Cortisol, 11-deoxycortisol, and ACTH concentrations after dexamethasone in depressed patients and healthy volunteers

The 1 mg dexamethasone suppression test was used to assess pituitary-adrenal activity in 23 depressed patients and 8 healthy volunteers. At 1600h, after administration of the test dose of dexamethasone at 2300h, levels of cortisol, 11-deoxycortisol, and corticotropin were determined following a chromatographic extraction step applying highly specific radioimmunoassay techniques. Cortisol nonsuppressors had significantly increased adrenocorticotropic hormone (ACTH) values and cortisol/11-deoxycortisol ratios. The cortisol/11-deoxycortisol ratio was regarded as a measure of biologically active ACTH. The present results, which indicate a concordance of corticotropin and corticosteroid response, suggest that the parent abnormality of dexamethasone-resistant cortisol concentrations is elevation of biologically active corticotropin.     

Cortisol, ACTH, and beta-endorphin after dexamethasone administration in Parkinson's dementia

The dexamethasone suppression test (DST) has been suggested as an effective tool for differentiating between depression and dementia. After administering 1 mg dexamethasone, we measured cortisol, ACTH, and beta-endorphin levels in 32 nondepressed patients with idiopathic Parkinson's disease (PD) (14 also with dementia) and 20 healthy, age-matched controls. Four of the 20 controls, 9 of the 18 with PD alone, and 8 of the 14 with PD and dementia were dexamethasone nonsuppressors (cortisol value greater than or equal to 5 micrograms/100 ml). PD patients without dementia (nonsuppressors) showed higher basal plasma values of cortisol (22.06 +/- 5.30 micrograms/100 ml) compared with the suppressors (13.38 +/- 3.30 micrograms/100 ml). Plasma ACTH and beta-endorphin responded in a coupled way to dexamethasone challenge. Higher basal levels of both peptides were found among PD patients (demented and nondemented), nonresponders to DST. Thus, the DST does not appear to be effective in differentiating between depression and dementia in PD. In addition, PD nonsuppressors showed higher basal values of plasma ACTH, beta-endorphin, and cortisol (similar to patients with major depression). This suggests that although the depression is clinically undetectable, both disorders may share some pathophysiological features at the hypothalamic hypophyseal adrenal level.     

Plasma ACTH and cortisol concentrations before and after dexamethasone

Alteration in the hypothalamic-pituitary-adrenal (HPA) axis occurs in up to 50% of depressed patients and is demonstrated by the failure to suppress cortisol concentrations after dexamethasone administration. Evidence suggesting that these cortisol abnormalities reflect hypothalamic-pituitary dysfunction has been inconsistent. We administered the dexamethasone suppression test to 28 psychiatric inpatients, including 17 cortisol suppressors and 11 nonsuppressors. Adrenocorticotropic hormone (ACTH) concentrations at 8 a.m. pre- and postdexamethasone were significantly greater in cortisol nonsuppressors than in suppressors. Our data support the hypothesis that pituitary ACTH secretion is altered in depressed patients who have HPA axis abnormalities demonstrated by plasma cortisol measurements.     

Cortisol, ACTH, prolactin and beta-endorphin responses to fenfluramine administration in major-depressed patients

In the past, some researchers found increased cortisol and prolactin responses to the administration of fenfluramine in major-depressed patients. It was believed that the fenfluramine test could prove to constitute another challenge probe to reflect the central serotonergic function. The present study was conducted in order to investigate the pituitary/adrenal responses to fenfluramine in major- versus minor-depressed patients. To this end we administered 60 mg D,L-fenfluramine p.o. to 40 depressed patients categorized according to the DSM-III. The basal levels of cortisol, adrenocorticotrophic hormone (ACTH), beta-endorphins and prolactin and their levels 2 and 4 h after fenfluramine administration were measured. We found no significant effect for fenfluramine treatment on cortisol, ACTH or beta-endorphins. There was a significant (p = 0.02) effect for fenfluramine treatment on prolactin. The enhanced secretion of prolactin was only significant (p = 0.006) in major (296.X2, 296.X3, 296.X4) and not in minor (300.40, 309.00) depressives. It was concluded that our findings corroborate the thesis of a hypersensitive serotonergic neurotransmission during a major depressive episode.     

