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

Central or visceral obesity is recognized as a main risk factor for cardiovascular disease and type 2 diabetes mellitus. The co-existence of visceral obesity, increased blood lipid levels, hypertension and impaired glucose tolerance defines the metabolic syndrome that today is widely recognized as one of the prime factors behind cardiovascular morbidity and mortality. Endocrine disorders such as insulinoma, hypothyroidism and hypercortisolism are known to cause obesity. However, it is only hypercortisolism that is associated with increased abdominal fat accumulation. Recently, new findings have shed light on subtle endocrinopathies that are prevalent in individuals presenting with the metabolic syndrome. Such derangements are of borderline character and often fall within the normal reference range. Intervention studies demonstrate that correction of relative hypogonadism in men with visceral obesity and other manifestations of the metabolic syndrome seem to decrease the abdominal fat mass and reverse the glucose intolerance, as well as lipoprotein abnormalities in the serum. Further analysis of the underlying mechanism has also disclosed a regulatory role for testosterone in counteracting visceral fat accumulation. Longitudinal epidemiological data demonstrates that relatively low testosterone levels are a risk factor for development of visceral obesity. The primary event that triggers the initial development of visceral obesity is not known, but it seems plausible that increased activity in the hypothalamus-pituitary-adrenal axis can be of major importance.
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PMID:Androgens and abdominal obesity. 1033 65

Gonadal failure induces bone loss while obesity prevents it. This raises the possibility that bone mass, body weight, and gonadal function are regulated by common pathways. To test this hypothesis, we studied leptin-deficient and leptin receptor-deficient mice that are obese and hypogonadic. Both mutant mice have an increased bone formation leading to high bone mass despite hypogonadism and hypercortisolism. This phenotype is dominant, independent of the presence of fat, and specific for the absence of leptin signaling. There is no leptin signaling in osteoblasts but intracerebroventricular infusion of leptin causes bone loss in leptin-deficient and wild-type mice. This study identifies leptin as a potent inhibitor of bone formation acting through the central nervous system and therefore describes the central nature of bone mass control and its disorders.
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PMID:Leptin inhibits bone formation through a hypothalamic relay: a central control of bone mass. 1066 43

Classic Cushing's syndrome is a rare disease with an estimated incidence of 1 case per 100,000 persons. With routine use of imaging techniques such as ultrasound and CT, adrenal masses are being detected with increased frequency. A substantial percentage of these incidentalomas are hormonally active, with 5% to 20% of the tumors producing glucocorticoids. Autonomous glucocorticoid production without specific signs and symptoms of Cushing's syndrome is termed subclinical Cushing's syndrome. With an estimated prevalence of 79 cases per 100,000 persons, subclinical Cushing's syndrome is much more common than classic Cushing's syndrome. Depending on the amounts of glucocorticoids secreted by the tumor, the clinical spectrum ranges from slightly attenuated diurnal cortisol rhythm to complete atrophy of the contralateral adrenal gland with lasting adrenal insufficiency after unilateral adrenalectomy. Patients with subclinical Cushing's syndrome lack the classical stigmata of hypercortisolism but have a high prevalence of obesity, hypertension, and type 2 diabetes. All patients with incidentally detected adrenal masses scheduled for surgery must undergo testing for subclinical Cushing's syndrome to avoid postoperative adrenal crisis. The best screening test to uncover autonomous cortisol secretion is the short dexamethasone suppression test. Because the adrenal origin of a pathologic cortisol secretion is anticipated, the author prefers a higher dexamethasone dose (3 mg instead of 1 mg) to reduce false-positive results. A suppressed serum cortisol level of less than 3 micrograms/dL (80 nmol/L) after dexamethasone excludes significant cortisol secretion by the tumor. A serum cortisol level greater than 3 micrograms/dL requires further investigation, including confirmation by high-dose dexamethasone (8 mg) suppression testing, a CRH test, and analysis of diurnal rhythm. Determination of urinary free cortisol is less useful because increased values are a late finding usually associated with emerging clinical signs of Cushing's syndrome. Patients with suppressed plasma ACTH in response to CRH generally have adrenal insufficiency after surgery and require adequate perioperative and postoperative substitution therapy. Whether patients with subclinical Cushing's syndrome should undergo adrenalectomy is a matter of debate. The author performs surgery in young patients (< 50 years), in patients with suppressed plasma ACTH, and in patients with a recent history of weight gain, substantial obesity, arterial hypertension, diabetes mellitus, and osteopenia. In completely asymptomatic patients with normal plasma ACTH concentrations and in patients older than 75 years, the author recommends a nonsurgical approach. A large prospective randomized study is necessary to evaluate the benefits of surgery versus conservative treatment in patients with subclinical Cushing's syndrome.
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PMID:Subclinical Cushing's syndrome. 1073 63

