Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P61278 (somatostatin)
 22,083 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Glucagon is secreted not only by A2-cells of the pancreatic islets but also by A cells in the gastric fundus and duodenum. Several reports have demonstrated that the glucagon plasma concentration is increased in genetic diabetes as well as in many conditions associated with a decreased glucose tolerance such as hepatic cirrhosis, myocardial infarction, infectious diseases, burns, taumatic shock, glucagonomas, acute pancreatitis, acromegaly, pheochromacytoma and Cushing's syndrome. Hyperglucagonemia is particularly important in diabetic ketoacidosis and in non-ketotic hyperosmolar coma. The mechanisms responsible for the diabetic's hyperglucagonemia remain controversial. According to several authors, the increased glucagon secretion is, for its main part, secondary to a prolonged defect in insulin secretion and thus relatively insensitive to an acute insulin administration. According to others, the A cell abnormality is of primary origin, independant from insulin deficiency and its effects are cumulative with those of the insulin lack. Several reports dealing with induced or spontaneous experimental diabetes are in favor of the first or the second hypothesis. It appears likely that glucagon plays a role in the metabolic derangments of diabetes. Indeed, hepatic glucose production is closely related to the ratio of molar concentrations of insulin and glucagon. Finally, in insulin-dependant diabetics, somatostatin infusion reduces plasma glucagon concentration and blood glucose and prevents the development of ketosis after withdrawal of insulin therapy. These results illustrate the contribution of glucagon in the pathogenesis of hyperglycemia and ketosis. Several arguments have been accumulated in favor of the following concept: diabetes hyperglycemia results both from glucose under-utilization secondary to insulin lack and from hepatic glucose over-production due to glucagon excess. Although controversial, the role of glucagon in ketogenesis appears likely.
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PMID:[The role of glucagon in hyperglycemia. A review (author's transl)]. 79 28

This article reviews the current general approach to the biochemical diagnosis and the treatment of pituitary tumors with special reference to medical treatment with dopamine agonists and somatostatin analogs. Dopamine agonists are the treatment of choice in patients with prolactin producing tumors. Octreotide is a major advance in the adjunctive treatment of growth hormone producing tumors. Trans-sphenoidal surgical decompression remains the primary treatment modality in gonadotrofinomas, clinically non-functioning pituitary tumors and thyroid stimulating hormone (TSH) producing tumors. Adrenocorticotrophin (ACTH) producing tumors are treated primarily by selective adenomectomy. The biochemical diagnosis of Cushing's syndrome is complex. Bilateral inferior petrosal sinus sampling for ACTH measurement is highly reliable in the differential diagnosis of ACTH dependent Cushing's syndrome, but needs expertise.
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PMID:Pituitary tumors: diagnosis and treatment. 128 25

The GH response to insulin-induced hypoglycaemia and growth hormone-releasing hormone (GHRH) has been shown to be impaired in subjects with Cushing's syndrome and in healthy volunteers given oral glucocorticoids. Pyridostigmine is an anticholinesterase that stimulates GH secretion, probably by inhibition of hypothalamic somatostatin secretion. This work was designed to study the site of action of glucocorticoids in inhibiting the secretion of GH. Eight healthy male volunteers were studied on three occasions in random order. They took 2 mg oral dexamethasone or placebo at precisely 6-hourly intervals for 48 h before receiving 120 mg oral pyridostigmine or placebo, followed 60 min later by GHRH (100 micrograms) i.v. Samples for measuring GH were obtained at 15 min intervals for 2 h. The 'area under the curve' (AUC) for each of the treatments was significantly different: dexamethasone-pyridostigmine-GHRH (mean +/- S.E.M., 1938 +/- 631 mU/min per l), dexamethasone-placebo-GHRH (634 +/- 211) and placebo-placebo-GHRH (4267 +/- 1183) (P < 0.02, Wilcoxon test). In conclusion, dexamethasone given for 48 h significantly inhibited the AUC for GH following treatment with GHRH. However, pretreatment with pyridostigmine significantly reversed the inhibition although this was still partial. Our data suggested that this short-term suppressive effect of dexamethasone was independent of GHRH, and most probably relates to stimulation of the release of somatostatin.
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PMID:Pyridostigmine partially reverses dexamethasone-induced inhibition of the growth hormone response to growth hormone-releasing hormone. 135 70

