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Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A benign virilizing adrenal adenoma is rare among adrenal neoplasms in middle-aged women. A 39-yr-old Japanese woman who presented with hirsutism, obesity, diabetes mellitus and hypertension was admitted. Plasma concentrations of testosterone and DHEAS were high. While the basal level of plasma ACTH was suppressed, serum cortisol level was high and its circadian rhythm was absent. Serum cortisol level was not suppressed with the low- and high-dose overnight dexamethasone suppression test. Abdominal computed tomography showed a left adrenal tumor, and an adrenocortical scintigraphy revealed uptake of the tracer on the left side. Polycystic ovaries were also found and bone mineral density revealed osteoporosis. Histopathological features of resected adrenal tumor were consistent with those of adrenocortical adenoma. Immunoreactivity of all the steroidogenic enzymes was apparent in the tumor cells and particularly dehydroepiandrosterone sulfotransferase (DHEA-ST) immunoreactivity was markedly expressed. Cortical atrophy and reduced expression of DHEA-ST were detected in the cortex of the adjacent non-neoplastic adrenal gland. Plasma testosterone, DHEAS and cortisol levels returned to normal after surgery, concomitantly with the disappearance of polycystic ovaries. This is a very rare case of virilizing adrenocortical adenoma complicated with Cushing's syndrome (CS).
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PMID:Unilateral adrenalectomy improves insulin resistance and polycystic ovaries in a middle-aged woman with virilizing adrenocortical adenoma complicated with Cushing's syndrome. 1847 59

Adiposity has been recognized as a risk factor for colorectal adenoma, but the influence of weight gain, adipose tissue distribution, and possible differences between ethnic/racial and gender groups remains unanswered. The aim of this prospective study was to examine the association between adiposity and weight change and colorectal adenoma risk. Over approximately 10-year period, anthropometric measures and other risk factors were measured at three time points in the multicenter multiethnic Insulin Resistance Atherosclerosis Study cohort. Colonoscopies were then conducted on 600 cohort participants regardless of symptoms whose mean age at colonoscopy was 64 years. Multivariate logistic regression analyses were used to assess the association between colorectal adenomas and measures of adiposity and weight change over the approximately 10-year period before colonoscopy. Obesity was positively associated with risk of colorectal adenomas at the time of colonoscopy [adjusted odds ratio (OR(adj)), 2.16; 95% confidence interval (95% CI), 1.13-4.14] and was stronger in women (OR(adj), 4.42; 95% CI, 1.53-12.78) than in men (OR(adj), 1.26; 95% CI, 0.52-3.07). The risk of adenomas increased among participants who gained weight compared with those who maintained weight over the approximately 5 years (OR(adj), 2.30; 95% CI, 1.25-4.22) and approximately 10 years (OR(adj), 2.12; 95% CI, 1.25-3.62). These associations were similar for both advanced and nonadvanced adenomas. These results suggest a positive association between obesity, weight gain, and colorectal adenoma risk. Stronger associations were observed when obesity was measured at the time of colonoscopy, suggesting that obesity may be a promoting factor in the growth of colorectal adenomas.
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PMID:Change in body size and the risk of colorectal adenomas. 1737 48

We reported a rare case of simultaneous primary aldosteronism and preclinical Cushing's syndrome due to unilateral double adrenocortical adenomas in a 57 year-old woman who had had hypertension for the last 10 years. Abdominal computed tomography showed double tumors in her right adrenal gland. Physical findings revealed simple obesity and hypertension, but no other abnormal findings were detected. Laboratory findings demonstrated that serum potassium was 3.8 mmol/l; plasma renin activity, 0.3 ng/ml/h; plasma aldosterone, 100 pg/ml, and aldosterone renin ratio (ARR), 33. Serum cortisol was 15.7 microg/dl. There was no circadian rhythm of serum cortisol, and no suppression of serum cortisol in response to exogenous dexamethasone administration. Right adrenalectomy was performed under laparoscopy. Two well-circumscribed tumors, whose sizes were 21 and 19 mm in greatest diameter, were detected. They were macroscopically composed of a golden-yellow portion admixed with a brown portion, which corresponded to clear cells and compact cells, respectively. Immunohistochemical staining for steroidogenic enzymes demonstrated the presence of all the enzymes involved in corticosteroidogenesis in these two adenomas, indicating that the two adenomas produced both cortisol and mineralocorticoid. Specifically, one adenoma mainly caused excessive production of cortisol as compared to the other one. These findings indicate that overproduction of both cortisol and mineralocorticoid was evident in the two adenomas of the right adrenal gland in immunohistochemical study for steroidogenic enzymes, whereas there was less clinical manifestation of primary aldosteronism and Cushing's syndrome in the present patient.
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PMID:Possibly simultaneous primary aldosteronism and preclinical Cushing's syndrome in a patient with double adenomas of right adrenal gland. 1737 61

