Evening urine cortisol excretion and DST results in depression and anorexia nervosa

Cortisol determination in a single one-hour urine sample collected between 2200 h and 2300 h has been shown to identify accurately patients with Cushing's disease. To examine the usefulness of this procedure for identifying psychiatric patients with a pituitary-adrenal disturbance, we studied 17 drug-free depressed patients, 6 euthymic anorectic patients and 10 healthy volunteers. We found that there was good agreement between DST results and evening urine cortisol excretion in this sample (when cortisol levels were expressed as ng of cortisol per mg of creatinine), and that adopting as a criterion a urine cortisol value two standard deviations above the mean cortisol value of the controls predicts 74% of the dexamethasone suppression test (DST) results. We would like to suggest that this measure deserves further study as a potentially useful and simple alternative to the DST for identifying psychiatric patients with a pituitary-adrenal disturbance.     

Liver function, plasma dexamethasone, and DST results in detoxified alcoholics

Alcohol abuse, alcohol withdrawal, and deterioration of hepatic function have been associated with abnormal dexamethasone suppression test (DST) results. Chronic alcohol abuse may also directly alter the pharmacokinetic disposition of dexamethasone. Plasma dexamethasone concentrations following a DST were determined in 53 detoxified alcoholics. Those with abnormal liver function had higher 4 p.m. plasma dexamethasone concentrations and lower DST cortisol concentrations. Those with normal liver function had lower plasma dexamethasone and higher DST cortisol concentrations consistent with induction of hepatic metabolic enzymes from chronic use of alcohol. The data indicate that liver function is one of the variables influencing dexamethasone disposition and DST cortisol suppression.     

Effect of age and sex on cortisol secretion in depressives and normals

The mean 24-hour plasma level of cortisol with plasma sampling every 20-30 minutes was determined in 32 normal women aged 12-73, 40 normal men aged 10-55, 21 depressed women aged 20-61, and 11 depressed men aged 22-66. The mean levels of cortisol were higher in the group of depressives compared with the controls. Cortisol levels showed a significant linear correlation with age in normal women but not in normal men. Both depressed women and men had a significant linear increase of cortisol levels with age. The finding that age substantially contributes to increased levels of cortisol calls for cautious interpretation of any data concerning that hormone when the variable of age is not adequately controlled. Furthermore, aging and depression may have some underlying mechanisms whose elucidation may contribute to the understanding of the pathophysiology of vulnerability to affective disorders.     

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 effect of weight loss and inappropriate plasma dexamethasone levels on the DST

Recent studies from different research groups have raised fundamental questions about the postulated specificity of the dexamethasone suppression test (DST) for endogenous depression. Findings in 116 psychiatric inpatients and 24 semi-starved healthy volunteers underline the importance of weight loss as a factor affecting DST results. A study of 160 DSTs in 93 psychiatric inpatients further revealed a significant negative correlation of plasma cortisol and plasma dexamethasone levels 10 hours after oral administration of 1 mg of dexamethasone. These results suggest a decisive effect of the pharmacokinetics of dexamethasone, at least on the 1-mg DST.     

Influence of age on the cortisol response to dexamethasone

Controversy exists regarding the association of age with postdexamethasone serum cortisol levels. We evaluated this relationship in 95 patients with major depressive disorder and 49 healthy controls. Age and 8 a.m. postdexamethasone cortisol levels were not correlated among the healthy controls, but were positively associated among the depressives. There was also a trend for age and 4 p.m. postdexamethasone cortisol levels to be positively associated in depressives. Multiple linear regression analyses revealed that these associations could not be explained by other variables such as sex, psychotic features, or familial subtype of depression. Several hypotheses that might account for these associations are examined.     

The dexamethasone suppression index: enhancement of DST diagnostic utility for depression by expressing serum cortisol as a function of serum dexamethasone

The authors sought to determine whether the performance of the dexamethasone suppression test (DST) could be enhanced by expressing cortisol as a function of dexamethasone. Because cortisol concentration is a function of the reciprocal of dexamethasone concentration, this relationship was approximated by calculating the product of cortisol and dexamethasone as a dexamethasone suppression index. Preliminary assessment of test performance measures (sensitivity, specificity, and predictive power) showed that use of the dexamethasone suppression index was an improvement over the use of cortisol levels alone. Factoring dexamethasone levels into post-dexamethasone cortisol level measures may enhance the utility of neuroendocrine assessment in psychiatry.     

Weight loss, cortisol levels, and dexamethasone suppression in major depressive disorder

Appetite and/or weight loss are integral, albeit not necessary, symptoms of depression. We explored the contribution of diminished appetite and/or weight loss ascertained by history to the hypothalamic-pituitary-adrenocortical (HPA) axis dysregulation in 120 patients with primary major depressive disorder. Significant positive relationship for both appetite and weight loss with cortisol levels in plasma and cerebrospinal fluid (CSF) were observed. Plasma cortisol levels were consistently higher in patients who noted both appetite and weight loss as opposed to patients without appetite or weight loss. Depressed patients with weight loss showed higher rates of dexamethasone-nonsuppression. Age and severity of depression influenced but did not eliminate the significance of the findings, suggesting that weight loss accounts in part for the HPA-axis function changes observed in depression.     

