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

SummaryThe results of 41 standardised dexamethasone suppression tests (DST) with the Newcastle Scale diagnostic weighting for endogenous depression correlated significantly (P

Urethane anaesthesia resulted in rapid and sustained increase in plasma corticosterone levels of adult female rats both in the (a.m.) AM and (p.m.) PM. Initial corticosterone levels of non-injected control rats showed marked AM-PM differences (i.e., 28.3 micrograms/dl and 52.6 micrograms/dl, respectively), but by 10 min post-injection, the morning corticosterone levels were increased (76.2 micrograms/dl) such that AM-PM differences were not observed. By 30 min post-injection, PM plasma corticosterone levels had increased significantly (88 micrograms/dl) but were not different from AM values for the remainder of the 2 h experiment. Saline injected controls showed the expected response to stress; plasma corticosterone levels were increased (P less than 0.01) at 10 min but were back to baseline by 45 min (9.0 micrograms/dl). Dexamethasone (100 micrograms/kg, sc) markedly suppressed both AM and PM urethane-stimulated corticosterone levels. However, diurnal differences in dexamethasone suppression were noted; whereas morning plasma corticosterone levels averaged 24.8 micrograms/dl over the five sampling times corresponding PM values averaged 54.3 micrograms/dl. Plasma corticosterone levels of non-anaesthetized, hypophysectomized ACTH-primed and injected rats were not different from those similarly treated and anaesthetized with urethane and urethane-induced increases in corticosterone were not abolished by hypothalamic isolation (HI). However, plasma corticosterone levels of HI rats were less than those of sham-operated controls (i.e., 58 micrograms/dl and 74 micrograms/dl, respectively). Collectively, these data indicate that urethane evokes a sustained increase in pituitary-adrenal activity, that the increased activity is dexamethasone sensitive and that a site of action for pituitary-adrenal activation is, at least in part, at the level of the hypothalamo-hypophyseal complex.

Dexamethasone suppression adrenal cortical scintiscanning was performed in 87 patients with primary aldosteronism. Fifty patients had adrenal cortical adenomas and 37 had bilateral adrenal hyperplasia. The diagnosis of adrenal cortical adenoma was confirmed by surgery in 49 of 50, and bilateral adrenal hyperplasia was confirmed by adrenal vein aldosterone sampling in 33 and at operation in four. Dexamethasone suppression adrenal scintigraphy correctly identified the lesion(s) in 82 of the 87 patients. There were three false-negative and two false-positive adrenal cortical scintiscanning results. Computed tomography was performed in 33 patients and correctly identified 14 of 23 patients with adrenal cortical adenomas and two of 10 patients with bilateral adrenal hyperplasia and bilateral enlarged adrenals, whereas the remaining eight were considered to have normal findings. These data indicate that, when properly performed, adrenal cortical scintigraphy is an accurate and efficacious modality for the localization of adrenal cortical adenomas and in the differentiation of adrenal cortical adenoma from bilateral adrenal hyperplasia in primary aldosteronism.

The authors compare the incidence of dexamethasone nonsuppression in a large group of child and adolescent inpatients (N = 94) diagnosed by two criteria ( DSM-III and Weinberg criteria). The incidence of dexamethasone suppression test nonsuppression in patients diagnosed with DSM-III major depressive disorder (n = 33) was 55%, compared to 11% in those with no affective disorder (n = 35). This was compared to the incidence of dexamethasone suppression test nonsuppression utilizing Weinberg criteria. In addition, symptoms that to varying degrees discriminated suppressors from nonsuppressors were examined. These included change in school performance and, to a lesser degree, somatic complaints and weight and appetite changes. Differences in the diagnostic criteria are discussed. ( J Child Neurol 1987;2:31-37).

