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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cushing's syndrome results from prolonged exposure to excess glucocorticoids. Patients with Cushing's syndrome may develop multiple metabolic problems including obesity, hyperglycemia, hypertension, depression, low bone mass, muscle atrophy, and hypogonadism. Cutaneous manifestations of hypercortisolism include skin atrophy, excessive bruising, purple striations, poor wound healing, facial plethora, vellous hypertrichosis and hirsutism. Diagnostic tests used to screen for Cushing's syndrome include 24-hour urine cortisol, the 1 mg dexamethasone suppresion test, and late night salivary cortisol. A normal screening test excludes the diagnosis of Cushing's. Patients with an abnormal screening test should be referred to an endocrinologist for complete evaluation of the pituitary-adrenal axis.
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PMID:Cushing's syndrome. 1682 7

Hypercortisolism is a common trait of Cushing's disease and depression. These two disorders also share hippocampal volume decrease and cognitive deficits. However, experimentally induced hypercortisolism induces neuronal atrophy, which has been proposed to be the phenomenon underlying the hippocampal shrinkage. We hypothesized that the above-mentioned atrophy is due to a deleterious effect of high concentrations of glucocorticoids on cytoskeletal proteins. One or two pellets (100 mg each) of corticosterone were subcutaneously implanted in adult rats. Twenty-one days later, light, medium and heavy subunits of intermediate neurofilaments (NFL, NFM and NFH) and the microtubule-associated protein 2 (MAP2) were quantified by immunohistochemistry in Ammon's horn and dentate gyrus. We also evaluated the in vitro glutamate release in hippocampal slices. Both doses of corticosterone induced a decrement of NFL, NFM and NFH in both hippocampal areas but only 200 mg decreased MAP2. This dose also diminished the potassium-stimulated glutamate release. All of these changes seemed not to be due to neuron loss, as no decrement in neuron-specific nuclear protein-positive cells was found. With the exception of NFL, the above-mentioned diminution was not observed in the globus pallidus, one of the brain regions with the lowest glucocorticoid receptor density. These results provide a subcellular insight into the trophic changes found in experimental models of hypercortisolism. The coincidence between decrements in MAP2 and glutamate release suggests possible links between high glucocorticoid levels, dendritic atrophy and the cognitive impairment reported in patients suffering from Cushing's disease and depression.
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PMID:Chronic treatment with high doses of corticosterone decreases cytoskeletal proteins in the rat hippocampus. 1722 84

The stress response is mediated by the hypothalamo-pituitary-adrenal (HPA) system. Activity of the corticotropin-releasing hormone (CRH) neurons in the hypothalamic paraventricular nucleus (PVN) forms the basis of the activity of the HPA-axis. The CRH neurons induce adrenocorticotropin (ACTH) release from the pituitary, which subsequently causes cortisol release from the adrenal cortex. The CRH neurons co-express vasopressin (AVP) which potentiates the CRH effects. CRH neurons project not only to the median eminence but also into brain areas where they, e.g., regulate the adrenal innervation of the autonomic system and affect mood. The hypothalamo-neurohypophysial system is also involved in stress response. It releases AVP from the PVN and the supraoptic nucleus (SON) and oxytocin (OXT) from the PVN via the neurohypophysis into the bloodstream. The suprachiasmatic nucleus (SCN), the hypothalamic clock, is responsible for the rhythmic changes of the stress system. Both centrally released CRH and increased levels of cortisol contribute to the signs and symptoms of depression. Symptoms of depression can be induced in experimental animals by intracerebroventricular injection of CRH. Depression is also a frequent side effect of glucocorticoid treatment and of the symptoms of Cushing's syndrome. The AVP neurons in the hypothalamic PVN and SON are also activated in depression, which contributes to the increased release of ACTH from the pituitary. Increased levels of circulating AVP are also associated with the risk for suicide. The prevalence, incidence and morbidity risk for depression are higher in females than in males and fluctuations in sex hormone levels are considered to be involved in the etiology. About 40% of the activated CRH neurons in mood disorders co-express nuclear estrogen receptor (ER)-alpha in the PVN, while estrogen-responsive elements have been found in the CRH gene promoter region, and estrogens stimulate CRH production. An androgen-responsive element in the CRH gene promoter region initiates a suppressing effect on CRH expression. The decreased activity of the SCN is the basis for the disturbances of circadian and circannual fluctuations in mood, sleep and hormonal rhythms found in depression. Neuronal loss was also reported in the hippocampus of stressed or corticosteroid-treated rodents and primates. Because of the inhibitory control of the hippocampus on the HPA-axis, damage to this structure was expected to disinhibit the HPA-axis, and to cause a positive feedforward cascade of increasing glucocorticoid levels over time. This 'glucocorticoid cascade hypothesis' of stress and hippocampal damage was proposed to be causally involved in age-related accumulation of hippocampal damage in disorders like Alzheimer's disease and depression. However, in postmortem studies we could not find the presumed hippocampal damage of steroid overexposure in either depressed patients or in patients treated with synthetic steroids.
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PMID:The stress system in depression and neurodegeneration: focus on the human hypothalamus. 1752 88

