Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The diagnosis of florid Cushing's syndrome is usually made without difficulty but diagnostic problems may arise. Five such cases are described. Difficulties may occur when the features of the syndrome are incomplete. Three such cases were encountered. In each only one clinical feature was present; these respectively were hypertension, osteoporosis and obesity. The diagnosis was confirmed, however, biochemically and eventually histologically and there was a good response to surgery in each case. Another diagnostic problem, both clinically and biochemically is the obese, hirsute, hypertensive female. Two such cases are described, in whom Cushing's syndrome was diagnosed clinically and biochemically but in whom there was no response to adrenalectomy. Retrospectively the validity of the original diagnosis is questioned. It is concluded that Cushing's syndrome may present in a very incomplete form and should be considered in the differential diagnosis, even if only one feature is present. It is stressed that obesity, hirsutism, hypertension and depression are commonly found in association with normal adrenal function. Urinary free cortisol and cortisol response to insulin induced hypoglycaemia may be of value in distinguishing these cases from those with endocrine disease.
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PMID:Problems in the diagnosis of Cushing's syndrome. 19 80

Plasma corticotrophin (ACTH) was lowered in 4 out of 5 patients with pituitary dependent Cushing's syndrome (one of whom was studied only after bilateral adrenalectomy) after a single oral dose of 2.5 mg bromocriptine, but plasma cortisols were unaltered in the 3 patients in whom it was measured. Three patients were observed during treatment with bromocriptine for 16 to 87 weeks. One improved symptomatically while maintained on a combination of metyrapone and bromocriptine, but plasma ACTH levels remained high even when the dose of bromocriptine was increased to 20 mg daily. Bromocriptine therapy was discontinued after 16 weeks in the second patient due to the development of mental depression. Her clinical features had not improved during this time. The third patient, who also underwent a course of pituitary irradiation, became, and remains, symptom free, with satisfactory plasma ACTH and cortisol levels for the 87 weeks he has received bromocriptine. The role of bromocriptine in the management of Cushing's disease seems limited despite the fact that plasma ACTH may fall after a test dose of the drug.
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PMID:ACTH and cortisol response to bromocriptine, and results of long-term therapy, in Cushing's disease. 21 17

The incidence of psychiatric abnormalities has been assessed in 38 patients with Cushing's syndrome and two with alcohol-induced pseudo-Cushing's syndrome. Twenty-six patients were examined by one of us using a standardized psychiatric interview, and this group included all those with severe to moderate psychiatric disorders. Depression was the commonest symptom: five patients (13%) were markedly or severely depressed, four (10%) were moderately depressed and 13 (32%) were mildly depressed. Four patients exhibited other, non-depressive psychiatric symptoms and only 14 (35%) were judged free from psychiatric abnormality. The first line of treatment was to reduce the circulating cortisol level either by adrenalectomy or by treatment with oral metyrapone; both patients with alcohol-induced pseudo-Cushing's syndrome were treated by alcohol withdrawal. Once the plasma cortisol level was successfully controlled, depressive symptoms were relieved in all five patients with marked or severe depression and in three of the four who were moderately depressed. Mild depressive symptoms were relieved in six of the 13 affected. It is concluded that metyrapone may be of considerable value in the management of the acute psychiatric states which may occur in Cushing's syndrome and these findings are discussed in the light of their possible pathogenesis.
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PMID:Psychiatric manifestations of Cushing's syndrome: response to lowering of plasma cortisol. 54 86

After exposure to a low and high dose dexamethasone regime, 11 of 34 acute psychiatric inpatients demonstrated abnormal dexamethasone suppression characterized by morning and/or mid-afternoon escape from suppression. This abnormality of suppression was found in primary depression, in mania, and in acute schizophrenia. In primary depression, the presence of abnormal dexamethasone suppression failed to discriminate "endogenous" depressed from "other depressed" subjects. Because nonsuppression to a high dose of dexamethasone is also found in patients with ectopic ACTH secretion and in patients with autonomous adrenal tumors, caution is necessary in the interpretation of nonsuppression which persists after recovery from psychiatric illness. As patients with Cushing's syndrome of uncertain etiology may be referred to a psychiatrist for a diagnostic evaluation, the psychological correlates of abnormal dexamethasone suppression need to be established with greater certainty.
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PMID:A two-dose dexamethasone suppression test in patients with psychiatric illness. 59 3

