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)

A 61 year old woman presented with profound hyponatremia and markedly low serum osmolality. Urine osmolality was greater than the serum osmolality, an abnormality that was corrected by water restriction, suggesting inappropriate ADH secretion. Although there were no physical signs of Cushing's syndrome, her serum potassium level was low and markedly elevated levels of plasma and urine corticosteroids were not altered by the administration of large amounts of dexamethasone, suggesting the ectopic ACTH-MSH syndrome. Plasma levels of immunoreactive ACTH and beta-MSH were elevated. At autopsy, a metastastic oat cell carcinoma of the lung, not detected antemortem by chest roentgenograms and bronchoscopy, was found. Immunoreactive ADH, ACTH and beta-MSH were detected in the primary tumor and in metastases to the liver. beta-MSH was also detected in the spleen, in which metastases were observed. This is the first documented case of the simultaneous production of ADH, ACTH and beta-MSH by neoplastic tissue associated with clinical manifestations of the syndrome of inappropriate ADH secretion and the ectopic ACTH-MSH syndrome.
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PMID:Ectopic production of antidiuretic hormone (adh), adrenocorticotrophic hormone (ACTH) and beta-melanocyte stimulating hormone (beta-MSH) by an oat cell carcinoma of the lung. 18 5

A 64-yr-old female presented with severe osteoporosis and easy bruisability of over 2-yr duration. Biopsy of a neck mass revealed medullary carcinoma of the thyroid. Subsequently, lymphangitic pulmonary metastases were demonstrated which had been present radiographically for at least 4 yr. Basal serum calcitonin was markedly elevated and increased during calcium infusion. The diagnosis of ectopic ACTH syndrome was first entertained when hypokalemic alkalosis was observed during evaluation of her carcinoma. Elevated urinary 17-hydroxycorticosteroids, 17-ketosteroids, plasma cortisol, and immunoreactive plasma ACTH levels were documented. Adrenal steroidogenesis seemed to suppress on high dose dexamethasone. The primary tumor and its metastases contained high concentrations of immunoreactive ACTH and beta-melanocyte-stimulating hormone. Hepatic metastases contained extremely high concentrations of calcitonin. In contrast to the usual presentation of the ectopic ACTH syndrome as primarily hypokalemic alkalosis and glucose intolerance, patients with relatively benign and indolent ACTH-secreting tumors, such as certain cases of medullary carcinoma of the thyroid, may present with more typical signs and symptoms of Cushing's syndrome. The more pronounced cushingoid features in this latter group presumably reflects a more prolonged period of exposure to elevated glucocorticoid levels. Ten cases of ACTH-secreting medullary carcinoma of the thyroid from the literature are discussed. Extopic ACTH production by such tumors should be considered in the evaluation of patients with Cushing's syndrome or unexplained severe osteopenia.
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PMID:ACTH-secreting medullary carcinoma of the thyroid presenting a severe idiopathic osteoporosis and senile purpura: report of a case and review of the literature. 23 64

Transgenic mice that developed adrenocorticotropic hormone (ACTH)-producing pituitary tumors were generated with the polyoma early region promotor linked to a cDNA encoding polyoma large T antigen (PyLT). Light microscopic examination of the pituitaries showed normal morphology at 4 months of age, either unremarkable morphology or microadenoma formation at 9 months of age, and up to 5 mm large adenomas in clinically ill transgenic mice at 13-16 months of age. At age 9 months, transgenic mice weighed significantly more than corresponding control mice, but they began wasting at approximately 1 year of age. The adrenal glands of these older PyLT-1 mice showed a weight increase and exhibited a medullary hyperplasia. Subcutaneous transplants of transgenic pituitary tumors to nontransgenic, immunocompetent mice resulted in tumors with a morphology and ACTH immunoreactivity similar to the primary tumor. The effects of hypercorticotropism were more enhanced and occurred with a shorter latency in the mice carrying transgene pituitary transplants than in the PyLT-1 transgenic mice themselves. Moreover, these transplanted mice showed a weight increase with an axial deposition pattern and hypertrophy of the adrenal cortex that resembled the findings in human Cushing's disease. Plasma ACTH levels were significantly increased in clinically ill transgenic mice and even higher levels were found in the transplant mice. Thus, both murine models should be useful for studying Cushing's disease.
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PMID:Transgenic mice that develop pituitary tumors. A model for Cushing's disease. 131 82