Endogenous Cushing's syndrome (CS) results from chronic exposure to excess glucocorticoids. CS can be ACTH-dependent, caused by ACTH-secreting pituitary or ectopic tumours, or ACTH-independent, caused by cortisol-secreting adrenal tumours. CS can be an extremely difficult diagnosis to make, and assessment will include clinical, biochemical and radiological evaluation. Several screening tests are used for the confirmation of hyper-cortisolaemia and its differentiation from other, more frequent, clinical abnormalities, such as simple obesity, hypertension, depression etc. Other dynamic tests are useful for establishing the aetiology. We have reviewed the current literature on the diagnosis of CS, and based on these data and our own experience, suggest the most useful tests and diagnostic criteria to be used. We conclude that even though laboratory testing is a fundamental part of the investigation of patients with CS, the interpretation of the tests should always be performed with extreme care, as none of the tests has proven fully capable of distinguishing all cases of CS. The biochemical results should be interpreted jointly with the clinical aspects and the radiology findings in a probabilistic matrix, and not as part of a uniform algorithm.
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PMID:Dynamic testing in Cushing's syndrome. 1803 6

Among endocrine disorders, Cushing's syndrome (CS) is certainly one of the most challenging to endocrinologists due to the difficulties that often appear during investigation. The diagnosis of CS involves two steps: confirmation of hypercortisolism and determination of its etiology. Biochemical confirmation of the hypercortisolaemic state must be established before any attempt at differential diagnosis. Failure to do so will result in misdiagnosis, inappropriate treatment, and poor management. It should also be kept in mind that hypercortisolism may occur in some patients with depression, alcoholism, anorexia nervosa, generalized resistance to glucocorticoids, and in late pregnancy. Moreover, exogenous or iatrogenic hypercortisolism should always be excluded. The three most useful tests to confirm hypercortisolism are the measurement of 24-h urinary free cortisol levels, low-dose dexamethasone-suppression tests, and determination of midnight serum cortisol or late-night salivary cortisol. However, none of these tests is perfect, each one has different sensitivities and specificities, and several are usually needed to provide a better diagnostic accuracy. The greatest challenge in the investigation of CS involves the differentiation between Cushing's disease and ectopic ACTH syndrome. This task requires the measurement of plasma ACTH levels, non-invasive dynamic tests (high-dose dexamethasone suppression test and stimulation tests with CRH or desmopressin), and imaging studies. None of these tests had 100% specificity and their use in combination is usually necessary. Bilateral inferior petrosal sinus sampling is mainly indicated when non-invasive tests do not allow a diagnostic definition. In the present paper, the most important pitfalls in the investigation of CS are reviewed.
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PMID:Pitfalls in the diagnosis of Cushing's syndrome. 1820 58

