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

The regulation of adipose tissue distribution is an important problem in view of the close epidemiological and metabolic associations between centralized fat accumulation and disease. With visceral fat accumulation multiple endocrine perturbations are found, including elevated cortisol and androgens in women, as well as low growth hormone (GH) and, in men, testosterone (T) secretion. These abnormalities probably derive from a hypersensitive hypothalamo-pituitary-adrenal axis, with hyperinsulinemia related to a marked insulin resistance as a consequence. These hormonal changes exert profound effects on adipose tissue metabolism and distribution. At the adipocyte level cortisol and insulin promote lipid accumulation by expressing lipoprotein lipase activity, while T, GH and probably estrogens exert opposite effects. The consequences will most likely be more expressed in visceral than subcutaneous adipose tissues because of a higher cellularity, innervation and blood flow. Furthermore, the density of cortisol and androgen receptors seems to be higher in this than other adipose tissue regions. The endocrine perturbations found in visceral obesity with an abundance of the lipid accumulating hormones cortisol and insulin, and a relatively low secretion of the lipid mobilizing sex steroid hormones and GH would therefore be expected to be followed by visceral fat accumulation. The potential significance of local synthesis of steroid hormones in adipose tissue requires more attention. Although studies in vitro are informative when elucidating detailed mechanisms of hormonal interactions, they might not give a true picture of the regional integrated regulation of adipose tissue lipid storage and mobilization. Such information can be obtained by regional measurements of lipid mobilization by free fatty acid turnover or by microdialysis techniques, both showing lower rates of mobilization in leg than in upper body adipose tissues. More detailed information can be obtained by physiological oral administration of triglycerides, labelled with a small amount of oleic acid, followed by measurements of the regional uptake and turn-over of adipose tissue triglycerides. Such studies show lipid uptake in the order omental = retroperitoneal > subcutaneous abdominal > subcutaneous femoral adipose tissues in men, with a similar rank order for half-life of the triglyceride, indicating also a turn-over of triglycerides in that order. T amplifies these differences in men. In premenopausal women subcutaneous abdominal has a higher turnover than femoral adipose tissue. Results of studies in vitro indicate that this difference is diminished at the menopause, and restored by estrogen substitution, suggesting that the functional effects of estrogens in women are similar to those of T in men. The mechanisms are, however, probably indirect because of the apparent absence of specific estrogen and progesterone receptors in human adipose tissue. This interpretation from the studies referred to above fits well with physiological, and clinical conditions with increased visceral fat mass, where the balance between the lipid accumulating hormone couple (cortisol and insulin) and the hormones which prevent lipid accumulation and instead activate lipid mobilization pathways (sex steroid hormones and GH) is shifted to the advantage of the former. Such conditions include Cushing's syndrome, the polycystic ovary syndrome, menopause, aging, GH-deficiency, depression, smoking and excess alcohol intake. With appropriate interventions against hypercortisolemia and substitution of deficient sex steroids and GH, visceral fat mass is decreasing. Based on this evidence from physiological, clinical, interventional observations and detailed studies of mechanisms at cellular and molecular levels it is suggested that the combined endocrine abnormalities in the syndrome of visceral obesity direct storage fat to visceral adipose depots. Therefore, measurements of visceral fat accumulat
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PMID:The regulation of adipose tissue distribution in humans. 868 Apr 55

Patients with Cushing's syndrome were studied (n = 209, 78% females). Control patients had pituitary adenomas secreting growth hormone or prolactin. Age at diagnosis of Cushing's syndrome was 8-74 (mean 39) years. Duration of symptoms was 0.2-9 (median 2.0) years. Adverse life events within the 2 years preceding the onset of Cushing's syndrome were not significantly commoner than in controls. Depressive illnesses were associated with the presence of adverse life events (p < 0.001). Depressive illness was more common in females (p < 0.01). There were no significant differences in the severity of depression in the different types of Cushing's syndrome. Pathological anxiety had been diagnosed in 26 patients (12%), mania or hypomania in six patients (3%) and confusion in three patients (1%). Psychotic illness had been diagnosed in 16 patients (8%) and was more common in adrenal carcinomas (p < 0.01). Significant psychiatric illness, usually depressive, preceded the onset of all symptoms and signs of Cushing's syndrome in 25 patients (12%); 23 of these developed pituitary Cushing's disease, and two adrenal adenomas. When Cushing's syndrome was diagnosed, significant psychiatric illness, usually depression, was present or had been a feature of Cushing's syndrome in 120 (57%) patients.
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PMID:Psychiatric aspects of Cushing's syndrome. 875 96

