cosyntropin and Depressive-Disorder

To determine the relationship of pretreatment hypothalamic-pituitary-adrenal cortical (HPA) axis measures in major depressives to the occurrence of relapse following discontinuation of successful treatment, we compared pretreatment demographic, clinical, and HPA axis measures in 35 patients with DSM-III-R primary major depression divided into two groups. One group (n = 26) required continuing treatment to hold their symptoms in abeyance, and the other group (n = 9) had been successfully tapered off medication, remained in remission, and had been medication-free for at least 1 month. The major features that differentiated the 26 patients who required continuing medication to abate their symptoms from the 9 patients who were successfully discontinued from treatment were trends toward a longer duration of episode prior to initial study and increased baseline corticotropin (ACTH) 1-39, and significantly higher baseline cortisol and cortisol response to ACTH 1-24, in the former group. These results suggest that measures of HPA axis hyperactivity, along with longer duration of the index depressive episode, may predict the need for continuing medication for patients to remain in remission.

Topics: Adrenocorticotropic Hormone; Adult; Antidepressive Agents; Corticotropin-Releasing Hormone; Cosyntropin; Depressive Disorder; Female; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Male; Middle Aged; Personality Inventory; Pituitary-Adrenal System; Prognosis; Recurrence; Substance Withdrawal Syndrome

To date, there appears to be no consensus of opinion as to whether the adrenal glands are hyperresponsive during depression and, if so, whether this a state-dependent phenomenon. We aimed to determine the effects of antidepressant treatment on ACTH-induced cortisol responses in patients with melancholic depression. Seven female patients with DSM-III-R major depressive disorder, non-psychotic, melancholic subtype, were evaluated using the following rating scales: the Hamilton Depression Rating Scale, the Montgomery-Asberg Depression Rating Scale and the Newcastle Endogenicity Scale. All subjects were then given an intravenous bolus dose (250 micrograms) of tetracosactrin, a potent stimulus of adrenocortical hormone secretion. Plasma levels of cortisol were measured at times 0, + 30, + 60, + 90, + 120 and + 180 min. Patients were then randomised to receive either 50 mg of sertraline or 20 mg of paroxetine (both of which are selective serotonin re-uptake inhibitors) and were re-tested while medication-free. Treatment resulted in a significant decrease in delta (the difference between the baseline values and the maximum increase post-ACTH administration) cortisol values of 1633.3 +/- 378.5 nmol/l vs. 595.1 +/- 207.7 nmol/l. Successful pharmacological treatment of major depressive disorder appears to be associated with a reduction in ACTH-induced cortisol release in drug-free patients.

Topics: Adult; Analysis of Variance; Antidepressive Agents, Second-Generation; Biomarkers; Cosyntropin; Depressive Disorder; Female; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Middle Aged; Pituitary-Adrenal System; Selective Serotonin Reuptake Inhibitors; Severity of Illness Index; Time Factors

Fatigue is a common symptom in patients visiting the clinic of psychosomatic medicine. A 250-μg synthetic ACTH (1-24) test (rapid ACTH test) and Beck depression inventory (BDI) were performed for 62 patients presenting with fatigue who visited the Department of Psychosomatic Medicine at Fukuoka Tokushukai Hospital. Patients were divided into 3 groups according to the serum cortisol response to the rapid ACTH test; those with a peak serum cortisol level of <15 μg/dL were defined as the adrenal insufficiency (AI) probable group, ≥15 μg/dL and <18 μg/dL as the AI suspected group, and ≥18 μg/dL as the non-AI group. Patients prescribed anti-depressants, had a BDI ≥16, and/or met the full criteria for major depression were diagnosed with depression. Five (8.0%) and 7 patients (11.3%) were assigned to the AI probable and AI suspected groups, respectively. All others were assigned to the non-AI group. Depression was observed in 37 patients (59.6%; 4 in the AI probable group [80.0%], 4 in the AI suspected group [57.1%], and 29 in the non-AI group [58.0%]). Users of exogenous steroids, such as inhaled steroids for bronchial asthma, were seen in the AI probable group (2; 40.0%), the AI suspected group (3; 42.8%), and the non-AI group (7; 14.0%) (χ

