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Query: UMLS:C0028754 (obesity)
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In the present study, we characterized the changes in plasma leptin levels in patients with pituitary Cushing's disease and in age- and sex-matched controls. Plasma levels of ACTH, cortisol, and leptin were measured before and after iv administration of ovine CRH in controls once and in patients twice (while they had active hypercortisolism and 10 days after successful surgery). Cushing's patients had elevated body mass indexes (34 +/- 1.9 vs. 22.9 +/- 0.8) and plasma leptin levels (35.6 +/- 3.4 vs. 9.2 +/- 1.9 ng/mL) compared to controls, which remained unchanged 10 days after successful transsphenoidal surgery and directly proportional to the body mass index. Plasma leptin levels were not affected by CRH infusion in either the controls or the patients despite clear-cut elevations in plasma ACTH and cortisol. These findings suggest that although acute changes in plasma cortisol do not affect plasma leptin, chronic hypercortisolism results in elevated leptin levels, probably by causing visceral obesity.
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PMID:Plasma leptin levels do not change in patients with Cushing's disease shortly after correction of hypercortisolism. 925 64

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 case records of six cats with hyperadrenocorticism presented to the Department of Clinical Veterinary Medicine, University of Cambridge, over an 11-year period were reviewed. Signalment and clinical signs were similar to previous reports but, in contrast to other reports, only three cats had diabetes mellitus on presentation. Abdominal radiographs revealed an adrenal mass in one case, obesity in all cases but no hepatomegaly. The adrenal glands were identified ultrasonographically in three out of six cases. Clinicopathological findings were non-specific. The diabetic cats had a significantly lower serum potassium concentration than the non-diabetic cats (P < 0.05). Results of adrenocorticotrophic hormone (ACTH) stimulation tests were supportive of a diagnosis of hyperadrenocorticism in the five cats in which they were performed. Five cats had pituitary-dependent hyperadrenocorticism (PDH) and one had an adrenal tumour. Differentiation between the two forms of hyperadrenocorticism was possible preoperatively in five out of six cats. Adrenal histopathology confirmed hyperplasia in four cats and adenocarcinoma in one cat. Three cats with PDH underwent bilateral adrenalectomy and two of these cats had low, flat ACTH stimulation tests postoperatively and survived for significant periods. The cat with an adrenal tumour underwent partial unilateral adrenalectomy, maintained a positive ACTH stimulation test postoperatively and was euthanased one week after surgery.
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PMID:Hyperadrenocorticism in six cats. 957 59

The clinical features of Cushing's syndrome (such as obesity, hypertension, and diabetes) are commonly encountered in clinical practice. Patients with Cushing's syndrome have been identified by an abnormal low-dose dexamethasone suppression test, elevated urine free cortisol (UFC), an absence of diurnal rhythm of plasma cortisol, or an elevated late-night plasma cortisol. Because the concentration of cortisol in the saliva is in equilibrium with the free (active) cortisol in the plasma, measurement of salivary cortisol in the evening (nadir) and morning (peak) may be a simple and convenient screening test for Cushing's syndrome. The purpose of this study was to evaluate the usefulness of the measurement of late-night and morning salivary cortisol in the diagnosis of Cushing's syndrome. We studied 73 normal subjects and 78 patients referred for the diagnosis of Cushing's syndrome. Salivary cortisol was measured at 2300 h and 0700 h using a simple, commercially-available saliva collection device and a modification of a standard cortisol RIA. In addition, 24-h UFC was measured within 1 month of saliva sampling. Patients with proven Cushing's syndrome (N = 39) had significantly elevated 2300-h salivary cortisol (24.0 +/- 4.5 nmol/L), as compared with normal subjects (1.2 +/- 0.1 nmol/L) or with patients referred with the clinical features of hypercortisolism in whom the diagnosis was excluded or not firmly established (1.6 +/- 0.2 nmol/L; N = 39). Three of 39 patients with proven Cushing's had 2300-h salivary cortisol less than the calculated upper limit of the reference range (3.6 nmol/L), yielding a sensitivity of 92%; one of these 3 patients had intermittent hypercortisolism, and one had an abnormal diurnal rhythm (salivary cortisol 0700-h to 2300-h ratio <2). An elevated 2300-h salivary cortisol and/or an elevated UFC identified all 39 patients with proven Cushing's syndrome (100% sensitivity). Salivary cortisol measured at 0700 h demonstrated significant overlap between groups, even though it was significantly elevated in patients with proven Cushing's syndrome (23.0 +/- 4.2 nmol/L), as compared with normal subjects (14.5 +/- 0.8 nmol/L) or with patients in whom Cushing's was excluded or not firmly established (15.3 +/- 1.5 nmol/L). Late-night salivary cortisol measurement is a simple and reliable screening test for spontaneous Cushing's syndrome. In addition, late-night salivary cortisol measurements may simplify the evaluation of suspected intermittent hypercortisolism, and they may facilitate the screening of large high-risk populations (e.g. patients with diabetes mellitus).
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PMID:Late-night salivary cortisol as a screening test for Cushing's syndrome. 970 31

