Effect of the ergot derivative lisuride hydrogen maleate on serum prolactin concentrations in female rats.

The influence of a new synthetic ergot derivative, lisuride hydrogen maleate (LHM) on serum prolactin (PRL) concentrations was investigated in female rats using different test models: 1. in reserpine (R)-pretreated intact females, and 2. in ovariectomized (OVX) estradiol benzoate (E2)-primed animals with or without an additional pretreatment with R. In all the models used LHM was strongly effective in lowering serum PRL. Doses from 0.025 to 0.5 mg/kg LHM, given orally as well as subcutaneously, suppressed serum PRL. Depending on the dose used, the serum PRL was lowered to a different extent for up to 12 h. LHM was at least as effective as the well-known potent inhibitor of PRL secretion CB-154 in lowering serum PRL in OVX rats primed with E2. The effects of R, E2, and LHM are described in relation to their mode of action within the hypothalamic-hypophyseal system which regulates PRL secretion. While the increase in serum PRL induced by R seems to be directly relatable to its known catecholamine depletion, the circadian rhythm of PRL secretion induced by E2 seems to be influenced or mediated by central neural mechanisms. The effects of LHM on serum PRL in these test models can be related to its dopaminergic action and constitute further evidence for the central functions of dopaminergic mechanisms in the regulation of PRL secretion.

Elevated 3,5-diiodothyronine concentrations in the sera of patients with nonthyroidal illnesses and brain tumors.

This study reports the development of a highly sensitive and reproducible RIA for the measurement of 3,5-diiodothyronine (3,5-T2) in human serum and tissue. The RIA employs 3-bromo-5-[125I]iodo-L-thyronine (3-Br-5-[125I]T1) as tracer, which was synthesized carrier free by an interhalogen exchange from 3,5-dibromo-L-thyronine (3,5-Br2T0). The detection limits were 1.0 fmol/g and 0.8 pmol/L in human brain tissue and serum, respectively. T3, diiodothyroacetic acid, and 3-monoiodothyronine cross-reacted with a 3,5-T2 antibody to the extent of 0.06%, 0.13%, and 0.65%, respectively. Serum concentrations of 3,5-T2 were measured in 62 healthy controls and 4 groups of patients with nonthyroidal illness, i.e. patients with sepsis (n = 24), liver diseases (n = 23), head and/or brain injury n = 15), and brain tumors (n = 21). The mean serum level of 3,5-T2 in the healthy subjects was 16.2 +/- 6.4 pmol/L. Concentrations of 3,5-T2 were significantly elevated in patients with sepsis (46.7 +/- 48.8 pmol/L; P < 0.01), liver diseases (24.8 +/- 14.9 pmol/L; P < 0.01), head and/or brain injury (24.1 +/- 11.3 pmol/L; P < 0.05), and brain tumors (21.6 +/- 4.8 pmol/L; P < 0.01). In all 4 patient groups, serum levels of T3 were significantly reduced, confirming the existence of a low T3 syndrome in these diseases. Serum concentrations of 3,5-T2 were significantly elevated in patients with hyperthyroidism (n = 9) and were reduced in patients with hypothyroidism (n = 8). The levels of T4, T3, and 3,5-T2 were measured in normal human tissue samples from the pituitary gland and various brain regions and in brain tumors. In normal brain tissue, the concentrations of 3,5-T2 ranged between 70-150 fmol/g, and the ratio of T3 to 3,5-T2 was approximately 20:1. In brain tumors, however, T3 levels were markedly lower, resulting in a ratio of T3 to 3,5-T2 of approximately 1:1. Recent findings suggest a physiological, thyromimetic role of 3,5-T2, possibly stimulating mitochondrial respiratory chain activity. Should this prove to be correct, then the increased availability of 3,5-T2 in nonthyroidal illness may be one factor involved in maintaining clinical euthyroidism in patients with reduced serum levels of T3 during nonthyroidal illness.

3,3'-Diiodothyronine concentrations in the sera of patients with nonthyroidal illnesses and brain tumors and of healthy subjects during acute stress.