Two types of hippocampal corticosteroid receptors play an important role in regulating the secretion of corticosterone: type I receptors are thought to regulate both the basal and stress induced release of corticosterone whereas type II receptors seem to be involved only in the stress response. Although these receptors are known to be regulated by circulating levels of corticosterone, there is also evidence for a direct neural control independent of hormonal influences. Furthermore, several studies suggest differential regulation of type I and type II corticosteroid receptors, with greater hormonal control of type II and greater neural control of type I. In order to investigate this theory of differential regulation of type I and type II corticosteroid receptors, we studied the effect of chronic treatment with either vehicle or the alpha 1 noradrenergic antagonist prazosin (0.5 mg/kg, i.p), on hippocampal corticosteroid receptors. Rats in one group had intact adrenal glands, whereas rats in a second group were adrenalectomized, their plasma corticosterone levels being maintained in the physiological range by implantation of corticosterone pellets. Thus, in the first group, the effects of drug-induced changes in both noradrenergic transmission and corticosterone secretion on corticosteroid receptors were investigated, whereas in the second group, the influence of altered noradrenergic transmission was effectively isolated. The results of this experiment show that, in comparison to the vehicle treatment, chronic treatment with the alpha 1 receptor antagonist prazosin decreased the number of type I corticosteroid receptors in adrenalectomized animals with corticosterone substitutive therapy. This effect on type I was not evident in adrenal-intact animals. In contrast, the prazosin treatment reduced the number of type II corticosteroid receptors in adrenal-intact animals, but not in adrenalectomized animals with corticosterone substitutive therapy. It has also been demonstrated here that, in the adrenal-intact animals, chronic prazosin induces hypersecretion of corticosterone after stress, which may account for the reduction of type II corticosteroid receptors noted in this group. Taken together, these results support the theory that type I and type II are differentially regulated: type I receptors can be regulated by noradrenaline independently of corticosterone, whereas type II receptors seem to be adjusted by circulating levels of corticosterone. These results may also suggest possible pharmacotherapies of hypothalamo-pituitary-adrenal axis dysregulation, such as that occurring during depression, Alzheimer's disease and Cushing syndrome, by targeting type I corticosteroid receptors.
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PMID:Hippocampal type I and type II corticosteroid receptors are differentially regulated by chronic prazosin treatment. 880 15

There have been few reports of factitious Cushing syndrome. To characterize the clinical and laboratory features leading to this unusual diagnosis, we describe 6 patients (5 women, 1 man), ages 31-44, identified retrospectively among 860 patients evaluated for hypercortisolism at the National Institutes of Health Clinical Center. All six patients had multiple surgeries unrelated to Cushing syndrome and a history of depression or anxiety. Four patients had close contact with the medical profession, three a history of drug abuse, and three had undergone previous treatment for Cushing syndrome. The physical features of Cushing syndrome were variable and not helpful in the differential diagnosis with endogenous Cushing syndrome. Four patients had striking variability in urine-free cortisol (UFC) and 17-hydroxysteroid (17-OHCS) values from low to high. Adrenal computed tomography, performed in two patients, showed small adrenal glands (n = 1) or a left-sided mass (n = 1), and adrenal magnetic resonance imaging, performed in one patient, showed atrophic glands. Pituitary magnetic resonance imaging, carried out in four patients, was either normal (n = 1) or exhibited questionable signs of microadenoma (n = 3). Determination of synthetic glucocorticoids by high pressure liquid chromatography (HPLC) was positive in the four patients in whom it was performed. Factitious Cushing syndrome is a difficult diagnosis. To conserve time and resources, high pressure liquid chromatography analysis of urine steroids, the most definitive test for the factitious disorder, should be performed whenever there is clinical suspicion of glucocorticoid abuse.
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PMID:Factitious Cushing syndrome. 885 3

