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)

Medical therapy with a dopamine agonist is the most effective for treatment of a prolactin-producing adenoma and is considered as primary treatment. Surgery and pituitary radiation are reserved for patients who either do not tolerate or do not respond to a dopamine agonist drug. A somatostatin analogue is effective medical therapy for patients with acromegaly, and this is usually administered if there is persistent GH hypersecretion after surgical resection. Medical treatment for patients with Cushing's disease is directed at the adrenal glands to reduce cortisol hypersecretion. Unfortunately, there is no effective medical therapy to reduce pituitary corticotropin production. Medical therapy for a gonadotrope adenoma with a dopamine agonist or somatostatin analogue has limited utility but is employed in patients who are unable to undergo surgery and may delay or prevent additional tumor growth. Many patients with a pituitary adenoma can be successfully treated with one treatment, either a dopamine agonist for a prolactinoma or surgery for other types of tumors. A substantial number of patients require multimodality therapy, however, including medical therapy, surgery, and pituitary radiation. Because the biologic behavior of pituitary adenomas varies considerably, a patient with a pituitary adenoma requires lifelong regular monitoring for hormone hypersecretion, tumor recurrence, and development of new pituitary hormone deficiency. A coordinated plan of care among endocrinologists, neurosurgeons, neuroophthalmologists, and radiation therapists is necessary to provide optimal care for these patients.
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PMID:Medical treatment of functional pituitary tumors. 1269 Sep 80

Somatostatin receptor (SSTR) subtypes 1, 2, and 5 are expressed in the normal human pituitary. SSTR2 and SSTR5 are expressed in almost all growth hormone (GH) cell adenomas, and prolactin (PRL)-secreting tumors express SSTR5 more than SSTR2. SSTR4 is not detected in all pituitary adenoma subtypes, and SSTR1 and SSTR3 are expressed in about 50% of tumors. Human GH is regulated through ligand binding to both SSTR2 and SSTR5, but octreotide and lanreotide, the two clinically available somatostatin analogs, bind to human SSTR2 much better than to SSTR5. Novel SSTR2- and SSTR5- selective analogs with improved binding affinity for these receptor subtypes are highly potent in suppressing GH release from cultures of human fetal pituitaries or GH-cell adenomas. Only SSTR5-selective analogs suppress in vitro PRL secretion from cultured prolactinomas. A new SSTR2+5 bispecific analog with high affinity and selectivity for both SSTR2 and SSTR5, and a somatostatin analog with a unique broad receptor (SSTR1, 2, 3, and 5) binding profile, are both able to inhibit in vitro GH release in GH cell adenomas partially sensitive to octreotide. Recently, a somatostatindopamine hybrid molecule was introduced with potentially functional synergy on GH and PRL release. Using the expanding knowledge on SSTRs and their ligand activation, the development of novel pharmacologic concepts may open new opportunities for effective manipulation of this complex intracellular signaling system. These concepts may achieve better control of pituitary hormone hypersecretion, pituitary size, as well as antitumor effects in patients with SSTR-expressing tumors.
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PMID:Somatostatin receptors in pituitary and development of somatostatin receptor subtype-selective analogs. 1272 6

Acromegaly is a debilitating disease usually caused by a growth-hormone secreting pituitary adenoma. Therapeutic goals include improvement of symptoms, reduction in tumor mass, biochemical normalization, and preservation of pituitary function. Treatment options include transsphenoidal surgery, radiation, and pharmacotherapy. In view of the good cure rate, surgery remains the therapeutic modality of choice for most patients with microadenomas or well-circumscribed macroadenomas. In contrast, >40% of patients with invasive macroadenomas (who make up the majority of patients with acromegaly) will have residual disease following surgery, and require additional therapeutic intervention. Somatostatin analogs result in biochemical normalization in >60% of non-operated patients, and are well tolerated. Therefore, somatostatin analogs have emerged as a rational first-line treatment for the appropriately selected patient with acromegaly.
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PMID:Somatostatin analogs as primary medical therapy for acromegaly. 1272 10