Incidentally discovered adrenal masses are mostly benign, asymptomatic lesions, often arbitrarily considered as nonfunctioning tumors. Recent studies, however, have reported increasing evidence that subtle cortisol production and abnormalities in the hypothalamic-pituitary-adrenal (HPA) axis are more frequent than previously thought. The purpose of this study was to investigate the clinical and hormonal features of patients with incidentally discovered adrenal adenomas, in relation to their clinical outcome. Fifty consecutive patients with incidentally detected adrenal adenomas, selected from a total of 65 cases of adrenal incidentalomas, were prospectively evaluated. All of them underwent abdominal computed tomography scan and hormonal assays of the HPA axis function: circadian rhythm of plasma cortisol and ACTH, urinary cortisol excretion, 17-hydroxyprogesterone, androgens, corticotropin stimulation test and low-dose (2 mg) dexamethasone test. The patients were reevaluated at regular intervals (6, 12, and 24 months) for a median period of 38 months. Subtle hypercortisolism, defined as abnormal response to at least 2 standard tests of the HPA axis function in the absence of clinical signs of Cushing's syndrome (CS), was defined as subclinical CS. Mild-to-severe hypertension was found in 24 of 50 (48%) patients, type-2 diabetes in 12 of 50 (24%), and glucose intolerance in 6 of 50 (12%) patients. Moreover, 18 of 50 patients (36%) were diffusely obese (body mass index, determined as weight/height2, > 25), and 14 patients (28%) had serum lipid concentration abnormalities (cholesterol > or = 6.21 mmol/L, low-density lipoprotein cholesterol > or = 4.14 mmol/L and/or triglycerides > or = 1.8 mmol/L). Compared with a healthy population, bone mineral density Z-score, determined by the DEXA technique, tended to be slightly (but not significantly) lower in patients with adrenal adenoma (-0.41 SD). Endocrine data were compared with 107 sex- and age-matched controls, and patients with adenomas were found to have heterogeneous hormonal abnormalities. In particular, significantly higher serum cortisol values (P < 0.001), lower ACTH concentration (P < 0.05), and impaired cortisol suppression by dexamethasone (P < 0.001) were observed. Moreover, in patients with adenomas, cortisol, 17-OH progesterone, and androstenedione responses to corticotropin were significantly increased (P < 0.001, all), whereas dehydroepiandrosterone sulfate levels were significantly lower at baseline, with blunted response to corticotropin (P < 0.001, both). However, the criteria for subclinical CS were met by 12 of 50 (24%) patients. Of these, 6 (50%) were diffusely obese, 11 (91.6%) had mild-to-severe hypertension, 5 (41.6%) had type-2 diabetes mellitus, and 6 (50%) had abnormal serum lipids. The clinical and hormonal features improved in all patients treated by adrenalectomy, but seemed unchanged in all those who did not undergo surgery (follow-up, 9 to 73 months), except for one, who was previously found as having nonfunctioning adenoma and then revealed to have subclinical CS. In conclusion, an unexpectedly high prevalence of subtle autonomous cortisol secretion, associated with high occurrence of hypertension, diabetes mellitus, elevated lipids, and diffuse obesity, was found in incidentally discovered adrenal adenomas. Although the pathological entity of a subclinical hypercortisolism state remained mostly stable in time during follow-up, hypertension, metabolic disorders, and hormonal abnormalities improved in all patients treated by adrenalectomy. These findings support the hypothesis that clinically silent hypercortisolism is probably not completely asymptomatic.
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PMID:Subclinical Cushing's syndrome in patients with adrenal incidentaloma: clinical and biochemical features. 1115 83

