Abnormal Dexamethasone Suppression Test Results Research Articles

MON-444 Defining Remission In Cushing Syndrome After Tumor Resection In Cases Of Non-suppressed Postoperative Serum Cortisol Levels

Background: Remission of Cushings syndrome (CS) is generally defined as morning serum cortisol (F) values <5mcg/dL or Urine Free Cortisol < 28 - 56 nmol/d (<10-20/ μg/d) after tumor resection, as normal pituitary corticotropes are suppressed by sustained hypercortisolism (1). In cases where eucortisolemia is achieved by pharmacologic therapy preoperatively, the corticotrope cells can recover their function leading to detectable postoperative cortisol levels not always indicative of unsuccessful tumor resection. Here we describe the use of the 1mg dexamethasone suppression test (DST) and night time serum cortisol as tools to establish criteria for remission in patients where normal pituitary corticotrophs may not have been suppressed. Methods: We retrospectively reviewed 19 patients (pts) with biochemical evidence of ACTH dependent CS who underwent tumor resection. All had measurable serum F measurements within post op day 7 and underwent a 1mg DST to determine if surgery was successful. Remission was defined as serum F value of <1.8 mcg/dl after DST. Recognizing that DST results can be affected by various factors such as concurrent medications or dexamethasone metabolism, in cases where post DST serum F was > 1.8mcg/dl, late night serum F levels were collected at 2330 and 2359. Definition of remission was established as late night F level < 7.5mcg/dl.Results: Of 19 pts, 11 had Ectopic ACTH Syndrome (EAS) and 8 had Cushing’s disease (CD). The median age was 54, 12/19 were female. 15 were deemed to be in surgical remission, 10 having passed the DST with F value <1.8 (range <1 - 5.4mcg/dl). The remaining 5 had night serum F values <7.5mcg/dl (range <1-5.9). 3/10 pts had DST results >2mcg/dl; one had a 2cm adrenal nodule secondary to CD, one had bilateral adrenal hyperplasia, and in the 3rd case a dexamethasone level was not measured. These 3 cases underwent 24 hour urine cortisol measurements, all found within the lower end of the reference range; 5mcg/24hr, 8mcg/24h and 5.2ug/24hr respectively. 12/15 had documented or reported history of cyclic CS and/or were treated with steroidogenesis inhibitors prior to surgery. 21% (4/19) pts were concluded to have persistent hypercortisolemia based on abnormal DST results (F range 4.7-10.8mcg/dl) with 2 also having abnormal night serum F (>20mcg/d). All had CD, and of these 2 had no tumor identified on pathology, one had persistent disease requiring a repeat pituitary surgery with subsequent cure and positive adenoma on pathology, and the 4th had residual disease. Conclusion: In cases of cyclic CS, or where medical management was used prior to surgical resection, normal corticotrophs may not be suppressed, resulting in measurable or normal serum cortisol values post operatively. We suggest the use of the 1 mg DST and/or night time serum cortisol samples to differentiate between persistent hypercortisolism and remission after successful tumor resection.

Benign adrenal adenomas secreting excess mineralocorticoids and glucocorticoids

Objective: To recognize that benign adrenal adenomas can co-secrete excess aldosterone and cortisol, which can change clinical management.Methods: We reviewed the clinical and histological features of an adrenal tumor co-secreting aldosterone and cortisol in a patient. Biochemical testing as well as postoperative immunohistochemistry was carried out on tissue samples for assessing enzymes involved in steroidogenesis.Results: A patient presented with hypertension, hypokalemia, and symptoms related to hypercortisolism. The case demonstrated suppressed renin concentrations with an elevated aldosterone:renin ratio, abnormal dexamethasone suppression test results, and elevated midnight salivary cortisol concentrations. The patient had a right adrenal nodule with autonomous cortisol production and interval growth. Right adrenalectomy was carried out. Postoperatively, the patient tolerated the surgery, but he was placed on a short course of steroid replacement given a subnormal postoperative serum cortisol concentration. Long-term follow-up of the patient showed that his blood pressure and glucose levels had improved. Histopathology slides showed positive staining for 3β-hydroxysteroid dehydrogenase, 11β-hydroxylase, and 21 hydroxylase.Conclusion: In addition to the clinical manifestations and laboratory values, the presence of these enzymes in this type of tumor provides support that the tumor in this patient was able to produce mineralocorticoids and glucocorticoids. The recognition of patients with a tumor that is co-secreting aldosterone and cortisol can affect decisions to treat with glucocorticoids perioperatively to avoid adrenal crisis.Learning points Recognition of the presence of adrenal adenomas co-secreting mineralocorticoids and glucocorticoids.Consideration for perioperative and postoperative glucocorticoid use in the treatment of co-secreting adrenal adenomas.