Cortisol response to dexamethasone and noradrenergic function in depression

Positive correlations between measures of hypothalamic-pituitary-adrenal (HPA)-axis activity and noradrenergic turnover have been reported in depression. To investigate this relationship the authors measured peak postdexamethasone cortisol levels (8 a.m., 4 p.m. and 11 p.m.) and the 24-hour urinary 3-methoxy-4-hydroxy-phenylglycol (MHPG) flow in 84 depressed patients. The results show that there is no positive association between those measures of HPA-axis and noradrenergic activity. On the contrary, patients with severe non-suppression (greater than or equal to 10 micrograms/dl or 277 nmol/l) tended to have a lower MHPG-excretion.     

The ACTH response to dexamethasone in PTSD

OBJECTIVE: Enhanced negative feedback and reduced adrenal output are two different models that have been put forth to explain the paradoxical observations of increased release of corticotropin-releasing factor in the face of low cortisol levels in posttraumatic stress disorder (PTSD). To discriminate between these models, the authors measured levels of adrenocorticopic hormone (ACTH) and cortisol at baseline and in response to dexamethasone in medically healthy subjects with and without PTSD. Under conditions of enhanced negative feedback inhibition, ACTH levels would not be altered relative to cortisol levels, but the ACTH response to dexamethasone would be augmented, in concert with the enhanced cortisol response to dexamethasone. In contrast, under conditions of reduced adrenal output, ACTH levels would be expected to be higher at baseline relative to cortisol levels, but the ACTH response to dexamethasone would be unchanged in PTSD relative to healthy comparison subjects. METHOD: The ACTH and cortisol responses to 0.50 mg of dexamethasone were assessed in 19 subjects (15 men and four women) with PTSD and 19 subjects (14 men and five women) without psychiatric disorder. RESULTS: The ACTH-to-cortisol ratio did not differ between groups before or after dexamethasone, but the subjects with PTSD showed greater suppression of ACTH (as well as cortisol) in response to dexamethasone. CONCLUSIONS: The data support the hypothesis of enhanced cortisol negative feedback inhibition of ACTH secretion at the level of the pituitary in PTSD. Pituitary glucocorticoid receptor binding, rather than low adrenal output, is implicated as a likely mechanism for this effect.     

Plasma dexamethasone concentrations and the dexamethasone suppression test

Altered bioavailability or altered pharmacokinetics of dexamethasone (dex) may contribute to a positive Dexamethasone Suppression Test (DST) in psychiatric patients. We measured plasma dex and plasma cortisol concentrations in 32 patients with primary major depressive disorder (MDD), 14 patients with other psychiatric disorders, and 16 normal controls. Cortisol was measured by the competitive protein binding (CPB) assay and dex by RIA (IgG Corp.). Additionally, cortisol was measured by a fluorescent polarization immunoassay (FPIA) available on the Abbott TDx analyzer in an attempt to validate this method for use in the DST. The agreement between FPIA and CPB cortisol results was excellent. Depressed nonsuppressors, by definition, had significantly higher mean plasma cortisol concentrations than depressed suppressors, psychiatric controls, and normal volunteers at 8:00 AM, 3:00 PM, and 10:00 PM postdex. When DST nonsuppressors and suppressors were compared regardless of diagnostic group, plasma dex concentrations were significantly lower (p less than 0.01) in the DST nonsuppressors. There was a significant negative correlation between plasma cortisol levels and plasma dex levels across all subjects at 8:00 AM (r = -0.365, n = 44, p less than 0.05). When the subjects were sorted by diagnostic category, there was a strong, but not statistically significant, trend toward lower plasma dex concentrations in the melancholic nonsuppressors versus the melancholic suppressors and between the psychiatric control non-suppressors and the corresponding suppressor group. These relationships disappeared when we restricted our analyses to an empirically derived middle range of plasma dex concentrations within which the DST results were considered to be valid. We conclude that bioavailability or pharmacokinetics of dex may significantly contribute to DST results. Further investigation is needed to determine whether or not the quantification of dex and its metabolites and their determination at which specific timepoints during the DST will enhance the predictive or interpretive value of the DST in psychiatric patients.     

