Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01275 (glucagon)
 26,492 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Gastric inhibitory polypeptide (GIP)-dependent Cushing's syndrome has been reported to occur either in unilateral adrenal adenoma or in bilateral macronodular adrenal hyperplasia. A 33-yr-old woman with Cushing's syndrome was found to have two 2.5- to 3-cm nodules in the right adrenal on computed tomography scan; the left adrenal appeared normal except for the presence of a small 0.8 x 0.6-cm nodule. Uptake of iodocholesterol was limited to the right adrenal. Plasma morning cortisol was 279 nmol/L fasting and 991 nmol/L postprandially, and ACTH remained suppressed. Plasma cortisol increased after oral glucose (202%) or a lipid-rich meal (183%), but not after a protein-rich meal (95%) or iv glucose (93%); the response to oral glucose was blunted by pretreatment with 100 microg octreotide, sc. Plasma cortisol and GIP levels were positively correlated (r = 0.95; P = 0.0001); cortisol was stimulated by the administration of human GIP iv (225%), but not by GLP-1, insulin, TRH, GnRH, glucagon, arginine vasopressin, upright posture, or cisapride orally. A right adrenalectomy was performed; GIP receptor messenger ribonucleic acid was overexpressed in both adrenal nodules and in the adjacent cortex. Histopathology revealed diffuse macronodular adrenal hyperplasia without internodular atrophy. Three months after surgery, fasting plasma ACTH and cortisol were suppressed, but cortisol increased 3.6-fold after oral glucose, whereas ACTH remained suppressed; this was inhibited by octreotide pretreatment, suggesting that cortisol secretion by the left adrenal is also GIP dependent. We conclude that GIP-dependent nodular hyperplasia can progress in an asynchronous manner and that GIPR overexpression is an early event in this syndrome.
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PMID:Asynchronous development of bilateral nodular adrenal hyperplasia in gastric inhibitory polypeptide-dependent cushing's syndrome. 1044 49

Regulation of cortisol secretion by aberrant hormone receptors may play a role in the pathogenesis of ACTH-independent Cushing's syndrome. In this study, the topic was evaluated by combining in vivo and in vitro approaches. Cortisol responses to various stimuli (standard meal, GnRH + TRH, cisapride, vasopressin, glucagon) were assessed in 6 patients with clinical or subclinical adrenal Cushing's syndrome, and non-functioning adrenal adenoma in two cases. Abnormal responses were observed in three patients with Cushing's syndrome; one patient showed a gastric inhibitory polypeptide (GIP)-dependent cortisol rise after meal, together with responses after GnRH and cisapride; the second patient showed an LH-dependent cortisol response to GnRH, and in the third cortisol rose after cisapride. The pattern of receptor expression performed by RT-PCR showed that while GIP-R was only expressed in tumor from the responsive patient, 5-hydroxytryptamine type 4 receptor and LH-R were also present in normal adrenal tissues and tissues from non-responsive patients. Interestingly, an activating mutation of Gsalpha gene was identified in one of these tumors. Therefore, cortisol responses to agents operating via Gs protein coupled receptors (in one case associated with Gsalpha mutation) were found in Cushing's patients, while these responses were absent in the others. The finding of receptor expression in normal and non-responsive tumors suggests that different mechanisms are probably involved in inducing in vivo cortisol responses.
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PMID:Assessing the presence of abnormal regulation of cortisol secretion by membrane hormone receptors: in vivo and in vitro studies in patients with functioning and non-functioning adrenal adenoma. 1613 68

Multiple endocrine neoplasm type 1 (MEN1) syndrome predisposes to the development of endocrine and non-endocrine tumors with an autosomal dominant pattern of inheritance. Different mutations have been found throughout the gene with a variable phenotype expression. The proband, a Caucasian man, was admitted to our department in 2001, at the age of 51 because of a 1-yr history of diarrhoea and hypertension. He reported a previous intestinal resection for bowel occlusion with a histological diagnosis of unspecified mesenchymal neoplasia. He had also undergone a left adrenalectomy for a large nonfunctioning adrenal adenoma. Subsequently, he had suffered from gastralgia and melena; a gastroduodenoscopy showed an erosive gastritis. His family history was negative for endocrine disorders. On physical examination, multiple abdominal cutaneous lipomas and facial angiofibromas were observed. Biochemical screening revealed a primary hyperparathyroidism and an increase in circulating levels of PRL, chromogranin-A, gastrin and glucagon. The whole body computed tomography (CT) scan, the 111In-octreotide scan and the pituitary magnetic resonance imaging (MRI) did not reveal any abnormality. The presence of small neuroendocrine tumors was suspected by a positron emission tomography uptake in the epigastric region. The endoscopic ultrasound revealed a pancreatic lesion sized 1.1 cm that is under evaluation. Direct DNA sequencing analysis of the proband MEN1 gene revealed the 579delG frameshift mutation in the exon 3. The genetic screening of the family revealed the same mutation in 3 out of 5 offspring. The biochemical screening revealed some features of the MEN1 syndrome in all three of them. In conclusion, a novel frameshift MEN1 mutation was found in kindred with an apparently negative family history. Our experience confirms that MEN1 syndrome is a complex and underestimated condition, unless specifically investigated by trained specialists.
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PMID:MEN1 family with a novel frameshift mutation. 1679 69

