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)

Somatostatin analogs have been shown to be effective for the treatment of TSH-secreting pituitary adenomas. However, their use in this indication is limited by the fact that available analogs require several daily sc injections. The present study was performed to evaluate the effects of a slow release formulation of the somatostatin analog lanreotide (SR-L) on both hormone secretion and tumor size and to assess the tolerance in a series of thyrotropinomas treated for 6 months. Eighteen patients with hyperthyroidism related to a TSH-secreting pituitary adenoma, evidenced by pituitary magnetic resonance imaging, were studied. After a basal assessment, each patient received 30 mg SR-L, im, every 14 days for 1 month. Then, according to the free T3 (fT3) plasma level measured, 9 of 18 patients were injected twice monthly, and 7 of 18 patients received SR-L every 10 days for 5 additional months. One patient was dismissed from the study in month 1 of the study for side-effects and another in month 3 for noncompliance to the protocol. Clinical and biological evaluations (plasma TSH, free alpha-subunit, fT4, fT3, and lanreotide levels) were performed before and in months 1, 3, and 6 of treatment. Pituitary magnetic resonance imaging and gallbladder ultrasonography were performed both at entry and at the end of the study. Clinical signs of hyperthyroidism improved within 1 month in all 16 evaluable patients. Mean (+/- SEM) plasma lanreotide levels reached 1.11 +/- 0.43 and 1.69 +/- 0.65 ng/mL in month 3 using 2 and 3 injections/month, respectively, then remained stable until the end of the study. During therapy, the plasma TSH level decreased from 2.72 +/- 0.32 to 1.89 +/-0.27 mU/L (P < 0.01), with parallel significant changes in free alpha-subunit. During the same period, plasma fT4 and fT3 levels decreased from 37.9 +/- 2.9 to 19.7 +/- 2.3 pmol/L (P < 0.01) and from 14.6 +/- 1.1 to 8.3 +/- 0.8 pmol/L (P < 0.01), respectively. No statistically significant change in mean adenoma size was observed after 6 months of treatment. Side-effects, including pain at the injection point, abdominal cramps, and diarrhea, were mild and transient and did not lead to interruption of the treatment. No gallstones occurred during the study. SR-L appears to be able to suppress clinical signs of hyperthyroidism in our series of patients with TSH-secreting pituitary adenomas. The analog also reduces plasma TSH and thyroid hormone levels, which were normalized in 13 of 16 cases. The effect was maintained throughout the treatment using 2 or 3 SR-L injections monthly without any problem of tolerance. We conclude that SR-L is a safe and effective treatment of thyrotropinomas and avoids the drawbacks of the modes of administration of other somatostatin analogs, given three times daily.
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PMID:Evaluation of the treatment of thyrotropin-secreting pituitary adenomas with a slow release formulation of the somatostatin analog lanreotide. 1077 Jan 86

Gigantism is caused by GH hypersecretion occurring before epiphyseal long bone closure and usually is associated with pituitary adenoma. A 15-yr-old female patient presented with accelerated growth due to a large pituitary tumor that was surgically resected to relieve pressure effects. Second surgery to remove residual tumor tissue was followed by administration of octreotide LAR, a long-acting depot somatostatin analog, together with long-acting cabergoline. Height was over the 95th percentile, with evidence of a recent growth spurt. Serum GH levels were more than 60 ng/mL (normal, <10 ng/mL) with no suppression to 75 g oral glucose, and serum PRL (>8,000 ng/mL; normal, <23 ng/mL) and insulin-like growth factor I levels (845 ng/mL; age-matched normal, 242-660 ng/mL) were elevated. Histology, immunostaining, and electron microscopy demonstrated a pituitary acidophil stem cell adenoma. Tumor tissue expressed both somatostatin receptor type 2 and dopamine receptor type 2. The Gs alpha subunit, GHRH receptor, and MEN1 genes were intact, and tumor tissue abundantly expressed pituitary tumor transforming gene (PTTG). Serum GH and PRL levels were controlled after two surgeries, and with continued cabergoline and octreotide LAR GH, PRL, and insulin-like growth factor I levels were normalized. In conclusion, administration of long-acting somatostatin analog every 4 weeks in combination with a long-acting dopamine agonist biweekly controlled biochemical parameters and accelerated growth in a patient with gigantism caused by a rare pituitary acidophil stem cell adenoma.
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PMID:Long-acting peptidomimergic control of gigantism caused by pituitary acidophilic stem cell adenoma. 1099 42