Cortisol suppression after dexamethasone administration in patients with dementia

Sixty-four nondepressed, carefully selected senile demented inpatients underwent two 1.0 mg overnight dexamethasone suppression tests (DSTs) separated by 7 days. These patients had been in a clinically stable and drug-free state for at least six months prior to testing. The Modified Ischemic Scale score and ICD-9 criteria for Alzheimer's disease were used to dichotomize subjects into Alzheimer's and multi-infarct types of dementia. Patients with vascular dementias were significantly more likely to evidence DST nonsuppression, furthermore, DSTs in this group were less reproducible from week to week than DSTs in Alzheimer's patients.     

Cortisol response to dexamethasone in women with premenstrual syndrome

There were no significant differences in post-dexamethasone cortisol between the follicular and luteal phase of the menstrual cycle in both women with premenstrual syndrome (PMS) and control subjects tested on these two occasions. Within each menstrual cycle phase, there were also no differences in post-dexamethasone cortisol between the two groups. In a second group of control subjects tested on a single occasion, post-dexamethasone cortisol values were higher when subjects were tested in the middle 2 weeks of the menstrual cycle compared with the first and last weeks of the cycle. This phenomenon, possibly due to estrogen effects, suggests that post-dexamethasone cortisol should be assessed weekly in women with PMS to determine whether they also manifest this normally observed menstrual cycle phase-related pattern, or whether it is absent, reflecting a reproductive endocrine abnormality in this patient group.     

Optimal use of markers for cobalamin and folate status in a psychogeriatric population

BACKGROUND: Cobalamin/folate deficiency is common in elderly subjects and may lead to psychiatric symptoms, but even more often it increases the severity of other organic and non-organic mental diseases. It is therefore of importance to evaluate the optimal use of different markers of cobalamin/folate status in a psychogeriatric population. METHODS: We measured serum cobalamin, blood folate, plasma homocysteine (tHcy) and serum methylmalonic acid (MMA) in 475 well-defined psychogeriatric patients. RESULTS: The findings in the present study showed that many (41%) of the patients with normal levels of serum MMA (< 0.41 micromol/l) had pathological values of at least one of the other markers for cobalamin/folate status, whereas only 17% of patients with normal plasma tHcy (< 19.9 micromol/l) had pathological levels of other markers. If patients with decreased levels of serum cobalamin and/or blood folate were also excluded from these patients, only nine patients with slightly elevated levels of serum MMA remained. In the present study different upper reference limits were also tested for both serum MMA and plasma tHcy. However, the use of these limits did not cause any diagnostic improvement in the evaluation of cobalamin-folate status. Plasma tHcy was increased in almost all diagnosis groups of the psychogeriatric patients, whereas serum MMA was increased in only some groups. The distribution of the two common polymorphisms of the methylenetetrahydrofolate reductase gene (C677T and A1298C) was similar in patients with elevated and normal plasma tHcy. CONCLUSIONS: The findings in the present study suggest the use of plasma tHcy, serum cobalamin and blood folate to evaluate cobalamin-folate status in psychogeriatric patients and to omit the use of serum MMA.     

A survey of frontal lobe dementia in a psychogeriatric day unit population

Nine (12%) of 78 consecutive first admissions to psychogeriatric day units fulfilled an operational definition for dementia of frontal lobe type (DFT). These cases showed many of the behavioural, neuropsychological and neurophysiological features of DFT reported in presenile subjects. They accounted for 14% of first admissions with organic brain syndromes and 37% of those showing marked apathy or disinhibition. These findings support the hypothesis that DFT is a common cause of referral to psychogeriatric services and a significant source of behavioural disturbances in such settings.     

Measurement of ACTH and prolactin in the dexamethasone suppression test

Plasma concentrations of ACTH and prolactin were measured in psychiatric inpatients at 8 a.m. and 4 p.m. before and after the standard 1 mg overnight Dexamethasone Suppression Test (DST). Plasma concentrations of cortisol were measured at 8 a.m. and 4 p.m., and 11 p.m. before and after 1 mg dexamethasone. Dexamethasone suppressed plasma concentrations of ACTH, prolactin and cortisol in the subject group as a whole. "Cut Points" obtained using Fisher's Exact Test identified plasma ACTH values at 8 a.m. baseline, 4 p.m. baseline and 8 a.m. post-dexamethasone and plasma prolactin values at all four times that significantly differentiated patients with bipolar depressive disorder and major depressive disorder from other psychiatric patients. There were no cut points found at any of the six times for plasma levels of cortisol that significantly differentiated between these two diagnostic groups. Of interest in this subject population, basal (pre-dexamethasone) plasma concentrations were of more diagnostic information than post-dexamethasone values. These pilot findings suggest that monitoring plasma prolactin and ACTH concentrations before and after dexamethasone might increase the sensitivity and specificity of this laboratory test for depression.     

