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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Corticosteroids (glucocorticoids), used frequently as potent anti-inflammatory agents, increase the risk of glaucoma by raising the intraocular pressure (IOP) when administered exogenously (topically, periocularly or systemically) and in certain conditions of increased endogenous production (e.g. Cushing's syndrome). Approximately 18 to 36% of the general population are corticosteroid responders. This response is increased to 46 to 92% in patients with primary open-angle glaucoma (POAG). Patients over 40 years of age and with certain systemic diseases (e.g. diabetes mellitus, high myopia) as well as relatives of patients with POAG are more vulnerable to corticosteroid-induced glaucoma. The association of corticosteroid-induced ocular hypertension in other conditions which are considered as risk factors for glaucoma (racial origins, hypertension, migraine, vasospasm) is likely but not fully established. The proposed mechanism of corticosteroid-induced glaucoma includes morphological and functional changes in the trabecular meshwork system and is similar to the pathogenesis of POAG. Trabecular cells exposed to corticosteroids in vitro show endoreplication of nuclei, an increase in cell size and excessive production of an approximately 56kD glycoprotein, identified as myocilin and transcribed by the GLC1A gene. Induction of ocular hypertension after corticosteroid administration depends on the specific drug, the dose, the frequency of administration and the corticosteroid responsiveness of the patient. The risk of corticosteroid-induced glaucoma can be minimised with judicious use of corticosteroids, as well as education of patients and medical practitioners. New treatment modalities include modified steroids and nonsteroidal anti-inflammatory agents that will have less effect on the elevation of IOP.
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PMID:Corticosteroids and glaucoma risk. 1064 55

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

A 63-year-old man with bilateral adrenal tumors was treated for hypertension and diabetes mellitus. Endocrinologic examination during follow-up revealed the production of cortisol to be independent of the regulation of the hypothalamo-pituitary-adrenal axis. Therefore, he was diagnosed as having subclinical Cushing syndrome, and these tumors were removed. Adrenocorticotropic hormone-independent macronodular adrenal hyperplasia (AIMAH) was endocrinologically and histopathologically diagnosed. This is the first report demonstrating that endocrinologic changes of AIMAH can be observed during long-term follow-up.
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PMID:Subclinical Cushing syndrome due to adrenocorticotropic hormone-independent macronodular adrenocortical hyperplasia: changes in plasma cortisol levels during long-term follow-up. 1075 62

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

A case is herein reported of pneumocystis carinii pneumonia in a 60-year-old female patient with ectopic production of ACTH at a position 2 cm superior to her right clavicle, revealed in an octreotide scan. Her extremely high plasma ACTH and cortisol levels (460 pg/ml and 80 microg/dl, respectively) were markedly decreased with the combined treatment of octreotide (300 microg/d) and ketoconazole (600 mg/d). As her serum cortisol concentration decreased, pneumocystis carinii pneumonia occurred on the third day of treatment. A secondary E. coli infection was superimposed and the patient died of disseminated intravascular coagulation and adult respiratory distress syndrome. This case suggests that primary prophylaxis for pneumocystis carinii infection should be initiated before cortisol lowering therapy, especially when the plasma cortisol concentration is excessively high, and that early adjunctive glucocorticoid therapy can reduce the acute mortality in patients with endogenous Cushing's syndrome and Pneumocystis carinii pneumonia. This case study would also like to point out that plasma ACTH and cortisol levels were decreased effectively by the combination of octreotide and ketoconazole in this instance of ectopic ACTH syndrome.
Exp Clin Endocrinol Diabetes 2000
PMID:Pneumocystis carinii pneumonia associated with a rapid reduction of cortisol level in a patient with ectopic ACTH syndrome treated by octreotide and ketoconazole. 1082 24

Three patients with functional adrenal tumors, Cushing's syndrome, primary aldosteronism and pheochromocytoma, who underwent adrenalectomy and were subsequently cured, were studied. All these patients had been treated for diabetes for several years before the diagnosis of adrenal tumors. In each case the state of diabetes before and after surgery, including parameters of insulin secretion and insulin resistance, was compared to demonstrate how the adrenal disorder influenced the nature of diabetes. In the case of Cushing's syndrome the hypercortisolemia caused insulin resistance in the peripheral tissues. In the case of primary aldosteronism, excessive production of aldosterone diminished insulin secretion possibly through hypokalemia. Pheochromocytoma affected both insulin secretion and insulin sensitivity through hypersecretion of catecholamines. In all these patients the adrenal tumors were found in clinical contexts other than management of diabetes itself. By careful retrospective review of these three patients' history, several important points that might have drawn the physician's attention to the underlying adrenal disorders were pointed out. These included past history of acute myocardial infarction with onset at unexpectedly young age in the case of Cushing's syndrome and unexpectedly high insulin resistance for the patient's body mass index in the case of pheochromocytoma.
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PMID:Three patients with adrenal tumors having been treated simply for diabetes mellitus. 1091 24