Obesity has consistently been associated with increased colorectal cancer risk in men, but not in women. In the absence of postmenopausal hormone use (PMH), adipose-derived estrogen is the primary determinant of circulating estrogen levels in postmenopausal women, perhaps ameliorating the mitogenic effects of obesity in this group. Using data from a case-control study in the United States, we examined associations among obesity, potential modifying effects of factors related to endogenous and exogenous estrogen levels, and risk of colorectal adenoma. Cases (n = 219) were women of ages 30 to 74 years with colonoscopy proven, incident, sporadic, pathology-confirmed, adenomatous polyps of the colon and rectum. Two control groups were recruited: colonoscopy-confirmed polyp-free women (n = 438) and age- and zip code frequency-matched women randomly selected from the community (n = 247). Multivariate odds ratios and 95% confidence intervals (95% CI) for obese [body mass index (BMI) >or=30.0; compared with nonobese, BMI <25.0] premenopausal women were 2.09 (95% CI, 0.81-5.41) versus colonoscopy controls, and 5.18 (95% CI, 1.40-19.32) versus population controls. For PMH users, the corresponding odds ratios were 0.29 (95% CI, 0.12-0.70) versus colonoscopy controls and 0.64 (95% CI, 0.23-1.83) versus population controls. There was no significant association of BMI with adenoma risk for PMH nonusers. Findings for waist-to-hip ratio were similar to those for BMI. These data support the hypothesis that risk for colorectal adenoma may be increased with obesity among premenopausal women but decreased among postmenopausal women, especially if they also take PMH.
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PMID:Do factors related to endogenous and exogenous estrogens modify the relationship between obesity and risk of colorectal adenomas in women? 1741 57

The present study aimed at evaluating the modulation of insulin-like growth factor I receptor (IGF-IR) and estrogen receptor beta (ER-beta) expression and their correlation during tumorigenesis of sporadic colorectal cancer, with particular interest in the insulin resistance syndrome. In a series of 100 individuals (54 men and 46 women; mean age, 67.3 +/- 9.4 years) with colorectal neoplasms, classified as early adenomas (n = 25), advanced adenomas (n = 44), and adenocarcinomas (n = 31), IGF-IR and ER-beta expression was quantified in formalin-fixed, paraffin-embedded biopsy specimens, using confocal laser scanning microscopy and a computer-based method for assessment of immunofluorescent staining. All individuals were evaluated for insulin resistance markers (hyperglycemia, dyslipidemia, central obesity, and arterial hypertension), and 50 (26 men and 24 women; mean age, 68.2 +/- 9.0 years) were diagnosed with the insulin resistance syndrome. For the sequence of early adenoma-advanced adenoma-adenocarcinoma, a gradual increase in IGF-IR expression and a gradual decrease in ER-beta expression were observed. The partial correlation coefficient between IGF-IR and ER-beta expression, controlled for age, sex, insulin resistance, type of lesion, and location of lesion was 0.295 (P = .004, 2-tailed significance). Analysis of variance demonstrated that the effect of the insulin resistance syndrome on IGF-IR and ER-beta expression was significant (P = .007 and P = .018, respectively). The results suggest the combined effect of IGF-I and estrogens in colorectal cancer, with a distinctive role in individuals with the insulin resistance syndrome.
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PMID:Insulinlike growth factor I receptor and estrogen receptor beta expressions are inversely correlated in colorectal neoplasms and affected by the insulin resistance syndrome. 1744 73