Specificity of Screening Tests for Cushing’s Syndrome in an Overweight and Obese Population

Recent reports suggest a higher prevalence (1-5%) of Cushing's syndrome in certain patient populations with features of the disorder (e.g., diabetes), but the prevalence in the overweight and obese population is not known. The aim of the study was to evaluate the diagnostic performance of screening tests for Cushing's syndrome in overweight and obese subjects with at least two other features of the disorder. We conducted a cross-sectional prospective study. A total of 369 subjects (73% female) completed two or three tests: a 24-h urine cortisol, and/or late-night salivary cortisol, and/or 1 mg dexamethasone suppression test (DST). If any result was abnormal [based on laboratory reference range or cortisol after DST > or = 1.8 microg/dl (50 nmol/liter)], tests were repeated and/or a dexamethasone-CRH test was performed. Subjects with abnormal DST results and a low dexamethasone level were asked to repeat the test with 2 mg of dexamethasone. In addition to obesity, subjects had a mean of five to six features of Cushing's syndrome. None was found to have Cushing's syndrome. Test specificities to exclude Cushing's syndrome for subjects who completed three tests were: urine cortisol, 96% [95% confidence interval (CI), 93-98%]; DST, 90% (95% CI, 87-93%); salivary cortisol, 84% by RIA (95% CI, 79-89%) and 92% by liquid chromatography-tandem mass spectrometry (95% CI, 88-95%). The combined specificity (both tests normal) for all combinations of two tests was 84 to 90%, with overlapping CIs. These data do not support widespread screening of overweight and obese subjects for Cushing's syndrome; test results for such patients may be falsely abnormal.

Interleukin-6 levels and HPA axis activation in breast cancer patients with major depressive disorder

An association or a casual link has been proposed between the neuroendocrinological and neuroimmunological changes attributed to either depression or cancer. This study investigated whether breast cancer patients with and without major depression exhibit plasma interleukin-6 abnormalities and dexamethasone suppression test results. Four groups, each consisting of 30 women (1—healthy women, 2—patients with major depression, 3—breast cancer patients without major depression, 4—breast cancer patients with major depression), were compared to each other. Psychiatric evaluations were made by structured clinical interview for DSM-IV. Severity of depression was measured with the Hamilton Depression Rating Scale. Plasma levels of interleukin-6 were measured. A dexamethasone suppression test was applied. Breast cancer patients with major depression had markedly higher plasma levels of interleukin-6 than the other group. All breast cancer patients with depression had abnormal dexamethasone suppression test results. These findings suggest a hypothalamo-pituitary–adrenal axis activation and plasma levels of interleukin-6 and plasma interleukin-6 elevation and plasma levels if interleukin-6 and plasma levels of post cortisol concentrations. Evidence for a casual link or association of major depression with immune and endocrinological activation needs to be investigated further.

Combined biological tests for suicide prediction

Disturbances in serotonin neuroregulation and in hypothalamic-pituitary-adrenal axis activity are both likely, and possibly independent, factors in the genesis of suicidal behavior. This analysis considers whether clinically accessible measures of these two disturbances have additive value in the estimation of risk for suicide. Seventy-four inpatients with RDC major or schizoaffective depressive disorders entered a prospective follow-up study from 1978–1981, underwent a dexamethasone suppression test (DST) and had fasting serum cholesterol levels available in the medical record. As reported earlier, patients who had had an abnormal DST result were significantly more likely to commit suicide during follow-up. Serum cholesterol concentrations did not differ by DST result and low cholesterol values were associated with subsequent suicide when age was included as a covariate. These results indicate that, with the use of age-appropriate thresholds, serum cholesterol concentrations may be combined with DST results to provide a clinically useful estimate of suicide risk.

The dexamethasone suppression test and suicide prediction.