The concentrations of immunoreactive (IR) corticotropin-releasing hormone (CRH) in 218 neuroendocrine tumors were determined by CRH radioimmunoassay. The tumors examined were 86 pancreatic endocrine tumors (PET), 22 neuroblastic tumors (NBT), 26 carcinoid tumors (CA), 24 pheochromocytomas (PHEO), 40 small cell lung carcinomas (SCLC) and 20 medullary thyroid carcinomas (MTC). IR-CRH was detectable in 21 neuroendocrine tumors (10 PET, four NBT, three CA, two PHEO and two SCLC) at levels of 10-2,700 ng/g wet weight (9.6%). The 21 patients with these CRH-producing tumors showed no clinical symptoms suggestive of Cushing's syndrome. The levels of plasma IR-CRH extracted by immunoaffinity chromatography were < 7.5 pg/ml in five normal subjects and a patient with a neuroblastic tumor containing 55 ng/g wet weight IR-CRH, but in a patient with a thymic carcinoid tumor containing 1,000 ng/g wet weight IR-CRH, the plasma level was elevated to 180 pg/ml. This patient did not have Cushing's syndrome nor an elevated plasma adrenocorticotropic hormone (ACTH) level. The concentrations of nine peptides (growth hormone-releasing hormone, somatostatin, ACTH, calcitonin, gastrin-releasing peptide, glucagon, vasoactive intestinal peptide, neuropeptide tyrosine and pancreatic polypeptide) were determined in extracts of the 21 IR-CRH-producing tumors. Some of these peptides were frequently found to be produced concomitantly with CRH. The results indicate IR-CRH to be produced by various neuroendocrine tumors, but Cushing's syndrome, due to the CRH, to be very rare. The results also show that CRH-producing tumors produce multiple hormones.
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PMID:Production of immunoreactive corticotropin-releasing hormone in various neuroendocrine tumors. 135 72

The recent availability of the long-acting somatostatin analogue, octreotide, has allowed its therapeutical use in a wide variety of human diseases, including some digestive, neoplastic and autoimmune disorders. This review focuses on the treatment of some endocrine disorders with octreotide. Evidence is accumulating that octreotide treatment is effective in improving the cure rate of pituitary surgery in acromegaly by shrinking the tumour size, and in lowering GH and IGF-I levels in the vaste majority of patients. Octreotide is also effective in ameliorating TSH-induced hyperthyroidism in patients with TSH-secreting adenomas. Moreover, octreotide has proved useful in the management of endocrine tumours of the gastroenteropancreatic tract (vipomas, glucagonomas, gastrinomas, insulinomas, and carcinoids) by reducing hormone levels and in some instances the size of the primary and/or metastatic lesions. Besides the above well-established indications there are some other potential indications (non-secreting pituitary tumours, medullary thyroid carcinoma, ectopic Cushing's syndrome, diabete mellitus, Graves' ophthalmopathy, tall children and polycystic ovary syndrome) that still await further investigation. Side-effects of octreotide, particularly the formation of gallstones, should be carefully monitored.
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PMID:[Therapeutic use of somatostatin analogues in endocrinology]. 136 50

A case of advanced cervical carcinoma of the uterus with ectopic adrenocorticotrophic hormone (ACTH) syndrome is described. The patient was seen for general malaise 21 months after surgical treatment of the primary lesion whose histology was undifferentiated small cell carcinoma of the uterine cervix. She had extensive metastases in the liver and the abdominal wall. In addition to the typical clinical manifestations of Cushing's syndrome such as moon face, central obesity and acne vulgaris, hyperglycemia was so severe that she was in a hyperosmolar non-ketotic coma. Endocrinological examinations revealed elevated plasma ACTH and cortisol, and urinary excretion of 17-hydroxycorticosteroids and 17-ketosteroids, which were not suppressed by high-dose dexamethasone administration. Based on these clinical and laboratory findings, a diagnosis of ectopic ACTH syndrome was made. Among the results of other endocrinological examinations conducted to find the etiological cause of the hyperglycemic coma, which seemed to be unusual for ectopic ACTH syndrome, the plasma somatostatin level was abnormally high. Metastatic tumors in the liver obtained at the time of autopsy contained large amounts of both ACTH and somatostatin, and gel filtration studies revealed that the peptides produced by the tumor had the molecular sizes of the biologically active forms of the respective peptides. These observations suggest possible involvement of the somatostatin in deteriorating glucose intolerance to develop hyperglycemic hyperosmolar non-ketotic coma as a drastic disturbance of metabolism.
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PMID:A case of cervical carcinoma of the uterus presenting with hyperosmolar non-ketotic coma as a manifestation of ectopic adrenocorticotropic hormone syndrome. 164 12

Described is the case of a 73-yr-old woman with metastatic pancreatic islet carcinoma that manifested initially as Zollinger-Ellison syndrome followed by onset of endogenous Cushing's syndrome, who developed Pneumocystis carinii pneumonia while on therapy with a long-acting somatostatin analog. Although P. carinii pneumonia has been observed in patients with Cushing's syndrome associated with other conditions, this is the first reported case in a patient with Zollinger-Ellison syndrome. Heightened awareness of the possibility of opportunistic infections in patients receiving somatostatin therapy for Cushing's syndrome of any cause, particularly Zollinger-Ellison syndrome, may be warranted.
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PMID:Pneumocystis carinii pneumonia complicating somatostatin therapy of Cushing's syndrome in a patient with metastatic pancreatic islet cell carcinoma and Zollinger-Ellison syndrome. 167 88

