Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0016382 (flushing)
 6,387 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Octreotide is a long-acting cyclic octapeptide with pharmacologic actions mimicking those of the natural hormone somatostatin. It can suppress the secretion of serotonin, as well as the gastroenteropancreatic peptides gastrin, vasoactive intestinal peptide (VIP), insulin, glucagon, secretin, motilin, and pancreatic polypeptide. It also suppresses growth hormone and decreases splanchnic blood flow. Octreotide is completely and rapidly absorbed following subcutaneous injection and has an elimination half-life of 1.5 hours. Clinical trials reviewed here show octreotide useful in the treatment of diarrhea associated with VIP secreting tumors, as well as diarrhea and flushing associated with carcinoid syndrome, both conditions for which the drug is approved. Clinical trials involving the use of octreotide in the treatment of acromegaly are also reviewed. Adverse reactions to octreotide are mild to moderate and most commonly involve injection site pain and diarrhea. Drug interactions are apparently related to the drug's pharmacologic effects. Octreotide is given subcutaneously two to three times daily, with daily doses ranging from 50mcg to 1,500mcg per day. Further research appears necessary to clarify dosing issues.
 ...
PMID:Debut of a somatostatin analog: octreotide in review. 255 39

Octreotide is a synthetic octapeptide somatostatin analogue which has higher potency and longer duration of action than the natural hormone. It is effective after subcutaneous administration and no rebound hypersecretion has been observed. Pharmacological effects of octreotide include inhibition of numerous hormones (growth hormone, TSH, insulin, glucagon and all gut hormones), of exocrine secretion (gastric acid, pancreatic enzyme), and of small-bowel absorption. This review deals with clinical application of octreotide in endocrine disorder. In patients with acromegaly octreotide treatment results in decrease of growth hormone (GH) and IGF-I together with tumour shrinkage and clinical improvement. Although variability in response to treatment is obvious for majority of patients the most effective dose is 100 mcg three times daily subcutaneously. Normalization of GH levels could be achieved in more than 50% of treated patients. It has also been shown that octreotide could be effective in TSH secreting pituitary adenoma, ACTH secreting adenoma as well as in non-secretory pituitary tumours. A marked biochemical and clinical responses together with longer survival have been reported in most of the patients with gastroenteropancreatic (GEP) tumours. Patients who benefit the most from octreotide therapy are those with carcionid syndrome (successful control of diarrhoea, flushing episodes and wheezing) and VIPomas (control of diarrhoea). In patients with insulin-dependent diabetes mellitus (IDDM) octreotide suppresses GH levels, postprandial blood glucose increases with resultant decrease in daily insulin requirements. In women with polycystic ovary syndrome (PCOS) octreotide has inhibitory effect on serum LH and ovarian androgens. This could have beneficial effect on ovulatory performance in women with PCOS.
 ...
PMID:[Clinical use of octreotide (Sandostatin) in endocrinology]. 799 11

The authors report their experience with octreotide in 20 patients (median age 57 years, 10 M, 10 F) from 1984 to 1991; 16 had metastatic APUDoma: 1 PPoma with VIPoma, 1 glucagonoma, 5 gastrinoma including 1 associated to PP-oma, 9 mid-gut carcinoid; 3 patients had multiple-endocrine neoplasia type I (MEN-I) with Zollinger-Ellison syndrome (ZES) and 1 patient a non-metastatic VIPoma. Octreotide (200-750 micrograms/day) was administered bid or tid with regular laboratory controls and morphological assessment. There was a striking improvement of symptoms, particularly in the carcinoid group (reduction of flushing in all patients and of diarrhoea in 3/5), in the patient with gastrinoma + acromegaly (regression of congestive heart failure) and in the patient with non-metastatic VIPoma. The hormonal markers were markedly reduced, particularly gastrin, PP (except in the patient with PPoma + VIPoma), VIP, GH and Somatomedin-C and urinary 5HIAA in 4/9 patients with carcinoid. There was only one partial regression of metastases (gastrinoma) and 4 apparent stabilizations of tumour growth, in the 16 metastatic cases. Among them, 4 patients died: 1 glucagonoma, 1 PPoma + VIPoma, 2 mid-gut carcinoids after a treatment of 5, 16, 30, 36 months, respectively. The patient with acromegaly + ZES died after 6 years of treatment at age 81. A patient with prolactinoma, resected insulinoma, hyperparathyroidism and ZES was not improved by a short course of octreotide (hypoglycemia); he died later of recurrent insulinoma. In conclusion, octreotide is a useful drug to control most of the symptoms related to gut endocrine tumours; it may inhibit tumour growth.
 ...
PMID:Use of octreotide in the treatment of digestive neuroendocrine tumours. Seven year experience in 20 cases including 9 cases of metastatic midgut carcinoid and 5 cases of metastatic gastrinoma. 826 71

Hypothalamic GHRH is secreted into the portal system, binds to specific surface receptors of the somatotroph cell and elicits intracellular signals that modulate pituitary GH synthesis and/or secretion. Moreover, GHRH is synthesized and expressed in multiple extrapituitary tissues. Excessive peripheral production of GHRH by a tumor source would therefore be expected to cause somatotroph cell hyperstimulation, increased GH secretion and eventually pituitary acromegaly. Immunoreactive GHRH is present in several tumors, including carcinoid tumors, pancreatic cell tumors, small cell lung cancers, endometrial tumors, adrenal adenomas, and pheochromocytomas which have been reported to secrete GHRH. Acromegaly in these patients, however, is uncommon. The distinction of pituitary vs. extrapituitary acromegaly is extremely important in planning effective management. Regardless of the cause, GH and IGF-1 are invariably elevated and GH levels fail to suppress (<1 microg/l) after an oral glucose load in all forms of acromegaly. Dynamic pituitary tests are not helpful in distinguishing acromegalic patients with pituitary tumors from those harbouring extrapituitary tumors. Plasma GHRH levels are usually elevated in patients with peripheral GHRH-secreting tumors, and are normal or low in patients with pituitary acromegaly. Unique and unexpected clinical features in an acromegalic patient, including respiratory wheezing or dyspnea, facial flushing, peptic ulcers, or renal stones sometimes are helpful in alerting the physician to diagnosing non pituitary endocrine tumors. If no facility to measure plasma GHRH is available, and in the absence of MRI evidence of pituitary adenoma, a CT scan of the thorax and abdominal ultrasound could be performed to exclude with good approximation the possibility of an ectopic GHRH syndrome. Surgical resection of the tumor secreting ectopic GHRH should be the logical approach to a patient with ectopic GHRH syndrome. Standard chemotherapy directed at GHRH-producing carcinoid tumors is generally unsuccessful in controlling the activated GH axis. Somatostatin analogs provide an effective option for medical management of carcinoid patients, especially those with recurrent disease. In fact, long-acting somatostatin analogs may be able to control not only the ectopic hormonal secretion syndrome, but also, in some instances, tumor growth. Therefore, although cytotoxic chemotherapy, pituitary surgery, or irradiation still remain available therapeutic options, long-acting somatostatin analogs are now preferred as a second-line therapy in patients with carcinoid tumors and ectopic GHRH-syndrome.
 ...
PMID:Neuroendocrine tumors secreting growth hormone-releasing hormone: Pathophysiological and clinical aspects. 1703 95