Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Discrepancy of plasma ACTH levels measured by different immunoradiometric assays (IRMA) in a case with malignant gastric carcinoid causing ectopic ACTH syndrome was examined by gel chromatography and immunohistochemical analysis. A 49-year-old male was found to have a large gastric tumor, with muscle wasting, hypertension, diabetes and hypokalemia caused by hypercortisolemia. His plasma ACTH levels, although initially elevated, were found to be almost in normal ranges. The discrepancy of plasma ACTH levels was proven to be due to different IRMA kits used; the initial assay was performed by a kit that could recognize high-molecular weight (HMW) form as well as ACTH(1-39), but the later assay by another kit that could recognize only ACTH(1-39). Pathological examination of the gastric tumor was consistent with the diagnosis of malignant carcinoid. Immunohistochemical study revealed that immunoreactivity of proopiomelanocortin (POMC) was positive within the tumor cells, whereas those of ACTH and prohormone convertase 1/3 were negative. Molecular sieving analysis of patient's plasma by gel chromatography coupled with ACTH radioimmunoassay which could recognize HMW form and ACTH(1-39) and two different IRMAs revealed that the predominant form of ACTH was HMW form with a minor peak of ACTH(1-39). This is a rare case of ectopic ACTH syndrome caused by malignant gastric carcinoid with preferential production of HMW form of ACTH, possibly due to unprocessed POMC.
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PMID:Malignant gastric carcinoid causing ectopic ACTH syndrome: discrepancy of plasma ACTH levels measured by different immunoradiometric assays. 1641 Jun 67

Hypoglycemia-associated autonomic failure (HAAF) occurs commonly in patients with longstanding diabetes, placing affected patients at increased risk for severe hypoglycemia. Previous studies have suggested that hypoglycemia-induced hypercortisolemia may be responsible for blunting subsequent sympathoadrenal responses to hypoglycemia; however, this view remains highly controversial. In this work, we sought to better define the role of antecedent hypercortisolemia in generating HAAF, using two complimentary experimental models in nondiabetic human subjects: 1) antecedent hydrocortisone infusions (simulating physiologic cortisol responses to hypoglycemia) and 2) antecedent hypoglycemia, with and without concurrent blockade of endogenous cortisol production using oral metyrapone. Our results showed no effect of antecedent hypercortisolemia on epinephrine responses to subsequent hypoglycemia (area under the curve/time 280 +/- 53 vs. 337 +/- 57 pg/ml, P = 0.16). Of particular importance, selective blockade of endogenous cortisol production during antecedent hypoglycemia had no effect on subsequent counterregulatory responses to hypoglycemia. Compared with epinephrine responses following antecedent euglycemia (area under the curve/time 312 +/- 38 pg/ml), epinephrine responses were comparably blunted following antecedent hypoglycemia, regardless of whether concurrent metyrapone blockade was employed (198 +/- 28 vs. 192 +/- 28 pg/ml, P = NS). Similar results were obtained for glucagon and ACTH levels. Considered together, these observations provide strong evidence that hypoglycemia-induced hypercortisolemia is not primarily responsible for the generation of HAAF.
Diabetes 2006 Apr
PMID:Antecedent hypercortisolemia is not primarily responsible for generating hypoglycemia-associated autonomic failure. 1656 37

Laser therapy (LRx) may affect the retinal ganglion cells (RGC), which play a role in circadian rhythms. This study assesses the effect of LRx on the circadian variation of cortisol (F), measured in 20 Type 2 diabetic patients (DM), 10 following LRx for diabetic proliferative retinopathy (DPR), and 10 control (CTR) without laser Rx or retinopathy. The diurnal F variation in the CTR followed a normal pattern. Compared with CTR, the F levels of the DPR group were significantly higher at 1600 and 2400 h (10.2+/-2.5 vs. 6.9+/-4.0 microg/dl, P<.05, and 6.4+/-2.5 vs. 2.6+/-1.7 microg/dl, P<.001, respectively). These results provide evidence that DM patients, following bilateral LRx for proliferative diabetic retinopathy, experienced nocturnal hypercortisolemia and loss of normal circadian cortisol variation, probably secondary to LRx damage to the RGC.
J Diabetes Complications
PMID:Laser damage to retinal ganglion cells: the effect on circadian rhythms. 1663 39

