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Query: UMLS:C0028754 (obesity)
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Differentiating Cushing's disease (CD) from pseudo-Cushing (PC) states may still be difficult in current practice. Because desmopressin (1-deamino-8D-arginine vasopressin, DDAVP), a vasopressin analogue, stimulates ACTH release in patients with CD but not in the majority of normal, obese, and depressed subjects, we investigated its ability to discriminate CD from PC states. One hundred seventy-three subjects (76 with active CD, 30 with PC, 36 with simple obesity, and 31 healthy volunteers) were tested with an iv bolus of 10 microg DDAVP. Sixty-one of these subjects also underwent a control study with saline. DDAVP induced marked ACTH and cortisol rises in CD (P < 0.005 vs. saline, for both ACTH and cortisol) but not in PC. A significant ACTH elevation occurred upon DDAVP administration also in normal and obese subjects, but it was much smaller than that observed in patients with CD (P < 0.0001). A peak absolute ACTH increase (> or =6 pmol/L), after DDAVP, allowed us to recognize 66 of 76 patients with CD and 88 of 97 subjects of the other groups. The same criterion correctly identified 18 of 20 patients with mild CD (24-h urinary free cortisol < or = 690 nmol/day) and 29 of 30 PC, resulting in a diagnostic accuracy of 94%, which was definitely higher than that displayed by urinary free cortisol, overnight 1-mg dexamethasone suppression test, and midnight plasma cortisol. In conclusion, the DDAVP test seems to be a useful adjunctive tool for the evaluation of hypercortisolemic patients chiefly because of its ability to differentiate mild CD from PC states.
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PMID:The desmopressin test in the differential diagnosis between Cushing's disease and pseudo-Cushing states. 1106 3

Evaluation of an overweight patient is the first step in any therapeutic program. The syndromes of obesity can be classified in several ways. The first is an anatomic classification based on the size, number, and distribution of fat cells and fat tissue. The second is an etiologic classification based on identification of specific diseases and settings that produce obesity. Hypothalamic injury and endocrine disease such as Cushing's disease and the polycystic ovary syndrome are three identifiable causes of obesity. In this medicated society drugs are always candidates to produce weight gain. The most common causes, however, are stopping smoking, overconsumption of high-fat foods, a decrease in the level of activity, and aging. The natural history of obesity provides a useful framework in which to view both preventive and therapeutic strategies. Some individuals will never become overweight, but of those who do, about one-third will do so during the first two decades, and the remaining two-thirds will become overweight after age 20. A number of epidemiological and metabolic factors can serve as a guide to those individuals who are at high risk. Having overweight parents tops the list, but multiple births, cessation of smoking, and a sedentary lifestyle are additional factors. Therapeutic decisions should be based on risk-benefit decisions. The risk can be assessed from the body mass index, the distribution of fat in upper or lower body obesity, the rate of weight gain, and the degree of physical inactivity. After assessing risk, the therapeutic choices can be selected from the age category of the patient. With any therapeutic activity, involvement of the patient in a realistic approach to the treatment process is essential.
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PMID:Clinical evaluation of the overweight patient. 1118 18

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

Cushing's syndrome is an uncommon but important disease. Twenty-one confirmed cases of spontaneous Cushing's syndrome were documented at the University Hospital of the West Indies over a 21-year period. They were predominantly young females (F:M ratio of 17:4; mean age 25 years and 3 months). The commonest presenting symptoms were amenorrhoea (41%) and obesity (19%). Common clinical features were cushingnoid features (95%), hypertension (76%) and hirsutism (82%). Twenty-nine per cent had frank hyperglycaemia. Cushing's syndrome was due to Cushing's disease in 10 cases, adrenal adenoma in 3 and adrenal carcinoma in 2 cases. In 4 cases with presumed adrenal hyperplasia, the histology was either unavailable or was not consistent with the diagnosis. Two cases appear now to have had the ectopic ACTH Syndrome. Adrenalectomy was the commonest treatment offered. There were no intra-operative or post-operative deaths but recurrence was common after subtotal adrenalectomy in Cushing's disease. Twenty-seven per cent of the patients developed Nelson's syndrome, which was fatal in 50%. Long-term hormone replacement therapy was unnecessary after surgery for adrenal adenomas. Treatment of Cushing's syndrome was well tolerated by the patients.
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PMID:A clinico-pathological study of Cushing's syndrome at the University Hospital of the West Indies and a review of the literature. 1139 90