Of the various hypothalamic-pituitary-end organ axes, the thyroid and adrenal systems have been implicated most often in affective disorders. Patients with primary thyroid disease have high rates of depression, and patients with Addison's disease or Cushing's syndrome have relatively high rates of affective and anxiety symptoms. However, the major support for these endocrine axes in the pathophysiology of mood disorders comes from studies in which alterations in components of the hypothalamic-pituitary-thyroid (HPT) and the hypothalamic-pituitary-adrenal (HPA) axes have been documented in patients with primary depression. Concerning the HPT axis, depressed patients have been reported to have: (a) alterations in thyroid-stimulating hormone response to thyrotropin-releasing hormone (TRH); (b) an abnormally high rate of antithyroid antibodies; and (c) elevated cerebrospinal fluid (CSF) TRH concentrations. Moreover, tri-iodothyronine has been shown conclusively to augment the efficacy of various antidepressants. Concerning the HPA axis, depressed patients have been reported to exhibit: (a) adrenocorticoid hypersecretion; (b) enlarged pituitary and adrenal gland size; and (c) elevated CSF corticotropin-releasing factor concentrations. All of the HPA axis alterations in depression studied thus far are state-dependent, whereas the HPT axis alterations may be partially trait and partially state markers.
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PMID:Depression and endocrine disorders: focus on the thyroid and adrenal system. 886 58

Antiprogestogens, which block the action of progesterone at the cellular level through binding to the progesterone receptor, are proving to be one of the most significant developments in endocrinology in recent years. Several hundreds of such compounds have been synthesized, but only a few of them have been evaluated to any significant extent in biological screening models and, to our knowledge, only three compounds, namely mifepristone, lilopristone (ZK 98.734) and onapristone (ZK 98.299) have been given to humans. Most of the clinical research to date has focused on the use of mifepristone given in combination with prostaglandin for termination of early pregnancy, an indication for which the compound is being used routinely in four countries so far, i.e. China, France, the UK and Sweden. The gynaecological and obstetrical applications in which antiprogestogens have been shown to be of value to date include ripening of the pregnant cervix prior to pregnancy termination, sensitization of the uterus to prostaglandins in second-trimester abortion, and induction of labour. Available data suggest that antiprogestogens have no place in the conservative treatment of ectopic pregnancy or in the treatment of premenstrual tension. In fertility regulation, the sequential combination regimen of mifepristone plus prostaglandin as used for inducing abortion has proved to be effective also for menses induction and can be expected to be an efficacious once-a-month contraceptive. Mifepristone alone, without adjuvant prostaglandin, has yielded promising results as an anti-implantation agent and in emergency contraception. Other potential uses include once-a-week contraception, ovulation inhibition (in a sequential regimen with a progestogen), and as a daily mini-pill. Mifepristone, and other antiprogestogens for which biological data have been reported also bind to the cellular receptors for glucocorticoid hormones and, consequently, possess antiglucocorticoid in addition to their antiprogestational activity. Because of this antiglucocorticoid effect, mifepristone has been employed successfully in the palliative treatment of hypercortisolism due to Cushing's syndrome, and its use has been proposed for treating certain forms of depression and of glaucoma, and in wound healing. However, for scientific and practical reasons, it would be preferable if molecules were developed that have only the antiprogestational or the antiglucocorticoid activity rather than both.
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PMID:Clinical uses of antiprogestogens. 908 Feb 4

The hypothalamic-pituitary-adrenal (HPA) axis and the female reproductive system are intertwined and exhibit a complex relationship. Thus, the HPA axis exerts profound, mostly inhibitory effects, on the reproductive axis, with corticotropin-releasing hormone (CRH) and CRH-induced propiomelanocortin peptides inhibiting hypothalamic GnRH secretion, and with glucocorticoids inhibiting pituitary LH and ovarian estrogen and progesterone secretion and rendering estrogen-target tissues, such as the endometrium, resistant to the gonadal steroid. These effects of the HPA axis are responsible for the "hypothalamic" amenorrhea of stress, depression and eating disorders, and the hypogonadism of Cushing's syndrome. Conversely, estrogen directly stimulates the CRH gene, which may explain the slight hypercortisolism of females and the preponderance of depressive, anxiety, and eating disorders, as well as Cushing's disease in women. Interestingly, several components of the HPA axis and their receptors are present in reproductive tissues, as autocoid regulators of their various functions. These include ovarian and endometrial CRH, which may participate in the inflammatory processes of the ovary, that is, ovulation and luteolysis, and of the endometrium, that is, implantation and menstruation. Finally, the hypercortisolism of the latter half of pregnancy can be explained by high levels of placenta CRH in plasma. This hypercortisolism causes a transient adrenal suppression in the postpartum period, which may explain the postpartum blues/depression and autoimmune phenomena of this period.
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PMID:The hypothalamic-pituitary-adrenal axis and the female reproductive system. 923 54