The purpose of this study was to compare the results of bilateral laparoscopic adrenalectomy (BLA) to bilateral open adrenalectomy (BOA) in the treatment of Cushing's disease. Twenty-four patients (23 Cushing's disease, 1 congenital adrenal hyperplasia) were divided into 3 groups. Group 1 patients (n = 15) underwent BCA using the lateral transabdominal approach, Group while 2 patients (n = 9) underwent laparoscopic adrenalectomy on one side and conventional open adrenalectomy on the contralateral side. Groups 1 and 2 were compared retrospectively to 15 patients (Group 3) who underwent BOA as part of larger series of 61 patients. There was no difference in the degree of hypercortisolism in the 3 groups. At the beginning of the experience, the duration of surgery was longer in Groups 1 and 2 compared to the open surgery group, but this difference subsequently decreased during the study. There was no difference in intraoperative blood loss or transfusion rate. Group 1 patients experienced fewer wound and intraabdominal complications and less postoperative pain, shorter hospitalization, and quicker recovery than groups 2 and 3 patients. Technically obesity and tissue fragility are easily overcome by the laparoscopic approach. BCA also achieves success rate of hypercortisolism correction. In conclusion, BLA is the surgical procedure of choice for the treatment of Cushing's disease when surgical therapy is indicated.
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PMID:[Bilateral video-endoscopic adrenalectomy in Cushing's disease. Experience in 24 patients]. 975 69

While the hyperleptinemia of obesity is likely to be associated with the metabolic complications of obesity/hyperinsulinemia/insulin resistance, it is not associated with diabetes, with the relative hypercortisolism of upper body obesity, with hypertension in women, (it is in men), or with dyslipidemia. Overall, the correlations between leptin and the metabolic diseases associated with obesity are weak. The equivocal results of an association of leptin with components of the metabolic syndrome make it unlikely that leptin affects these directly. (On the other hand, these correlations, when found, preclude any causal relationship between leptin and metabolic diseases.) There are experimental data showing a definite role for insulin and glucocorticoids in the regulation of leptin, and of leptin in the regulation of insulin. More data are required on the effects of leptin, but it is likely that leptin will not be a major link between obesity and the metabolic syndrome. Certainly, however, when leptin is available for clinical use, its effect on different aspects of the metabolic syndrome will be worth studying.
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PMID:Therapeutic controversy: Obesity--a modern-day epidemic. 992 54

The natural course of adrenal incidentalomas and the risk that such lesions evolve toward hormonal hypersecretion or malignancy are still under evaluation. Of 246 consecutive patients with adrenal incidentaloma studied at our institution in the last 15 yr, 91 underwent surgery. Of the remaining patients, a group of 75 (52 females and 23 males; median age, 56 yr; range, 19-77 yr) with incidentally discovered asymptomatic adrenal masses (60 unilateral and 15 bilateral; median diameter, 2.5 cm; range, 1.0-5.6) was enrolled in an endocrine and morphological follow-up of at least 2 yr after diagnosis (median, 4 yr; range, 2-10). During follow-up, no patients developed malignancy; 9 showed mass enlargement, with appearance of a new mass in the contralateral gland in 2; 3 developed adrenal hyperfunction (overt Cushing's syndrome in 2, nonclinical hypercortisolism in 1); and 3 showed adrenal mass enlargement associated with adrenal hyperfunction (nonclinical hypercortisolism in 2, pheochromocytoma in 1). The estimated cumulative risks to develop mass enlargement and hyperfunction were 8% and 4%, respectively, after 1 yr, 18% and 9.5% after 5 yr, and 22.8% and 9.5% after 10 yr. Nine risk factors for adrenal mass enlargement or hyperfunction were arbitrarily selected and evaluated: sex, age, presence of obesity, hypertension, diabetes, abnormal endocrine tests, mass size, mass location, and scintigraphic uptake pattern. Three of them attained statistical significance: mass size of 3 cm or more at diagnosis and exclusive radiocholesterol uptake by the mass at scintigraphy had relevance for the occurrence of adrenal hyperfunction, whereas the presence of endocrine test abnormalities at diagnosis had predictive value for mass enlargement. It is concluded that subtle hormonal abnormalities are risk factors for mass size increase, which is not a sign of malignant transformation. Both mass size of 3 cm or more at diagnosis and exclusive radiocholesterol uptake, indicating higher risks of hyperfunction, should be considered to plan a more thorough endocrine follow-up.
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PMID:Risk factors and long-term follow-up of adrenal incidentalomas. 1002 10

