Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01189 (beta-endorphin)
 21,003 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The most common ectopic production of a pituitary hormone is the one of ACTH leading to Cushing's syndrome. Ectopic ACTH-hypersecretion is the cause of Cushing's syndrome in 10-15% of all cases. The ACTH-secreting tumours are often oat-cell carcinomas of the lung, less frequently pancreatic cancers, hypernephromas, or C-cell carcinomas of the thyroid. Some of these tumours may be benign or semi-benign as the rare carcinoid tumours and cause great problems in the differential diagnosis of ACTH-dependent hypercortisolism. Out of 173 of our patients with Cushing's syndrome observed in the last 12 years 21 were caused by ectopic ACTH-production. Of these 21 patients 13 have a small cell carcinoma of the lung. The ectopic ACTH-syndrome often has typical clinical features caused by the levels of ACTH and cortisol leading to hypocalcemic alkalosis with muscle weakness and wasting, carbohydrate intolerance, and hypertension with oedema. The survival time in many of these patients is not long enough to allow them to develop typical signs of Cushing's syndrome though they are often highly pigmented. These patients are easily diagnosed. However, patients with small tumours which do not cause very elevated ACTH-levels and who have the more typical clinical signs of full-blown Cushing's syndrome are difficult to recognize. For the differential diagnosis of ACTH-dependent Cushing's syndrome the corticotropin-releasing hormone (CRH) stimulation test and dexamethasone suppression test with high doses are helpful. In special cases the venous sampling procedure for ACTH-measurements is necessary, also CT or NMR is helpful. Ectopic CRH-production is a rare cause of ACTH-dependent Cushing's syndrome. Patients with ectopic CRH-production and consecutive ACTH-hypersecretion from the pituitary have not been studied extensively. There are especially no well documented results of the use of the CRH-stimulation test in vivo in this group of patients with Cushing's syndrome. On the other hand, in the documented cases, not only CRH-, but also ACTH-production was found in the tumours. So far, this rare cause of ACTH-dependent Cushing's syndrome has to be excluded or confirmed by the measurement of endogenous CRH-levels. But until now we have not been able to detect one single case of ectopic CRH-production using a sensitive homologous CRH-radioimmunoassay over a period of more than 8 years in which we have seen nearly 120 newly diagnosed patients with ACTH-dependent Cushing's syndrome. Only in the plasma and tumour tissue of two patients of other groups have we found high CRH-levels.
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PMID:Ectopic production of ACTH and corticotropin-releasing hormone (CRH). 132 73

A 49-year old woman with a 5-year history of Cushing's syndrome was evaluated. Biochemical measurements revealed high cortisol and adrenocorticotropic hormone (ACTH) levels consistent with the ACTH-dependent type of Cushing's syndrome. However, the source of ACTH seemed to be autonomous as she demonstrated abnormal feedback control, with lack of response to metyrapone and high coses of dexamethasone. A search for an ectopic ACTH-secreting nonpituitary neoplasm was unsuccessful. Transsphenoidal pituitary exploration revealed a normal pituitary gland, but an ectopic pituitary adenoma was found incidentally in the mucosa of the sphenoid sinus. This adenoma stained strongly positive for ACTH on immunocytochemical studies. Resection of this lesion led to remission of the Cushing's syndrome. This variant of ACTH-dependent Cushing's syndrome can mimic the ectopic ACTH-dependent type and should be looked for in patients who fail to respond to pituitary operation.
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PMID:Cushing's syndrome caused by an ectopic pituitary adenoma. 282 48

ACTH concentration was measured in simultaneously drawn blood samples from the left and right inferior petrosal sinuses before and after administration of corticotropin-releasing hormone (CRH). Such samples were successfully obtained in 20 of 21 patients with ACTH-dependent Cushing's syndrome on whom it was attempted. In 11 of the 20 patients there was no concentration difference between petrosal sinus and peripheral blood. But 13 of 19 patients had a unilateral central to peripheral concentration gradient greater than 1.4 after CRH administration. In the other six patients no ipsi- to contralateral gradient was demonstrable. Two of these patients had a proven ectopic ACTH-producing tumor; no adenoma was found at operation in three; on patient is awaiting operation. In 10 of 13 patients with unilateral gradient a microadenoma was found on the same side at operation. One patient had a hemi-hypophysectomy on the side of the higher gradient: hypocortisolemia developed in her postoperatively. Two other patients are awaiting operation. The results indicate that simultaneous bilateral catheterization of the inferior petrosal sinus with CRH stimulation is a highly informative examination with few side-effects and will contribute to better diagnosis and treatment of Cushing's syndrome.
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PMID:[Simultaneous bilateral catheterization of the inferior petrosal sinus in Cushing's syndrome. ACTH determination for the diagnosis and location of the side of a hypophyseal microadenoma before and after administration of corticotropin-releasing hormone]. 282 62