Five patients were found to have hyperthecosis ovarii as evidenced by the presence of large lipid containing thecal cells in the ovarian stroma. The clinical picture was similar in all of them, featuring mild virilization, obesity and oligomenorrhea, with refractoriness to clomid therapy. Plasma FSH levels were low normal, while LH levels were slightly elevated. Urinary 17-ketosteroids levels were elevated, and plasma testosterone concentrations were upper normal. The response to dexamethasone suppression and HCG stimulation is discussed. The effect of wedge resection on the clinical and endocrinologic pictures is evaluated.

The effect of synthetic MIF (H-Pro-Leu-Gly-NH2) on beta-MSH secretion was studied in five patients with Nelson's syndrome and in one patient with Addison's disease. Two milligrams of the tripetide were injected intravenously (1 mg in an acute injection, followed by a 30-minute-infusion of 1 mg in 20 ml of saline solution). No consistent effect could be observed during the 90-minute period after the beginning of the infusion. In the same patients, LVP stimulation and dexamethasone suppression tests brought about significant changes in the plasma beta-MSH and ACTH levels.

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.

The present paper reports the results of high-dose intravenous antidepressive treatment performed at the Psychiatric Department of the Hungarian Central Hospital in Budapest. Based on the differences in the comparative dexamethasone suppression tests (DSTs), prolactin (PRL) responses and Fischer Symptom Check List (FSCL) scores, it is hypothesized that a high parenterally administered dose of dibenzepine acts differently in comparison to oral drugs, which are extensively metabolized in the hepatic microsomal system. The results obtained so far suggest that the effect of high-dose intravenous dibenzepine in endogenous depressive states is comparable to that of electroconvulsive therapy (ECT), as far as the regression of symptoms and biochemical changes are concerned.

Sixteen depressed patients underwent 1- and 2-mg overnight dexamethasone suppression tests in balanced order. Serum cortisol concentrations at all time points were significantly higher after the 1-mg dose. Nine patients were nonsuppressors after the 1-mg dose, and 4 after the 2-mg dose.

Dexamethasone suppression tests were given to seven children with major depression, six dysthymic children, and 17 children without affective disorders. The test showed sensitivity for major depressive disorder (87%) but a low specificity (53%).

SummaryMelancholia is thought by many investigators to have a biological basis, and biological research, particularly on abnormalities of the neuroendocrine system and of the sleep electroencephalogram, is now beginning to yield results which can help in the differential diagnosis of depressive illness. This review will focus on the most widely studied neuroendocrine disturbance: disinhibition of the hypothalamus-pituitary-adrenal cortex (HPA) system as revealed by the dexamethasone suppression test (DST).

The effect of serotonin (5-HT) deficiency on hypothalamic-pituitary-adrenal (HPA) activity was investigated by using 5,7-dihydroxytryptamine (5,7-DHT) for the selective destruction of central 5-HT neurons, and corticosterone response to suppression by dexamethasone as the index of HPA activity. Dexamethasone was shown to significantly suppress serum corticosterone levels in sham-treated rats, but did not suppress corticosterone in the 5,7-DHT-lesioned animals. This finding supports the conclusion that 5-HT is involved in the negative feedback mechanism of HPA regulation.

The effect of dexamethasone-induced alteration of adrenocortical activity was assessed in two species of New World primates: Saimiri sciureus and Callicebus moloch. Basal and stress levels of corticosteroids were determined following treatment with three doses of dexamethasone (0, 50, or 500 μg/kg). Saimiri showed substantially higher basal levels of corticosteroids than did Callicebus and a greater incremental corticosteroid response to physical restraint. Dexamethasone was found to reduce basal corticosteroids in both species, although this effect was greater for Callicebus than for Saimiri Moreover, the adrenocortical response to physical restraint was reduced by dexamethasone treatment in Callicebus but not in Saimiri. The pattern of results suggests that the species differ in the mechanisms mediating adrenocortical activity.

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.