Topics: Administration, Inhalation; Adrenal Cortex Function Tests; Adrenal Cortex Hormones; Adrenal Insufficiency; Adult; Antidepressive Agents; Cosyntropin; Depressive Disorder; Fatigue; Female; Hormones; Humans; Hydrocortisone; Male; Middle Aged; Psychosomatic Medicine

Early adverse life events may predispose individuals to the development of mood and anxiety disorders in adulthood, perhaps by inducing persistent changes in corticotropin-releasing factor (CRF) neuronal systems. The present study sought to evaluate pituitary-adrenal responses to standard hypothalamic-pituitary-adrenal axis challenge tests in adult female survivors of childhood abuse with and without major depressive disorder.. Plasma ACTH and cortisol responses to the administration of 1 microg/kg ovine CRF and plasma cortisol responses to the administration of 250 microg ACTH(1-24) were measured in healthy women without early life stress (N=20), women with childhood abuse without major depressive disorder (N=20), women with childhood abuse and major depressive disorder (N=15), and women with major depression but no early life stress (N=11).. Abused women without major depressive disorder exhibited greater than usual ACTH responses to CRF administration, whereas abused women with major depressive disorder and depressed women without early life stress demonstrated blunted ACTH responses. In the ACTH(1-24) stimulation test, abused women without major depressive disorder exhibited lower baseline and stimulated plasma cortisol concentrations. Abused women with comorbid depression more often suffered from posttraumatic stress disorder and reported more recent life stress than abused women without major depressive disorder.. These findings suggest sensitization of the anterior pituitary and counterregulative adaptation of the adrenal cortex in abused women without major depressive disorder. On subsequent stress exposure, women with a history of childhood abuse may hypersecrete CRF, resulting in down-regulation of adenohypophyseal CRF receptors and symptoms of depression and anxiety.

Topics: Adrenocorticotropic Hormone; Adult; Age Factors; Child; Child Abuse; Comorbidity; Corticotropin-Releasing Hormone; Cosyntropin; Depressive Disorder; Disease Susceptibility; Down-Regulation; Female; Humans; Hydrocortisone; Life Change Events; Pituitary Gland, Anterior; Receptors, Corticotropin-Releasing Hormone; Stress Disorders, Post-Traumatic; Survivors

We measured adrenal gland volume and both baseline and stimulated pituitary and adrenal cortical hormones in 35 unmedicated, major depressives and 35 individually matched normal control subjects. Mean adrenal volume in the depressives was significantly larger, by about 38%, than the adrenal volume of their matched controls. Basal plasma adrenocorticotropic hormone (ACTH)1-39 was significantly lower, and basal plasma cortisol was significantly higher, in the patients. In contrast, basal plasma ACTH determined by radioimmunoassay (RIA) was not significantly different between the two groups. The ACTH response to ovine corticotropin-releasing hormone (oCRH), whether measured specifically as ACTH1-39 or by the less-specific RIA, was highly significantly lower in the depressives than in the controls. However, neither the cortisol response to oCRH nor its response to low-dose ACTH 1-24 differed significantly between groups. In both groups of subjects, correlations between adrenal gland volume and all the hormone measures were low, and none represented more than 4% shared variance. In the patients, adrenal volume did not correlate significantly with duration of the present episode, lifetime number of episodes, melancholic subtype, Hamilton Depression Scale total score, or the Hamilton suicidality item. However, adrenal volume was significantly positively related to the somatization factor of the Hamilton scale, which was almost totally accounted for by the specific items of somatic symptoms and somatic anxiety.

Topics: Adolescent; Adrenal Cortex; Adrenal Glands; Adrenocorticotropic Hormone; Adult; Corticotropin-Releasing Hormone; Cosyntropin; Depressive Disorder; Female; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Magnetic Resonance Imaging; Male; Middle Aged; Organ Size; Personality Inventory; Pituitary-Adrenal System; Radioimmunoassay