A case is described of a patient with a small-cell prostatic carcinoma containing immunoreactive CRH, in conjunction with ACTH-dependent Cushing's syndrome. The serum concentrations of CRH, ACTH, beta-endorphin and calcitonin were all found to be above normal. Post-mortem examination revealed a prostatic tumour with multiple metastases, and a diffuse hyperplasia of pituitary corticotropic cells and adrenal cortical cells. In sections of the primary prostatic tumour, immunoreactive cells were demonstrable with antisera raised against human CRH, TSH, calcitonin and somatostatin, but not with antisera against ACTH or beta-endorphin. By radioimmunoassay the CRH-like material could also be demonstrated in extract of the prostatic tumour and the material from both plasma and tumour extract eluted at the position of human CRH on gel chromatography (Sephadex G-75). These findings provide support for the interpretation that the patient's Cushing's syndrome was due to a CRH-producing prostatic tumour. Finally, the origin and the clinical significance of the neuroendocrine cells in the prostatic carcinoma is discussed.
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PMID:Carcinoma of the prostate with Cushing's syndrome. A case report with histochemical and chemical demonstration of immunoreactive corticotropin-releasing hormone in plasma and tumoral tissue. 326 36

Corticotropin-releasing factor, a hypophyseo-tropic hormone that stimulates adrenocorticotropic hormone (ACTH) secretion, has recently been isolated, characterized, and synthesized in the sheep and rat. We report on a patient with metastatic carcinoma of the prostate presenting with anterior and posterior pituitary hormone deficiency together with ACTH-dependent Cushing's syndrome. At postmortem examination, large areas of the median eminence and pituitary stalk were replaced by tumor, but the corticotrophs were markedly hyperplastic. Immunostaining of tumor cells was positive for corticotropin-releasing factor and was negative for ACTH and a wide range of other hormones. Radioimmunoassay and bioassays showed that tumor extracts and further purified fractions were active in corticotropin-releasing factor, and the tumor material coeluted with corticotropin-releasing factor on high-pressure liquid chromatography. These studies demonstrate that ectopic secretion of corticotropin-releasing factor is a cause of Cushing's syndrome in human beings. The features of this syndrome include hypercortisolism, pituitary corticotroph hyperplasia, elevation of circulating ACTH levels, and failure to suppress the pituitary-adrenal axis with exogenous glucocorticoids.
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PMID:Ectopic secretion of corticotropin-releasing factor as a cause of Cushing's syndrome. A clinical, morphologic, and biochemical study. 632 3

We present the case of a 65-year-old woman with an adrenocorticotropic hormone (ACTH) secreting bronchopulmonary carcinoid. This patient showed the typical long history of Cushing's syndrome, including hypokaliemia, impaired glucose tolerance, high levels of ACTH and beta-endorphin, and coproduction of other peptides. At the onset of clinical symptoms in 1979 an adrenal adenoma was suspected, and left-sided adrenalectomy was performed. The symptoms soon recurred, and the diagnosis of ACTH-dependent Cushing's syndrome was made. As no ACTH-secreting tumor was found, the right adrenal was resected, and the patient was followed up regularly. Fourteen years later chest roentgenography and computed tomography revealed a para-aortic pulmonary lesion, which was suspicious for a bronchopulmonary carcinoid. ACTH and beta-endorphin were excessively, pancreatic polypeptide slightly elevated at that time. The final diagnosis was made using somatostatin receptor scintigraphy which confirmed the hormonal activity of the suspicious lesion; no additional focus was found. This method turned out to be not only a useful additional localization technique but also a promising tool for characterization and staging of a suspected ACTH-producing carcinoid. The tumor was resected curatively, and the diagnosis was confirmed histologically.
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PMID:Ectopic ACTH secretion due to a bronchopulmonary carcinoid localized by somatostatin receptor scintigraphy. 789 18