Despite the substantial risks of eventual suicide associated with major depressive disorder, clinicians lack robust predictors with which to quantify these risks. This study compared the validity of demographic and historical risk factors with that of the dexamethasone suppression test (DST), a clinically practical measure of hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis. Seventy-eight inpatients with Research Diagnostic Criteria major depressive disorder or schizoaffective disorder, depressed type, entered a long-term follow-up study between 1978 and 1981, and, in addition, underwent a 1-mg DST. The number of suicides in this group during a 15-year follow-up period was determined, and the predictive validity of four demographic and historical risk factors reported in the literature to be consistently predictive of suicide in depressed patients was compared to the predictive validity of the DST results. Thirty-two of the 78 patients had abnormal DST results. Survival analyses showed that the estimated risk for eventual suicide in this group was 26.8%, compared to only 2.9% among patients who had normal DST results. None of the demographic and historical risk factors examined in the study significantly distinguished those who later committed suicide from those who did not. In efforts to predict and prevent suicidal behavior in patients with major depressive disorder, HPA-axis hyperactivity, as reflected in DST results, may provide a tool that is considerably more powerful than the clinical predictors currently in use. Research on the pathophysiology of suicidal behavior in major depressive disorder should emphasize the HPA axis and its interplay with the serotonin system.

The dexamethasone suppression test in patients with mood disorders.

This study was undertaken to (1) determine whether the endogenous/nonendogenous mood disorder dichotomy is validated by the dexamethasone suppression test (DST); (2) determine whether other subtyping schemes (unipolar/bipolar, DSM-III melancholic/nonmelancholic, Winokur's family history subtypes) relate to the DST; (3) evaluate the relative contributions of symptom severity, weight loss, and other factors to DST status; and (4) assess the relative sensitivity of various post-dexamethasone cortisol determinations in the detection of dexamethasone nonsuppression. 487 consecutive adult inpatients (N = 131) and outpatients (N = 356) with unipolar (N = 422) or bipolar disorder (N = 65) underwent the 1.0-mg DST. Nonsuppression was defined as at least one post-dexamethasone cortisol measurement > 4.0 micrograms/dL. Nonsuppression occurred in 27% of all patients with major depression and 43% of all bipolar depressed phase patients. For outpatients, dexamethasone nonsuppression occurred in 35.2% of subjects with endogenous (unipolar + bipolar; N = 145) and 9.0% of those with nonendogenous (unipolar only; N = 211) depressions (single 4 p.m. post-dexamethasone cortisol). For inpatients, dexamethasone nonsuppression was found in 61.5% of subjects with endogenous (N = 104) and 18.5% of those with nonendogenous (N = 27) depressions (three post-dexamethasone cortisol determinations). For the inpatient and outpatient sample together, the DST had a sensitivity of 46.2% and a specificity of 89.9% in differentiating endogenous from nonendogenous major depressive episodes. Weight loss, gender, and symptom severity added little to the endogenous/nonendogenous dichotomy. The Research Diagnostic Criteria (RDC) primary/secondary and Winokur and colleagues' family history subtypes for unipolar depression were not strongly validated by the DST. The 4 p.m. and 11 p.m. samples together detected 91.0% of those inpatients with abnormal three-sample DST results. The 8 a.m. sample alone detected 30% of those, the 4 p.m. sample alone detected 67%, and the 11 p.m. sample alone detected 62%. The RDC endogenous/nonendogenous dichotomy was validated by the DST.

Growth hormone response to clonidine and the cortisol response to dexamethasone in depressive patients

The dexamethasone suppression test (DST) and the clonidine stimulation test (CST) were studied in 47 depressed patients. Issues addressed included (1) the usefulness of both tests as markers of major depression; (2) the relationship between the two tests and the pathophysiology underlying this relationship; and (3) the psychopathological correlates of both tests. The widely reported link between abnormal DST results and melancholic depression was confirmed. The DST and the CST showed extensive overlap, suggesting a relationship in major depression between the biological abnormalities indexed by each test (i.e., hypothalamic-pituitary-adrenal axis and noradrenergic system). Finally, the psychopathological correlates of various subgroups categorized on the basis of test responses (e.g., normal test results, blunted CST results, and both abnormal DST and CST results) confirmed significant differences between groups on two items of the Hamilton Rating Scale for Depression: psychic anxiety and somatic anxiety. The results suggest that particular patterns of neuroendocrine abnormalities may be associated with particular profiles of depressive symptomatology.