Symmetrical mediatinal lipomatosis is a rare benign condition characterized by deposition of a large amount of mature adipose tissue within the mediastinum. Usually secondary to exogenous obesity, administration of steroids and Cushing's disease, it is more common in middle-aged males and is associated with alcohol abuse. Various other associations have been reported. CT and MRI can decisively diagnose this benign condition, which also helps in deciding treatment options. We present a case of a young female with a bizarre appearance on chest radiographs. Isolated, bilaterally symmetrical mediastinal lipomatosis was diagnosed on CT and MRI. The patient was thin and did not consume alcohol or steroids. Cushing's disease and other known associations were excluded.
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PMID:Isolated symmetrical mediastinal lipomatosis. 1184 11

In this study, 55 patients with Cushing's syndrome (CS) (50 female, 5 male; mean age 34 +/- 12.3 yr) who attended our clinics between the years 1983 and 2000 were retrospectively evaluated for clinical and laboratory features and modalities and results of therapy, due to a few similar studies over the last ten years. Cushing's disease was diagnosed in 39 patients (71%), adrenal adenoma in 13 patients (23.6%) and adrenal carcinoma in 3 patients (5.5%). Centripedal obesity, moon face, hypertension, hirsutism and purplish stria were the most frequent findings. Loss of normal serum F circadian rhythm was found in all patients with CS. The overnight 1 mg oral dexamethasone suppression test and low-dose dexamethasone suppression test (LDDST) yielded 100% and 100% diagnostic sensitivity for CS, respectively. Sensitivity and specivity of the high-dose dexamethasone suppression test (HDDST) in distinguishing Cushing's disease was found to be 82% and 100%, respectively. All of the patients with adrenal CS were not suppressed with HDDST. Sellar CT and/or MRI accurately identified the tumor in 58% of these patients. Recurrence was observed in 3 (11%) of the 28 patients with Cushing's disease, treated by transsphenoidal adenomectomy. Recurrence was diagnosed 1.5, 3 and 6 yr after the operation in these 3 patients. One patient had residue tumor. In our case series, bilateral adrenalectomy plus pituitary irradiation achieved the highest remission rate (100%) in Cushing's disease. In 2 out of 4 patients (50%) treated by left adrenalectomy associated with pituitary irradiation, recurrence was observed. Panhypopituitarism due to tumor apoplexy was observed in one of the patients with Cushing's disease. All of the patients with adrenal CS, the tumor was accurately localized with imaging methods before the operation. The appropriate operative procedure resulted in complete remission in patients with adrenal adenoma. Consequently, Cushing's disease was the most common form of CS. The overnight 1 mg oral DST and 24-h urine free F excretion (UFC) as screening tests, 2-day LDDST as diagnostic test and 2-day HDDST as differential diagnostic test were good studies. More successful outcomes have been achieved in treatment of Cushing's disease with the development of pituitary surgery in the recent years, as well as in our case series. Surgery is also curative for adrenal adenoma patients. Survival remains poor among carcinoma patients.
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PMID:Clinical laboratory findings and results of therapy in 55 patients with Cushing's syndrome. 1260 37

The pathogenesis of nephrolithiasis in Cushing's syndrome is still not completely clarified. The current study aimed at investigating prevalence of nephrolithiasis and role of different lithogenic factors in Cushing's disease (CD). Forty-six CD patients (24 with active and 22 with cured disease) and 46 sex- and age-matched controls entered the study. Body mass index, blood pressure, fasting glucose and insulin, serum and urinary creatinine, urea, uric acid, electrolytes, and cystine, urinary volume, pH, oxalate, and citrate levels, and renal ultrasonography (US) were performed in all patients and controls. Nephrolithiasis was found in 50% of active patients, 27.3% of cured patients, and 6.5% of controls (P < 0.001). Compared with controls, patients with active disease had a significantly increased prevalence of obesity, arterial hypertension, diabetes mellitus, hypercalciuria, hypocitraturia, and hyperuricosuria, significantly higher levels of serum and urinary cystine, urinary creatinine, urea, uric acid, potassium, calcium, phosphorus, and oxalate, significantly lower levels of urinary citrate levels. Compared with controls, patients cured from CD had a significantly increased prevalence of obesity, systemic arterial hypertension, and diabetes mellitus, whereas urinary citrate was significantly decreased. At multivariate analysis, a significantly increased risk to develop kidney stones was independently associated with urinary excretion of uric acid (odds ratio = 1.6, confidence interval = 1.0-2.5) and systemic arterial blood pressure (odds ratio = 2.6, confidence interval = 1.1-6.6). In conclusion, patients with active CD have an increased prevalence of nephrolithiasis compared with general population, which decreases but not disappears in patients successfully cured from the disease. This complication is likely caused by the synergic effect of different hypercortisolism-dependent metabolic and hemodynamic abnormalities, among which systemic arterial hypertension and excessive urinary uric acid excretion seem to play a pivotal role.
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PMID:Nephrolithiasis in Cushing's disease: prevalence, etiopathogenesis, and modification after disease cure. 1272 57