In this article we describe the development of a highly sensitive, accurate, and reproducible RIA for the measurement of 3,3'-diiodothyronine (3,3'-T2) in human serum and brain tissue. The detection limits were 1.8 fmol/g and 1.5 pmol/L in human brain tissue and serum, respectively. Serum concentrations of 3,3'-T2 were measured in 4 groups of patients with nonthyroidal illnesses (NTI), i.e. brain injuries (n = 15), sepsis (n = 24), liver disease (n = 22), and brain tumors (n = 23). The mean serum concentration of 3,3'-T2 in 62 healthy controls was 46.6 +/- 20.0 pmol/L. 3,3'-T2 levels declined significantly with increasing age. They were significantly lower in patients with brain injury (34.2 +/- 19.4 pmol/L; P = 0.006), were at the upper limit of normal in patients with sepsis (57.0 +/- 36.9 pmol/L; P = 0.06), and were elevated in patients with liver disease (72.6 +/- 56.7 pmol/L; P = 0.04) and brain tumors (89.0 +/- 40.9 pmol/L; P = 0.01). The serum levels of T3 were significantly lower than those in controls in all 4 patient groups. Serum concentrations of 3,3'-T2 were significantly enhanced in 9 patients with hyperthyroidism (85.4 +/- 43.0 pmol/L; P = 0.01) and were reduced in 12 patients with hypothyroidism (14.9 +/- 9.2 pmol/L; P = 0.001). In both normal brain tissue, obtained either intraoperatively or excised postmortem, and brain tumors, the concentrations of 3,3'-T2 ranged between 50-300 fmol/g. In healthy controls, 2 different forms of acute stress (sleep deprivation and delivering a lecture) significantly increased serum levels of T4 and T3, but did not affect those of 3,3'-T2 or 3,5-T2. In conclusion, our results show that, contrary to expectation, a low T3 syndrome in NTI is not always associated with low serum concentrations of 3,3'-T2. The production of 3,3'-T2 in NTI seems to be regulated in a disease-specific manner, resulting in unchanged, reduced, or elevated hormone concentrations.

Lisuride hydrogen maleate: evidence for a long lasting dopaminergic activity in humans.

In 12 acromegalics a single oral dose of 0.2 mg lisuride, an ergoline derivative, significantly reduced plasma PRL but not GH concentrations. Three-tenths milligram of the drug significantly reduced plasma levels of the two hormones. Four-tenths milligram of lisuride did not augment this inhibitory effect. Plasma PRL levels were suppressed in all patients, whereas GH levels were reduced by more than 50% of the base-line values in only seven patients who also responded to the administration of 2.5 mg bromocriptine (CB154). In the patients unresponsive to lisuride, CB154 also failed to change GH levels. The suppressive effect of lisuride started at 60 min (at 150 min for CB154) and plasma GH and PRL levels were still markedly suppressed at 300 min. Plasma GH and PRL concentrations were consistently reduced in two acromegalic patients during 2 weeks of chronic treatment with 0.3 mg lisuride four times a day. In six normal subjects, TRH-induced PRL release was significantly inhibited by pretreatment with 0.3 mg of the drug. The similarity in the effects of lisuride and CB154 suggests that the observed effects of lisuride on GH and PRL are attributable to the known dopaminergic activity of the drug. This conclusion is supported by the data showing that pimozide effectively counteracted the inhibitory action of lisuride on GH and PRL release. We suggest that lisuride may be of value in the medical treatment of acromegaly and hyperprolactinemic states.

Influence of the dopamine D2 receptor (DRD2) genotype on neuroadaptive effects of alcohol and the clinical outcome of alcoholism.

The present study was performed to test the hypotheses that allelic variants at the human dopamine D2 receptor gene locus (DRD2) confer susceptibility to alcoholism or are associated with clinical subtypes of alcoholism. We investigated an A --> G substitution polymorphism in the 3'-untranslated region of exon 8 (E8) of DRD2 with allele frequencies of f(G) = 0.295 - 0.329. No significant association of the DRD2 genotype or allele frequencies with alcoholism was found in an association study including 283 alcoholics and 146 non-alcoholic controls. However, the frequent homozygous E8 A/A genotype with f(AA) = 0.47 - 0.48 was associated with increased anxiety and depression scores in alcoholics during the follow up after clinical detoxification treatment. In addition, E8 A/A was associated with increased suicide attempts and showed a tendency towards more severe withdrawal symptoms, early relapse and reduced responsiveness to the dopaminergic agonist apomorphine. Regression analysis revealed the DRD2 E8 genotype as the only significant factor determining withdrawal severity in female alcoholics. The findings suggest an influence of the DRD2 genotype on the neuropharmacological effects of chronic alcohol exposure and the clinical course of alcoholism.