Administration of growth hormone (GH) induces changes in body composition, namely, increases in both bone and lean mass and a decrease in fatty tissue. However, the contrary issue, i.e. the way in which body composition affects the secretion of GH, is highly controversial. Disease states such as obesity and chronic hypercortisolism are associated with increased adiposity and/or the central distribution of fat. Ageing, characterized by excess adiposity, is also associated with impaired secretion of GH. In these states, both spontaneous and stimulated secretion of GH is severely impeded. At the other extreme, malnutrition and fasting are both associated with increased secretion of GH when confronted with most, if not all, stimuli. As the common factor in all of these situations is the increased or decreased adiposity, or the changes in energy homeostasis, it has been postulated that adipose tissue exerts a relevant role in the control of GH secretion in man. The link between adipose tissue and GH seems to be exerted through at least two signals produced by adipocytes: free fatty acids (FFA) and the recently cloned protein, leptin. An increase in FFA blocks secretion of GH, while a decrease in FFA enhances secretion. Leptin, a hormone whose main role is to regulate the intake of food and energy expenditure, seems to regulate GH secretion by acting at the hypothalamic level. In summary, body composition affects GH secretion by way of the degree of adiposity, and free fatty acids and leptin would appear to be the messages through which adipocytes participate in the regulation of GH secretion. This framework clarifies the metabolic control of GH, a hormone with profound metabolic activities.
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PMID:Interaction between body composition, leptin and growth hormone status. 1008 98

It has been proposed that both hypercortisolism and low sympathetic nervous system (SNS) activity contribute to obesity. Because glucocorticoids inhibit SNS activity, we hypothesized that hypercortisolism and low SNS activity may be found in association in Pima Indians, a population with a high prevalence of obesity. We therefore measured indices of hypothalamic-pituitary-adrenal (HPA) axis and SNS activities in 39 nondiabetic men, 20 Pimas (age, 30+/-5 years; weight, 94+/-26 kg; 35%+/-8% body fat [mean +/- SD]) and 19 Caucasians (33+/-9 years, 91+/-23 kg, 28%+/-11% body fat). HPA axis activity was assessed by measurements of morning fasting plasma corticotropin (ACTH) and cortisol concentrations and 24-hour urinary free cortisol (UFC) excretion. SNS activity was assessed as muscle sympathetic nerve activity (MSNA) by microneurography and by measurement of catecholamines (fasting plasma concentration and 24-hour urinary excretion). Plasma ACTH and cortisol and UFC were similar in Pimas and Caucasians. MSNA was positively correlated with percent body fat (r = .49, P = .002) and was lower in Pimas compared with Caucasians after adjustment for percent body fat (24+/-9 v 31+/-10 bursts/min, P = .04). We conclude that Pima Indians, a population with a high prevalence of obesity, have lower SNS activity but normal HPA axis activity compared with Caucasians.
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PMID:Hypothalamic-pituitary-adrenal axis and sympathetic nervous system activities in Pima Indians and Caucasians. 1009 20

A retrospective analysis of Cushing's syndrome from the retrieved records of 24 out of a total of 27 referred cases over a period of 10 years (January 1985-January 1995) showed confirmation in 16 cases. Fourteen (88%) were females, 9 (56%) were in their third decade. Duration of symptoms before admission was one year or less in eleven (69%) patients. Among symptoms weakness, fatigue and weight gain and among signs moon face, truncal obesity and buffalo hump were found in all patients. Amenorrhea occurred in all the women of childbearing age. Basal urinary 17-hydroxycorticoid (17-OHCS) values were elevated in 9/12 patients and low dose dexamethasone suppression test favoured Cushing's syndrome in 8/9 patients. Definitive treatment consisted of bilateral adrenalectomy in 7 and transfrontal pituitary adenomectomy in 3. Two patients declined surgery; 4 patients were lost to follow up before definitive treatment. Two patients who had bilateral adrenalectomy and two who had transfrontal adenomectomy died subsequently while three remained in good health on corticosteroid replacement therapy. Three of the 7 patients who had bilateral adrenalectomy developed Nelson's syndrome. It is concluded that Cushing's disease is the most frequent cause of Cushing's syndrome in our series. The patients presented with the well-known clinical manifestations of hypercortisolism. However, our laboratory facilities require considerable improvement to serve as a reliable adjunct to clinical evaluation. Since Cushing's syndrome, whatever the cause, is eventually fatal if left untreated, surgical intervention is mandatory after confirmation of the cause with appropriate laboratory tests.
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PMID:Cushing's syndrome: a ten year experience at Tikur Anbassa Hospital. 1021 44


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