Hypercortisolism is a frequent endocrine sign in major depression and cortisol is a well-known anti-insulinergic hormone. Impaired oral glucose tolerance has already been described in major depression. However, thus far no information is available on spontaneous, circadian insulin secretion in patients. We studied 26 depressed inpatients along with 33 age- and sex-matched controls. Blood samples were collected at 30-minute intervals over a period of 26 hours (h) for estimation of cortisol, insulin and glucose. No differences in 24 h mean-insulin and glucose concentrations were detectable despite significantly reduced caloric consumption in patients. At the second morning a strictly standardized test meal of 2125 kjoule was given. Insulin and glucose responses to the test meal were significantly increased in hypercortisolemic patients compared to controls. Hence, patients with major depression have an impaired insulin sensitivity.
Exp Clin Endocrinol Diabetes 2000
PMID:Major depression and impaired glucose tolerance. 1092 14

It is known that either chronic glucocorticoid administration or endogenous hypercortisolism frequently induce an hypercoagulable condition. Since little is known about the evaluation of markers of haemostatic and fibrinolytic systems in other adrenal disorders, we studied plasminogen activator inhibitor (PAI-1), tissue-plasminogen activator (t-PA), fibrinogen and von Willebrand factor antigen (vWF-Ag) levels in 11 patients with Cushing's syndrome and in 12 patients with adrenal incidentaloma. In patients with Cushing's syndrome mean PAI-1, t-PA and vWF-Ag levels did not significantly differ from those found in 50 age- and sex-matched controls, while mean fibrinogen levels were significantly higher in patients (337.0+/-39.1 mg/dl) than in normal subjects (278.9+/-8.4 mg/dl). Patients with adrenal incidentaloma showed PAI-1, t-PA and vWF-Ag mean levels superimposable to those in controls, while fibrinogen (319.7+/-27.9 mg/dl) was slightly, although not significantly, higher than in normals. Considering the limits of normal values (as mean+/-2 SD) obtained in the control group, high PAI-1 levels were found in 2 patients with Cushing's syndrome and in 3 patients with incidentaloma. An elevation of fibrinogen levels was found in 3 patients with Cushing's syndrome and in 3 with incidentaloma. Increased vWF-Ag levels were found only in 1 patient with Cushing's syndrome. An increased t-PA level was occasionally observed only in the patient with adrenal carcinoma. On the whole, an alteration of at least one of haemostatic and fibrinolytic parameters was detected in 55% of the patients with Cushing's syndrome and in 42% of those with adrenal incidentaloma. In conclusion, early alterations of coagulation and fibrinolytic systems may be found in some patients with adrenal disorders, thus suggesting the opportunity of an accurate follow-up in order to identify possible risk factors for cardiovascular disease and thromboembolism.
Exp Clin Endocrinol Diabetes 2000
PMID:Evaluation of haemostatic and fibrinolytic markers in patients with Cushing's syndrome and in patients with adrenal incidentaloma. 1096 61

In addition to diabetes mellitus and obesity, acromegaly, Cushing's syndrome, hypopituitarism, hypo- and hyperthyroidism, hyperparathyroidism and polycystic ovary syndrome are associated with either increased mortality from, or increased prevalence of, cardiovascular disease (CVD). Recently, endothelial dysfunction has been identified as an early marker of CVD and has been shown to predict future coronary artery disease, before atherosclerotic changes appear in arteries. Thus, measurement of endothelial function might identify at-risk individuals early and be a useful means of assessing response to treatment aimed at reducing long-term morbidity and/or mortality from CVD. Such studies are being undertaken in hypopituitarism and other endocrinopathies, and are reviewed herein. Endothelial function in large vessels can be measured noninvasively by ultrasound measurement of flow-mediated endothelium-dependent dilation (FMD). Serum markers of endothelial function, such as von Willebrand's factor, thrombomodulin, E-selectin and intercellular adhesion molecule 1, could be increased and be useful for evaluation of treatment, because they correlate inversely with FMD.
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PMID:Endothelial dysfunction in endocrine disease. 1144 43

With increasing case reports, it has been indicated that some cases with adrenocorticotropic hormone (ACTH)-independent macronodular adrenal hyperplasia (AIMAH) show abnormal responses in cortisol to various stimulation tests. Here we report a case of AIMAH that showed an aberrant response to angiotensin II via AT1 receptor in cortisol hypersecretion. A 53-yr-old man was admitted to our division seeking further examinations for the possible diagnosis of Cushing's syndrome. He had hypertension, diabetes mellitus, and physical stigmata, such as moon face and central obesity. His plasma ACTH level was undetectable, and plasma cortisol level was high. Plasma cortisol showed no normal diurnal rhythm and was not suppressed after the administration of 8 mg of dexamethasone. Abdominal computed tomography demonstrated nodular enlargement of bilateral adrenal glands. He was diagnosed with Cushing's syndrome owing to AIMAH. An injection of arginine vasopressin (AVP) increased plasma cortisol and aldosterone levels, whereas ACTH remained undetectable. After 4 h in an upright position, plasma cortisol and aldosterone levels were increased. Pretreatment with candesartan, angiotensin II receptor AT1 antagonist, blocked the increase in plasma cortisol level. These results suggested a possibility of adrenal hypersensitivity to angiotensin II and AVP in cortisol secretion. Bilateral laparoscopic adrenalectomy was performed. The histological findings of the specimen were compatible with AIMAH. In summary, we have made the first report on a case of AIMAH with possible hypersensitivity to angiotensin II.
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PMID:Case of adrenocorticotropic hormone-independent macronodular adrenal hyperplasia with possible adrenal hypersensitivity to angiotensin II. 1157 27


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