Pituitary adenomas are mostly benign tumours that originate from differentiated anterior pituitary cells. Altered expression of growth factors or their receptors could enhance clonal expansion of pituitary adenoma cells. GHRH overstimulation or an activating point mutation in the Gs a-subunit leads to increased GH secretion and tumour formation. In contrast, IGF-I suppresses basal and GHRH-stimulated GH secretion in pituitary adenoma cells, whereas prolactin secretion is unaffected. Somatostatin analogues and pegvisomant, a novel growth hormone-receptor antagonist, results in a reduction of serum IGF-I levels and clinical improvement in patients suffering from pituitary adenoma. Thus, this review focuses on the role of the growth hormone/insulin-like growth factor system in pituitary tumorigenesis with particular focus on the genetic alterations described in pituitary adenomas up to now.
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PMID:The role of the GH/IGF system in pituitary tumorigenesis. 1471 Mar 44

We report a case of acromegalic cardiomyopathy in a 46-year-old Japanese man with pituitary adenoma. Increased secretion of growth hormone and insulin-like growth factor I were detected. He had left ventricular hypertrophy, impaired cardiac function, and frequent ventricular premature complexes. After 2-month treatment with octreotide, a long-acting somatostatin analogue, levels of both hormones were decreased. At the same time, left ventricular hypertrophy (intraventricular septal thickness: 22.5 to 17.8 mm), cardiac function (ejection fraction: 38 to 50%), and frequency of ventricular premature complexes (17,249 to 2,882 beats a day) were improved. Transsphenoidal surgery was then safely performed. Treatment with octreotide is thought to have some effect on improvement of ventricular arrhythmia in acromegalic heart.
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PMID:Improvement of ventricular arrhythmia by octreotide treatment in acromegalic cardiomyopathy. 1471 Nov 97

In recent years, the medical therapy for prolactinomas and GH-secreting adenomas has greatly improved due to the availability of new, highly effective, long-acting dopamine and somatostatin analogues. Although medical therapy has for some time been the first-line approach to prolactinoma management, the incidence of patients requiring surgery for resistance or intolerance/noncompliance is likely to decrease substantially with these new agents. Increasing efficacy and greater ease of administration of somatostatin analogues for GH, and for rare TSH, adenomas are also anticipated to lead to less reliance on surgery and radiation therapy as the primary therapy in these disorders. Although somewhat unclear at this time, GH antagonists hold promise for alternative or adjunct therapy for acromegaly. Given the significant morbidity and mortality associated with acromegaly, these advances are quite encouraging. Unfortunately, little if any progress has been made toward establishing an effective medical treatment for gonadotropin or nonsecreting tumors. However, new approaches to delivery of radiation therapy may reduce some of the inconvenience and risk of this treatment for patients when surgery alone is inadequate. In all of these disorders, the challenge to physicians and their patients remains one of choosing a rational combination of medical, surgical, and radiation therapy. Fortunately, for most patients, control, if not cure, of their pituitary adenoma is a reasonable expectation.
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PMID:Diagnosis and management of pituitary tumors: recent advances. 1502 95

The aim of the study was to investigate the mechanism of action of somatostatin analogues (SSA), ionizing radiation, and their combination on pituitary adenoma cells with special emphasis on proliferative and apoptotic activity. In the 14 GH-secreting adenomas pretreated with SSA before surgery, more prominent regressive changes were found accompanied by compensatory increase in perivascular fibrosis than in the reference group of 17 unpretreated adenomas. The proliferative Ki-67 labeling index was significantly lower in the treated group (median 1.6 per 1000) than in the untreated patients (median 5.0 per 1000). Apoptosis was detected in only 2 of the 14 pretreated adenomas, and it was more frequent (9/17) and more prominent in the untreated group. In cell lines, the SSA had minimal antiproliferative effect, and they were unable to induce apoptosis. Ionizing radiation at doses of 5-20 Gy induced apoptosis in the corticotroph cell line AtT20 with no cell-cycle block. In the somatotroph GH3 cell line, the early (premitotic) apoptosis was detectable using only a high dose of 200 Gy; after irradiation with doses of 20-50 Gy, apoptosis appeared with the latency of 48-72 hours, and was preceded by cell-cycle arrest in the G(2)/M phase. The treatment with somatostatin-14 during irradiation increased the percentage of apoptotic cells in culture 10 days after irradiation (11% versus 3% using 20 Gy).
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PMID:The role of apoptosis in pituitary adenomas in the field of conventionally used therapeutic approaches. 1503 83