Plasma testosterone and 17-ketosteroids (androstenedione and dehydroepiandrosterone),as well as an index of the unbound testosterone concentration, were assayed in 7 girls with the appearance of sexual hair as an isolated phenomenon. Six had elevation of dehydroepiandrosterone sulfate, accompanied by parallel but slight increases in unbound testosterone into the low adult female range. This pattern of plasma androgens differed from that seen after ACTH stimulation prepubertally and suggests that these children were undergoing premature production of pubertal adrenal 17-ketosteroids. Dexamethasone suppression was undertaken in one child; the results indicated the production of androgens to be ACTH dependent. One child had no detectable abnormality of plasma androgens.

Nichols, Nugent, and Tyler (1965) reported that while a small single dose of 0.5 mg. of dexamethasone given at 08.00 or 16.00 hours to normal healthy male subjects caused only tem porary suppression of cortisol production, the same dose given at midnight produced virtually complete suppression for 24 hours. This observation was used as the basis of a rapid simple single-dose dexamethasone suppression test for the diagnosis of Cushing's syndrome (Nugent, Nichols, and Tyler, 1965; Pav latos, Smilo, and Forsham, 1965) in which plasma cortisol (17 OHCS) levels were measured at 08.00 hours after administra tion of 1 mg. of dexamethasone at 23.00-24.00 hours. More recently McHardy-Young, Harris, Lessof, and Lyne (1967) reported results of a similar test in which a 2-mg. dexamethasone dose was used. We wished to use a single-dose test on patients with chronic congestive cardiac failure in whom we had found a disturbance of the circadian rhythm in plasma cortisol levels and a dimi nished response to dexamethasone (Connolly and Wills, 1967). In a preliminary study we attempted to find a dose of dexa methasone which, given at midnight, consistently suppressed the plasma cortisol level at 09.00 hours below the lower limits of the normal range for this time of day, not only in healthy controls but also in hospital inpatients. This paper presents our findings.

Adrenocortical overactivity as a theory in the pathogenesis of depression cannot be supported on the basis of this study. Plasma cortisol response to dexamethasone was normal in both bipolar and unipolar depressives, reactive depressives and schizophrenics. As a group, schizophrenics showed significantly higher morning cortisol values than the depressed population.

Elevated plasma and urinary corticosteroid levels, a disturbed diurnal rhythm, and adrenocortical resistance to dexamethasone suppression were seen in three patients with severe depression. These abnormalities of pituitary-adrenal function are similar to those observed in Cushing's syndrome, but they disappeared with successful treatment of the depression. Diagnostic confusion could arise in a patient with depression and suspected Cushing's syndrome.

Two cases of Cushing's syndrome caused by ACTH secreting bronchial adenomas are reported. In one ACTH was demonstrated in the tumor by bioassay and in the other by radioimmunoassay. In one patient the adenoma was found at autopsy, in the other the adenoma was discovered at the time Cushing's syndrome was recognized. In this latter patient Cushing's syndrome disappeared after resection of the tumor. Careful search for such a tumor should be made in every patient thought to have pituitary Cushing's syndrome in order to select the most appropriate therapy. Presently available functional studies such as dexamethasone suppression and the response to metyrapone do not distinguish between these patients and those with Cushing's syndrome due to excessive pituitary secretion of ACTH.

The value of measurements of plasma corticosteroids in the resting state and following dexamethasone suppression and adrenocorticotrophin stimulation in the differential diagnosis of canine Cushing’s disease has been studied. Resting plasma levels appear to be rarely of value. An overnight dexamethasone suppression test depresses plasma levels below 5 pg/lOO ml in normal but not in Cushing dogs. Marked increase in plasma levels occurs in Cushing dogs following sub-optimal adrenocorticotrophin stimulation but not in normal dogs. A comparison of a fluorimetric and a competitive protein binding method for the assay of dog plasma corticosteroids has been made.

