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

Pituitary tumors cause symptoms by secreting hormones (prolactin, PRL, responsible for amenorrhea-galactorrhea in women and decreased libido in men; growth hormone, GH, responsible for acromegaly; adrenocorticotropic hormone, ACTH, responsible for Cushing's syndrome; thyroid-stimulating hormone, TSH, responsible for hyperthyroidism), depressing the secretion of hormones (hypopituitarism), or by mass-related effects (headaches, visual field abnormalities...). All patients with pituitary tumors should be evaluated for gonadal, thyroid and adrenal function as well as PRL and GH secretion. Specific stimulation and suppression tests for pituitary hormones are performed in selected situations for detecting the type of hypersecretion or the response to treatment. Imaging procedures (mainly magnetic resonance imaging, MRI, nowadays) determine the presence, size and extent of the lesion. The classification of pituitary tumors is based on the staining properties of the cell cytoplasm viewed by light microscopy and immunocytochemistry revealing the secretory pattern of the adenoma. Treatment of pituitary adenomas consists of surgery (performed in more than 99% of cases via a transphenoidal route) and radiotherapy, generally fractionated or, in selected cases, using stereotactic techniques such as gamma-knife. The availability of medical treatment (dopamine, DA, agonists, somatostatin analogs, GH-receptor antagonists...) has profoundly modified the indications of radiotherapy, drugs being now generally used as a second-line treatment, after surgery (or even as first-line treatment). Based on the results of the different treatment modalities for each type of pituitary adenoma, recommendations will be proposed. They may be summarized as follows. For treatment of GH-secreting adenomas, trans-sphenoidal surgery is the first-line therapy except when the macroadenoma is giant or if surgery is contra-indicated; postoperative radiation therapy (fractionated, or by gamma-knife) is performed for partially resected tumors or when GH levels remain elevated (eventually after a trial of somatostatin analog). Somatostatin analogs, now available in slow release form, are proposed when surgery is contra-indicated, or has failed to normalize GH levels, or in waiting for the delayed effects of radiation therapy. If the probability of surgical cure is low (e.g. in patients with very large and/or invasive tumors), then somatostatin analogs may be reasonable primary therapeutic modality provided that the tumor does not threaten vision or neurological function. Pegvisomant, the new GH-receptor antagonist, is indicated in case of resistance to somatostatin analogs. Patients with PRL-secreting microadenomas may be treated either with trans-sphenoidal surgery or medically with DA agonists. In patients with macroadenomas, even in the presence of chiasmatic syndrome, DA agonists are now proposed as primary treatment. Indeed, effects on visual disturbances are often very rapid (within a few hours or days) and tumoral shrinkage is usually very significant. For patients with ACTH-secreting adenomas, primary therapy is generally trans-sphenoidal surgery by a skilled surgeon, whether or not a microadenoma is visible on MRI. Radiotherapy is reserved for patients who are subtotally resected or remain hyper-secretory after surgery. In waiting for the effects of radiotherapy, adrenal steroidogenesis inhibitors (mitotane, ketoconazole) may be indicated. If drugs are not available or not tolerated, bilateral adrenalectomy may be proposed. For patients with clinically non functioning adenomas (generally gonadotropin-secreting adenomas on immunocytochemistry), trans-sphenoidal surgery with or without postoperative radiation therapy is performed for almost all patients whether or not they have visual consequences of their tumor. Selected patients with small, incidentally discovered microadenomas may be carefully followed without immediate therapy.
 ...
PMID:Diagnosis and treatment of pituitary adenomas. 1576 32