Major depressive illness is frequently associated with cortisol hypersecretion. The pathophysiologic significance of this is unknown, although it is possible that hypercortisolemia exacerbates or perpetuates depressive symptoms. In both depression and Cushing's syndrome, certain depressive symptoms are correlated with cortisol levels and, in the latter condition, therapeutic lowering of cortisol levels is associated with remission of psychiatric symptomatology. We review the behavioral effects of anticortisolemic drug administration in Cushing's syndrome and major depression. Preliminary data from small-scale studies suggest that ratings of depressive symptoms in hypercortisolemic major depression may be lowered by such interventions. Such results, if confirmed in larger scale, double-blind studies, might help clarify the role of endocrinologic disturbance in psychiatric symptomatology and might lead to the development of a novel class of antidepressant agent for hypercortisolemic depressed patients.
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PMID:Antiglucocorticoid strategies in hypercortisolemic states. 148 Jul 27

We evaluated 20 patients with Cushing's disease (i.e., Cushing's syndrome due to ACTH-secreting pituitary microadenoma) and 20 patients with Major Depressive Disorder (MDD) using the Structured Clinical Interview for DSM-III-R (SCID) and Research Diagnostic Criteria. The diagnosis of Generalized Anxiety Disorder (GAD) was most common in Cushing's disease (79%), followed by MDD (68%), and Panic Disorder (PD) including subthreshold PD (53%). The combination of MDD and GAD and/or PD was also common in Cushing's disease (63%). Behavioral symptoms, if present, usually first occurred at or after the onset of the first physical symptoms. However, the onset of PD was associated with more chronic stages of Cushing's disease. In both Cushing's disease and MDD, more female than male relatives suffered from MDD, whereas more male than female relatives suffered from substance abuse. The data demonstrate a syndrome of anxious depression in patients with active Cushing's disease; such comorbidility has not been previously noted. The data also point to intriguing epidemiological, clinical, and biological associations between Cushing's disease, MDD and substance abuse.
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PMID:Psychiatric phenomenology in Cushing's disease. 152 59

CRF is released in response to various stressors and regulates ACTH secretion and glucocorticoid production. CRF overproduction has been implicated in affective disorders, such as depression and anorexia nervosa, and may lead to Cushing's syndrome. To test whether CRF overproduction leads to Cushing's syndrome and to develop an animal model of chronic pituitary-adrenal activation, the CRF gene was expressed under control of the metallothionein promoter in transgenic mice. CRF transgenic animals exhibit endocrine abnormalities involving the hypothalamic-pituitary-adrenal axis, such as elevated plasma levels of ACTH and glucocorticoids. These animals display physical changes similar to those of patients with Cushing's syndrome, such as excess fat accumulation, muscle atrophy, thin skin, and alopecia. These findings indicate that chronic production of excess CRF results in sustained stimulation of pituitary corticotrope cells, resulting in elevated ACTH and consequent glucocorticoid overproduction, a condition that leads to the development of Cushing's syndrome. Analysis of CRF mRNA distribution revealed that transgene expression is primarily restricted to cells that express the endogenous CRF gene and does not follow the pattern predicted of a metallothionein-regulated gene. These results suggest that DNA elements located outside of the CRF promoter but present within the CRF intron, coding, or 3'-flanking regions may contribute to the cell type specificity of CRF gene expression.
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PMID:Development of Cushing's syndrome in corticotropin-releasing factor transgenic mice. 159 49