Prolactin in patients with major depressive disorder and in healthy subjects. I. Cross-sectional study of basal and post-TRH and postdexamethasone prolactin levels.

Prolactin (PRL) levels were investigated in patients with major depressive illness and in healthy subjects. Basal and postdexamethasone levels were measured in 27 patients, and levels after thyrotropin-releasing hormone (TRH) stimulation (delta PRL) were measured in 22 patients. Basal and delta PRL were also determined in 64 age- and sex-matched healthy subjects. Both basal and postdexamethasone PRL levels were normal in depressed patients, with the postdexamethasone levels in particular showing no correlation to postdexamethasone cortisol concentrations. One milligram oral dexamethasone did not influence 4:00 PM PRL levels in 15 healthy subjects. delta PRL was significantly elevated in both male and female patients. These increases were not correlated with severity of illness and are difficult to interpret owing to the complexity of the PRL regulatory system. No significant correlations were found between basal or post-TRH PRL and cortisol, thyroid-stimulating hormone (TSH), thyroid hormones, gonadotropins, or estradiol in the patients. However, surprisingly significant positive correlations between basal PRL and basal cortisol, T4 and reverse T3 occurred in healthy subjects. It is as yet unclear how this finding can be explained and what relevance it has. Women tended to have higher basal PRL concentrations than men, but the difference was not significant in either group. delta PRL was significantly higher in women than in men in both patients and controls. No significant influence of age was found.

Prolactin in patients with major depressive disorder and in healthy subjects. II. Longitudinal study of basal prolactin and post-TRH-stimulated prolactin levels.

Longitudinal investigations of basal prolactin (PRL) and prolactin concentrations following thyrotopin-releasing hormone (TRH) stimulation (delta PRL) were conducted in 17 patients with major depressive disorder and healthy subjects. The patients were being treated with either clomipramine or maprotiline. Both basal and delta PRL increased significantly after clinical response during treatment with both drugs. However, these increases in basal and delta PRL were independent of each other. Surprisingly, elevations of basal PRL were significantly greater in responders than in nonresponders, whereas those in delta PRL showed no corresponding significant difference. These results suggest that the two drugs stimulate basal and delta PRL by different mechanisms. The increases in basal prolactin levels found in responders may possibly be due to weaker inhibition of prolactin due to "down-regulated" beta adrenergic receptors and/or enhanced activity of supersensitive serotonergic receptors. Neither basal PRL nor delta PRL proved to be a predictor of therapy response. The intraindividual retest reliabilities of both basal and delta PRL in healthy subjects was so good that a single blood sample would seem to be sufficient for investigating most issues involving PRL in psychiatric patients.

Prolactin in patients with major depressive disorder and in healthy subjects. III. Investigation of basal and post-TRH prolactin during different forms of acute and chronic psychological stress.

Prolactin (PRL) levels after thyrotropin-releasing hormone (TRH) (delta PRL) were determined 4 times and basal prolactin levels 6 times in 10 healthy medical students before, during, and after a major examination in medicine. No significant differences in basal or delta PRL levels occurred during the examination period. Basal PRL was also measured in 14 doctors of medicine after delivering a paper at a clinical conference and a further 9 doctors both before and after delivering a paper. PRL was measured serially at 20-min intervals in 4 doctors on the day on which they presented the paper. No significant differences in PRL levels were found in any of the tests conducted during this kind of stress as compared with the corresponding values obtained under nonstressful conditions. Increases in PRL before delivering the paper were seen in 3 subjects, but such increases also occurred completely independently of stress. An 18-hr fast did not influence PRL secretion in 11 healthy volunteers. Both the information obtained from a review of the literature on the influence of stress on PRL secretion and our own results strongly suggest that contrary to common opinion, there is no evidence at all that psychological stress affects PRL secretion in man.

Neuroendocrinological investigations during sleep deprivation in depression. I. Early morning levels of thyrotropin, TH, cortisol, prolactin, LH, FSH, estradiol, and testosterone.

Measurements of 12 hormones were conducted in patients with major depressive disorder at 8 AM on the morning before and at 8 AM on the morning after total sleep deprivation (SD). Thyrotropin (TSH), thyroxine (T4), triiodothyronine (T3), and free T3 (fT3) were measured in 50 patients, free T4 in 39 patients, reverse T3, cortisol, prolactin, luteinizing hormone, and follicle-stimulating hormone in 21, estradiol in 20 (women), and testosterone in 14 (men). After SD, there was a significant rise in TSH, T4, T3, and fT3 concentrations and a significant fall in testosterone levels. The increases in TSH levels were significantly correlated to clinical response. Responders to SD had higher T4, fT4, rT3, and testosterone concentrations before SD. Neither age, gender, polarity, nor antidepressant medication had a clearly significant effect on the response to SD.