Although somatostatin inhibits a variety of pituitary and non-pituitary hormones, not univocal data on its effects on ACTH release have been reported so far. In this study we investigated the effects of somatostatin or octreotide on ACTH levels of patients with corticotropin hypersecretion: 7 patients with Addison's disease, 2 patients previously adrenalectomized for Cushing's disease, 4 patients with Cushing's disease and 3 patients with ectopic ACTH syndrome. Plasma ACTH and cortisol levels were determined after somatostatin (500 micrograms over 60 min) infusion or octreotide (100 micrograms sc) injection. In 5 other patients with Cushing's disease ACTH and cortisol responses to CRH (1 microgram/kg iv) were evaluated in basal conditions and after octreotide acute administration. In no patients with Addison's disease any inhibitory influence of somatostatin (delta % = -21, -25) or octreotide (delta % = -38 +/- 12 vs -39 +/- 12 after saline) on plasma ACTH was found. Somatostatin did not significantly inhibit plasma ACTH in the two patients previously adrenalectomized for Cushing's disease and in 3 patients with Cushing's syndrome; in other 4 patients with Cushing's syndrome octreotide did not affect plasma ACTH levels. In 5 patients with Cushing's disease the plasma ACTH and cortisol responses to CRH were similar both before (ACTH from 9.9 +/- 1.7 pmol/L to 19.4 +/- 6.1 pmol/L; cortisol from 496 +/- 43.9 nmol/L to 923 +/- 355 nmol/L) and after octreotide injection (ACTH from 8.8 +/- 2.4 pmol/L to 19.1 +/- 8.2 pmol/L; cortisol from 510 +/- 54.6 nmol/L to 735 +/- 220 nmol/L). In conclusion, the acute administration of somatostatin or octreotide is not able to modify ACTH levels in patients with corticotropin hypersecretion either due to hypocortisolemic state or consequent to ACTH-secreting pituitary or ectopic tumors; moreover, octreotide does not affect the pituitary-adrenal responsiveness to CRH in patients with Cushing's disease.
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PMID:Failure of somatostatin and octreotide to acutely affect the hypothalamic-pituitary-adrenal function in patients with corticotropin hypersecretion. 197 78

Three patients with Cushing's disease and one patient with paraneoplastic hypercortisolism were treated for 24-49 days with the long-acting analogue of somatostatin, SMS 201-995, Sandoz (SMS), administered in increasing doses up to 400-1200 micrograms daily. In the three Cushing's patients during SMS treatment plasma ACTH displayed an initial rise and a subsequent decrease. The pattern of urinary free cortisol (UFC) tended to be opposite to that of ACTH. In one of these patients, UFC continued to decrease throughout the treatment, without becoming normal. In the patient with paraneoplastic hypercortisolism, SMS was associated with a progressive decrease, though not the normalization, of UFC and of ACTH and cortisol levels. The reciprocal changes of the ACTH and UFC levels observed in the three Cushing's patients receiving SMS suggest that the peptide may act temporarily by inhibiting glucocorticoid secretion. In view of the marked reduction of UFC recorded in 1 of the 3 Cushing's patients and in the patient with paraneoplastic Cushing's syndrome, administration of SMS seems worth trying in cases of ACTH-dependent hypercortisolism requiring medical treatment.
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PMID:Treatment of Cushing's syndrome with the long-acting somatostatin analogue SMS 201-995 (sandostatin). 216 Aug 71

Growth hormone (GH) secretion in patients with Cushing's syndrome is diminished to all the stimuli tested so far but the precise mechanisms through which this occurs are unknown. In order to investigate whether increased somatostatinergic tone might be responsible for this alteration, we studied the effect of pyridostigmine (120 mg p.o. at -60 min), which activates cholinergic synapses and thus suppresses hypothalamic somatostatin release on GH responses to GHRH (100 micrograms, i.v. at 0 min), in six patients with Cushing's syndrome. We found that while pyridostigmine markedly potentiated GH responses to GHRH, in all the normal subjects tested (n = 12), neither GHRH alone nor GHRH plus pyridostigmine elicited any increase in GH secretion in any of the patients with Cushing's syndrome. This suggests that chronic glucocorticoid excess induces marked alterations in the hypothalamic control of GH secretion.
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PMID:Effect of enhancement of endogenous cholinergic tone with pyridostigmine on growth hormone (GH) responses to GH-releasing hormone in patients with Cushing's syndrome. 222 84


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