In major depression there are two well-documented biochemical abnormalities: hypercortisolism, and its resistance to dexamethasone suppression. It therefore seems reasonable to see if giving drugs which interfere with cortisol biosynthesis might bring about a remission. An open trial was begun in our institution of 20 refractory patients with major depression. Aminoglutethimide, metyrapone, ketoconazole or combinations of these drugs along with a maintenance dose of cortisol were used for eight weeks. Of the 17 completers, eleven patients were considered to have good responses and two partial responses. Four had complete remissions lasting several years. A similar study of four patients who received oral RU 486 also gave encouraging results. Two patients with obsessive compulsive disorder associated with depression showed striking improvement on aminoglutethimide combined with a serotonin re-uptake inhibitor. In addition to a case report in 1988 by Ravaris et al. of a patient hypophysectomized for previous Cushing's syndrome whose depression responded to ketoconazole, several other studies over the past five years have had similar favorable results. Wolkowitz et al. (1993) gave oral ketoconazole to 10 depressed patients for three weeks which resulted in a significant drop in their Hamilton Depression Scale ratings. O'Dwyer et al. (1995) conducted a placebo-controlled single-blind crossover study using lifetyrapone and maintenance cortisol in eight inpatients for two weeks; six responded. Thakore and Dinan (1995) studied eight inpatients using ketoconazole for four weeks; there were five responders and three partial responders. Anand et al. (1995) conducted a four-week double-blind trial of ketoconazole in a single treatment-refractory patient with good results. Arana et al. (1995) used a different approach but one which also leads to suppression of endogenous corticosteroids-i.e. short-term dexamethasone suppression (4 mg/day for four days). When tested at 14 days, 7/19 of the dexamethasone group had responded well while only 1/18 of the placebo group had responded. While these studies have shortcomings, antiglucocorticoid therapy appears to be an effective tool in the treatment of major depression. Possible mechanisms are discussed, and a unifying hypothesis is attempted.
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PMID:Antiglucocorticoid therapies in major depression: a review. 926 59

The overnight dexamethasone (DXM) test can give false-positive results in a few conditions (e.g. stress, strenuous exercise, depression, anorexia, anxiety, anticonvulsive therapy) in diagnosing simple obesity and hypercortisolism (HC). The loperamide (LP; a peripheral opioid agonist) test has proven useful in such conditions in adults. Thirty-one obese subjects (age 10.0-19.7 y) were studied by both overnight DXM test and LP test (8 mg orally, samples for cortisol at 0, 90, 150, 180 and 210 min) on 2 separate days. LP suppressed cortisol (< or = 138 nmol l-1) at a dose of 0.1 mg kg-1 bw (half the minimum recommended dose for the drug's antidiarrhoea effect) in 14 subjects who had normal urinary (< 4970 nmol l-1) and serum (< 552 nmol l-1) cortisol, in the absence of signs and symptoms of HC (group A). The DXM test failed to suppress cortisol in three subjects in group A, two of whom were on anticonvulsive treatment. The LP test suppressed cortisol in all of 13 subjects with elevated urinary and/or serum cortisol and/or with signs or symptoms of HC (but in whom HC was subsequently excluded on clinical grounds) (group B), while the DXM test failed to suppress cortisol in three subjects of this group. One of these was under anticonvulsive treatment and one suffered from anxiety and depression. In four patients with Cushing's syndrome (group C) neither DXM nor LP could suppress cortisol levels. Therefore, the sensitivity was 100% for both DXM and LP, while the specificity was 84% for DXM and 100% for LP. No side-effects were observed with either drug. In conclusion, LP is a useful alternative to DXM in those particular conditions that can affect its specificity in children.
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PMID:Loperamide test: a simple and highly specific screening test for hypercortisolism in children and adolescents. 940 9

The mechanisms and pathophysiology of sleep disturbances in patients with endocrine diseases are reviewed. Abnormalities in sleep regulations were demonstrated in patients with thyrotoxicosis and hypothyroidism in a use of electroencephalogram during sleep. Mental disorders are one of the causes of sleep disturbance, for example insomnia due to depression in Cushing's syndrome. Metabolic abnormalities such as hyponatremia and hypoglycemia due to adrenal insufficiency could also contribute to sleep disturbance. Obstructive, central and mixed types of sleep apnea syndrome are known to occur in hypothyroidism, acromegaly and diabetic neuropathy with autonomic dysfunction. Thus, multiple factors are involved in sleep disturbance in patients with endocrine disorders.
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PMID:[Sleep disorders in several pathologic states--endocrine diseases]. 950 51


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