The results of dexamethasone suppression tests (DST) in the screening of subclinical hypercortisolism are not readily comparable. Aim of the present study was to review the effectiveness of overnight 1-mg DST and 8-mg DST to look for functional autonomy of clinically inapparent adrenal adenomas. Sixty-eight consecutive patients with clinically inapparent adrenal adenomas were enrolled. All patients underwent 1-mg DST. The 8-mg DST was performed in the 11 patients who had post 1-mg DST cortisol138 nmol/l and in 11 patients who had post 1-mg DST cortisol between 50 and 138 nmol/l. The a priori probability to have autonomous cortisol secretion was defined by the presence of at least two alterations of the hypothalamic-pituitary-adrenal axis among reduced ACTH concentrations, elevated urinary free cortisol (UFC) or elevated midnight serum cortisol. Cortisol levels138 nmol/l after the 1-mg DST increases the post-test probability of adrenal functional autonomy to 55%, whereas cortisol levels50 nmol/l reduce the post-test probability to 8%. Cortisol levels recorded after the 8-mg DST were nonsignificantly lower than after the 1-mg DST and all the patients with cortisol138 nmol/l after the 1-mg DST maintained cortisol above this cut-point. The 1-mg DST should be considered as the more effective test to detect autonomous cortisol secretion by a clinically inapparent adrenal adenoma when cortisol levels are138 nmol/l, while cortisol levels50 nmol/l reduce remarkably the post-test probability of this event. The 8-mg DST seems to replicate by large the results of the 1-mg DST.

Urinary free cortisol (UFC) was measured in the basal state and on 2nd day of the low-dose dexamethasone (2 mg daily for 2 days) suppression test (LDDT) in 182 subjects. At first examination the results were in good agreement with the definite diagnosis in 21 of 27 patients with Cushing's syndrome (CS) and in 145 out of 155 obese subjects. In two obese subjects the basal UFC was increased and the response to the test insufficient. At re-examination their laboratory findings became normal. In 14 subjects the basal UFC was increased but the response to the test was normal. With nine of them, repeated examinations were performed over a period of 1-7 years. Six subjects progressed into obvious CS, while in two hypercortisolism spontaneously regressed and in one it remained unchanged. The combination of elevated basal UFC with a normal suppressibility during the LDDT is considered a borderline adrenocortical impairment.

The author performed weekly dexamethasone suppression tests on five nondepressed male chronic schizophrenic patients over 12 weeks. Nonsuppression occurred three times in two patients, twice in two patients, and once in one patient.

To investigate the potency of dexamethasone in suppressing adrenocortical function, we gave various evening doses to laboratory staff members. Plasma corticotropin, cortisol, and dehydroepiandrosterone sulfate concentrations were measured the following day, to quantitate the degree of suppression after both short- and long-term treatments. We found that the minimum amount for effective suppression was 1 mg for a single evening dose, 0.5 mg per day for a long-term evening dose. On these regimens plasma corticotropin and cortisol were consistently suppressed, but plasma dehydroepiandrosterone sulfate was suppressed only with long-term treatment.

Two patients treated with alprazolam for panic disorder and agoraphobia developed a manic episode. Two biological markers--shortened REM latency and nonsuppression on the dexamethasone suppression test--suggested that both patients may have had an underlying affective disorder.

In 10 native 21-HD patients, 5 newborns and 5 older patients (aged 1-10 yr), salivary 17-OH progesterone (17-OHP) and androstenedione (A-dione) concentrations were measured, along with plasma concentrations. Prepubertal upper reference limits were for 17-OHP≤4 yr: 16 ng/dl, 4-10 yr: 7 ng/dl and for A-dione all ages ≤ 10 yr: 7 ng/dl. In the 21 HD-patients salivary 17-OHP values varied from 56 to 1782 ng/dl and A-dione values from 4 to 720 ng/dl. Newborns had considerable higher levels than older patients. Correlation coefficients for salivary versus plasma concentrations were 0.957 (17-OHP) and 0.863 (A-dione). Newborns did not show a diurnal variation, while in the older patients 1800 h. values averaged 23% (17-OHP) and 39% (A-dione) of the 0900 h. values, correlation coefficients for saliva versus plasma concentrations being 0.689 (17-OHP) and 0.990 (A-dione). After dexamethasone suppression salivary concentrations paralleled plasma values (r = 0.916 for 17-OHP and r = 0.858 for A-dione). The mean salivary concentrations decreased to 9.2% (17-OHP) and 14.0% (A-dione) of the initial values, in most patients reaching the normal range. It is concluded that salivary steroid determination is a suitable and reliable index for the diagnosis of 21-hydroxylase deficiency.