The successful treatment of Cushing syndrome depends on specific therapy directed against the etiology of hypercortisolism. In addition to surgical procedures, various drugs have been employed in the management of this difficult disease. Compounds with neuromodulatory properties have been effective in only a limited number of cases of hypothalamic-pituitary-dependent Cushing disease, the most common form of Cushing syndrome. These agents include serotonin antagonists (cyproheptadine, ketanserin, ritanserin), dopamine agonists (bromocriptine, cabergoline), GABA agonists (valproic acid [sodium valproate]), and somatostatin analogs (octreotide). Interesting new avenues at the pituitary level involve the potential use of thiazolidinedione compounds, such as rosiglitazone, and of retinoic acid, which are ligands of different nuclear hormone receptors involved in hypothalamic-pituitary regulation. The most exciting news, however, in the pharmacologic approach to Cushing syndrome refers to the adrenal corticotropin (adrenocorticotropic hormone; ACTH)-independent forms, in which aberrant adrenal receptors, through the binding of their respective ligands, could lead to chronic cortisol overproduction. They include receptors for gastric inhibitory peptide (GIP), beta-adrenergic agonists, luteinizing hormone (LH)/human chorionic gonadotropin, serotonin (5-HT(4) receptor), vasopressin (V(1) receptor), and angiotensin II (AT(1) receptor). In GIP-dependent Cushing syndrome, the most frequent subtype of ACTH-independent macronodular adrenal hyperplasia associated with the presence of aberrant adrenocortical hormone receptors described so far, octreotide administration before each meal showed clinical efficacy only in the first few months, probably because of somatostatin receptor downregulation in GIP-secreting cells. Long-term medical treatments with propranolol and the gonadotropin-releasing hormone analog leuprorelin (leuprolide acetate) were effective in patients with catecholamine-dependent and LH-dependent Cushing syndrome, respectively. The oral vasopressin V(1) receptor antagonist OPC-21268 and the angiotensin II (AT(1)) receptor antagonist candesartan cilexetil were also able to decrease cortisol levels during the few days of administration of the drugs in patients with specific receptor abnormalities. These adrenal forms of Cushing syndrome are rare, and clinical data are scarce. Moreover, the real clinical significance of aberrant hormone receptors is still under investigation, as is the possibility of avoiding surgery by pharmacologic manipulation. Patients in whom these intriguing syndromes are suspected require detailed investigation protocols, which should be carried out in specialized centers. While awaiting further developments, the use of traditional medical treatment at the adrenal level with adrenal steroid inhibitors is still valuable in several instances.
 ...
PMID:Pharmacologic management of Cushing syndrome : new targets for therapy. 1578 46

Cushing's syndrome (CS) in medullary thyroid carcinoma (MTC) is rare. Only 50 cases have been reported. We report 10 cases of MTC with ectopic adrenocorticotropic hormone (ACTH)-dependent syndrome (EAS), analyzed retrospectively. Among 1640 patients with MTC, 13 developed EAS (0.7%). In 10 patients CS could unequivoqually be related to MTC (0.6%). CS was always clinically obvious. It revealed MTC in 3 cases and followed diagnosis by an average of 34.5 months in the others. Metastases were often present at diagnosis. Immunohistochemistry with ACTH antibodies was positive in one case. Diagnosis of ectopic CS was established according to clinical and biologic features, and absence of corticotropic adenoma as well as parallel evolution between tumor and CS. Therapy was medical and surgical: anticortisolic drugs alone or in association with somatostatin analogue, somatostatin analogue alone, and bilateral adrenalectomy. Eight patients died within 2 to 30 months, 4 of hypercortisolism complications (3 peritonitis and 1 hypokalaemia), 4 of MTC progression. EAS is a rare complication of MTC. The prognosis is poor because of frequency of metastasis at diagnosis. Persistent hypercortisolism can, by itself, lead to death, and has to be treated specifically.
 ...
PMID:Ectopic adrenocorticotropic hormone-syndrome in medullary carcinoma of the thyroid: a retrospective analysis and review of the literature. 1602 31

We can define paraneoplastic syndromes as a combination of effects occurring far from the original location of the tumour and independently from the local repercussion of its metastases. Paraneoplastic hormonal syndromes depend on the secretion of hormonal peptides or their precursors, cytokines and, more rarely, thyroidal hormones and Vitamin D, which act in an endocrine, paracrine or autocrine way. Sometimes, paraneoplastic syndromes can be more serious than the consequences of the primary tumour itself and can precede, develop in parallel, or follow the manifestations of this tumour. It is important to recognise a paraneoplastic hormonal syndrome for several reasons, amongst which we would draw attention to three: 1) It can lead to the diagnosis of a previously undetected, underlying malign or benign neoplasia; 2) It can dominate the clinical picture and thus lead to errors with respect to the origin and type of primary tumour; and 3) It can follow the clinical course of the underlying tumour and thus be useful for monitoring its evolution. The molecular mechanisms responsible for the development of these syndromes are not well-known, but it is believed that they might be inherent to the mutations responsible for the primary tumour or depend on epigenetic factors such as methylation. In this review, we consider the following paraneoplastic hormonal syndromes: malign hypercalcaemia, hyponatraemia (inappropiate secretion of the antidiuretic hormone), ectopic Cushing's syndrome, ectopic acromegaly, hypoglycaemia due to tumours different from those of the islet cells and paraneoplastic gynaecomastia; we make a brief final reference to other hormones (calcitonin, somatostatin, and VIP).
 ...
PMID:[Paraneoplastic hormonal syndromes]. 1615 18