True gigantism is rare in early childhood and is usually due to excess GH secretion from a pituitary adenoma. We report a case in which the endocrine abnormality is secondary to an optic glioma. Careful endocrine evaluation has shown that GH peak amplitude was not increased but rather there was failure of GH levels to suppress to baseline and a lack of pulsatility. There is no evidence of a direct secretory role for the tumour and we postulate that the tumour is affecting GH secretion through an effect on somatostatin tone. Specific tumour therapy is not indicated for this patient in the absence of mass effect or visual disturbance. The GH excess is being treated with somatostatin analogue (Octreotide) and as he has developed precocious puberty he is also receiving long acting GnRH analogue (Zoladex). This boy appears likely to have neurofibromatosis type 1 (NF1) which raises the question of subtle GH excess in NF1 patients with tall stature.
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PMID:Gigantism due to growth hormone excess in a boy with optic glioma. 1101 81

We report a case of acromegaly with relatively low GH secretion in a patient with GH-secreting pituitary macroadenoma. The 44-year-old male patient presented with left temporal hemianopsia and characteristic acromegalic face, but had relatively low baseline and post-glucose GH levels. IGF-1 and IGFBP-1 were elevated. Transsphenoidal surgery did not achieve clinical or biochemiacl remission, and the patient still had elevated IGF-1 levels with low GH. Histological examination of the resected tumor revealed a pituitary adenoma stained weakly for GH. The patient was treated then with monthly injections of Sandostatin-LAR, with clinical improvement and suppression of IGF-I to the normal range. This is a rare case of acromegaly without elevated GH levels, and good response to treatment with somatostatin analog, as expected in classical GH-secreting pituitary adenomas.
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PMID:Acromegaly with normal growth hormone levels: response to Sandostatin-LAR treatment. 1108 Nov 51

The reported cases of hyperthyroidism due to a TSH-secreting pituitary adenoma have steadily increased in previous years; however, information about the results and long term outcome after pituitary surgery is scanty. Twenty-four patients with a TSH-secreting adenoma underwent pituitary surgery at our department in the last 15 years. Hypersecretion of other pituitary hormones was diagnosed in 7 patients. Three patients were euthyroid at the time of surgery because of previous ablative thyroid therapies. The success rate of surgery strictly depends on the criteria used. Normalization of elevated FT3 and FT4 levels occurred in 17 of the 21 patients with preoperative hyperthyroidism: however, only those with early postoperative undetectable TSH level (12 cases) had no recurrence of disease during follow-up and no residual tumor tissue on postoperative MRI, whereas recurrence of hyperthyroidism occurred in 3 of the 5 patients without postoperative TSH inhibition. All 3 euthyroid patients had a subtotal removal of the tumor, as judged by postoperative MRI. Surgical removal is the therapy of choice of TSH-secreting adenomas, whereas radiotherapy and medical treatment with somatostatin analogues are usually reserved to patients with incomplete tumor removal. A thorough postoperative evaluation is necessary to discriminate between complete and partial remission of disease.
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PMID:Surgical management of thyrotropin-secreting pituitary adenomas. 1108 Nov 63

Acromegaly, a chronic disease of growth hormone (GH) hypersecretion, is most typically caused by a pituitary adenoma. Early diagnosis is critical for prompt intervention to prevent deleterious effects of prolonged exposure to elevated GH and insulin-like growth factor Type I (IGF-I) levels. Current therapy for acromegaly includes several options: surgery, radiotherapy and pharmacotherapy. Transsphenoidal adenomectomy remains a mainstay of therapy for acromegaly. Cure rates are high in microadenomas, but < 50% in macroadenomas. Conventional and stereotactic procedures for radiation therapy are also effective in decreasing GH levels in acromegalic patients, but they need years to normalise GH hypersecretion and carry with them the risk of hypopituitarism. The major classes of drugs currently used to treat acromegaly are dopamine agonists and analogues of somatostatin. Dopamine agonists bind to the D2 receptor and suppress GH hypersecretion in some patients with acromegaly. Their clinical effectiveness is modest, although promising results have been obtained with two novel compounds, quinagolide and cabergoline, that possess long duration of action. Somatostatin analogues have been shown to improve clinical symptoms of acromegaly, decrease hypersecretion of GH and IGF-I and reduce tumour volume in a clinically significant number of patients. Octreotide is administered by s.c. route several times a day, but the recently developed sustained release formulations (octreotide LAR and SR lanreotide) are administered only every 7-28 days by i.m. injections. The complications associated with somatostatin analogues are small, relative to the benefits. Lastly, compounds with a novel mechanism of action, the GH receptor antagonists, are presently under investigation.
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PMID:Current management of acromegaly. 1124 4