1. Petrosal sinus sampling has been used to establish the source of adrenocorticotropin (ACTH) in ACTH-dependent Cushing's syndrome. Naloxone, an opioid antagonist, stimulates ACTH secretion, probably via release of endogenous hypothalamic corticotropin releasing hormone (CRH). 2. Three patients with hypercortisolism were studied. Two showed suppressed (> 50%) urinary-free cortisol excretion with high-dose dexamethasone treatment (2 mg every 6 h for 2 days), one did not suppress. The patients were subjected to bilateral simultaneous inferior petrosal sinus sampling (BSIPSS) with simultaneous peripheral venous (forearm) samples. Basal (unstimulated) samples were taken and naloxone (125 micrograms/kg bodyweight) was given intravenously with subsequent simultaneous sampling. Plasma ACTH was measured by radio-immunoassay (RIA). 3. All cases exhibited a marked rise in immunoreactive (IR)-ACTH levels (pmol/L) after naloxone injection, basal to peak: case 1, left 11.5-22.1, right 9.8 with no rise, peripheral 9.1-9.5; case 2, left 456-863, right 125-501, peripheral 59-82; case 3, left 12.7-13.0, right 277-431, peripheral 12.1-11.7. All results indicate pituitary Cushing's syndrome, with a central to peripheral ratio > 2.3:1. Pituitary Cushing's syndrome was confirmed on the results of trans-sphenoidal pituitary surgery in cases 1 and 3. 4. It is suggested that naloxone injection during petrosal sinus sampling in Cushing's syndrome may assist in the diagnosis of ACTH source, by enhancing ACTH release from a pituitary micro-adenoma.
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PMID:Naloxone stimulation of ACTH secretion during petrosal sinus sampling in Cushing's syndrome. 839 44

The diagnosis of endogenous Cushing's syndrome requires demonstration of an increased cortisol secretion rate, best achieved by urinary free cortisol excretion determinations. In borderline or confusing cases, loss of diurnal cortisol rhythmicity, a combined dexamethasone/corticotropin releasing hormone (CRH) test, or close monitoring of the patient for a few months will be helpful in ruling out pseudo-Cushing's. Primary adrenal Cushing's syndrome can be ruled out on the basis of a normal or elevated basal and/or CRH-stimulated plasma adrenocorticotropin (ACTH) and a negative adrenal computed tomography. ACTH-dependent Cushing's syndrome can then be differentiated on the basis of a CRH test and imaging procedures. A discrete pituitary lesion on magnetic resonance imaging and a standard CRH test with results consistent with such a lesion are sufficient to proceed to transsphenoidal surgery. If no discrete pituitary lesion is present, or if the CRH test is equivocal, bilateral simultaneous inferior petrosal sinus sampling with CRH administration is necessary to distinguish between a pituitary and an ectopic source. Surgery is the treatment of choice for all types of Cushing's syndrome. In the few cases in which transsphenoidal surgery fails or the disease recurs, repeat transsphenoidal surgery, or radiation therapy in association with mitotane treatment, is a reasonable alternative. Bilateral adrenalectomy effectively cures hypercortisolism if resection of the ACTH-secreting tumor is unsuccessful and radiation/medical therapy fails.
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PMID:Differential diagnosis and management of Cushing's syndrome. 871 94

Diagnosis of Cushing's syndrome is quite difficult in endocrinology. Spontaneous Cushing's syndrome is usually divided into two subgroups, one which is dependent on corticotropin (ACTH) and another one which is not. In the first class are Cushing's disease, the ectopic corticotropin syndrome and the rare ectopic corticotropin-releasing hormone (CRH) syndrome; these ACTH-dependent Cushing's syndrome have usually diffusely enlarged adrenal glands. In the second class are cortisol producing unilateral adrenocortical adenomas or carcinomas, and the recent Cushing's syndrome with food dependent periodic hormonogenesis. This food dependent Cushing's syndrome is an ACTH-independent Cushing's syndrome with multinodular enlargement of both adrenal glands. Pathogenesis is an aberrant adrenal sensitivity to physiologic secretion of gastric inhibitory peptide (GIP). Ectopic expression of GIP receptors on adrenal cells involve pathologic food induced cortisol secretion. Food dependent Cushing's syndrome is a new cause of Cushing's syndrome. Food induced cortisol secretion may have to be explored in the ACTH-independent Cushing's syndrome.
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PMID:[Food-dependent Cushing syndrome: a new entity of organic hypercorticism]. 875 32

Eutopic corticotroph pituitary adenomas and adrenal cortisol-producing adenomas do not usually express somatostatin receptors. However, ectopic corticotropin (ACTH)-producing tumors often express somatostatin receptors. Thus, the octreoscan can detect and localize tumors in 80% of patients with ectopic ACTH syndrome, and so it can be used to differentiate between eutopic and ectopic ACTH-dependent bilateral adrenal hyperplasia. Octreotide therapy can produce a rapid and sustained reduction of ACTH and cortisol levels in patients with ectopic ACTH-dependent Cushing's syndrome and, in some, may be the only long-term therapy possible. Although no large series have been reported, a review of the literature reveals a large number of case reports that have demonstrated the effectiveness of octreotide.
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PMID:Somatostatin analogs in ectopic corticotropin production. 876 7


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