Diagnostic testing for pituitary pars intermedia dysfunction in horses

Summary Pituitary pars intermedia dysfunction is a slowly progressive disorder that afflicts most breeds of horses. Because it shares features with human Cushing disease, it has been referred to as equine Cushing disease. A variety of tests of pituitary-adrenocortical function were performed on horses with evidence of pituitary pars intermedia dysfunction, and results were compared with those in healthy control horses. Diurnal variations in plasma cortisol concentration were not statistically different between control horses and those with pituitary pars intermedia dysfunction. An ACTH stimulation (1 U of natural ACTH gel/kg of body weight, IM) test or a combined dexamethasone suppression test (10 mg, IM) and ACTH stimulation (100 mg of synthetic ACTH, IV) test also failed to distinguish horses with pituitary pars intermedia dysfunction from control horses. A significant (P &lt; 0.001) dose-related suppression of cortisol concentration in response to increasing doses (5, 10, 20, and 40 μg/kg) of dexamethasone was observed in control horses but not in those with pituitary pars intermedia dysfunction. On the basis of plasma cortisol concentration, the dexamethasone suppression test, using 40 μg/kg, whether initiated at 5 PM with sample collection at 15 (8 AM) and 19 (12 PM) hours after dexamethasone administration, or initiated at 12 AM with sample collection at 8 (8 AM), 12 (12 PM), 16 (4 PM), 20 (8 PM), and 24 (12 AM) hours after dexamethasone administration, reliably distinguished between control horses and those with pituitary pars intermedia dysfunction. Several horses did not have clinical evidence of pituitary pars intermedia dysfunction, but did have abnormal dexamethasone suppression test results. In these horses, adenomatous hypertrophy and hyperplasia of the pars intermedia of the pituitary gland was confirmed at necropsy.

DST abnormality as a predictor of course in major depression

Seventy-six inpatients with major depression received a 1-mg dexamethasone suppression test (DST) and began a semi-annual follow-up lasting 5 years. The 20 subjects with abnormal baseline DST results were significantly more likely to make psychologically serious suicide attempts during follow-up though baseline suppressors were as likely as non-suppressors to make non-serious attempts. Patients who were non-suppressors at the beginning of follow-up were also more likely to develop mania or hypomania, whether or not they had a bipolar diagnosis at intake.

Dexamethasone suppression test in patients with Parkinson's disease

The Dexamethasone Suppression Test (DST), supposed to effectively distinguish between endogenous and nonendogenous depression, was performed in a group of 34 patients with Parkinson's disease. Abnormal DST results were observed in 50% of the patients. The patients were clinically divided into subgroups of depressed and nondepressed parkinsonians. Abnormal DST results were significantly more frequent in depressed (75%) than in nondepressed parkinsonians (27.7%).

The dexamethasone suppression test: Its relationship to diagnoses, severity of depression and response to treatment

1. The dexamethasone suppression test (DST) was applied to 40 depressed patients, 40 healthy volunteers and 40 patients with other psychiatric disorders. 2. The post-dexaniethasone cortisol level, adopted as the non-suppres sion criterion and established locally, was 3.0 μg/dl. 3. The DST sensitivity in depression was 45%, with a specificity of 95% and a positive predictive value of 90%. 4. There was a significant correlation (r = 0.38, p<0.05) between HDRS scores of depressed patients and their post-dexamethasone cortisol levels. 5. A prospective study of the depressed group, which was assessed with three depression rating scales, showed differences between non-suppressors and suppressors regarding to the symptoms severity and response to the treatment. It suggests that an abnormal DST result could have a prognostic value to antidepressant drugs and ECT. 6. The DST specificity in depression was also calculated from its performance in the group with other psychiatric disorders, and their diagnoses as well as the abnormal DST results were critically discussed.

Neuroendocrine Aspects of Suicidal Behavior

To assess biologic risk factors in suicidal behavior accurately, it is necessary to distinguish prospective from retrospective design. The former studies are more likely to elicit information concerning possible risk factors in suicide, whereas the latter may be better indicators of biologic traits. In both types of investigations, measures taken close to the suicide attempt are more likely to reflect the biologic state of the individual at the time of the behavior. Although the abnormalities present in suicidal individuals are not entirely clear, most evidence to date suggests an overactivity of the hypothalamic-pituitary-adrenal axis and a dysregulation of both serotonin and adrenergic metabolism. These systems are interrelated. Both animal and human studies have established that a multivariate biologic approach is necessary to the understanding of the pathophysiology of suicide.

Pre- and postdexamethasone cortisol and prolactin levels in sexual dysfunction and normal controls

Initially, the Dexamethasone Suppression Test (DST) was reported to be a specific marker for endogenous depression (Carroll 1982). Recent studies however suggest that supposedly abnormal DST results may also occur in healthy controls (Stokes et al. 1985) and in a number of other psychiatric disorders (Holsboer and Benkert 1985), though the rate of nonsuppressors is higher in major depressive disorder (Stokes et al. 1985). Dexamethasone has also been shown to decrease prolactin levels, an effect that is more often found in normal controls and in nonendogenous depression than in endogenous depression (Rupprecht et al. 1987). Hyperprolactinemia may induce sexual dysfunction (Braunstein 1983), whereas in psychogenic sexual dysfunction, Benkert and Witt (1980) and Miller et al. (1980) reported normal prolactin levels, and others even lowered prolactin levels (Natoli et al. 1985). As no data are available

