The dexamethasone suppression and metyrapone tests in depression

The dexamethasone suppression test (DST) and the metyrapone test (MT), a useful and reliable procedure for assessing the integrity of the hypothalamic-pituitary-adrenal (HPA) axis, were performed in 28 patients suffering from major depressive illness with melancholia. The relationship between the DST and MT appeared to be complex. Patients who failed to suppress cortisol secretion after dexamethasone administration had higher postmetyrapone cortexolone levels and cortexolone/cortisol ratios than suppressors. However, there was a wide range of metyrapone responses in patients exhibiting abnormal DST results. This suggests that failure of adequate suppression after 1 mg of dexamethasone in depressed patients does not necessarily reflect homogeneity in the HPA axis disturbances of such patients.     

The dexamethasone suppression test and depressive symptoms in early and late withdrawal from alcohol

Results of the dexamethasone suppression test (DST) in 30 alcoholic patients tested on day 5 and again on day 25 after their last drink are presented. Nineteen patients (63%) failed to suppress cortisol on day 5; three (11%) failed to suppress cortisol on day 25. Depressive symptoms, measured by the Beck Depression Inventory, were significantly correlated with DST results; the lifetime diagnosis of depressive illness was not. The authors conclude that the DST is not useful in detecting primary affective disorders during the early phase of withdrawal from alcohol.     

Nonsuppression of cortisol in depression and immune function

Eighteen depressive patients and twenty-five healthy control subjects were studied using a comprehensive immunological test system and the dexamethasone suppression test (DST) as well as some additional neuroendocrine parameters. In addition, immune functions of six of the patients were studied serially three times at 1-2 month's intervals. The OKT 4+/8+ ratio (OKT 4+ = helper/inducer phenotype; OKT 8+ = suppressor/cytotoxic phenotype) was slightly higher in those ten depressive patients showing suppression in the DST than in healthy controls, but there were no significant differences between the nonsuppressor and suppressor groups or between the nonsuppressor and suppressor groups or between nonsuppressors and control subjects. Lymphocyte transformation responses induced by phytohaemagglutinin (PHA) were similar in the nonsuppressors and suppressors, but lower in both groups than in control subjects. The number of Ig-secreting cells measured in the absence and presence of pokeweed mitogen (PWM) were similar in the nonsuppressor and suppressor groups. Four of the depressive patients tested repeatedly exhibited an abnormal response in the DST at the beginning of the study. During the follow-up period two of them recovered completely from depression as well as the patients with a normal suppression in the DST. The proportions of T and B lymphocytes and regulatory T lymphocyte subsets as well as the functions of T and B lymphocytes of the nonsuppressors and suppressors in the DST were within normal ranges before and after recovery from depression and comparable to healthy controls in repeated testing. The results indicate that in spite of the importance of cortisol in immunoregulation, the increased cortisol secretion and typical resistance to dexamethasone suppression in endogenously depressive patients is not profoundly and consistently reflected in immune functions. Neither does normalization of cortisol responses induce any major changes in immune status during a patient's recovery from depression. Previous work indicates that suppressed immunity may play an important role in the increased morbidity and mortality associated with bereavement. In the light of present findings we suggest that endogenous depression differs also in this respect from grief reactions.     

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.     

Cortisol and corticosterone response after syn-corticotropin in relationship to dexamethasone suppressibility of cortisol

The current study was designed to investigate whether glucocorticoid output after syn-ACTH stimulation is different in depression associated with dexamethasone suppression test (DST) nonsuppression from the euthymic state and DST suppression. We gave 28 depressives a DST and an adrenocortical challenge with synthetic ACTH. Fourteen patients were nonsuppressors on the DST. After successful drug treatment, the subjects were reinvestigated by both tests; all DSTs revealed plasma cortisol concentrations below the criterion value of 50 ng/ml. Cortisol and corticosterone responses after syn-ACTH tended to be higher during depression. After clinical remission, higher cortisol and corticosterone responses occurred in those patients who were DST nonsuppressors during depression. This finding suggests that patients who suffer from a depression which is linked to an abnormal pituitary--adrenocortical regulation develop an enhanced sensitivity of the adrenal cortex to ACTH.     

Dexamethasone suppression test and depressive symptoms in bereaved children: a preliminary report

Eighteen bereaved children and adolescents were assessed using the dexamethasone suppression test (DST) and the Diagnostic Interview for Children and Adolescents 4 weeks following parental death. Thirty-nine percent had a positive (nonsuppressed) DST. DST-positive subjects reported more DSM-III-R depressive symptoms (6.3 +/- 2.9 vs. 3.9 +/- 2.7, means +/- SD) than DST-negative subjects. Most frequently reported symptoms included dysphoria, loss of interest, sleep disturbance, appetite disturbance, psychomotor disturbance, and morbid and suicidal ideation. Post-dexamethasone cortisol levels were significantly correlated with the total number of depressive symptoms and suicidal ideation.     

