Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Patients with simple exogenous obesity are characterized by increased B-endorphin (B-EP) plasma levels, despite normal ACTH and B-Lipotropin (B-LPH). To evaluate the origin of such an hyperendorphinemia, 42 obese patients were submitted to a short overnight dexamethasone suppression test (DST: 1 mg at 23:00 h). Blood samples were taken in basal conditions and 9, and 17 h after DST. The same procedure was applied in 12 healthy, normal weight volunteers. In further five patients, 0.5 mg per 4/die were given. B-EP was measured by radioimmunoassay (RIA) after silicic acid extraction and Sephadex G-75 column chromatography. ACTH and Cortisol were measured by direct IRMA and RIA, respectively. Basal B-EP levels of patients (24.2 +/- 16.5, fmol/ml, M +/- SD) were double than in normal weight controls (10.8 +/- 4.6), while ACTH and cortisol fell in the normal range. ACTH and cortisol were significantly reduced by DST in both patients and controls, while B-EP in patients did not. Cortisol, however, was not suppressed in 7 patients (16%). At 08:00, the suppression of B-EP in controls was 49.0 +/- 18.4%, while in obese patients it was only 21.2 +/- 38.8% (p less than 0.01). However, patients with weight excess below 50% normally suppressed B-EP (41.6 +/- 15.3%), while those with weight excess over 75% did not (11.3 +/- 47.5%). The doubling of dexamethasone intake does not lead to a suppression of plasma B-EP in these last patients. These data indicate the existence of neuroendocrine abnormalities in the hypothalamus-pituitary-adrenal axis of obese patients and suggest that their hyperendorphinemia originates outside the anterior pituitary.
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PMID:Plasma B-endorphin resistance to dexamethasone suppression in obese patients. 283 30

Abnormalities of the adrenal cortex may be associated with extreme obesity but there is little information about hypothalamic-pituitary function. We have investigated this by measuring plasma ACTH and cortisol responses to ovine corticotrophin releasing factor (CRF-41), 0.5 microgram/kg/body weight, in 10 obese women and seven age-matched normal weight women. The cortisol response to insulin-induced hypoglycaemia and intravenous synacthen (2.5 ng/kg/body weight) were also measured on different occasions in some of the subjects. The peak ACTH response to CRF was less in the obese but this was not significant (obese ACTH +/- SEM, 31 +/- 4 ng/l, controls 39 +/- 4 ng/l) whereas the peak cortisol was significantly reduced in the obese (obese cortisol, 456 +/- 21 nmol/l, controls 638 +/- 50 nmol/l). Doubling the dose of CRF did not significantly alter either ACTH or cortisol responses in six of the obese patients. The peak cortisol response to symptomatic hypoglycaemia and following i.v. low dose synacthen stimulation was similar in the obese and normal weight women. We conclude that obese women have a normal cortisol response to hypothalamic-pituitary stimulation by hypoglycaemia and direct adrenal stimulation by synacthen but an impaired adrenal response to pituitary stimulation with CRF. Although the explanation for these findings is uncertain, our study underlines the importance of considering an individual's body weight when assessing the cortisol response to CRF stimulation.
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PMID:The cortisol response to corticotrophin-releasing factor is blunted in obesity. 284 43

The role of alpha 2-adrenoceptor stimulation by clonidine on the secretion of beta-endorphin, ACTH, and cortisol in essential hypertension and obesity was studied in 45 subjects: 15 non-obese hypertensives, 10 obese hypertensives, 11 obese normotensives, and 9 healthy subjects. The circadian rhythm of plasma beta-endorphin, ACTH, and cortisol was determined after placebo and after three days on clonidine 0.45 mg daily. Clonidine lowered the blood pressure and blood ACTH and cortisol levels in all the subjects. A significant decrease in beta-endorphin after clonidine occurred in the healthy subjects. In obese normotensives basal beta-endorphin concentrations were significantly higher than in healthy subjects and did not change after clonidine. In about 50% of non-obese and obese hypertensives a significant increase in beta-endorphin secretion after clonidine was noted (responders). In the subgroup of non-obese hypertensive responders no circadian rhythm of beta-endorphin was observed. The results suggest that adrenergic regulation of beta-endorphin secretion is altered in obesity and in certain patients with essential hypertension.
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PMID:Effect of clonidine on beta-endorphin, ACTH and cortisol secretion in essential hypertension and obesity. 284 28