Patients with endogenous depression (major affective disorder) frequently have high cortisol levels, but the diurnal rhythm is usually maintained and they do not develop the physical signs of Cushing's syndrome. On the other hand, depression is a frequent feature of Cushing's syndrome regardless of etiology, and it is often relieved when the cortisol levels are reduced, by whatever means. The mechanisms of the hypercortisolemia and resistance to dexamethasone suppression commonly found in endogenous depression are poorly understood; contrary to expectations, ACTH levels are not clearly elevated. There is a striking difference in the psychiatric features seen in endogenous hypercorticism compared to those seen after exogenous administration of glucocorticoids or ACTH. This suggests that either there are other stimulating or modifying factors besides ACTH or that the steroids stimulated by ACTH or other peptides differ from those in control subjects, i.e. there may be an alteration in the metabolism of steroids in depression. Little is known about the metabolic changes or the many steroids besides glucocorticoids produced by the hyperactive steroid-producing tissue. Preliminary studies suggest that major depression may be improved by steroid suppression. It is hypothesized that steroids themselves may be important in causing and perpetuating depression.
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PMID:Steroids and depression. 164 86

Even though the DST has not proved successful as a marker for depression, it has stimulated a considerable amount of research into the interaction between neuroendocrine function and mood states. With the objective of perfecting the DST methodology, investigators have explored the interaction between dexamethasone plasma concentrations and cortisol response, and have found that there is a significant inverse correlation between dexamethasone concentrations and cortisol concentrations. Although this relationship is one of the factors that affects cortisol response in depressed patients, it usually explains less than 20 percent of the variance of cortisol response. One can only conclude that the affective state explains a certain amount of the remaining variance. Dexamethasone plasma concentrations may be altered by a variety of drug and disease interactions. Many enzyme inducers, including phenytoin, carbamazepine, and phenobarbital, increase dexamethasone CL, but some drugs that might be expected to alter dexamethasone CL, such as cimetidine and tobacco smoke, do not affect it. Any disease that causes hepatic dysfunction could be expected to decrease dexamethasone CL, whereas renal failure may increase dexamethasone CL. Neither Cushing's syndrome nor congenital adrenal hyperplasia appear to alter dexamethasone CL. Alcoholism has a dual effect on the DST. Chronic alcohol abuse may cause a cushingoid state, which could interfere with the DST interpretation. Also, chronic alcohol use may result in hepatic dysfunction, or an induction of P-450 enzymes. As a result of these different actions, alcohol could result in either an increase or decrease in dexamethasone CL. Studies of dexamethasone pharmacokinetics conducted in depressed patients are few, but they generally agree that DST nonsuppressors exhibit an increased dexamethasone CL when compared with suppressors. The only two studies to investigate this population longitudinally report somewhat contradictory results; one study reports an increase in dexamethasone CL following recovery from depression, and the other a decrease. Since only one of the studies was conducted using intravenous dexamethasone, differences in bioavailability might explain some of the differences in results between the two studies. In spite of the unresolved questions, these studies have stimulated research into an entirely new area: the possibility that affective diseases may alter the pharmacokinetics of some drugs.
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PMID:The impact of dexamethasone pharmacokinetics on the DST: a review. 181 2

Because of the similarities in the psychiatric symptoms of Cushing's syndrome and those of major depression, and because the former generally remits when the hyperadrenalism is alleviated, an open clinical trial of the effect of steroid suppression in major depression was undertaken. Ten patients satisfying the DSM-III-R criteria for major depression, and classified as treatment-resistant, were included. Eight patients completed the study, which consisted of discontinuation of other psychotropic drugs and 2 months' treatment with one or more steroid suppressive agent (aminoglutethimide, ketoconazole and/or metyrapone). Six were classified as responders, and two as partial responders. In six, the improvement has been sustained for longer than 5 months after withdrawing the drugs. Side effects were mild to moderate. These results provide some evidence that steroids are involved in the maintenance of major depression, and that their suppression may lead to a readjustment of the hypothalamic-pituitary-adrenal axis with remission of the depression.
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PMID:Response to steroid suppression in major depression resistant to antidepressant therapy. 157 41


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