The means by which obesity leads to high bone density and protects individuals from osteoporosis is not known. The study of bone biology in two mouse models of obesity, leptin-deficient (ob/ob) and leptin receptor-deficient (db/db) mice, points to a role for leptin in the control of bone density. When leptin action is missing in these mice, bone density is high. This is true despite concurrent hypogonadism and hypercortisolism, two strong proresorptive signals that would normally lead to low bone density. Curiously, leptin does not have a direct effect on osteoblasts, which suggests the existence of a central, neuroendocrine pathway that controls bone mass.
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PMID:Leptin and bone: does the brain control bone biology? 1094 Dec 57

The stress system coordinates the adaptive response of the organism to real or perceived stressors. The main components of the stress system are the corticotropin-releasing hormone (CRH) and locus ceruleus-norepinephrine/ autonomic (LC/NE) systems and their peripheral effectors, the hypothalamic-pituitary-adrenal (HPA) axis, and the limbs of the autonomic system. Activation of the stress system leads to behavioral and peripheral changes that improve the ability of the organism to adjust homeostasis and increase its chances for survival. Thus, CRH and the LC/NE system stimulate arousal and attention, as well as the mesocorticolimbic dopaminergic system, which is involved in anticipatory and reward phenomena, and the amygdala, which are responsible for the generation of fear. Hypothalamic CRH plays an important role in inhibiting gonadotropin-releasing hormone secretion during stress, while via somatostatin it also inhibits growth hormone, thyrotropin-releasing hormone and thyrotropin secretion, suppressing thus reproduction, growth and thyroid function. Glucocorticoids directly inhibit pituitary gonadotropin, growth hormone and thyrotropin secretion and make the target tissues of sex steroids and growth factors resistant to these substances. In addition, glucocorticoids stimulate hepatic gluconeogenesis, and inhibit or potentiate insulin actions on skeletal muscle and adipose tissue respectively, ultimately promoting visceral adiposity and the metabolic syndrome. Glucocorticoids also have direct effects on the bone, inhibiting osteoblastic activity and causing osteoporosis. Obese subjects with psychiatric manifestations ranging from those of melancholic depression to anxiety with perception of 'uncontrollable' stress, frequently have mild hypercortisolism, while carefully screened obese subjects with no such manifestations are eucortisolemic. The former may have stress-induced glucocorticoid-mediated visceral obesity and metabolic syndrome manifestations, which in the extreme may be called a pseudo-Cushing state that needs to be differentiated from frank Cushing syndrome. Stress-induced hypercortisolism and visceral obesity and their cardiovascular and other sequelae increase the all-cause mortality risk of affected subjects by 2-3-fold and curtail their life expectancy by several years.
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PMID:The role of stress and the hypothalamic-pituitary-adrenal axis in the pathogenesis of the metabolic syndrome: neuro-endocrine and target tissue-related causes. 1099 9

The specificity of conventional radiography in assessing canine hyperadrenocorticism was evaluated by comparing the Incidence of related radiographic findings in 24 hyperadrenocorticoid, 15 diabetic and 20 hypothyroid dogs. Hyperadrenocorticoid dogs showed significantly more perihilar bronchial mineralisation than other groups. There was no significant variation between the disease groups with respect to obesity, hepatomegaly, contour of the caudoventral hepatic margin, peripheral bronchial mineralisation or osteopenia. Adrenal mineralisation and calcinosis cutis were rare findings observed only in hyperadrenocorticoid dogs. The effect of obesity on the radiographic appearance of bone was studied using a dissected lumbar spine from a canine cadaver. An osteopenic effect could be demonstrated by superimposition of a 10 cm-thick fat block. The low specificity of almost all common signs in canine hyperadrenocorticism and the low incidence of characteristic findings demonstrate the limited potential of radiography in assessing this condition. Radiographic assessment of bone density is unreliable because of artefactual osteopenic effects of high kVp settings necessary in obese dogs.
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PMID:Osteopenia and other radiographic signs in canine hyperadrenocorticism. 1110 87