Tumor growth depends on several factors, including angiogenesis. Tumors cannot grow if new vessels are not formed to supply the cells with oxygen and other nutrients and to remove waste products. Increased angiogenesis can be correlated with tumor growth and metastatic potential in many tumor types, indicating that neoformation of vessels is a prognostic indicator of tumor behavior. We evaluated microvessel densities in 157 various pituitary adenoma types and seven pituitary carcinomas using immunocytochemistry for CD-34 antigen, a reliable marker of endothelial cells. The lowest percentage of microvessel density was found in growth hormone-producing adenomas, the highest level in pituitary carcinomas. In general, no major correlation was found between MIB-1 index (an indicator of cell proliferation) and microvessel density. The statistical study also demonstrated no gender-dependent changes in the microvessel density of pituitary tumors. Although the microvessel density was not significantly different in relation to invasiveness of pituitary tumors, our results demonstrate a tendency of invasive pituitary tumors to be more highly vascularized than non-invasive ones. Dopamine agonist and long-acting somatostatin analog treatment compared with untreated tumors did not significantly affect microvessel densities. Statistical differences were demonstrated in the microvessel density of macroadenomas between patients older and patients younger than 40 years. Significant differences were also apparent in the microvessel densities between microadenomas and macroadenomas diagnosed in young patients but not in the older age group. The strongly positive correlation observed between microvessel density and age is consistent with the view that age of the host may have an influence on the extent of neovascularization of pituitary adenomas.
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PMID:Microvessel density in pituitary adenomas and carcinomas. 1146 92

Angiogenesis, the formation of a new blood supply, is an essential step in tumorigenesis. Although vascular endothelial growth factor (VEGF) is known to be a very potent angiogenic factor in most solid tumors, little is known about its production and regulation in pituitary adenomas. We have investigated basal and stimulated VEGF production by rodent pituitary tumor cells (mouse corticotrope AtT20, rat lactosomatotrope GH3, mouse gonadotrope alpha T3-1 and mouse folliculostellate TtT/GF cells), and by hormone-inactive (27), corticotrope (9), lactotrope (3) and somatotrope (21) human pituitary adenoma cell cultures. All 4 pituitary cell lines secreted VEGF, which in the case of AtT20, GH3 and TtT/GF cells was inhibited by approximately 50% by dexamethasone. TtT/GF cells were the most responsive to the different stimuli used since basal values were augmented by pituitary adenylate cyclase activating polypeptide-38 (PACAP-38), interleukin-6 (IL-6), transforming growth factor-alpha (TGF-alpha), IGF-I and the somatostatin analogue ocreotide. However, in GH3, AtT20 and alpha T3-1 cells, basal VEGF levels where not enhanced with any of the stimuli tested. The majority of the human adenomas tested (92%) basally secreted measurable VEGF which was inhibited by dexamethasone in most cases (84%). VEGF levels were increased in hormone inactive adenomas, somatotrope tumors and prolactinomas by TGF-alpha, PACAP-38, and 17 beta-estradiol, respectively. In conclusion, pituitary tumor cells are capable of producing VEGF which may be involved in tumoral angiogenesis. Our results concerning the suppression of VEGF by dexamethasone suggest that glucocorticoids may have anti-angiogenic properties and therefore therapeutic relevance for the treatment of pituitary adenomas.
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PMID:Vascular endothelial growth factor production and regulation in rodent and human pituitary tumor cells in vitro. 1147 17