Hyperactivity of the pituitary-adrenocortical axis is the most prominent neuroendocrine abnormality in major depression. It is state-related, returning to normal with resolution of the depressive episode. Adrenal gland enlargement also has been reported in patients with major depression and has been hypothesized as an index of cumulative lifetime depression. However, whether or not adrenal enlargement decreases with successful treatment of depression has not yet been studied, to our knowledge. We, therefore, determined adrenal gland volume in patients with major depression before and after treatment and in matched normal controls, and compared adrenal size with functional indexes of pituitary-adrenocortical activity.. Adrenal volumes were measured by magnetic resonance imaging in nine adult and two adolescent patients with major depression during their illness and during full remission when medication had been stopped for at least 1 month, and in nine adult and two adolescent normal control subjects individually matched to the patients. Basal, 4 to 7 PM plasma corticotropin 1-39 and cortisol levels, and corticotropin 1-39 and cortisol responses to administration of ovine corticorelin and lowdose cosyntropin also were measured.. Mean adrenal gland volume was significantly larger, by about 70% in the patients while depressed than after successful treatment, and it also was significantly larger, again by about 70%, than the mean adrenal gland volume of their matched controls. After treatment, the mean adrenal volume of the patients decreased and was no longer significantly different from that of their controls at baseline. The magnitude of the decrease was significantly positively correlated with the duration of the depressive episode. Basal, late-afternoon plasma corticotropin 1-39 levels were significantly lower in the patients while depressed than in their matched controls, but basal plasma cortisol levels did not differ significantly among the three groups, nor did the corticotropin 1-39 and cortisol responses to corticorelin or the cortisol response to cosyntropin. Correlations between adrenal gland volume and basal corticotropin and cortisol levels, and the corticotropin and cortisol responses to hormone challenge, were not consistently in the expected direction in any of the three groups of subjects.. Adrenal gland enlargement occurring during an episode of major depression appears to be state-dependent, in that it reverts to the normal size range during remission after treatment. It thus does not appear to be an index of cumulative lifetime depression. The lack of a discernible relationship between adrenal volume and pituitary-adrenocortical activity remains to be explained and might be related to noncorticotropin influences on the adrenal gland, including other tropic hormones and/or neural mechanisms.

Topics: Adolescent; Adrenal Glands; Adrenocorticotropic Hormone; Adult; Ambulatory Care; Antidepressive Agents; Circadian Rhythm; Corticotropin-Releasing Hormone; Cosyntropin; Depressive Disorder; Female; Humans; Hydrocortisone; Magnetic Resonance Imaging; Male; Middle Aged; Treatment Outcome

Topics: Adrenal Cortex; Adult; Cosyntropin; Depressive Disorder; Dexamethasone; Female; Humans; Infusions, Intravenous; Male; Middle Aged

There is evidence that excessive cortisol secretion in depressed patients might result, in part, from an enhanced adrenocortical sensitivity to corticotropin. This phenomenon has been examined using the cosyntropin (alpha1-24-corticotropin) stimulation test. Most studies have used supramaximal doses of cosyntropin administered in the morning, when adrenal sensitivity to corticotropin is at its maximum. This could partially obscure subtle differences in adrenocortical sensitivity in depression that might otherwise be evident at lower cosyntropin doses given later in the day. To test this hypothesis, we administered two consecutive cosyntropin tests on separate occasions employing a submaximal 0.05-microgram/kg dose and a maximal 0.2-microgram/kg dose. The cortisol centered cumulative response over 240 minutes was measured after each test in 12 depressed patients (7 melancholic, 5 nonmelancholic) and 6 healthy volunteers. When the difference in mean cortisol centered cumulative response values was determined, healthy controls demonstrated a significant increase in cortisol centered cumulative response, while the nonmelancholic patients had a less robust increase in cortisol centered cumulative response. In contrast, the melancholic patients demonstrated cortisol responses similar to those of the healthy subjects after each cosyntropin dose, suggesting an enhanced adrenocortical sensitivity to corticotropin. These data support the hypothesis that increased glucocorticoid secretion in depression may result from abnormalities at several sites within the hypothalamic-pituitary-adrenocortical axis.

Topics: Adrenal Cortex; Circadian Rhythm; Cosyntropin; Depressive Disorder; Dose-Response Relationship, Drug; Humans; Hydrocortisone

Topics: Adrenal Cortex; Adrenocorticotropic Hormone; Circadian Rhythm; Cosyntropin; Depressive Disorder; Dexamethasone; Humans; Hydrocortisone; Research Design

Adrenal responsiveness to Cosyntropin (synthetic ACTH) 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 micrograms/kg body weight) was monitored for 2 1/2 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.