Pseudo-Cushing syndromes are a heterogeneous group of disorders, including alcoholism, anorexia nervosa, visceral obesity, and depression, which share many of the clinical and biochemical features of Cushing's syndrome. The mechanisms responsible for the genesis of pseudo-Cushing's syndrome are poorly understood. It has been suggested that hypercortisolism of pseudo-Cushing syndrome may be the result of increased hypothalamic corticotrophin-releasing hormone (CRH) secretion in the context of a hypothalamic-pituitary-adrenal axis that is otherwise normally constituted. The substantial overlap in clinical and biochemical features among several patients with Cushing syndrome and those with pseudo-Cushing syndromes can make the differential diagnosis difficult. Distinguishing between pseudo-Cushing's syndrome and true Cushing's syndrome is critical for preventing the unnecessary and potentially harmful treatment of such patients. This brief review summarizes the main pathophysiological events of pseudo-Cushing syndromes and provides a useful strategy for differential diagnosis.
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PMID:[Pseudo-Cushing states]. 1820 68

The activity of the pituitary-adrenal axis can profoundly impact on body composition. This is dramatically seen in Cushing's syndrome (CS) but changes in body composition are also implicated in depression and alcoholic pseudocushing's. The pathophysiological mechanisms underlying these changes remain poorly understood. Changes to body composition in CS include increased fat mass, decreased bone mass, thinning of the skin and reduced lean mass. Why these tissues are affected so dramatically is unclear. Additionally, the change in body composition between individuals varies considerably for reasons which are only now becoming evident. This paper reviews the phenotypic changes with altered pituitary-adrenal axis activity and discusses the mechanisms involved. The primary focus is on adipose, bone, muscle and skin since the most dramatic changes are seen in these tissues.
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PMID:The pituitary-adrenal axis and body composition. 1832 75

The many similarities between the metabolic syndrome and Cushing's syndrome led to the hypothesis that excess glucocorticoids (GC) are part of the pathogenesis linking their features. We review recent work that confirms the initial similarities (obesity, glucose intolerance, hypertension, and hyperlipidemia) and extends them to associated features of both syndromes (osteopenia, hypogonadism, leukocytosis, depression, and muscle weakness). Recent studies report that these features also occur in subclinical Cushing's syndrome, hypercortisolemic depression, and the transgenic overexpression of 11beta-hydoxysteroid dehydrogenase type 1 (11beta-HSD1) in mouse models of excess GC in adipose tissue. Reducing excess GC--in the clinical syndromes and in the mouse model-reverses many of these features. Because local tissue excess GC may have a central role in the pathogenesis of the metabolic syndrome, selective 11beta-HSD1 inhibitors are under active development by several pharmaceutical companies.
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PMID:Adrenal steroids and the metabolic syndrome. 1836 16

A 56-year-old woman suffered from severe depression due to Cushing's syndrome with right adrenal adenoma. She had a normal mental state before developing Cushing's syndrome. Because of her depressive state, informed consent for the treatment could not be obtained, and oral administration of 1.5 g/day metyrapone was commenced. After two weeks, her mental state had markedly improved. She subsequently underwent a right adrenalectomy, and metyrapone administration was terminated on the day of surgery. Without modification on the replacement of corticosteroids, the postoperative course was uneventful. Preoperative management of Cushing's syndrome with metyrapone may be useful in cases of severe psychiatric disturbances due to hypercortisolism.
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PMID:Preoperative management of Cushing's syndrome with metyrapone for severe psychiatric disturbances. 1838 Aug 29

Fat is stored around the abdomen in both subcutaneous and intra abdominal (visceral) sites. Visceral fat is associated in its own right with a set of metabolic abnormalities, including non insulin dependent diabetes, hypertension and dyslipidaemias. States of marked hypercortisolaemia, for example Cushing's syndrome, lead to the preferential accumulation of visceral fat. Since melancholic depression is known to be associated with elevated plasma Cortisol levels, this review explores whether depressed patients are prone to excess visceral fat storage, with the subsequent risk of developing the associated metabolic disturbances. Though the literature is limited, there is evidence that intra abdominal fat is increased in major depression. There is also evidence that depression is associated with increased risk of death from cardiovascular disease. Is visceral fat and its association with metabolic abnormalities the link between depression and physical illness?
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PMID:Melancholic depression and abdominal fat distribution: a mini-review. 1901 89


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