Cushing syndrome (CS) during pregnancy is a rare condition with only a few cases reported in the literature. Misdiagnosis of CS is common because of overlapping features like fatigue, weight gain, striae and emotional changes that can occur during normal pregnancy. Changes in maternal hormones and their binding proteins complicate assessment of glucocorticoid hormone levels during gestation. CS during pregnancy is most frequently due to an adrenal adenoma and to a lesser degree to adrenocorticotropic hormone (ACTH) hypersecretion by a pituitary adenoma. Furthermore, aberrant expression of luteinizing hormone (LH) receptors in the adrenal cortex has been suggested to be involved in the pathogenesis of adrenal CS during pregnancy. We report three pregnant women with ACTH-independent Cushing's syndrome and an adrenal tumor. After uncomplicated delivery, patient 1 underwent in vivo testing for aberrant hormone receptor expression by the adenoma. Cortisol responses were found after administration of luteinizing hormone-releasing hormone (LHRH), human chorionic gonadotropin (hCG), glucagon, vasopressin and a standard mixed meal. All patients were treated with laparoscopic adrenalectomy. Adrenal tumor tissue of two patients showed positive immunohistochemical staining of LH receptors. Considering the cortisol responses to LHRH and hCG, and the development of CS during pregnancy in these patients, it is likely that ACTH-independent hypercortisolism was induced by the pregnancy-associated rise in hCG levels that activated aberrantly expressed LH receptors in the adrenal adenoma. Remarkably, adrenal adenomas may simultaneously express multiple aberrant receptors and individual ligands may play a role in the regulation of cortisol production in CS during pregnancy.
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PMID:Adrenal Cushing's syndrome during pregnancy. 2881 15

With fewer than 200 reported cases, Cushing's syndrome (CS) in pregnancy remains a diagnostic and therapeutic challenge. In normal pregnancies, misleading signs may be observed such as striae or hypokalemia, while plasma cortisol and urinary free cortisol may rise up to 2- to 3-fold. While the dexamethasone suppression test is difficult to use, reference values for salivary cortisol appear valid. Apart from gestational hypertension, differential diagnosis includes pheochromocytoma and primary aldosteronism. The predominant cause is adrenal adenoma (sometimes without decreased ACTH), rather than Cushing's disease. There are considerable imaging pitfalls in Cushing's disease. Aberrant receptors may, in rare cases, lead to increased cortisol production during pregnancy in response to HCG, LHRH, glucagon, vasopressin or after a meal. Adrenocortical carcinoma (ACC) is rare and has poor prognosis. Active CS during pregnancy is associated with a high rate of maternal complications: hypertension or preeclampsia, diabetes, fractures; more rarely, cardiac failure, psychiatric disorders, infection and maternal death. Increased fetal morbidity includes prematurity, intrauterine growth retardation and less prevalently stillbirth, spontaneous abortion, intrauterine death and hypoadrenalism. Therapy is also challenging. Milder cases can be managed conservatively by controlling comorbidities. Pituitary or adrenal surgery should ideally be performed during the second trimester and patients should then be treated for adrenal insufficiency. Experience with anticortisolic drugs is limited. Metyrapone was found to allow control of hypercortisolism, with a risk of worsening hypertension. Cabergoline may be an alternative option. The use of other drugs is not advised because of potential teratogenicity and/or lack of information. Non-hormonal (mechanical) contraception is recommended until sustained biological remission is obtained.
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PMID:MANAGEMENT OF ENDOCRINE DISEASE: Management of Cushing's syndrome during pregnancy: solved and unsolved questions. 2952 33