Neuroendocrine Aspects of Suicidal Behavior

To assess biologic risk factors in suicidal behavior accurately, it is necessary to distinguish prospective from retrospective designs. The former studies are more likely to elicit information concerning possible risk factors in suicide, whereas the latter may be better indicators of biologic traits. In both types of investigations, measures taken close to the suicide attempt are more likely to reflect the biologic state of the individual at the time of the behavior. Although the abnormalities present in suicidal individuals are not entirely clear, most evidence to date suggests an overactivity of the hypothalamic-pituitary-adrenal axis and a dysregulation of both serotonin and adrenergic metabolism. These systems are interrelated. Both animal and human studies have established that a multivariate biologic approach is necessary to the understanding of the pathophysiology of suicide.

The hypothalamic-pituitary-adrenal system in panic disorder.

The authors evaluated 24 outpatients with panic disorder by means of the afternoon continuous test for cortisol and the 1-mg dexamethasone suppression test (DST) and compared the results with those of 38 outpatients with major depressive disorder and 61 healthy control subjects. The mean basal cortisol level of the patients with panic disorder was significantly higher than that of the normal control subjects but almost identical to that of the depressed patients. Only three of the patients with panic disorder had abnormal DST results. These results indicate that patients with panic disorder have an abnormality of at least one function of the hypothalamic-pituitary-adrenal system which overlaps the abnormality in major depressive disorder.

Does the dexamethasone suppression test relate to subtypes, factors, symptoms, or severity?

Results of the dexamethasone suppression test (DST) are frequently abnormal in depression but not always. We performed the DST in 95 depressed inpatients to determine whether abnormal DST results were associated with individual symptoms of depression, latent behavioral "factors," melancholia, or severity of depression. Initial insomnia, agitation, loss of sexual interest, and weight loss correlated significantly with nonsuppression. Using multiple regression, these four symptoms contributed independently to the variance in DST results and more closely associated with the DST results than did severity or the diagnosis of melancholia or endogenous subtype. Factor analysis failed to identify a factor that correlated with the DST results more significantly than did the individual symptoms. Our findings and a literature review suggest that DST nonsuppression associates with certain vegetative signs of depression but not with such symptoms as loss of interest or anhedonia nor with "psychological" symptoms such as guilt, worthlessness, helplessness, hopelessness, or suicidal ideation.

Dexamethasone suppression test in dementia

AbstractThe performance of the Dexamethasone Suppression Test (DST) was investigated in 60 demented patients including 14 patients admitted to a psychogeriatric assessment ward, 29 electively admitted patients and 17 long‐stay patients in comparison with 37 normal control subjects. It was shown that acutely admitted patients had the highest rate of DST non‐suppression (86%), whilst electively admitted patients had the lowest rate (55%) in comparison with normal controls (11%). In the electively admitted group abnormal DST results and Cortisol Suppression Index and DST non‐suppressors showed depressive signs more frequently than suppressors. There was no association between DST results and age, weight, cognitive, behavioural, cortical dysfunction and degree of cerebral atrophy as determined by CT scan results.

Serial dexamethasone suppression tests in psychiatric illness: Part III. The influence of intervening variables

The effects of different intervening variables on dexamethasone suppression test (DST) results were evaluated in depressed, schizophrenic, and manic pstients. There was a significant correlation between age and DST results in major depression. Some “isolated peaks” of DST nonsuppression were explained by low dexamethasone serum levels. In schizophrenic and manic patients, the dexamethasone concentrations increased to above the normal range during the study period. A significant negative correlation between dexamethasone concentrations and DST results was found in schizophrenia and mania, but not in depression. Dexamethasone levels were generally higher in men than in women. Weight loss and hospital admission affected the DST in individual cases, whereas length of episode and drug withdrawal did not. Thus, the intervening variables accounted for some of the abnormal DST results, but other factors such as severity of illness, nonspecific stress, or possibly depression itself emerged as the main causes of abnormal DST results.

Dexamethasone suppression test testing of depressed alcoholics.

In order to determine the sensitivity of the dexamethasone suppression test (DST) for major depression in alcoholics, we administered this test to 27 alcoholics with major depression. Sixteen of 27 had abnormal DST results, yielding a 59% sensitivity for depression in alcoholics. When combined with previously reported specificity findings of 100%, the DST significantly (p less than 0.001) distinguished depressed from nondepressed alcoholics.