Dose-dependence of the nifedipine-digoxin interaction?

The dose-dependence of the nifedipine-digoxin interaction was investigated in seven healthy subjects. After an adequate loading dose of digoxin for 2 weeks, 0.25 mg digoxin b.i.d. was given by mouth by itself. Afterwards, 0.25 mg digoxin was given twice a day for three 1-week periods in combination with capsules of nifedipine, 5, 10, or 20 mg, respectively, given on a thrice-daily basis. The study ended with a digoxin monotherapy phase lasting 7 days. All three doses of nifedipine significantly increased digoxin plasma concentrations and AUC compared with digoxin monotherapy. Thus, for example, the AUC was 10.16 +/- 0.88 ng/ml . hr (mean +/- SE) when digoxin was given alone and 12.33 +/- 1.59 ng/ml . hr with concurrent nifedipine, 5 mg t.i.d. (P less than 0.05). Nifedipine causes a slight but significant increase (15%) in digoxin plasma concentrations and AUC. This effect did not depend on the nifedipine dose given in the range studied.

Dopaminergic responsivity in alcoholism: trait, state, or residual marker?

OBJECTIVE: In order to classify neuroendocrine abnormalities in alcohol-dependent patients as trait, state, or residual markers, growth hormone (GH) secretion was assessed longitudinally. METHOD: GH secretion, stimulated by the dopaminergic agonist apomorphine, was evaluated in 21 alcohol-dependent patients (16 men, five women) and 10 healthy comparison subjects (eight men, two women). The patients were tested during early withdrawal, after 8 days of abstinence, and after 3 months. RESULTS: Patients who relapsed within 3 months (N = 8) showed significantly less GH secretion in all neuroendocrine tests than did either the patients who abstained from ethanol consumption for 6 months (N = 13) or the healthy comparison subjects. The relapsers and abstainers did not differ significantly in any of their clinical or pathophysiological data, in the severity of their withdrawal symptoms, or in antecedent or concomitant illnesses associated with alcoholism. CONCLUSIONS: GH blunting appears to be a residual marker of clinical relevance in alcoholism.

Treatment of refractory depression with high-dose thyroxine.

In an open clinical trial we investigated whether addition of supraphysiological doses of thyroxine (T4) to conventional antidepressant drugs has an antidepressant effect in therapy-resistant depressed patients. Seventeen severely ill, therapy-resistant, euthyroid patients with major depression (12 bipolar, five unipolar) were studied. The patients had been depressed for a mean of 11.5 +/- 13.8 months, despite treatment with antidepressants and, in most cases, augmentation with lithium, carbamazepine, and neuroleptics. Thyroxine was added to their antidepressant medication, and the doses were increased to a mean of 482 +/- 72 micrograms/day. The patients' scores on the Hamilton rating Scale for Depression (HRSD) declined from 26.6 +/- 4.7 prior to the addition of T4 to 11.6 +/- 6.8 at the end of week 8. Eight patients fulfilled the criteria for full remission (a 50% reduction in HRSD score and a final score of < or = 9) within 8 weeks and two others fully remitted within 12 weeks. Seven patients did not remit. The 10 remitted patients were maintained on high-dose T4 and followed up for a mean of 27.2 +/- 22.0 months. Seven of these 10 remitted patients had an excellent outcome, two had milder and shorter episodes during T4 augmentation treatment, and one failed to profit from T4 treatment during the follow-up period. Side effects were surprisingly mild, and no complications were observed at all. In conclusion, augmentation of conventional antidepressants with high-dose T4 proved to have excellent antidepressant effects in approximately 50% of severely therapy-resistant depressed patients.

The effect of FK506 versus cyclosporine on glucose and lipid metabolism--a randomized trial.