Ectopic adrenocorticotropin secretion (EAS) accounts for 10-15% of cases of Cushing's syndrome and comprises a spectrum of tumours from undetectable isolated lesions to widespread metastatic and aggressive malignancies. EAS is often associated with severe hypercortisolaemia causing hypokalaemia, diabetes, generalized infections, hypertension and psychotic reactions. Surgical resection of the primary lesion, achievable with a curative intent in about 40% of patients with EAS, is associated with complete remission in up to 80% of such cases. It is therefore mandatory to localize the source of ectopic ACTH hypersecretion in order to stage the disease and adopt optimal treatment modalities. Modern cross-sectional imaging techniques can identify the majority of the ACTH secreting lesions, either initially or at follow-up reassessment. However, in approximately 10-20% of patients with EAS, the source of ACTH hypersecretion remains occult in spite of extensive investigation and prolonged followup. In such cases, control of the hypercortisolemia can be achieved with long-term adrenolytic medication. When conditions require a prompt and definitive resolution of the hypercortisolaemia (i.e. as in pregnancy), bilateral adrenalectomy remains an alternative option. This review focuses on the clinical features, diagnostic pitfalls, management and long-term followup of the EAS based on the extensive experience of major referral centres.
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PMID:Ectopic ACTH syndrome. 1680 30

The overnight one-mg dexamethasone suppression test has been used for many years to screen for Cushing's syndrome. This test has usually been evaluated in controls versus patients with severe hypercortisolism. Under these conditions, the overnight dexamethasone suppression test has been reported to have high sensitivity and specificity. The objective of this study was to determine the sensitivity of the one mg overnight dexamethasone suppression test in patients with mild and/or periodic Cushing's syndrome. Therefore, an overnight dexamethasone suppression test was performed in 17 consecutive patients presenting to an endocrinology clinic with signs and symptoms of hypercortisolemia who were later proven to have Cushing's syndrome. The majority of patients were found to have both mild and periodic hypercortisolism. One mg of dexamethasone was given at midnight and a plasma cortisol was measured by radioimmunoassay at 08:00 the following morning. Using a cut-off for a morning cortisol following overnight dexamethasone of > 5 microg/dL, only three of 17 patients failed to suppress to a value less than this cut-off (sensitivity 18 %). A cut-off of > 2 microg/dL gave similar sensitivity. Even with a stringent cut-off point of > 1.8 microg/dL, only seven of 17 patients failed to suppress to a value less than this cut-off point (sensitivity of 41 %). These results demonstrate that the great majority of patients with mild and/or periodic Cushing's syndrome suppress to overnight dexamethasone. Since patients with mild and/or periodic Cushing's syndrome are the patients in whom the identification of hypercortisolism is difficult, our results from this relatively small study suggest that this test should no longer be used to exclude these patients from further workup for Cushing's syndrome.
Exp Clin Endocrinol Diabetes 2006 Jul
PMID:An update on the overnight dexamethasone suppression test for the diagnosis of Cushing's syndrome: limitations in patients with mild and/or episodic hypercortisolism. 1691 37

Increased cytokines secretion occurs in several different disorders. Hemophagocytic lymphohystiositosis (HLH) and metabolic syndrome (MS) are consist two of them. Hemophagocytic lymphohystiositosis results from uncontrolled macrophage activation and huge amounts of cytokine secretion. The metabolic syndrome is a multicomponent condition characterized by insulin resistance, dyslipidemia, abdominal obesity, hypertension, and increased level of proinflammatory cytokines. It was presented a 6.8 years old girl, diagnosed as HLH. Because she was morbid obese, endocrinological investigation had been done and metabolic syndrome, thyroid hormone dysfunction, and hypercortisolemia with disturbances of diurnal rhythm were detected. During follow-up of patient, metabolic syndrome components disappear gradually while haemophagocytosis was recovered. Endocrine system can be affect during HLH attack, and MS can be developed. Cytokines seems to act central role of pathological changes for both diseases.
Exp Clin Endocrinol Diabetes 2009 Feb
PMID:Cytokines as a common components of two different disorders: metabolic syndrome and hemophagocytic lymphohystiositosis. 1852 32