We have studied the regulation of adrenal function in male rats treated neonatally with monosodium glutamate (MSG) and in littermate controls. When 6-7 months old, MSG-treated rats presented reduced body, adrenal and pituitary weight, obesity, atrophy of the optic nerve and damage of the arcuate nuclei (ARN) of the hypothalamus. MSG-treated rats showed increased serum corticosterone (CORT) levels under resting conditions; after ether stress the increase in serum CORT was greater in MSG animals when compared to littermate controls. Plasma ACTH followed the same trend although it reached significance after ether stress only. Both circulating CORT and ACTH were normally suppressed by dexamethasone (DEX) administration. Levels of corticosteroid binding globulin were also increased, whereas daily circadian rhythm of serum CORT was blunted. We also determined cytosolic receptors in areas suggested to participate in the negative feedback of glucocorticoids at the central level. Binding of (3H)-DEX in MSG rats was similar to controls in hippocampus, whole hypothalamus and anterior pituitary, but a significant reduction (approximately equal to 50%) was obtained after microdissection in the area normally occupied by the ARN, without changes in the ventromedial nuclei of the hypothalamus. These results suggest that the ARN may be involved in the regulation of the pituitary-adrenal axis, although the abnormalities observed in the MSG syndrome partially differ from those in rats with hippocampal damage, previously studied in our laboratory.
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PMID:Regulation of the central nervous system-pituitary-adrenal axis in rats after neonatal treatment with monosodium glutamate. 285 47

An increase in the number of diagnostic parameters (in addition to the determination of the urine level of 17-OCS, a study was also made of the level of 17-KS, blood concentrations of ACTH, prolactin, cortisol, and glucose before and after dexamethasone administration at a dose of 0.5 mg every 6 h for 2 days) and strict rules to be observed by examinees prepared for test performance made in possible to raise the differential-diagnostic role of Liddle's minor dexamethasone test. This conclusion was based on the examination of 34 persons without obesity, 25 patients with exogenous constitutional obesity, 75 patients with juvenile pubertal dyspituitarism, 107 patients with hypothalamic obesity, 8 patients with Cushing's syndrome determined by adrenal corticosteroma, one patient with ACTH-ectopic syndrome, and patients with Itsenko-Cushing disease (128 untreated patients, 99 patients with recurrence, 98 patients in remission). The comparison of clinico-instrumental results with the results of the test has shown its informative value for objective assessment of the gravity of disease. Stages of body responses to small doses of dexamethasone (the stage of lost responses, the stage of incomplete loss and the stage of recovered responses) were identified contributing to objective assessment of the gravity, course, presence, recurrence and remission of Itsenko-Cushing disease.
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PMID:[Use of the "extended" minor dexamethasone test in Itsenko-Cushing disease]. 285 54

To evaluate whether or not patients with Cushing's disease can be differentiated from those with obesity by the determination of 24-hour integrated serum concentrations of cortisol we studied healthy, nonobese males (n = 5), as well as patients with marked obesity (n = 5) and with Cushing's disease (n = 7) in whom diagnosis was established biochemically and subsequently confirmed by surgery. Serum cortisol concentrations in samples collected continuously by a portable blood withdrawal pump during 24 hours (08:00-08:00h) were 6.6 +/- 1.7 micrograms/dl and 8.4 +/- 1.5 micrograms/dl in nonobese and obese individuals, respectively. Patients with Cushing's disease presented a mean cortisol concentration of 21.4 +/- 6.4 micrograms/dl (p vs normal: less than 0.005; vs obesity: less than 0.005). Collecting consecutive samples in 4-h periods the decline of serum cortisol from peak to nadir values was 73 +/- 10% and 57 +/- 23% in normal males and obese subjects, respectively, while a decline of only 22 +/- 8% was seen in patients with Cushing's disease. Three of the patients with Cushing's disease exhibited a circadian rhythm of cortisol albeit on an elevated level. These results may reflect variable stages of autonomy in pituitary ACTH-production and hence a possible criteria for differentation of hypothalamic and pituitary forms of Cushing's disease. In regard to differential diagnosis between Cushing's disease and obesity the 24-hour cortisol profile obtained by multiple sampling did not provide additional information to that obtained by a single sample pooled for 24 hours, which was diagnostic in each case.
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PMID:24-hour serum concentration profile of cortisol in patients with Cushing's disease. 285 18

A patient with Cushing's syndrome due to ectopic ACTH secretion was treated successfully with the new glucocorticoid antagonist RU 486 [17 beta-hydroxy-11 beta-(4-dimethylamino phenyl) 17 alpha-(1-propynyl)estra-4,9-dien-3-one]. This compound is a 19-nor steroid with substitutions at positions C11 and C17 which antagonizes cortisol action competitively at the receptor level. Oral RU 486 was given in increasing doses of 5, 10, 15, and 20 mg/kg . day for a 9-week period. Treatment efficacy was monitored by assessment of clinical status and by measuring several glucocorticoid-sensitive variables, including fasting blood sugar, blood sugar 120 min after oral glucose administration, and plasma concentrations of TSH, corticosteroid-binding globulin, LH, testosterone-estradiol-binding globulin, and total and free testosterone. With therapy, the somatic features of Cushing's syndrome (buffalo hump, central obesity, and moon facies) ameliorated, mean arterial blood pressure normalized, suicidal depression resolved, and libido returned. All biochemical glucocorticoid-sensitive parameters normalized. No side-effects of drug toxicity were observed. We conclude that RU 486 may provide a safe, well tolerated, and effective medical treatment for hypercortisolism.
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PMID:Successful treatment of Cushing's syndrome with the glucocorticoid antagonist RU 486. 299 27