In order to evaluate the effect of cyclosporine (CsA) versus FK506 on glucose and lipid metabolism, an oral glucose tolerance test (OGTT) was performed in 101 patients after orthotopic liver transplantation (OLT) (mean interval after OLT: 511 days). The liver graft recipients had been randomized prospectively to two groups prior to OLT to receive either immunosuppression with CsA, azathioprine, and corticosteroids (CsA group) or FK506 and corticosteroids (FK group). Along with the OGTT, serum insulin, insulin C-peptide and glucagon as well as serum lipids were monitored. There was no statistically significant difference in the occurrence of impaired glucose tolerance (IGT) or manifest diabetes mellitus disease between the two groups. In fact, not a single patient developed new-onset diabetes in any group. In male and female patients, serum levels of cholesterol and triglycerides increased significantly under FK506 and CsA treatment after OLT. Cholesterol was significantly higher in the CsA group in men, in women this was marked, but not significant. While triglycerides were significantly higher in women on CsA treatment, there was no such difference in men. In conclusion, both CsA and FK506 proved to have similar effects on glucose metabolism, while there was a different spectrum of serum lipid alterations.

Homologous radioimmunoassay for canine prolactin and its application in various physiological states.

The purification of canine prolactin and the development of an homologous radioimmunoassay including several physiological studies in the Beagle dog are described. The assay measured immunoreactive canine prolactin with a sensitivity limit of 0-6 ng/ml. Purified canine luteinizing hormone gave no significant inhibition in the assay whereas purified canine growth hormone inhibited the binding of 125I-labelled canine prolactin to antiserum only at very high dose levels. In Beagle dogs. basal serum prolactin concentrations were in the range 1-2 ng/ml in normal male, normal female (metoestrus and anoestrus) and oophorectomized-hysterectomized female dogs. The prolactin concentration in one sample of amniotic fluid was in the same range, while in hypophysectomized male dogs no serum prolactin could be detected by our assay system. Serum prolactin concentrations tended to increase during late pregnancy and parturition, remaining high during the first 9 days of lactation. In consequence, a negative correlation was suggested between serum prolactin and serum progesterone concentrations.

Effect of physical fitness and body composition on sleep and sleep-related hormone concentrations.

The study assessed the effect of physical fitness and body composition on sleep and the nighttime secretion of the hormones, human growth hormone (hGH), prolactin, and cortisol. Two groups of 17 subjects, one of fit athletes and the other of unfit nonathletes, were selected so that the groups were matched for weight, height, lean body mass (LBM), and fat levels. Subjects slept in a sleep laboratory for 3 nonconsecutive nights: 1 adaptation night and 2 experimental nights. On 1 experimental night blood samples were collected; on the other, baseline sleep was assessed and the catheter was not inserted. Weight and height were measured and LBM assessed by 24 h urinary creatinine. The effect of physical fitness was tested by a comparison of the two groups; body composition was assessed by correlation analyses. Physical fitness did not have a significant effect on either sleep or hormone levels, although in the latter case the results were marginal. In contrast, body composition was related to both sleep and hGH. Percentage LBM was negatively correlated with slow-wave sleep and positively correlated with hGH levels. These results were significant for all subjects combined and for the fit group, although not the unfit group alone.

Plasma cortisol levels before and during "low-dose" hydrocortisone therapy and their relationship to hemodynamic improvement in patients with septic shock.

OBJECTIVES: To compare cortisol levels during "low-dose" hydrocortisone therapy to basal and ACTH-stimulated endogenous levels and to assess whether clinical course and the need for catecholamines depend on cortisol levels and/or pretreatment adrenocortical responsiveness. DESIGN AND SETTING: Prospective observational study in a medical ICU of a university hospital. PATIENTS: Twenty consecutive patients with septic shock and a cardiac index of 3.5 l/min or higher, started on "low-dose" hydrocortisone therapy (100 mg bolus, 10 mg/h for 7 days and subsequent tapering) within 72 h of the onset of shock. MEASUREMENTS AND RESULTS: Basal total and free plasma cortisol levels ranged from 203 to 2169 and from 17 to 372 nmol/l. In 11 patients cortisol production was considered "inadequate" because there was neither a response to ACTH of at least 200 nmol/l nor a baseline level of at least 1000 nmol/l. Following the initiation of hydrocortisone therapy total and free cortisol levels increased 4.2- and 8.5-fold to median levels of 3,587 (interquartile range 2,679-5,220) and 1,210 (interquartile range 750-1,846) nmol/l on day 1, and thereafter declined to median levels of 1,310 nmol/l and 345 nmol/l on day 7. Patients with "inadequate" steroid production could be weaned from vasopressor therapy significantly faster, although their plasma free cortisol concentrations during the hydrocortisone treatment period did not differ. CONCLUSIONS: (a) During proposed regimens of "low-dose" hydrocortisone therapy, initially achieved plasma cortisol concentrations considerably exceed basal and ACTH stimulated levels. (b) Cortisol concentrations decline subsequently, despite continuous application of a constant dose. (c) "Inadequate" endogenous steroid production appears to sensitize patients to the hemodynamic effects of a "therapeutic rise" in plasma cortisol levels.