Excessive bioavailability of Zn causes Cu and Mg deficiencies resulting in hyperglycemia and hyperinsulinemia/insulin resistance. These defects may ameliorate if the ionic imbalance in them is corrected. In view of this, three groups of rats were included in this study. Initially, they were fed on semi-synthetic equicalories basal diet containing 20 mg Zn (control, group-I), on 40 mg Zn (group-II) and 80 mg Zn/kg diet (group-III) respectively for 3 months. Thereafter, half of the rats in group-II and III were shifted on Cu and Mg enriched modified poultry egg (ME(Psi)) mixed diets (groups-IIME and IIIME) while the remaining were continued to feed on their respective diets for another 3 months completing a total of 6 months. Hyperglycemia, hyperinsulinemia, hypercortisolemia, hyperzincemia, hypercupremia and hypermagnesaemia with corresponding increase of lipid droplets in the zona fasciculate of adrenal cortex and reduction in liver glycogen content in rats of groups-II and III were recorded. These changes were linked with a rise in Zn and fall in Cu and Mg in their liver. The addition of ME(Psi) in their diets led to fall of Zn and rise in liver Cu and Mg, and fall in serum Zn, Cu and Mg resulting in the improvement of glucose disposal, increase in insulin sensitivity, reduction in lipid droplets in zona fasciculate and increase in glycogen content in the liver approaching closer to the control group-I. The data suggest that these ME(Psi) can serve as non-pharmacological dietary supplement to prevent insulin resistance/hyperinsulinemia in populations who are at higher risk of diabetes mellitus either due to their genetic predisposition of excessive absorption and retention of Zn or due to higher Zn content in the food chain.
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PMID:Modulation of Zn-induced hyperinsulinemia/insulin resistance in Wistar rat fed modified poultry egg(psi). 1956 73

Cushing's syndrome during pregnancy is rare, and rather than being of pituitary origin most patients exhibit ACTH-independent adrenal hypercortisolism. In some cases the syndrome has spontaneously resolved post partum, suggesting the presence of a pregnancy-associated stimulatory factor(s). We describe a case with aberrant adrenal LH/hCG receptors in a large adrenal tumor as a possible explanation for cortisol hypersecretion and tumor growth in Cushing s syndrome during pregnancy. A 27-yr-old woman presented with hypertension and diabetes mellitus in early pregnancy. Investigations revealed hypercortisolemia, suppressed ACTH-levels, and a 6.4- cm right adrenal tumor. The tumor was successfully removed by laparoscopy at 26th week of pregnancy. Hypercortisolism and hypertension resolved post-operatively. The tumor displayed higher LH/hCG receptor mRNA and protein positivity than adjacent normal adrenal tissue as examined by in situ hybridization and immunocytochemistry. High physiological levels of hCG, in conjunction with aberrant adrenal LH/hCG receptor overexpression, may have contributed to the development of Cushing's syndrome in pregnancy.
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PMID:Adrenocorticotropin-independent Cushing's syndrome in pregnancy related to overexpression of adrenal luteinizing hormone/human chorionic gonadotropin receptors. 1963 97

Although cardiovascular complications are the major determinant of the prognosis of Cushing's syndrome (CS), factors contributing to the cardiovascular lesions are still unclear. We investigated clinical factors determining cardiac function in patients with adrenal CS. Fifty patients with adrenal CS were studied. Patients were divided into 3 groups based on their NYHA classification and electrocardiographic (ECG) findings: group A with NYHA grade 0 and normal ECG, group B with NYHA grade I and abnormal ECG, and group C with NYHA grade II or higher. Clinical and echocardiographic findings were compared between the groups. Heart failure of grade I or higher was seen in 40% and grade II or higher was seen in 8% of the patients. Age, HbA1c, and prevalence of diabetes mellitus were positively correlated and serum potassium levels were negatively correlated with the severity of cardiac dysfunction. Decreased ejection fraction (EF) and the ratio of the peak to late transmittal filling velocities (E/A), and increased left ventricular mass index (LVMI) were frequently observed. Multivariate analysis demonstrated that serum potassium and HbA1c levels were independent factors contributing to EF, while serum potassium and cortisol levels were independent factors contributing to LVMI. These results clearly demonstrated that hypokalemia, diabetes mellitus, and hypercortisolemia are the major contributing factors to cardiac dysfunction in adrenal CS. Strict control of these conditions is warranted for the prevention of cardiac dysfunction in adrenal CS.
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PMID:Hypokalemia, diabetes mellitus, and hypercortisolemia are the major contributing factors to cardiac dysfunction in adrenal Cushing's syndrome. 1978 19

An 11-year-old male mixed breed dog diagnosed with Cushing's disease and diabetes mellitus was treated by hypophysectomy. After surgery, the hypercortisolemia disappeared and the diabetes status improved. The insulin requirement to control hyperglycemia gradually decreased. At 12 weeks after surgery, there was no requirement for insulin and we suspected the diabetes was completely resolved. In the present case, diabetes mellitus seems to be secondary to Cushing's disease. In conclusion, this mixed breed dog with coexisting Cushing's disease and diabetes mellitus is the first case showing the effectiveness of hypophysectomy to treat diabetes mellitus secondary to Cushing's disease in dogs.
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PMID:Hypophysectomy for a dog with coexisting Cushing's disease and diabetes mellitus. 1995 15


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