To investigate the specificity of the dexamethasone suppression test (DST) for the diagnosis of major depression in patients with diabetes mellitus, we administered 1 mg of dexamethasone to 30 nondepressed diabetics and to 58 normal controls at 11 PM. Diabetic subjects received hemoglobin A1 (Hb A1) determinations, the Hamilton Rating Scale for Depression (HRSD), and five to eight blood glucose determinations during the 48 hours surrounding the DST. Results demonstrated a significantly higher rate of nonsuppression (plasma cortisol level, greater than or equal to 5 micrograms/dL) at 4 PM the following day among diabetics (43%) than among controls (7%) but no difference between these groups in the rate of nonsuppression at 8 AM. Plasma cortisol level at 4 PM correlated with Hb A1 level but not with duration of illness, HRSD score, mean blood glucose level, or maximum blood glucose excursion. These results suggest that the results of the DST used as a diagnostic test for major depression must be interpreted with caution in patients with diabetes.

• Pilot studies suggest that changes in response to the dexamethasone suppression test (DST) in melancholic patients receiving antidepressants might represent a laboratory marker of clinical progress. We performed weekly DSTs in 31 hospitalized patients with major depressive disorder, primary and endogenous subtypes, during drug-free and subsequent treatment periods. Most nonsuppressors had progressive normalization of DST responses in conjunction with clinical improvement, DST normalization usually preceded or coincided with good clinical response, and failure to normalize was often associated with poorer clinical outcome. Occasional patients with baseline dexamethasone suppression become nonsuppressive after withdrawal from medication, but the DST has no apparent value as a serial marker in patients with welldocumented normal DST findings. Our results extend the construct validity of the DST as a state-related marker in nonsuppressors and suggest future clinical applications.

4 patients (If, 3m, 15–18 yrs) presented with clinical CS. Urinary 170HC were increased (16.9 mg/24 h), but classic criteria excluded CS (2 mg dexamethasone suppression, normal plasma F and diurnal rhythm). Urinary THE, THF-allo THF and cortolone determined by gas chromatography on capillary column were slightly increased (sum = 11.4 mg/m2/24h), but β-cortolone was normal. Free urinary F was increased (206 μg/m2/24h). In 1 case, the metabolism of exogenous F and E was studied. i.v.F and p.o.E resulted in increased THF and THE respectively, as in controls. The pattern after p.o.F, however, was different : THE and THF remained low, but β-cortolone increased, while THF increased in controls. Phenobarbital reduced all steroids in the patient. In 3 cases, serum LDH was found to be high, suggesting impaired liver function. It is concluded that CS in these cases might be due not to increased F production, but to altered F catabolism, possibly in the liver.

To the Editor. —Reding et al 1 have reported on dexamethasone suppression tests (DSTs) in stroke, and found that they correlate with depression but are not predictive of rehabilitation outcome. Unfortunately, their study has not specified whether and how patients' depressions were treated. If the depressed patients received treatment, the effect of treatment outcome on rehabilitation outcome would require assessment. If the patients with depression were not treated, ethical questions could be raised. Furthermore, two methodologic points need attention. First, the authors lumped dysthymic disorder and major depressive disorder together as "depression." In most of the psychiatric DST literature, it is major depression that is associated with abnormal DST results. A 49% prevalence of abnormal DST results in dysthymic disorders would be highly unusual. Thus, it would be useful to know how the patients were divided into major depressed and dysthymic groups. Second, the authors employed a 5-μg/dL cutoff for