Topics: Adrenocorticotropic Hormone; Adult; Age Factors; Body Weight; Cosyntropin; Depressive Disorder; Dexamethasone; Female; Humans; Hydrocortisone; Male; Middle Aged; Sex Factors

Failure to suppress cortisol secretion after administration of dexamethasone occurs in up to 50% of depressed patients. To test whether this hypothalamic-pituitary-adrenal (HPA) overactivity is associated with adrenocortical hyperresponsiveness, we performed dexamethasone suppression tests (DSTs) and adrenocorticotropic hormone (ACTH) stimulation tests in depressed subjects and subjects with other psychiatric disorders. Three groups were defined: depressed nonsuppressors, depressed suppressors, and other suppressors. While predexamethasone and postdexamethasone cortisol concentrations were greater in the depressed nonsuppressor group, ACTH concentrations did not differ among groups. After receiving alpha-ACTH[1-24] (4.2 micrograms/kg), depressed nonsuppressors had greater increases in stimulated cortisol secretion than the other groups. These results demonstrate that in a subgroup of depressed patients, HPA overactivity is associated with adrenocortical hyperresponsiveness.

Topics: Adrenal Cortex; Adrenocorticotropic Hormone; Adult; Cosyntropin; Depressive Disorder; Dexamethasone; Female; Humans; Hydrocortisone; Male; Middle Aged

ACTH alpha 1-24 (cosyntropin) (250 micrograms by intravenous bolus) was given to 38 medicated patients with major depressive disorder (MDD) and to 34 normal control subjects. Patients with MDD had significantly higher plasma cortisol concentrations and significantly higher increases in plasma cortisol levels 60 minutes after cosyntropin infusion than did control subjects. Patients who were nonsuppressors in the dexamethasone suppression test had significantly higher 60-minute cortisol concentrations and cortisol increases than did normal subjects and patients with MDD who were suppressors. There were significant, strongly positive correlations between cortisol secretory responses to cosyntropin and postdexamethasone cortisol concentrations in patients with MDD. These findings confirm that adrenal sensitivity to corticotropin (ACTH) is enhanced in MDD and suggest that this endocrine abnormality may be related pathophysiologically to the resistance of cortisol secretion to dexamethasone suppression.

Topics: Adolescent; Adrenal Glands; Adrenocorticotropic Hormone; Adult; Age Factors; Aged; Circadian Rhythm; Cosyntropin; Depressive Disorder; Dexamethasone; Female; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Male; Middle Aged; Pituitary-Adrenal System; Stimulation, Chemical

Excessive cortisol secretion after cosyntropin (adrenocorticotropic hormone; ACTH) infusion in some depressed patients has suggested the possibility that the adrenal cortex may have heightened responsiveness to ACTH, and that this may contribute, in part, to activation of the hypothalamic-pituitary-adrenocortical axis. We administered an ACTH test and dexamethasone suppression test (DST) to 32 patients before and after treatment. Maximal cortisol response to ACTH demonstrated a significant decrease after treatment in the subgroup of melancholic/DST nonsuppressors (p = 0.04). When the cumulative cortisol response (CCR) to ACTH was examined, the DST nonsuppressors had a greater CCR decrease than suppressors (p = 0.03), and the melancholics a greater decrease than nonmelancholics (p = 0.02). The melancholic/DST nonsuppressor subgroup had the largest CCR decrease after treatment (p = 0.03), and these patients may represent a group of depressives with altered adrenocortical function that tends to "normalize" with clinical recovery.

Topics: Adrenocorticotropic Hormone; Adult; Aged; Antidepressive Agents; Cosyntropin; Depressive Disorder; Female; Follow-Up Studies; Humans; Hydrocortisone; Male; Middle Aged

Cosyntropin (ACTH alpha 1-24) infusion caused significantly higher cortisol concentrations, with earlier peak responses, in patients with endogenous depression than in normal subjects. There was no relationship between the cortisol levels after administration of dexamethasone and cosyntropin.

Topics: Adrenocorticotropic Hormone; Adult; Cosyntropin; Depressive Disorder; Dexamethasone; Female; Humans; Hydrocortisone