Adrenal incidentalomas (AIs) have been associated with an increased incidence of several cardiovascular risk factors, similar to overt Cushing syndrome. Data about the involvement of the adipokines in the development of insulin resistance and atherosclerosis in AI are completely lacking. The aim of the present study was to evaluate plasma interleukin 6 (IL-6), adiponectin, resistin, tumor necrosis factor alpha (TNF-alpha), and monocyte chemoattractant protein 1 (MCP-1) levels in patients with AI. Plasma IL-6, adiponectin, resistin, TNF-alpha, and MCP-1 levels were measured in 20 healthy subjects (6 males; 14 females; age, 58.5 +/- 2.2 years; body mass index, 28.1 +/- 0.9 kg/m(2)) and in 20 patients (5 males; 15 females; age, 57.9 +/- 2.0 years; body mass index, 28.0 +/- 0.8 kg/m(2)) with AI and typical computed tomographic features of cortical adenoma, who were not affected by diabetes mellitus, hypertension, or other relevant diseases. All patients underwent anthropometric measurements and determination of basal corticotropin, cortisol, and urinary free cortisol excretion. Overnight dexamethasone test and 250-microg corticotropin test were performed in all cases. A subclinical Cushing syndrome was found in 3 patients, whereas the others had apparently nonfunctioning masses. Plasma IL-6, adiponectin, resistin, TNF-alpha, and MCP-1 levels were higher in patients than in controls (64.4 +/- 2.8 vs 5.5 +/- 0.6 pg/mL, 13.7 +/- 1.3 vs 3.6 +/- 0.5 microg/mL, 12.5 +/- 1.9 vs 5.1 +/- 0.2 ng/mL, 27.0 +/- 1.5 vs 22.2 +/- 1.5 pg/mL, 172.5 +/- 20.0 vs 104.4 +/- 19.5 pg/mL, respectively; P < .05) and apparently not affected by the presence of visceral obesity. Plasma IL-6 levels were negatively correlated with urinary free cortisol (r = -0.461, P < .05), and TNF-alpha levels were positively correlated with cortisol after the administration of 1 mg dexamethasone (r = 0.636, P < .01). In conclusion, patients with AI may show increased levels of adipokines (apparently not related to the presence of diabetes, hypertension, or obesity), which may be affected by the presence of the adrenal adenoma. For some adipokines, a direct production from the adrenal gland may be hypothesized even if other studies are needed to better investigate the role of adipokines in states of altered cortisol secretion.
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PMID:Adipokine levels and cardiovascular risk in patients with adrenal incidentaloma. 1744 45

Recent evidence indicates that obesity and related metabolic abnormalities are associated with increased incidence or mortality for a number of cancers, including those of the colon, prostate, and pancreas. Obesity, physical inactivity, visceral adiposity, hyperglycemia, and hyperinsulinemia are relatively consistent risk factors for colon cancer and adenoma. Also, patients with type 2 diabetes mellitus have a higher risk of colon cancer. For prostate cancer, the relationship to obesity appears more complex. Obesity seems to contribute to a greater risk of aggressive or fatal prostate cancer but perhaps to a lower risk of nonaggressive prostate cancer. Furthermore, men with type 2 diabetes mellitus are at lower risk of developing prostate cancer. Long-standing type 2 diabetes increases the risk of pancreatic cancer by approximately 50%. Furthermore, over the past 6 years, a large number of cohort studies have reported positive associations between obesity and pancreatic cancer. Together with data from prediagnostic blood specimens showing positive associations between glucose levels and pancreatic cancer up to 25 years later, sufficient evidence now supports a strong role for diabetes and obesity in pancreatic cancer etiology. The mechanisms for these associations, however, remain speculative and deserve further study. Hyperinsulinemia may be important, but the role of oxidative stress initiated by hyperglycemia also deserves further attention.
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PMID:The role of obesity and related metabolic disturbances in cancers of the colon, prostate, and pancreas. 1749 13