Young and mature, genetically obese and non-obese, spontaneously hypertensive rats (SHR) were injected with saline (controls) or naloxone for 12 weeks. Naloxone stilled the hyperphagia to a normal intake in the obese SHR (Obese/SHR) so that young Obese/SHR did not develop their usual massive obesity and mature Obese/SHR that had become massively obese were reduced to leanness. The naloxone-treated young, obese and non-obese SHR (controls) exhibited marked reduction of the weight of their pituitary and adrenal glands, whereas the pituitary and adrenal glands of naloxone-treated mature, obese and non-obese/SHR were greatly increased in weight. The elevated systolic blood pressure of the obese and non-obese rats was reduced after chronic treatment with naloxone. Naloxone treatment caused reduction of blood ACTH, corticosterone, and beta endorphin levels but elevated growth hormone levels. The characteristic hyperinsulinemia, hyperlipidemia, hyperglycemia, elevated BUN levels, and the Cushingoid spectrum of degenerative changes found in Obese/SHR did not appear in naloxone-treated rats.
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PMID:Anti-opiate (naloxone) suppression of Cushingoid degenerative changes in obese/SHR. 299 79

Recent studies have found that the hyperphagia and obesity resulting from lesions of the ventromedial hypothalamus (VMH) are both reversed and prevented by complete adrenalectomy. Several previous experiments, however, reported little or no suppression of VMH weight gain in hypophysectomized (HYPOX) rats. This study directly compared the effects of hypophysectomy and adrenalectomy on hypothalamic obesity in adult female rats. Complete adrenalectomy (i.e, stress-induced plasma corticosterone less than 1.0 micrograms/dl) totally suppressed abnormal weight gain in the first 20 days after VMH lesions but did not affect intracranial self-stimulation. Hypophysectomy also resulted in suppression of weight gain, but the HYPOX-VMH rats nevertheless gained significantly more weight than HYPOX rats with sham lesions. However, the HYPOX-VMH animals had very low levels of plasma corticosterone and adrenocorticotropin (ACTH) (from residual pituitary tissue or of diencephalic origin), and incompletely adrenalectomized rats with similar low levels of plasma corticosterone gained an equal amount of weight after VMH lesions. It was concluded that adrenal glucocorticoid hormones play a largely permissive role in the VMH syndrome, with only very small levels required for the manifestation of obesity.
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PMID:Hypothalamic obesity after hypophysectomy or adrenalectomy: dependence on corticosterone. 299 9

The physiological control of adrenal androgen secretion has not been definitively established. However, there is evidence to suggest that a dexamethasone-suppressible factor other than ACTH may have a specific role to play. The majority of patients with idiopathic hirsutism (hirsutism associated with regular menstruation) have findings suggestive of adrenal androgen excess, including enhanced androgen responsiveness following administration of metyrapone, and respond to treatment with dexamethasone, 0.5 mg given each night. Patients with idiopathic hirsutism have elevated androgens but normal oestrogen and gonadotrophin levels. In contrast, while patients with polycystic ovary syndrome (PCOS) also demonstrate evidence of adrenal androgen excess, these patients have elevated oestrone levels and gonadotrophin secretion is abnormal. Approximately 50% of patients with PCOS treated with dexamethasone resume regular menstruation. Oestrone excess appears to be primary to the abnormal gonadotrophin secretion and to the development of PCOS. In non-obese patients with PCOS elevated oestrone appears to occur as a consequence of the availability of the excessive amounts of its immediate precursor, androstenedione, an androgen mainly of adrenal origin. Androstenedione is converted to oestrone in fat. Obese amenorrhoeic subjects have normal androstenedione values but elevated oestrone levels with abnormal gonadotrophin secretion as seen in PCOS. These findings indicate that abnormal gonadotrophin secretion is associated with elevated oestrone levels whether these occur as a consequence of excessive adrenal androgen secretion, or the excessive conversion of normal amounts of available androstenedione. Patients with idiopathic hirsutism and elevated androstenedione levels but normal oestrone values appeared to be protected against the development of PCOS by relatively poor conversion of androstenedione to oestrone. It is likely, therefore, that if patients with idiopathic hirsutism gain additional adipose tissue, elevated oestrone levels will result and PCOS will develop. These observations explain the frequent association of PCOS and obesity. There is a close clinical association between elevated androgen levels and hirsutism and between elevated oestrone levels and menstrual disturbances. However, some patients with amenorrhoea but without hirsutism may demonstrate marked elevations of androgens and oestrone, the correction of which leads to the resumption of regular ovulation. This presentation, 'amenorrhoea with cryptic hyperandrogenaemia', is probably explained by diminished sensitivity of androgen receptors.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:The adrenal cortex and virilization. 300 82


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