Cushing's disease is uncommon in childhood. It is usually caused by the oversecretion of adrenocorticotrophic hormone (ACTH) by a pituitary corticotroph adenoma. Clinical abnormality is often undetected for long periods of time. The principal clinical features are growth retardation and obesity. We present four patients who were diagnosed with Cushing's disease in a tertiary hospital from January 1995 to December 2002. There were two boys and two girls, aged 10-15 years. The main clinical features at presentation were growth failure and excessive weight gain. The interval between onset of symptoms and diagnosis ranged from 2.5 to 5 years. All patients presented moon face and increased fat around the neck. In all patients, 24-hour urinary free cortisol was high and loss of normal serum cortisol circadian rhythm (3/3) and suppression of cortisol to less than 50 % of the basal level with high-dose but not with low-dose dexamethasone (2/2) were observed. Pituitary microadenoma was detected by magnetic resonance imaging in three patients; no tumor was detected in the fourth patient and inferior petrosal sinus sampling was performed, showing left lateralization of ACTH central secretion. Therapy consisted of transsphenoidal surgery in all patients. Two patients are in remission, one patient presented disease recurrence requiring total hypophysectomy because the tumor could not be completely removed and one patient had persistent disease after a second intervention and required pituitary radiotherapy. Two patients showed pituitary hormone deficiency after therapy.
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PMID:[Diagnosis, treatment and long-term outcome in Cushing's disease]. 1288 47

Two isoforms of 11beta-hydroxysteroid dehydrogenase (11beta-HSD) interconvert the active glucocorticoid, cortisol, and inactive cortisone. 11beta-HSD1 acts predominantly as an oxo-reductase in vivo using NADP(H) as a cofactor to generate cortisol. In contrast, 11beta-HSD2 is a NAD-dependent dehydrogenase inactivating cortisol to cortisone, thereby protecting the mineralocorticoid receptor from occupation by cortisol. In peripheral tIssues, both enzymes serve to control the availability of cortisol to bind to corticosteroid receptors. 11beta-HSD2 protects the mineralocorticoid receptor from cortisol excess; mutations in the HSD11B2 gene explain an inherited form of hypertension, the syndrome of 'apparent mineralocorticoid excess', in which 'Cushing's disease of the kidney' results in cortisol-mediated mineralocorticoid excess. Inhibition of 11beta-HSD2 explains the mineralocorticoid excess state seen following liquorice ingestion and more subtle defects in enzyme expression might be involved in the pathogenesis of 'essential' hypertension. 11beta-HSD1 by generating cortisol in an autocrine fashion facilitates glucocorticoid receptor-mediated action in key peripheral tIssues including liver, adipose tissue, bone and the eye. 'Cushing's disease of the omentum' has been proposed as an underlying mechanism in the pathogenesis of central obesity and raises the exciting possibility of selective 11beta-HSD1 inhibition as a novel therapy for patients with the metabolic syndrome. 'Pre-receptor' metabolism of cortisol via 11beta-HSD isozymes is an important facet of corticosteroid hormone action. Aberrant expression of these isozymes is involved in the pathogenesis of diverse human diseases including hypertension, insulin resistance and obesity. Modulation of enzyme activity may offer a future therapeutic approach to treating these diseases whilst circumventing the endocrine consequences of glucocorticoid excess or deficiency.
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PMID:Tissue-specific Cushing's syndrome, 11beta-hydroxysteroid dehydrogenases and the redefinition of corticosteroid hormone action. 1294 16

The present study reports a rare case of full-blown Cushing's disease several years after an episode of pituitary apoplexy. A 60 year-old woman complained of muscular weakness and generalized malaise. Ten years ago she had an episode of pituitary apoplexy. Diabetes mellitus was diagnosed at age 56, and thereafter she had been controlled her plasma glucose with diet therapy and oral hypoglycemic agents. She exhibited cushingoid feature of moon face and central obesity. Both plasma ACTH and serum cortisol levels were elevated to 170 pg/ml and 19.6 microg/dl, respectively. Dexamethasone suppression test showed that a large dose of 8 mg dexamethasone, but not a small dose of 2 mg, suppressed the pituitary-adrenocortical axis. CRH and methyrapone caused increases in plasma ACTH and serum cortisol levels. Brain T(1)-weighted magnetic resonance imaging depicted a low signal of pituitary tumor, which was not enhanced by gadolinium. The pituitary tumor was removed by transsphenoidal adenomectomy, and immunohistochemistry revealed an ACTH-producing adenoma. The evidence suggested the possibility that the two pituitary tumors with dormant period of several years were a recurrence of ACTH-producing tumors in the present patient.
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PMID:Full-blown Cushing's disease after an episode of pituitary apoplexy. 1461 5


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