The aim of this article is to briefly review the physiology of growth hormone-releasing hormone (GHRH) and the diagnosis and treatment of GHRH-mediated acromegaly. Moreover, the role of GHRH and its antagonists in the pathogenesis and treatment of cancer will be reviewed. 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. GHRH-producing neurons have been well characterized in the hypothalamus by immunostaining techniques. Hypothalamic tumors, including hamartomas. choristomas, gliomas. and gangliocitomas. may produce excessive GHRH with subsequent GH hypersecretion and resultant acromegaly. 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 and increased GH secretion. The structure of hypothalamic GHRH was infact elucidated from material extracted from pancreatic GHRH-secreting tumors in two patients with acromegaly. Immunoreactive GHRH is present in several tumors, including carcinoid tumors, pancreatic cell tumors, small-cell lung cancers, adrenal adenomas, and pheochromocitomas which have been reported to secrete GHRH. Acromegaly in these patients. however, is uncommon. In a retrospective survey of 177 acromegalic patients only a single patient was identified with elevated plasma GHRH levels. Measuring GHRH plasma levels therefore provides a precise and cost-effective test for the diagnosis of ectopic acromegaly. Peripheral GHRH levels are not elevated in patients with hypothalamic GHRH- secreting tumors, supporting the notion that excess eutopic hypothalamic GHRH secretion into the hypophyseal portal system does not appreciably enter the systemic circulation. Elevated circulating GHRH levels, a normal or small-size pituitary gland, or clinical and biochemical features of other tumors known to be associated with extrapituitary acromegaly, are all indications for extrapituitary imaging. An enlarged pituitary is, however, often found on MRI of patients with peripheral GHRH-secreting tumors, and the radiologic diagnosis of a pituitary adenoma may be difficult to exclude. Surgical resection of the tumor secreting ectopic GHRH should reverse the hypersecretion of GH, and pituitary surgery should not be necessary in these patients. Nonresectable, disseminated or reccurrent carcinoid syndrome with ectopic GHRH secretion can also be managed medically with long-acting somatostatin analogs (octreotide and lanreotide). The presence of GHRH and its receptors in several extrahypothalamic tissues, including ovary, testis and the digestive tract, suggests that GHRH may have a regulatory role in these tissues. As previously mentioned, biologically or immunologically active GHRH and mRNA encoding GHRH have been found in several human malignant tumors. including cancers of the breast, endometrium and ovary and their cell lines. The synthesis and evaluation of analogs with various modifications revealed that certain hydrophobic and helix-stabilizing amino acid substitutions can produce antagonists with increased GH releasing inhibitory potencies and GHRH receptor-binding affinities in vitro. The review of experimental results of these substances are promising altrough no clinical data are yet available. Finally, the advent of these antagonists has allowed significant progress in the understanding of the role of the central and tissue GHRH-GH-IGFs system in the pathogenesis of tumors.
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PMID:Ectopic secretion of growth hormone-releasing hormone (GHRH) in neuroendocrine tumors: relevant clinical aspects. 1176 59

Acromegaly is caused by excessive secretion of growth hormone by a hypophyseal adenoma type of somatotropinoma. IGF-I is formed in the liver and mediates most biological actions of GH. Treatment of adenomas, which secrete GH, involves pharmacotherapy followed by surgery. Modern pharmacotherapy leaning is based on somatostatin analogues (factor restrictive secretion GH): octreotide, octreotide LAR and lanreotide. The aim of our study was estimation of efficiency of octreotide LAR in the patients with somatotropinoma prepared to neurosurgery intervention. We examined 16 patients (10 of women and 6 men) with the features of active acromegaly. In all cases the increased concentration of HGH and IGF-I were observed. The presence of pituitary adenoma in all patients was confirmed by MRI. The patients were treated with octreotide LAR monthly in dose 20 mg and 30 mg respectively. Before and after application of somatostatin analogues the concentration HGH, IGF-I, PRL in serum were marked. The concentration of GH before octreotide LAR therapy in all patients increased remarkable and ranged from 15.6 to 78.6 ng/ml, mean: 31.20 +/- 16.84 (norm: 0-10 ng/ml), also, in all cases the serum IGF-I level was increased and ranged from 451 to 1107.6 ng/ml, mean: 801.75 +/- 207.82 (norm: 100-400 ng/ml). The prolactin concentration ranged from 7.4 to 49.9 ng/ml, mean: 22.8 +/- 13.7 (norm: 2-20 ng/ml) and in 8 (50%) cases the increased of PRL concentration in serum was observed. After the administration of octreotide LAR the level of: GH [mean: 12.99 +/- 17.16 ng/ml (p < 0.001)], of IGF-I [mean 422.8 +/- 229 ng ml (p < 0.01)] statistical important decreased and prolactin in 8 with increased concentration [mean: 12.45 +/- 5.57 (p < 0.01)] were observed. Long acting somatostatin analogues--octreotide LAR is particular efficient in lowering of growth hormone and IGF-I in patients with somatotropinoma and shows efficiency in normalization of increased prolactin concentration. Because of extreme effectiveness of octreotide LAR, it should be used the routine treatment at the patients suffering from active acromegaly and preparing to neurosurgical treatment.
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PMID:[Estimation of efficacy of the octreotide LAR administration in the patients with somatotropinoma]. 1192 44


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