Cortisol levels in plasma after dexamethasone administration and the nosology of depression

The authors have studied 89 depressed patients diagnosed according to three different systems: DSM-III, Kiloh and Garside, Winokur. They administered 1 mg of Dexamethasone at 11 pm; blood samples were taken at 8 am and 8 pm the next day. They find the most significant differences in cortisol levels according to the DSM classification whereas there are no significant differences according to the Winokur classification. They refer the great variance obtained in the endogenous groups to a high incidence of suppressors in these non-suppressor groups. In 26 non-depressed patients, they found 10 non-suppressors. According to the authors, these results demonstrate the importance of DST and other biological tests in the reformation of nosology in psychiatry.     

实验性过敏性脑脊髓炎豚鼠血浆PGE2、ACTH和皮质醇的水平变化

用放射免疫分析法剥定EAE豚鼠血浆PGE2、ACTH和皮质醇的水平。结果发现发病重的动物血浆PGE2水平显著低于正常和发病轻的动物，而发病轻的动物PGE2水平略高于正常动物，但两者比较无统计学差异，提示PGE2可能对神经系统炎性脱髓鞘病的发生和发展有调节作用。EAE发病动物血浆ACTH和皮质醇的水平显著高于正常动转。发病重的动物ACTH水平高于发病轻的动物，但两者比较无统计学差异；而发病重的动物皮质醇水平显著高于发病轻的动物。血浆ACTH和皮质醇水平的增高，一方面是对应激的反应，另一方面可能是自身保护性的反馈调节。以上PGE2、ACTH和皮质醇水平变化的研究，可能有助于对EAE病情进一步做出判断和评价。     

Ability of the mini-mental state examination to discriminate diagnostic entities in a psychogeriatric population

The Mini-Mental State Examination (MMSE) is widely used in clinical practice. A standardized MMSE (SMMSE) was used to differentiate those patients with dementia or delirium from those with functional psychiatric disorders. Seventy psychogeriatric patients from Royal Park Psychiatric Hospital were interviewed. The SMMSE and the Hamilton Rating Scale for Depression (HRSD) were administered at two time points, 3 weeks apart. The study found that the SMMSE did differentiate those with dementia or delirium from those with functional psychiatric disorders. However, caution should be exercised when interpreting SMMSE results in community settings.     

Cortisol response to ACTH infusion in depressed patients: comparison with age-, sex-, and weight-matched normal subjects

Adrenal responsiveness to Cosyntropin (synthetic ACTH_1–24) was investigated in five patients with major depression and five individually matched normal subjects. Three hours following suppression of endogenous ACTH secretion with dexamethasone (1 mg orally), the adrenal response to a 10-min infusion of Cosyntropin (0.05 μg/kg body weight) was monitored for hr by plasma cortisol measured at 15-min intervals. The depressed patients had significantly higher baseline plasma cortisol, but not higher baseline ACTH, than the controls. During the 3-hr post-dexamethasone (and prior to Cosyntropin infusion), the depressed patients maintained significantly higher cortisol secretion, but not higher ACTH secretion, than the controls. After Cosyntropin infusion, there were no differences in ACTH and cortisol increases between the two groups. These findings stand in contrast to previous reports of enhanced adrenal responsiveness to the administration of much larger amounts of Cosyntropin in major depression.     

Cortisol responses to combined dexamethasone/CRH test in outpatients with a major depressive episode

The DEX/CRH test is now a well established method to test the hypothalamic–pituitary–adrenal (HPA) axis for depressed patients in an inpatient setting. The aim of this study was to evaluate this test in an outpatient population suffering from major depression compared to a healthy control group. The main result is a statistically significant difference concerning the delta value for cortisol plasma value on the DEX/CRH test for depressed patients with two or more previous episodes compared to healthy controls. On the contrary, the difference was not statistically significant for patients with only one or no previous episodes. In future studies, it could be interesting to use this test more specifically by dividing ambulatory patients into subgroups according to their past depressive history. It could also be interesting to measure the ACTH level.