In recent years, somatostatin analogs have been proposed and used in the diagnosis and therapy in Cushing's syndrome (CS). In these last few years, the potential therapeutic effects of somatostain analogs have been studied in different aspects of CS. The strong expression of somatostatin receptors (SSTR) type 5 in human corticotroph cells and the demonstrated efficacy of SOM230, a novel multi-ligand somatostatin analog, in inhibiting ACTH release in vitro suggest that this new drug may be effective in the treatment of ACTH hypersecretion. Very preliminary in vivo results suggest that SOM230 could be a promising drug in medical therapy for patients with Cushing's disease (CD). Prolonged treatment and more data will be needed in order to evaluate its long-term therapeutic efficacy.
 ...
PMID:Potential indications for somatostatin analogs in Cushing's syndrome. 1662 58

Clinical application of natural somatostatin is limited due to its short effect (the half-life of the preparation is less than 3 min), and a rebound effect after its administration. For these reasons, synthetic analogues of somatostatin, among which sandostatin (octreotide acetate) was the first one, were developed. Other cyclic analogues with similar sensitivity and activity profile, such as lanreotide (somatulin), somatostatin-14, and SOM 230, have been developed as well. These preparations seem to possess certain antiproliferative activity. Somatostatin analogues may be administered in repeated hypodermic injections, or repeated or prolonged intravenous infusions. Long-acting intramuscular preparations (sandostatin LAR) are usually administered once in four weeks, while long-acting lanreotide (somatulin) is administered once in two weeks. Sandostatin therapy is indicated to patients with functionally active neuroendocrine tumors of the stomach, duodenum, small bowel, or appendix. Glucagonomas, vipomas, and, to a lesser degree, gastrinomas and metastatic insulinomas are examples of functionally active endocrine pancreatic tumors that should be treated with sandostatin. Patients are selected according to a positive result of OcreoScan test. Other syndromes, which should be treated with octreotide, include ectopic secretion of adrenocorticotropic hormone in Cushing syndrome, oncogenic osteomalacia, and hypercalciemia resulting from ectopic secretion of parathyroid-like peptide. In patients with an advanced carcinoid syndrome, the starting dose of sandostatin (ocreotide) is 150 mcgr administered three times a day in hypordermic injections during 10 to 14 days, after which sandostatin LAR is administered in a dose of 20 mg once a month. Sandostatin is usually administered for the life-term of the patient, exept cases of intractable adverse effects or the development of total insensitivity.
 ...
PMID:[Somatostatin analogues in treatment of gastrointestinal and pancreatic neuroendocrine tumors]. 1675 46

Several new therapeutic options both medicinal and surgical, have emerged for the treatment of Cushing's syndrome. In Cushing's disease caused by an adrenocorticotropin (ACTH) secreting pituitary adenoma, the introduction ofendoscopic pituitary surgery offers better visualization of the sella than does the traditional explorative surgery. However, at present it is unclear whether this will result in a better outcome. New drugs under investigation include universal somatostatin analogues such as SOM230, and a combination of a somatostatin analogue and dopamine agonist known as dopastatin. These agents may also be effective for the medicinal treatment of ectopic ACTH-secretion. Treatment with radioactive-labelled somatostatin-analogues such as 177lutetium octreotate is another option for these patients. The primary treatment for ACTH-independent Cushing's syndrome is laparoscopic adrenalectomy. In rare cases of bilateral adrenal hyperplasia, medicinal treatment aimed at new regulatory pathways of cortisol secretion can be applied.
 ...
PMID:[Cushing's syndrome. II. New forms of treatment]. 1732 80