• This study was designed to compare the antidepressant effects of alprazolam, a triazolobenzodiazepine, with amitriptyline hydrochloride in a group of patients with nonpsychotic, major depressions diagnosed by Research Diagnostic Criteria. A mean rapid eye movement latency of less than 65 minutes was required to enter this study. Dexamethasone suppression tests were conducted before treatment. By strictly applied Research Diagnostic Criteria, 83.6% of the subjects were endogenous, and 34.7% were inpatients. A significantly greater percentage of alprazolam-treated patients responded within the first seven days of treatment. By the end of this sixweek trial, alprazolam was associated with significant reductions in Hamilton, Beck, Covi, Raskin, and Carroll Rating scores (pretreatment to posttreatment). However, by the end of treatment the effects of amitriptyline exceeded those of alprazolam on both the Hamilton and Beck scales. These data indicate that alprazolam is not as effective as amitriptyline in major depressions with a shortened rapid eye movement latency.

To the Editor.— In reference to the Schlesser et al article, "Hypothalamic-Pituitary-Adrenal Axis Activity in Depressive Illness: Its Relationship to Classification" (Archives1980;37:737-743), the conclusions drawn by the authors do not appear to be valid based on the methodology used in their study. Carroll et al 1 have shown that most patients with "endogenomorphic" depression did not show escape from dexamethasone suppression of cortisol until late afternoon (4Pm) or evening (12Am) on the day following dexamethasone administration. This point was also brought up by Brown and Shuey in their article, "Response to Dexamethasone and Subtype of Depression," which appeared in the same issue of theArchives(1980;37:747-751). The methodology used by Schlesser et al (ie, measuring only the 8Amcortisol levels after dexamethasone administration) could have missed a substantial proportion of patients with familial pure depressive disease (FPDD), sporadic depressive disease (SDD), or depressive spectrum disease (DSD)

Controversy exists as to the pathophysiology in Cushing's syndrome with nodular adrenocortical hyperplasia. Of the eight patients reported by Meador et al in 1967, all showed resistance to dexamethasone suppression. 1 However responses to corticotropin and metyrapone were variable, and plasma adrenocorticotropic hormone (ACTH) levels by bioassay, ranged from low to normal. Consequently, opinion has differed as to whether this condition represents a primary hypothalamic pituitary defect, primary adrenal autonomy, or a combination of both. The patient with nodular adrenocortical hyperplasia reported here illustrates the complex combination of pituitary-adrenal control that may be present and the danger of isolated measurements of plasma ACTH concentration and dexamethasone suppression. Patient Summary A 44-year-old woman entered Cincinnati General Hospital in June 1966, referred by her private physician who diagnosed possible Cushing's syndrome. She was in good health until six years prior to this admission, when she began to experience menorrhagia, hot flushes, and

THERE has been an increasing interest in the adrenocortical response to behavior. Alterations of 17-hydroxycorticosteroids (17OHCS) have been reported in a variety of different emotional states, including depression and psychic stress in combat troops. 1-6 It has been shown also that elevations in 17-OHCS may occur in suicidal patients. 7-9 Most of these studies, showing steroid alterations accompanying various psychic conditions, have utilized baseline urinary 24-hour 17-OHCS determinations. Recently, Fawcett and Bunney reported a failute of dexamethasone suppression in some depressed patients. 1 This finding has been confirmed by Carroll et al utilizing plasma 11-hydroxycorticoste roids. 10 This latter group also noted that coincident with recovering from depression, normal dexamethasone suppression returned. Military basic trainees are under varying degrees of emotional stress during their training period. Some tolerate these stresses less well than others and are referred to the Mental Hygiene Clinic for evaluation and therapy. It is the purpose of