dexamethasone levels at 0900 hr and the plasma cortisol levels at 1600 hr was recognized (n = 21, r - 0.631, p < 0.01). These results suggest that the blood dexamethasone levels as well as body weight might contribute to the abnormalities of DST seen in patients with eating disorders.     

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.     

The dexamethasone suppression test: a study in a normal population

One hundred healthy, non-depressed volunteers were given a standard dexamethasone suppression test (DST) to determine the appropriate criterion values of plasma cortisol to define suppression or nonsuppression. By radioimmunoassay (RIA) of cortisol, the criterion value for 5% nonsuppression was plasma cortisol greater than 187 nmol/l, and for suppression less than 153 nmol/l, with an indeterminate range between these values. Use of the widely accepted pre-determined criterion value of 138 nmol/l gave a significantly greater frequency of nonsuppression. Values of cortisol measured by two RIAs in a subset of 43 volunteers were not equivalent. With the experimentally determined criterion value, no significant differences between nonsuppressors and suppressors were found for any measured physical or psychological parameters. Women taking oral contraceptives had significantly higher plasma cortisol pre-dexamethasone and post-dexamethasone. Their exclusion did not alter the calculated criterion value for the remainder, but their separately estimated criterion value was significantly higher. Caution should be exercised when classifying the DST status of women on oral contraceptives, particularly when values are at the lower end of the nonsuppressor range. Determination of a separate normal range for them may be warranted.     

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.