Knowledge of hypophysis could hardly stagnate in a context of general progress in medical science as such. New knowledge in physiology, pathology and treatment of hypophysis diseases is vast and only some of it could be included in the article. New regulators of hypophysial secretion have been discovered. Among them are hypothalamic chemokines and the KISS-1 gene product--kisspeptin. Impulses coming to the hypophysis from the brain centres and the periphery need to be integrated. This is provided by a system of folliculo-stellate cells, paracrine mechanisms and hypophysial microcirculation. Are there stem cells in the hypophysis, too? It seems there are. It could be the above mentioned folliculo-stellate system cells, or the recently discovered SP (side population) cells. Massive injuries such as multiple traumas, severe burns and shock states provoke a double-phase response of the hypophysis. The acute phase is characterised by hypersecretion of most of hypophysial hormones and peripheral resistance to their actuation. In the subsequent chronic phase, however, the secretion of all hypophysial hormones is reduced, except for ACTH. Clinically relevant hypophysial adenomas affect approximately 1 per thousand of population. Two thirds of the above number are prolactinomas. Most prolactinomas can be cured without major difficulty, only those resistant to pharmacological treatment can become a problem. In such cases, Leksell gamma knife can play an important role. The treatment of acromegaly is far more difficult, though. We have developed our own acromegaly treatment method. We treat adenomas surgically, expose possible residua to Leksell gamma knife irradiation and apply pharmacological therapy until the effect of irradiation has been achieved. The therapeutic options are ordered in a cost sequence: cabergolin, somatostatin analogues, pegvisomant. Similar approach is applied to patients with central etiology Cushing's syndrome, the only difference being the fact that the pharmacological therapy preceding the effect of the gamma knife treatment uses ketoconazol and metyrapone. Like in the case of acromegaly, also in that of Cushing's disease, new drugs are developed which promise greater therapeutic advantages.
 ...
PMID:[Quo vadis, hypophysis? Some news and prospects]. 1791 19

The treatment of choice for Cushing's syndrome remains surgical. The role for medical therapy is twofold. Firstly it is used to control hypercortisolaemia prior to surgery to optimize patient's preoperative state and secondly, it is used where surgery has failed and radiotherapy has not taken effect. The main drugs used inhibit steroidogenesis and include metyrapone, ketoconazole, and mitotane. Drugs targeting the hypothalamic-pituitary axis have been investigated but their roles in clinical practice remain limited although PPAR-gamma agonist and somatostatin analogue som-230 (pasireotide) need further investigation. The only drug acting at the periphery targeting the glucocorticoid receptor remains Mifepristone (RU486). The management of Cushing syndrome may well involve combination therapy acting at different pathways of hypercortisolaemia but monitoring of therapy will remain a challenge.
 ...
PMID:Pharmacological management of Cushing's syndrome: an update. 1820 72

Somatostatin (SS) and dopamine (DA) receptors are widely expressed in neuroendocrine tumours that cause Cushing's Syndrome (CS). Increasing knowledge of specific subtype expression within these tumours and the ability to target these receptor subtypes with high-affinity compounds, has driven the search for new SS- or DA-based medical therapies for the various forms of CS. In Cushing's disease, corticotroph adenomas mainly express dopamine receptor subtype 2 (D(2)) and somatostatin receptor subtype 5 (sst(5)), whereas sst(2) is expressed at lower levels. Activation of these receptors can inhibit ACTH-release in primary cultured corticotroph adenomas and compounds that target either sst(5) (pasireotide, or SOM230) or D(2) (cabergoline) have shown significant efficacy in subsets of patients in recent clinical studies. Combination therapy, either by administration of both types of compounds separately or by treatment with novel somatostatin-dopamine chimeric molecules (e.g. BIM-23A760), appears to be a promising approach in this respect. In selected cases of Ectopic ACTH-producing Syndrome (EAS), the sst(2)-preferring compound octreotide is able to reduce cortisol levels effectively. A recent study showed that D(2) receptors are also significantly expressed in the majority of EAS and that cabergoline may decrease cortisol levels in subsets of these patients. In both normal adrenal tissue as well as in adrenal adenomas and carcinomas that cause CS, sst and DA receptor expression has been demonstrated. Although selected cases of adrenal CS may benefit from sst or DA-targeted treatment, its total contribution to the treatment of these patients is likely to be low as surgery is effective in most cases.
 ...
PMID:Somatostatin and dopamine receptors as targets for medical treatment of Cushing's Syndrome. 1864 88


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>