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 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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 preoperative evaluation and safe anesthetic treatment of patients with endocrine gland tumors mandate an understanding of the physiologic dysfunctions attributable to these tumors. Some patients will exhibit various signs and symptoms characteristic of the MEN syndromes. In the patient with acromegaly, a fiberoptic-guided intubation of the trachea to secure the airway before induction of general anesthesia must be anticipated. Anesthetic treatment of the patient with hyperadrenocorticism requires knowledge of the physiologic effect of excess cortisol. In the patient with severe hyperparathyroidism, we attempt to correct the markedly elevated plasma calcium levels and maintain adequate hydration and urine output perioperatively. Following thyroidectomy for MCT, 2 potential problems of concern are upper airway obstruction and aspiration resulting from injury (unilateral or bilateral) to the recurrent laryngeal nerve and the superior laryngeal nerve, respectively. The major focus during excision of an insulinoma is prevention of wide swings in blood glucose concentrations. In the gastrinoma patient, the anesthesiologist not only must correct any intravascular fluid volume deficit or electrolyte imbalance but must also consider the patient to have a full stomach at the time of anesthetic induction. Correction of hypokalemia and control of hypertension may be required in the preoperative preparation of the patient with an adrenal cortex tumor. Preoperative alpha-adrenergic blockade must be initiated in the patient with a pheochromocytoma to prevent dangerous elevations in blood pressure during anesthesia and surgery for the tumor's removal. Vasodilators with rapid onset and short duration are used to treat intraoperative hypertension. After ligation of the tumor's blood supply, falls in blood pressure may require treatment with fluids and vasopressors. Carcinoid syndrome patients should be treated with somatostatin to prevent stimuli such as anxiety, abdominal scrubbing, or tumor manipulation from precipitating severe hypotension, hypertension, bronchospasm, or tachycardia. In both pheochromocytoma and carcinoid patients, a smooth anesthetic induction and tracheal intubation plus avoidance of drugs that release histamine or activate the sympathetic nervous system may also prevent intraoperative crises.
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PMID:Anesthetic implications for surgical patients with endocrine tumors. 1081 14

HIV infection has reached endemic proportions in many African countries. In addition, HIV infection is a significant cause of renal dysfunction in the United States. HIV patients are at higher risk of developing hypertension at a younger age than the general population. Predisposing factors for developing hypertension include vasculitis in small, medium, and large vessels in the form of leukocytoclastic vasculitis, and aneurysms of the large vessels such as the carotid, femoral, and abdominal aorta with impairment of flow to the renal arteries. A syndrome of acquired glucocorticoid resistance has been described in patients with HIV with hypercortisolism and a lower affinity of the glucocorticoid receptors. The syndrome is characterized clinically by weakness, hypertension or hypotension, and skin pigmentation changes. Acute and chronic renal failure is often associated with HIV infection. The associated dysfunction in water and salt handling often induces hypertension. Finally, atherosclerosis has been described in young adults with HIV infection secondary to receiving highly active antiretroviral therapy.
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PMID:Hypertension in the HIV-infected patient. 1099 24

It is known that the prevalence of cardiovascular diseases, hypertension, noninsulin dependent diabetes mellitus and dyslipidemia in the late adulthood are in connection with intrauterine retardation, characterized by low birth weight. One possible explanation of this phenomenon is the abnormality of hypothalamus-hypophysis-adrenal cortex axis due to the accelerated growth. The authors investigated the steroid levels of young adults; whom birth weight were under 2500 g, and examined the relationship between hormone levels and some parameters of glucose metabolism and cardiovascular system. 75 subjects (43 female and 32 male patients, mean age: 19.6 and 19.8 years, respectively; range 18-22 ys) with low birth weight and without any sign of chronic disease, and 30 healthy, age-matched controls with normal birth weight were investigated. The basal serum cortisol, dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulphate (DHEAS), androstenedione (AD), 17-hydroxyprogesterone (17OHP), estradiol (OE), sex-hormone binding globulin (SHBG), FSH, LH and insulin levels were determined. Moreover, oral glucose tolerance test with 75 g glucose (OGTT), impedance cardiography as well as ambulatory blood pressure monitoring were done by all subjects. In both sexes in subjects with low birth weight the mean serum cortisol level was significantly higher, than in the normal controls. In female patients the serum DHEA, DHEAS, AD, and 17OHP levels were significantly higher than in the controls. Moreover, among these females a relationship was found between the elevations of adrenal and gonadal steroids and hyperinsulinemia, characterized by increased insulin response during OGTT. In male subjects a significant correlation was found between serum cortisol levels and systolic blood pressure and heart rate. In females there was a positive relationship between serum DHEA and heart rate. Summarized, the basic abnormality in patients with low birth weight seems to be a relative hypercortisolism, and in females because of hyperinsulinemia exists a mild hyperandrogenism as well. The hypercortisolism may cause cardiovascular abnormalities in males directly, while in females indirectly through the hyperinsulinemia and hyperandrogenism. These subtle abnormalities can be detected when no clinical signs present themselves, in young adulthood, giving the opportunity of taking preventive actions.
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PMID:[Low birth weight, adrenal and sex hormones and their correlation with carbohydrate metabolism and cardiovascular physiology, investigated in young adulthood] . 1103 33