Dexamethasone suppression test in patients with primary obsessive-compulsive disorder and in healthy controls

The dexamethasone suppression test (DST) was performed in 18 patients (11 women and 7 men) who met the DSM III-R criteria for obsessive-compulsive disorders (OCD), and in 20 healthy volunteers (12 women and 8 men). At 4.00 p.m., following dexamethasone administration, 5 patients (27.7%) and 1 healthy subject (5%) displayed plasma cortisol values well above the cut-off value of 50 ng/dl. A significantly different sex ratio was observed between suppressor and nonsuppressor patients with OCD (chi 2 = 4.40, p less than 0.03), because all nonsuppressor patients were male. Compared to the suppressors, nonsuppressor patients with OCD did not differ in any of the clinical and demographic variables investigated. Moreover, in our patient sample, the mean +/- SD total Hamilton Depression Rating Score (HDRS) was 14.8 +/- 2.5, and none of the nonsuppressors with OCD had a total HDRS greater than 17. These data suggest that a subgroup of OCD patients, particularly males, may escape the DST independently from the coexistence of depressive features.     

The dexamethasone suppression test in depressed and non-depressed geriatric medical inpatients

The frequency of an abnormal response to the dexamethasone suppression test (DST) was examined in 38 geriatric patients hospitalized for medical illnesses and affected by depressive disorders diagnosed according to the DSM III, and in 18 medical patients (used as controls) hospitalized in the same ward. Only 11% of the controls and 11% of those affected by dysthymic disorder had an abnormal DST vs 73% of the patients with major depressive disorder (MDD). The sensitivity of the DST for MDD, in this particular setting, was found to be about 73% and the specificity 89%. The importance of this clinical adjunct in diagnosing the severe depressive disorders is discussed.     

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.     

Serial dexamethasone suppression tests in psychiatric illness: Part II. A study in major depressive disorder

Weekly dexamethasone suppression tests (DSTs) were performed in 35 patients with major depressive disorder until clinical response. At initial evaluation, 65% of the patients showed nonsuppression, and 85.7% showed nonsuppression at least once during the treatment period. Normalization of the DST results usually coincided with or occurred before clinical recovery, although isolated "peaks" of DST nonsuppression occurred in 45.7% of the patients, irrespective of the clinical course. The test was not useful as a predictor of clinical recovery or relapse. Moderately ill depressed patients had significantly higher nonsuppression rates than schizophrenic or manic patients with corresponding severity scores, indicating that different factors might be associated with nonsuppression in different diagnoses. However, many abnormal DST results could neither be related to the course of the depression nor to the severity of illness; thus other factors must also be responsible for DST nonsuppression.     

Sleep deprivation and hypothalamic-pituitary-adrenal (HPA) axis activity in depressed patients

In the present study we investigated HPA axis activity in depressed patients treated with partial sleep deprivation (PSD) in order to identify endocrinological characteristics related to PSD responsiveness. Thirty-three drug-free patients (14 men, 19 women) suffering from major depression according to DSM-IV criteria were treated with PSD. Response to PSD was defined as a reduction of at least 30% according to the 6-item version of the Hamilton Depression Scale (6-HAMD). Subsequently, the combined dexamethasone-suppression/CRH-stimulation test (DEX/CRH test) was performed. Patients were pretreated with 1.5 mg dexamethasone (DEX) at 23:00 h and challenged with 100 microg corticotropin-releasing hormone (CRH) the following day. Postdexamethasone cortisol concentrations (before CRH administration) served as parameters for the DST status (dexamethasone suppression test). The cortisol stimulation after CRH was used as measurement for the DEX/CRH test status. Of the depressive patients, 54.5% (18 out of 33) responded to PSD. DST suppressors (postdexamethasone cortisol levels < 15 ng/ml) showed a significantly greater reduction in 6-HAMD scores after PSD than DST nonsuppressors. Furthermore, a significant negative correlation between postdexamethasone cortisol levels and reduction in 6-HAMD scores after PSD could be established. However, there was no relationship between the cortisol stimulation following CRH challenge and response to PSD. Although the combined DEX/CRH challenge test is a more sensitive marker for HPA axis dysregulation in depression than the standard DST, the negative feedback of the HPA system reflected by the DST status is apparently more closely associated with response to partial sleep deprivation in major depressive disorder.     

Weekly monitoring of dexamethasone suppression response in depression: its relationship to change of body weight and psychopathology

Weekly dexamethasone suppression tests (DST) were performed in 19 hospitalized patients with major depressive disorder, endogenous subtype, and who had an abnormal DST at admission. Depression scores (Hamilton Rating Scale) and weight changes were collected by investigators who were blind to the test results. Major findings were: (1) the DST gradually normalized 3-4 weeks prior to full resolution of clinical symptomatology; (2) weight loss was an important patient variable which may have contributed to false positive DST results; however, the positive correlation between changes in DST results and changes in depression scores in all our patients with or without weight loss suggests that psychopathological factors other than weight change participate in the development of dexamethasone resistance in depression; (3) the low dose (1 mg) version of the test requires careful control of minor medical disturbances, which can make the test result ambiguous. The data suggest that after resolution of some methodological issues the DST may serve as a valuable laboratory test to monitor clinical progress during drug treatment.     