Adrenalectomy continues to play an important role in the management of Cushing's syndrome (CS). Untreated CS causes considerable physical and mental morbidity and mortality. However, little information is available on the effect of adrenalectomy in ameliorating functional disabilities in CS patients. Our study assesses the long-term outcome of adrenalectomy in patients with CS. This is a retrospective analysis of CS patients managed during 1990-2005 at a tertiary care center. We analyzed the clinical presentation, endocrine evaluation, and surgical management preoperatively and following adrenalectomy. The subjects were 37 patients with CS (age 24.5 +/- 15 years, range 1-60 years; male:female 1.0:1.2). There were various etiologies--unilateral adrenocortical adenoma (n = 11), adrenocortical carcinoma (n = 13), pituitary ACTH-secreting adenoma with failed transsphenoidal surgery (n = 4), ectopic unidentified ACTH source (n = 7), bilateral adrenal macronodular hyperplasia (n = 1), primary pigmented nodular adrenal hyperplasia (n = 1) --for which the patients underwent adrenalectomy: unilateral (n = 22), bilateral (n = 13), or adrenonephrectomy (n = 2). Two patients died during the perioperative period owing to chest infection and sepsis. At the median follow-up of 60 months (range 6-144 months), the patients exhibit significant persistence of obesity (41%), proximal muscle weakness (44%), menstrual irregularity (8%), hypertension (31%), and insulin-dependent diabetes (29%). Hirsutism and psychological abnormalities persisted to a lesser extent. All patients had biochemical cure of CS following surgery evidenced by the 8 a.m. basal cortisol < or = 5 microg/dl. The hypothalamic-pituitary-adrenal axis recovered as shown by normalization of the short synacthen-stimulated cortisol level (peak level > or = 20 microg/dl) after a median follow-up of 9 months (range 6-18 months). Incomplete clinical recovery following adrenalectomy emphasizes the need of early recognition and prompt treatment of CS. Surgery for adrenocortical adenoma is safe and effective; however, survival of patients with CS due to adrenocortical carcinoma remains poor. Bilateral adrenalectomy provides early control of hypercortisolism in selected cases of unlocalized ectopic ACTH syndrome or failed transsphenoidal surgery. Even though functional recovery is incomplete after adrenalectomy, quality of life improves considerably.
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PMID:Outcome of adrenalectomy for Cushing's syndrome: experience from a tertiary care center. 1753 56

Colorectal cancer is related to diet, lifestyle, physical inactivity, and obesity. The responsible carcinogens cause mutations or enhance cell growth. Inulin-type fructans may counteract the effects via their gut flora-mediated fermentation products in vitro and in vivo. Important products formed by fermentation of inulin-type fructans with human gut flora are short-chain fatty acids. Of these, butyrate and propionate inhibit growth of colon tumor cells and histone deacetylases. Butyrate also causes apoptosis, reduces metastasis in colon cell lines, and protects from genotoxic carcinogens by enhancing expression of enzymes involved in detoxification. Fermentation supernatants of inulin have similar growth-inhibitory effects on colon adenoma and carcinoma cells and induce histone hyperacetylation by inhibiting histone deacetylases. In animal models inulin-type fructans prevent and retard colorectal carcinogenesis. Several studies reported the reduction of chemically induced preneoplastic lesions or tumors in the colon of rodents treated with inulin-type fructans. The human intervention study (SYNCAN project) sought to provide the experimental evidence for risk reduction by inulin-type fructans in humans. One group of polypectomized people at high risk for colon cancer and another of colon cancer volunteers after curative resection were given a synbiotic preparation. There were clear functional effects of the synbiotic because numerous different cancer risk markers were favorably altered. In conclusion, there is considerable experimental evidence that inulin modulates parameters of colon cancer risks in human colon cells, in animals, and in a human intervention trial. The involved mechanisms possibly include reduction of exposure to risk factors and suppression of tumor cell survival.
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PMID:Overview of experimental data on reduction of colorectal cancer risk by inulin-type fructans. 1795 7

Enterocytes assemble dietary lipids into chylomicron particles that are taken up by intestinal lacteal vessels and peripheral tissues. Although chylomicrons are known to assemble in part within membrane secretory pathways, the modifications required for efficient vascular uptake are unknown. Here we report that the transcription factor pleomorphic adenoma gene-like 2 (PlagL2) is essential for this aspect of dietary lipid metabolism. PlagL2(-/-) mice die from postnatal wasting owing to failure of fat absorption. Lipids modified in the absence of PlagL2 exit from enterocytes but fail to enter interstitial lacteal vessels. Dysregulation of enterocyte genes closely linked to intracellular membrane transport identified candidate regulators of critical steps in chylomicron assembly. PlagL2 thus regulates important aspects of dietary lipid absorption, and the PlagL2(-/-) animal model has implications for the amelioration of obesity and the metabolic syndrome.
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PMID:Loss of the PlagL2 transcription factor affects lacteal uptake of chylomicrons. 1798 86


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