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

A number of patients with adrenal incidentaloma are exposed to a slight degree of cortisol excess resulting from functional autonomy of the adrenal mass (usually a cortical adenoma). At present, there are only scant data on the unwanted effects of this endocrine condition referred to as subclinical Cushing's syndrome. The aim of the present study was to look for some features of the metabolic syndrome in patients with incidental adrenal adenoma. Forty-one patients (9 men and 32 women) bearing adrenal incidentaloma with typical computed tomography features of cortical adenoma were studied. For both patients and controls, exclusion criteria were age equal to 70 yr or greater, previous history of fasting hyperglycemia, or impaired glucose tolerance (IGT), severe hypertension, current use of medication or concomitant relevant illnesses, and body mass index (BMI) equal to 30 kg/m(2) or greater. Forty-one patients with euthyroid multinodular goiter accurately matched for sex, age, and BMI served for a 1:1 case-control analysis. The study design included an oral glucose tolerance test (75 g) and an endocrine workup aimed at the study of the hypothalamic-pituitary-adrenal axis. Age and BMI were fully comparable between patients (54.0 +/- 10.7 yr, 23.8 +/- 2.4 kg/m(2)) and controls (52.2 +/- 11.6 yr, 23.5 +/- 2.8 kg/m(2)). Fasting glucose and fasting insulin levels were not different between the two groups (4.96 +/- 0.61 mmol/liter vs. 4.88 +/- 0.58 mmol/liter; 67 +/- 34 pmol/liter vs. 59 +/- 32 pmol/liter), but the 2-h postchallenge glucose was significantly higher in patients than in controls (7.43 +/- 2.49 mmol/liter vs. 6.10 plus minus 1.44 mmol/liter, P = 0.01). Fifteen patients (36%) reached the World Health Organization criteria for IGT and two other patients (5%) reached those for diabetes, and 14% of the controls qualified for IGT (P = 0.01). No difference in the lipid pattern was seen between the two groups, but either systolic or diastolic blood pressure were higher in patients (135.4 +/- 15.5 mm Hg vs. 125.0 +/- 15.6 mm Hg, P = 0.003; 82.9 +/- 9.1 mm Hg vs. 75.3 +/- 6.6 mm Hg, P < 0.0001). We calculated the whole-body insulin sensitivity index derived from the oral glucose tolerance test that was significantly reduced in the patients (4.3 +/- 1.7 vs. 5.7 +/- 2.5, P = 0.01). In a multiple regression analysis, 2-h glucose was associated with BMI and midnight cortisol values (r(2) = 0.36, P = 0.002). The comparison of the patients with nonfunctioning adenoma (n = 29) with those with subclinical Cushing's syndrome (n = 12) yielded significant differences as to 2-h glucose and triglyceride levels, which were significantly higher in the second group (7.02 +/- 1.76 mmol/liter vs. 8.72 +/- 3.17 mmol/liter, P = 0.03; 1.06 +/- 0.4 mmol/liter vs. 1.73 +/- 0.96 mmol/liter, P = 0.002), but the insulin sensitivity index was conversely reduced (5.2 +/- 1.4 vs. 2.9 +/- 1.2, P < 0.0001). In conclusion, many patients with incidental adrenal adenoma display altered glucose tolerance, that may be explained by reduced insulin sensitivity, and increased blood pressure levels in comparison with carefully age- and BMI-matched controls. The slight hypercortisolism observed in some such patients may significantly contribute to this state of insulin resistance. Midnight serum cortisol appears as a sensitive marker of the metabolic effects of subclinical Cushing's syndrome.
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PMID:Adrenal incidentaloma: a new cause of the metabolic syndrome? 1292 19

Glucocorticoids regulate diverse functions important for the maintenance of central nervous system, cardiovascular, metabolic, and immune homeostasis. The actions of these hormones are mediated by the specific intracellular glucocorticoid receptors (GRs). Pathologic conditions associated with changes of tissue sensitivity to these hormones have been described. The syndrome of familial/sporadic glucocorticoid resistance is characterized by hypercortisolism without Cushing syndrome stigmata. Many of the patients present with hypertension, with or without hypokalemic alkalosis, as a result of elevated concentrations of cortisol and other salt-retaining steroids. The molecular defects of 4 kindreds and one sporadic case have been elucidated as inactivating mutations in the ligand-binding domain of the GR. In two patients in whom the GR was mutated at amino acid isoleucine 559 to aspartic acid (GRalphaI559N) and isoleucine 747 to methionine (GRalphaI747M), respectively, glucocorticoid resistance developed at the heterozygous state, with transdominant negative activity of each of the mutant receptors upon the wild-type protein. Retention of the wild-type receptor in the cytoplasm by the mutant receptor was found in the former, while inappropriate accumulation of p160-type coactivators on the promoter region of glucocorticoid-responsive genes, because of a defective interaction between the AF2 region of the mutant receptor and the LXXLL motif of the coactivators, was determined in the latter. These results suggest that the pathologic mechanisms of glucocorticoid resistance is quite broad, and this is reflected in the wide variability of the clinical picture in patients with the syndrome.
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PMID:Familial/sporadic glucocorticoid resistance syndrome and hypertension. 1238 45


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