Dexamethasone suppresion test (DST) and plasma dexamethasone levels in depressed patients

The dexamethasone suppression test (DST) was evaluated in newly hospitalized patients with a DSM-III diagnosis of major depression. Patients with other psychiatric disorders and a normal control group were also studied. Plasma dexamethasone levels were obtained in all patients, and the relationship between plasma cortisol and plasma dexamethasone was examined. Rates of non-suppression in patients with major depression (39%) were not significantly different from those in patients with minor depression (25%), mania (38%), or other psychiatric illnesses (17%). The ranges of dexamethasone levels at 8 a.m. and 4 p.m. were similar between patient groups and controls. However, there was a significant difference in dexamethasone levels between suppressors and nonsuppressors, irrespective of diagnosis, which could not be explained by differences in weight or plasma dexamethasone half-life. Inappropriately high dexamethasone levels were found in some patients with a 1 mg test, a problem that critically affects the sensitivity of the test procedure.     

Association between low plasma levels of dexamethasone and elevated levels of cortisol in psychiatric patients given dexamethasone

In psychiatric inpatients, positive results on 40 dexamethasone suppression tests (elevated cortisol levels) were strongly associated with low plasma levels of dexamethasone. Bioavailability or pharmacokinetic factors may contribute importantly to the outcome of the dexamethasone suppression test.     

Salivary cortisol levels and their correlation with plasma ACTH levels in depressed patients before and after the DST.

OBJECTIVE: The aim of this work was to study the clinical utility of salivary cortisol concentrations in a group of depressed patients undergoing the dexamethasone suppression test (DST) and the correlation of these concentrations with plasma ACTH levels. METHOD: Twenty outpatients from the psychiatric department of a Barcelona hospital who were diagnosed as having nonendogenous (N = 9) or endogenous (N = 11) depression according to DSM-III criteria and the Newcastle scale participated in the study. The comparison group consisted of 12 healthy volunteers. Blood and saliva samples were taken before and after administration of 1 mg of dexamethasone Salivary cortisol and plasma ACTH concentrations were determined by direct iodine-125 radioimmunoassay with commercial kit reagents. RESULTS: Predexamethasone salivary cortisol concentrations were significantly higher in the group with endogenous depression than in the comparison group. A significant correlation was obtained between plasma ACTH and predexamethasone salivary cortisol levels in the group with nonendogenous depression and in the comparison subjects. CONCLUSIONS: These preliminary findings indicate that salivary cortisol could substitute for plasma cortisol in clinical studies in which the DST and hypercortisolemia are evaluated. The lack of correlation between ACTH and cortisol levels in saliva in the group of endogenously depressed patients could indicate a disturbance in the regulation of cortisol secretion in major depression.     

Prediction of postdexamethasone cortisol levels by serum sodium levels in patients with major depression

The authors analyzed the dexamethasone suppression test (DST) results of 54 patients with major depressive disorder in relation to their pre-DST levels of cholesterol, sodium, potassium, and blood glucose, which are thought to have adrenocorticotrophic links. Discriminant analysis revealed that sodium alone was a significant predictor of nonsuppression. Validation of the predictive power of sodium could minimize the need for DST administration.     

Effect of high plasma dexamethasone levels on DST sensitivity: dose-response study in depressed patients and controls

The aim of this study was to examine cortisol dynamics over a range of plasma dexamethasone (DEX) levels using a two-dose dexamethasone suppression test (DST). Two doses of DEX (0.5 and 1.5 mg) were administered in a randomized crossover design to 29 inpatients with major depression and 26 controls to identify the upper range of plasma DEX levels that would allow reliable interpretation of DST results. It was hypothesized that due to inappropriately high plasma DEX levels following 1.5 mg, several depressed patients would switch from suppressors after the 1.5 mg dose to nonsuppressors after 0.5 mg. In contrast, the nondepressed controls with high DEX levels following 1.5 mg would remain suppressors after the lower dose. Fourteen patients were identified as having high 4 p.m. DEX levels (greater than 4 nmol/l) after the 1.5 mg DST. Cortisol was suppressed in all of the subjects with high DEX levels. After 0.5 mg, five of the eight depressed patients with high DEX levels switched to nonsuppressors. In contrast, all six controls with high DEX levels remained suppressors. These results indicate that patients with high DEX levels after a 1 mg DST should be retested with a lower dose. This strategy enhances the sensitivity of the DST without loss of specificity.     

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.     

Age and cortisol suppression by dexamethasone in normal subjects

A study of 60 healthy volunteers ranging from 19-88 yr of age found nonsuppression rare (5%) and confirmed that the dexamethasone suppression test (DST) of the reactivity of the hypophyseal-pituitary-adrenal axis to negative feedback inhibition requires 0800 h plasma dexamethasone (DEX) levels in excess of 220 ng/dl. All of the subjects with inadequate DEX levels (N = 3) were older than 50 yr of age as were the nonsuppressors (N = 3); two of the three nonsuppressors had inadequate DEX concentrations. Thus, DST may be more often invalid in elders than in younger adults because of inadequate plasma dexamethasone (DEX) concentration, indicating that plasma DEX levels should be assayed concomitantly with DST in elders.     

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.     

Serum dexamethasone concentrations in endogenous depressives before, during, and after treatment: preliminary observations

The 1.0-mg Dexamethasone (DEX) Suppression Test (DST) was performed in 10 endogenous depressives prior to treatment, during treatment, and again when the patients were medication- and symptom-free. Five of the 10 patients were DST escapers prior to treatment, and all 10 patients were DST suppressors following treatment. During treatment, 6 patients were DST escapers, 2 of them having been suppressors initially. There were no significant differences in serum DEX concentrations before, during, and after treatment in either the 5 DST escapers or the 5 DST suppressors. These results lend further support to the concept that reduced serum DEX concentrations are not the major factor underlying DST nonsuppression.