Melanocyte stimulating hormone (alpha-MSH, alpha-melanotropin),Ac-Ser-Tyr-Ser-Met-Glu-His-Phe-Arg-Trp-Gly-Ly-Pro-Va l-NH2, regulates melanogenesis within epidermal melanocytes of many animals. An MSH analogue ([Nle4,D-Phe7]alpha-MSH) that exhibits superpotency and prolonged biological activity has been synthesized, biologically characterized, and is presently in clinical trials to determine its possible clinical use in tanning of the skin. It also has potential for the diagnosis, localization, and chemotherapy of melanoma. The effects of this analogue on the growth, metastatic behavior, and invasive potential of a melanotic variant of Cloudman S-91 murine melanoma are reported here. In an intracutaneous murine model of melanoma cell tumor growth, the analogue did not increase primary tumor growth (size) after the period of administration of the peptide hormone analogue and did not affect spontaneous lung metastases. Survival times for the control and melanotropin-treated groups were similar, suggesting that overall tumor burden was not affected by treatment with the hormone analogue. Last, melanoma cell invasion through a human amniotic basement membrane in vitro was not enhanced compared to untreated cells.
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PMID:Effects of a melanotropic peptide on melanoma cell growth, metastasis, and invasion. 133 2

A uterine cervical cancer is reported in a woman who developed Cushing's syndrome. The tumor measured 1.3 x 0.7 cm, and was a pure small cell carcinoma, identical to that in the lung. The primary tumor cells showed argyrophilia with Grimelius staining and reacted positively to the anti-chromogranin antibody. Clinically, the neoplasm behaved in an aggressive manner in spite of adjuvant chemotherapy and radiotherapy, and the patient died of widespread metastasis. Cushing's syndrome was noted after the occurrence of liver metastasis with an elevation of the serum adrenocorticotropin hormone (ACTH) level. At autopsy, metastatic tumor cells from the liver reacted immunohistochemically positively not only to anti-ACTH but also to antichromogranin, anti-gastrin and anti-calcitonin antibodies. This is the first report of an immunohistochemical analysis of, and comparison of primary and metastatic sites in cervical carcinoma showing Cushing's syndrome.
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PMID:Small cell carcinoma of the uterine cervix showing Cushing's syndrome caused by ectopic adrenocorticotropin hormone production. 165 16

Cushing's syndrome represents a constellation of symptoms of various origins. In most patients, detailed endocrinologic and radiologic testing will differentiate between Cushing's disease, adrenal adenoma, adrenal carcinoma, primary bilateral nodular hyperplasia, and ectopic corticotropin-producing tumors. Although adrenal surgery affords rapid and reliable remission in patients with Cushing's syndrome, it is associated with significant morbidity and mortality. Complications can be minimized by careful perioperative preparation. The indications for adrenal surgery for Cushing's disease have been altered radically by the success and low morbidity of transsphenoidal surgery. Total adrenalectomy is indicated in patients with bilateral nodular hyperplasia and should be considered for adults who have failed selective pituitary adenectomy or hypophysectomy and in whom ectopic corticotropin secretion has been unequivocally ruled out. At the Lahey Clinic, total adrenalectomy is performed through an anterior abdominal incision. Anterior approaches are especially indicated in those patients who require abdominal exploration for other intra-abdominal pathologic conditions that require surgery. Total adrenalectomy is indicated in the very rare patient who has Cushing's syndrome caused by ectopic corticotropin production when the patient is severely ill, a primary tumor is not found, and medical therapy fails or is poorly tolerated. Small adrenal tumors are best approached through a flank incision. Larger potentially malignant tumors should be approached through a thoracoabdominal incision.
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PMID:Surgical management of Cushing's syndrome. 266 80

A 57-year-old man with a history of hepatic adenocarcinoma was referred 3 years after his diagnosis with a choroidal tumor in the right eye. Results of a transscleral excision biopsy revealed the tumor to be an amyloid-rich neuroendocrine metastasis. The patient subsequently developed cushingoid features and investigations revealed ectopic corticotropin syndrome, an elevated urinary 5-hydroxyindoleacetic acid level, and neuroendocrine metastasis in several locations. The choroidal neuroendocrine metastasis stained negative for serotonin and corticotropin. The source of the ectopic corticotropin and the location of the primary tumor have not been found. This case demonstrates that disseminated neuroendocrine tumors may rarely cause ocular lesions before systemic endocrine sequelae arise.
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PMID:A choroidal amyloid-rich neuroendocrine tumor: initial manifestation of Cushing syndrome. 1044 55