Neuroendocrine interrelationships in major depressive disorder

The authors administered the thyrotropin-releasing hormone (TRH) stimulation test and the dexamethasone suppression test (DST) to 54 patients who met DSM-III criteria for major depressive disorder and to 19 nondepressed patients. A blunted thyrotropin (TSH) response to TRH injection was noted in 18 depressed patients (33%) but in no nondepressed patients. An escape from dexamethasone suppression was noted in 23 depressed patients (43%) but in only 2 nondepressed patients (11%). The combined sensitivity of the DST and the TRH test in identifying major depressive disorder was 67% with 92% specificity. Only 6 depressed patients (11%) had abnormal responses to both the DST and the TRH test, suggesting that the hypothalamic-pituitary-adrenal axis dysregulation and hypothalamic-pituitary-thyroid axis dysregulation are independent phenomena. These findings support the combined use of these neuroendocrine tests in clinical practice.     

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.     

Abnormal dexamethasone suppression test in primary obsessive-compulsive patients: A confirmatory report

The dexamethasone suppression test (DST) was administered after baseline cortisol measurements in 20 patients (10 males, 10 females) who met DSM-III criteria for obsessive-compulsive disorder (OCD). Six patients (30%) showed an abnormal escape from dexamethasone suppression. DST suppressors vs. DST nonsuppressors showed no differences in age, rate of secondary depressive disorders, or scores on the Hamilton Rating Scale for Depression, the Minnesota Multiphasic Personality Inventory D scale, or OCD rating scales. Surprisingly, there was a trend for suppressors to have a stringer family history of depressive disorders, and for nonsuppressors to include an excess of male subjects. Moreover, there was a significant correlation between levels of cortisol before and after DST. In five of six nonsuppressors, both depressive symptoms and obsessive- compulsive behaviors showed a diminution in response to antidepressant therapy combined, in one case, with intensive behavior therapy. The relationships between OCD and endogenous depression, as well as the specificity of the DST, are discussed.     

Repeated dexamethasone suppression test in major depression

A review is made on the repeated dexamethasone suppression test (DST) in patients with a major depression. In those patients treated with conventional antidepressants the gradual normalization of the DST results is significantly correlated with the evolution of the clinical picture as measured with the Hamilton Depression Rating Scale. Normalization of the DST precedes symptomatic improvement and can be used as a predictor of good clinical outcome. Persistent dexamethasone non-suppression after treatment and complete clinical recovery predicts early clinical relapse. Patients with recurrent depression tend to have consistency of their response to dexamethasone over multiple depressive episodes.     

A follow-up study of elderly depressives and Alzheimer-type dementia—relationship with DST status

Seventy-three elderly patients (38 with Alzheimer-type dementia (ATD) and 35 with major depressive disorder) were followed up 2–5 years after an index admission during which a dexamethasone suppression test (DST) had been performed. Clinical state, cognitive function, neurological status and repeat DST were assessed where possible. The death rate was high in both groups (greater in the ATD group) but was not influenced by original DST status. Original DST status did not predict on survival time, development of physical illness or admission rate in either group, but DST non-suppression in the depressed group was associated with significant cognitive decline and abnormal neurological features. Possible mechanisms of the association are discussed.     

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.     

The endocrine abnormalities of depressive patients]

In the present study, the levels of the baseline cortisol, thyrotropin (TSH), triiodothyronine (T3), thyroxine (T4) and growth hormone (GH) were determined in 64 depressive patients, 17 patients with other depressive disorders and 19 normal controls. Meanwhile, dexamethasone suppression test (DST) and insulin tolerance test (ITT) were conducted. The baseline cortisol level at 23:00 in the depressive group (8.12 +/- 5.55 micrograms/dl) was significantly higher than that in the normal control group (4.80 +/- 2.10 micrograms/dl), and DST nonsuppression ratio in the depressive group (14.5%) was significantly higher than those in the other two groups (0%). There were not significantly differences in the levels of the baseline TSH, T3 and T4 between the three groups. There were not significantly differences in the baseline GH level between the three groups, but GH level in the depressive group at 90 min. after infusing insulin was significantly lower than that in the normal control group. The results showed the HPA axis hyperactivity, normal thyroid function and blunted GH response to insulin-induced hypoglycemia at 90 min. in ITT in the depressive patients.     

The thyrotropin-releasing hormone and dexamethasone suppression tests in the familial classification of depression

Eighty-eight depressed patients who had received a dexamethasone suppression test (DST) and thyrotropin-releasing hormone (TRH) test were divided into four subgroups based on family history of psychiatric illness. Nonsuppression on the DST was found in 46% of familial pure depressive disease (FPDD) patients, 38% of sporadic depressive disease (SDD) patients, 38% of depressive spectrum disease (DSD) patients, and 50% of mixed depressive disease patients (patients with both a first degree relative with alcoholism and one with depression). A blunted thyroid-stimulating hormone response to TRH was found in 50% of FPDD patients, 56% of SDD patients, 47% of DSD patients, and 56% of mixed depressive disease patients. Neither the DST nor TRH test was found to distinguish significantly among the four familial subgroups of depression.