Thyrotropin (TSH) and thyroid hormone concentrations during partial sleep deprivation in patients with major depressive disorder.

Thyrotropin (TSH), thyroxine (T4), free T4, triiodothyronine (T3), and free T3 (fT3) concentrations were measured in 25 patients with major depressive disorder at 8 a.m. both before and after partial sleep deprivation (PSD) during the second half of the night. Significant increases in TSH and T3 levels and a corresponding trend in fT3 levels were seen. No convincing correlations occurred between changes in the secretion of any of the hormones and the antidepressant effect of PSD. However, this does not rule out the possibility that the two phenomena, which occur in depression at different anatomical levels with presumably different degrees of disturbance in the respective receptor systems, have common underlying neurochemical mechanisms. Comparison of the effect of the PSD on changes in hormone secretion and mood with the corresponding effects in a sample of depressed patients who underwent total sleep deprivation showed no significant differences between the effects of these two forms of sleep deprivation on either variable.

The hypothalamic-pituitary-thyroid axis in patients maintained on lithium prophylaxis for years: high triiodothyronine serum concentrations are correlated to the prophylactic efficacy.

Serum concentrations of thyrotropine (TSH), thyroxine (T4), free T4 (fT4), triiodothyronine (T3) and reverse T3 (rT3) were measured 4 x during a 12-month period in 28 patients with major depressive disorder maintained on lithium prophylaxis for 4-23 years (mean = 11.8). The course of illness was carefully monitored and documented for all patients throughout a 3.5-year period. All hormones were also measured in 41 healthy controls matched for age and gender. Patients on lithium had normal serum concentrations of TSH, T4, fT4 and T3 only the levels of rT3 were elevated. The efficacy of the lithium prophylaxis was significantly correlated to the serum concentrations of T3, i.e., the higher the patients' serum levels of T3, the shorter was the overall duration of recurrences of depression within the 3.5-year period. We conclude that: (1) thyrotropine and the thyroid hormones, which are often abnormal during the first weeks or months of lithium treatment, returned to normal when lithium prophylaxis was maintained for years; (2) a possible explanation for the higher T3-serum concentrations in responders might be that lithium interacts with thyroid hormone metabolism in the CNS, leading to enhanced T3 concentrations in the tissue and to a secondary increase in the serum concentrations of T3.

Secondary abscess formation in pituitary adenoma after tooth extraction. Case report.

The presence of an abscess in a pituitary tumor is a very rare finding. The authors report the case of a 69-year-old man with a pituitary adenoma confirmed by neuroimaging results, in whom a high fever, meningismus, and left-sided ophthalmoplegia developed 4 days after tooth extraction. The results of serial cranial magnetic resonance imaging were highly indicative of an abscess formation within the pituitary adenoma. During surgery the tumor was approached transsphenoidally and removed. Histological examination confirmed the presence of an abscess formation within the pituitary adenoma. It is most likely that the tooth extraction caused a bacteremia, which led to an inflammation with abscess formation within the pituitary adenoma. The authors conclude that invasive dental procedures should be avoided before planned resection of a pituitary adenoma.

Serial dexamethasone suppression tests in psychiatric illness: Part I. A study in schizophrenia and mania.

Weekly dexamethasone suppression tests (DSTs) were performed in 15 patients with schizophrenia (n = 12) and mania (n = 3) until clinical response. At initial evaluation, 53.4% of the patients were nonsuppressors, and 93.3% showed nonsuppression at least once during the treatment period. There was a tendency for DST results to normalize coincident with clinical improvement, although single peaks of DST nonsuppression occurred in several patients irrespective of clinical course. The tests did not prove useful as predictors of recovery or relapse. DST nonsuppression occurred significantly more often in severely ill patients than in moderately ill patients or in patients after recovery, emphasizing the effects of nonspecific stress factors and/or severity of illness on the DST. The cutoff point, established on the basis of DST results in 67 healthy controls, was lower than in other studies, and nonsuppression among healthy controls was associated with low dexamethasone serum levels.