Ectopic adrenocorticotropic hormone (ACTH) and/or corticotropin-releasing hormone (CRH) are associated with a growing list of tumors. We report a 69-year-old white man with a history of high-grade prostate carcinoma and widely metastatic adenocarcinoma who presented with metabolic alkalosis, hypokalemia, and hypertension secondary to ectopic ACTH and CRH secretion. Laboratory values were consistent with hypokalemia and metabolic alkalosis. Markedly elevated serum cortisol (135 microg/dL), ACTH (1,387 pg/dL), CRH (69 pg/dL), and urine free cortisol (16,276 microg/24 h) levels were found. Chest computed tomographic (CT) scan showed small noncalcified parenchymal densities; however, bronchoscopy and bronchoalveolar lavage washings were unremarkable for a neoplastic process. Abdominal CT scan and magnetic resonance imaging showed multiple small liver lesions and multiple thoracic and lumbar intensities consistent with diffuse metastatic disease. Histological analysis of a biopsy specimen from the thoracic spine showed an undifferentiated adenocarcinoma consistent with a prostate primary tumor. The severe metabolic alkalosis secondary to glucocorticoid-induced excessive mineralocorticoid activity was treated with potassium supplements, spironolactone, and ketoconazole. In this case report, we describe an unusual tumor associated with ectopic ACTH and CRH production and the pharmacodynamic relationship of plasma cortisol levels and urinary cortisol excretion with ketoconazole treatment.
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PMID:Hypokalemia, metabolic alkalosis, and hypertension: Cushing's syndrome in a patient with metastatic prostate adenocarcinoma. 1127 85

Most patients suffering from breast carcinoma do not die due to the primary tumor but from the development of metastases. Active migration of cancer cells is a prerequisite for development of these metastases. We used time-lapse videomicroscopy and computer-assisted cell tracking of MDA-MB-468 human breast carcinoma cells, which were incorporated into a three-dimensional collagen matrix, in order to analyze the migratory activity of these cells in response to different neurotransmitters. Our results show that met-enkephalin, substance P, bombesin, dopamine, and norepinephrine have a stimulatory effect on the migration of the breast cancer cells; moreover, these cells show positive chemotaxis towards norepinephrine as was analyzed by the directionality and persistence on a single-cell basis. Gamma-aminobutyric acid (GABA) however has an inhibitory effect. Endorphin and leu-enkephalin, as well as histamin and acetylcholine, had no influence on the migratory activity of the cells. In summary, we provide evidence for a strong regulatory involvement of neurotransmitters in the regulation of breast cancer cell migration, which might provide the basis for the use of the pharmacological agonists and antagonists for the chemopreventive inhibition of metastasis development.
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PMID:Effects of neurotransmitters on the chemokinesis and chemotaxis of MDA-MB-468 human breast carcinoma cells. 1288 99

We present a 54-yr-old woman with ectopic corticotropin syndrome caused by a neuroendocrine tumor of the pancreas. At initial presentation, the patient suffered from diarrhea, heartburn, and nonspecific abdominal pain. There was no evidence of Cushing's syndrome. A neuroendocrine tumor in the head of the pancreas with metastases into peripancreatic lymph nodes was diagnosed and completely resected. Fourteen months later, abdominal computed tomography and scintigraphy with (111)In-labeled octreotide suggested relapse of the tumor. The patient again had no evidence of Cushing's syndrome. A second in toto tumor resection was performed. Another 8 months later, the patient developed forgetfulness, depressive episodes, muscle weakness, new-onset hypertension, hypokalemia, plethora, diabetes mellitus, polyuria, and weight loss. Endocrine testing suggested a source of ectopic ACTH production. An octreotide scan showed an intense uptake ventromedial of the left kidney, an area that showed a mass lateral of the superior mesenteric artery on abdominal magnetic resonance imaging. A complete pancreatectomy with splenectomy and left-sided adrenalectomy were performed. At this second relapse, this neuroendocrine tumor clinically had changed its hormonal profile. Immunohistochemically, in contrast to primary tumor and first relapse, we found strong immunostaining for ACTH in tumor cells of the second relapse and a MIB-1 index greater than 20%. To our knowledge, this is the first report describing a pancreatic neuroendocrine tumor that started to secrete ACTH de novo at the time of the second relapse after two former complete tumor resections. This case underscores the pluripotency of neuroendocrine tumor cells and the importance of keeping in mind a possible shift in hormone production during tumor evolution and progression.
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PMID:Pancreatic neuroendocrine tumor with ectopic adrenocorticotropin production upon second recurrence. 1529 97


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