Visual improvement following octreotide for growth hormone secreting pituitary macroadenomas is uncommon without tumour shrinkage. A 45-year old lady presented with blurred vision for 12 months. Visual assessment revealed a bitemporal hemianopia and CT scan demonstrated a large pituitary tumour with lateral and suprasellar extension. Acromegaly was confirmed by 75 g glucose tolerance testing. Primary transsphenoidal surgery was performed with normalisation of visual acuity and fields of vision. Post-operatively she had anterior pituitary hormone deficiency. As GH and IGF-1 levels remained elevated she underwent external pituitary irradiation. CT scanning demonstrated tumour shrinkage associated with a modest fall in GH levels. IGF-1 levels remained elevated falling to the age-related upper limit of normal after 5 years. At regular review she had stable visual acuity and fields of vision. She presented as an emergency 7 years from presentation with reduced vision and recurrence of bitemporal hemianopia. An MRI demonstrated a large pituitary adenoma. We therefore undertook a carefully monitored trial of octreotide with great caution with daily reassessment of acuity and fields. A decision was made to proceed to surgery in the event of deterioration or lack of improvement after a short trial over 5-7 days. We observed normalisation of visual acuity and perimetry within 3 days. She then commenced long-acting octreotide (Sandostatin LAR) 20 mg every 28 days. MRI after 1 week showed shrinkage of the tumour by a few millimetres. Five months later repeat MRI failed to show any further improvement in tumour size. However she remains well 29 months from treatment with normal vision and is being monitored carefully as her chosen form of therapy. Somatostatin analogues may be effective as therapy in a selected group of patients with acromegaly and visual loss who are not suitable for pituitary surgery. If used in this way the drug must be given cautiously with frequent detailed ongoing visual assessments. In this present case there has been a restoration of vision but the long-term outlook remains guarded without significant tumor shrinkage.
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PMID:Sustained improvement in vision in a recurrent growth hormone secreting macroadenoma during treatment with octreotide in the absence of marked tumour shrinkage. 1523 32

The treatment of acromegaly has changed considerably over the last few decades. In the late 1970s, the introduction of the dopamine receptor agonists made it possible to reduce growth hormone (GH) secretion by somatotropinomas for the first time. Thereafter, the introduction of the somatostatin analogues in the early 1980s had major implications. Recently, the first data on the use of genetically engineered human GH receptor (GHR) antagonists that block GH actions have become available. These GHR antagonists reduce both the biochemical abnormalities of acromegaly, as well as improve clinical signs and symptomatology. In this article we firstly review available data on dopamine agonists. Currently these compounds should be considered in patients with a mixed GH-prolactin secreting pituitary adenoma and/or those in whom pre-treatment insulin-like growth factor (IGF)-I concentrations are below 750 microg/L. We then discuss the somatostatin analogues. These compounds are capable of achieving biochemical control of GH and IGF-I in 50-60% of patients and tumour shrinkage in some 30%. In particular, candidates for treatment with these compounds are those patients who have undergone an unsuccessful transsphenoidal operation or who await the therapeutic effect of external pituitary irradiation. In selected patients primary medical therapy with somatostatin analogues is certainly a feasible option. To date, pegvisomant is the only available member of a new class of drugs that was especially designed to block the GHR. Pegvisomant is the most effective treatment for normalising IGF-I concentrations and appears to have a good safety profile. However, liver function tests should be regularly monitored and tumour size should be closely followed. Finally, we propose a treatment algorithm for acromegaly.
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PMID:Pharmacological therapy for acromegaly: a critical review. 1530 64

Acromegaly is a rare but disabling condition associated with reduced life expectancy. It is caused almost invariably by a growth hormone-secreting pituitary adenoma. Transsphenoidal surgery and/or radiotherapy are still considered to be the treatment of choice, but despite recent advances in both these forms of treatment, the overall surgical cure rate remains approximately 60%, and radiotherapy is characterised by delayed effect and a high incidence of hypopituitarism. Medical therapy in the form of dopamine agonists and somatostatin analogues has traditionally been used as an adjunct to surgery and/or radiotherapy, but is increasingly being used as first line therapy in the treatment of acromegaly. Recently, a third form of medical therapy, the growth hormone receptor antagonist, pegvisomant, has been licensed for use in acromegaly. This article examines the design, properties, clinical efficacy and safety of pegvisomant.
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PMID:The role of growth hormone-receptor antagonism in relation to acromegaly. 1550 Mar 74


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