The authors analyse hormonal and morphological characteristics of adrenal incidentalomas, i.e. pathological adrenal masses accidentally found on CT scan performed due to extraadrenal causes of other causes of adrenal pathology. The group of patients was consisted by 42 patients at the age 24-79 years (27 females and 15 males). The most frequent clinical symptoms included arterial hypertension, diabetes mellitus and obesity. CT examinations revealed 36 cases of unilateral lesions (in 21 cases the lesions were localised on the right and in 15 cases on the left) and 6 bilateral lesions. The size of adrenal masses ranged from 7 mm to 12 cm. The CT examination helped in characterising myelolipomas in 3 cases, cysts in two cases, and pre-assuming malignity in 6 cases. Hormonal analyses have revealed primary aldosteronism in 2 cases, subclinical hypercortisolism in 1, steroid enzymopathy in 2 and secondary hyperaldosteronism in 2 patients. No patient had catecholamine overproduction. 19 patients were indicated for adrenalectomy with the following histological findings.: adenoma (n = 5), cyst (n = 2), myelolipoma (n = 3), carcinoma (n = 3), feochromocytoma, ganglioneuroma, metastases, lymphoma, sarcoidosis and pseudodrenal structure--Gravitz tumor (n = 1, respectively). The size of all neoplasms exceeded 3 cm, therefore the authors recommend adrenalectomy in incidentalomas with hormonal activity exceeding 3 cm in size. (Tab. 2, Fig. 1, Ref. 17.)
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PMID:[Hormonal and morphologic characteristics of adrenal incidentalomas]. 1118 53

Little is known on the epidemiology of Cushing's disease (CD) as relevant data on such a rare disease can only be obtained from large-scale studies. We addressed this topic analyzing the data obtained in the Italian multicenter study which comprised nearly 300 patients with CD. The number of newly diagnosed patients with CD increased markedly in the second decade of the study (from 7.4 +/- 0.71 pts/year prior to 1987 to 26.4 +/- 4.12 after 1987) probably reflecting the heightened awareness of the disease and the increased availability of diagnostic tools. Urinary free cortisol (UFC) levels were significantly higher in men than in women and were inversely correlated with the time interval between appearance of symptoms and diagnosis. Recognition of CD among patients presenting with common diseases such as obesity, diabetes and hypertension requires highly sensitive screening tests (e.g. UFC, midnight cortisol in saliva, overnight dexamethasone suppression test) which however may yield false positive results. In doubt, second line testing using dex-CRH or desmopressin may distinguish between CD and pseudo Cushing. The different prevalence of CD and ectopic ACTH secretion (ES) undermines the diagnostic accuracy of tests used for the differential diagnosis of ACTH-dependent Cushing's syndrome (i.e. CRH, high dose dexamethasone, IPSS). Tests aimed at identifying ES rather than CD are needed to overcome this bias. Transsphenoidal surgery was the preferred choice of treatment for patients with CD, resulting in remission in 70% operated patients with a 15% relapse rate over 10 years follow-up. Definition of remission after surgery and parametres predictive of relapse, however, vary according to studies and long-term follow-up is required to establish their validity. Most clinical manifestations of hypercortisolism disappeared after remission although some long-lasting effects on the cardiovascular system had been observed. Finally, according to recent reports, mortality rates for patients cured of CD appear comparable to those of the general population.
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PMID:Epidemiology and follow-up of Cushing's disease. 1135 89

This is a case report of a 23 year old female. She had earlier been diagnosed to have Cushing's syndrome due to macronodular adrenal hyperplasia, for which bilateral adrenalectomy was performed three years before. The initial full recovery was sustained for about one and a half years, following which there was progressive recurrence of obesity, hypertension and hypercalcaemia. Plasma cortisol concentrations were markedly elevated and a diagnosis of recurrent Cushing's syndrome was made. Pre-operative localisation of the source of hypercortisolism through intravenous urogram, abdominal ultrasonogram and computerised tomogram was unfruitful, thus an exploratory laparatomy was undertaken. At surgery, extensive and dense adhesions were seen which caused difficult dissection and accidental injury to the patient's liver and kidney, necessitating massive intra-operative blood transfusions. The patient died within two hours of recovery from anaesthesia of acute massive pulmonary embolism. We postulate that the recurrent Cushing's syndrome in this patient could have been due autografting of remnants of adrenal tissue within the abdominal cavity. A pre-operative localisation with radio-labelled cholesterol scanning may have made reoperation of the patient easier.
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PMID:A follow up report: recurrent Cushing's syndrome after bilateral adrenalectomy. 1150 90


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