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)

The cyclic somatostatin analog, octreotide, forms the mainstay of medical treatment for acromegaly. In addition to lowering circulating growth hormone levels and shrinking tumor size, octreotide may provide symptomatic relief of headaches associated with growth hormone secreting tumors. The majority of reported complications of octreotide therapy are gastrointestinal and metabolic. The present case illustrates the development of acute bilateral cavernous sinus syndrome with loss of eye movement bilaterally during octreotide therapy. Serial MRI examination suggest tumor infarction as the etiology. The symptoms resolved over 2 months as the tumor shrunk in size and growth hormone was dramatically reduced.
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PMID:Somatotropinoma infarction during octreotide therapy leading to bilateral cavernous sinus syndrome. 1138 84

Neuroendocrine tumors (NET) of the pancreas are distinguished in functional (85%) and non functional (15%) in relation to the production and release of the hormone produced. Functional tumors show early, because the neoplasm release the hormone produced when they are still small. Non functional tumors show late when the tumor grows. The localization and the evaluation of the extensive of these tumors has come fundamentally important both in correct presurgical detection and also in the diagnosis of metastases which excluded surgery. Also, as the survival of 20% of the patients with metastases is only five years, the use of non-invasive imaging techniques is very important for the evaluation of results of the various therapies (chemotherapy, interferon, somatostatin). Recent studies have shown that in patients with Zollinger-Ellison syndrome, SRS is the most sensitive non invasive method in localizing primitive tumors and metastases. The accuracy of this technique has not yet been provided in the study of tumors like insulinomas which do not have a high percentage of somatostatine receptors on their cell membranes. The sensitivity obtained in recent studies on a large number of patient and the low cost, lower than all the other imaging technique in use today, surely make SRS the first choice in the study of NET. Where SRS is negative and surgery is possible, Spiral CT or better still MRI is the best tool to check the results of chemotherapy in patients with hepatic metastases (already detected by SRS), because it is easier to compare the changes in size and morphology of metastases.
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PMID:[Imaging of neuroendocrine tumors]. 1144 22

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

A 31-year-old woman presented with progressive weight gain, facial acne, round facies, hirsutism, and secondary amenorrhea. Her plasma cortisol, urinary free cortisol, and plasma ACTH were elevated. CT scan of abdomen revealed bilateral diffuse adrenal enlargement. MRI of pituitary failed to identify a lesion. CT scan of chest revealed an 8 mm nodule in the lower lobe of the left lung. The diagnosis of ectopic Cushing's syndrome was made. The lung tumor was surgically removed. The tumor measured up to 1.5 cm in diameter. By light microscopy, a tumor with characteristic features of bronchial carcinoid was noted. Immunostains were positive for neuron-specific enolase, synaptophysin, chromogranin, low-molecular-weight keratin, ACTH, beta endorphin, corticotropin-releasing hormone, bombesin, alpha subunit, and somatostatin. Electron microscopy revealed an endocrine neoplasm. The secretory granules displayed great variation subdividing the endocrine neoplasm. The secretory granules displayed great variation subdividing the cell population into an undetermined number of phenotypes. In situ hybridization demonstrated positivity for pro-opiomelanocortin mRNA in the tumor cells. Postoperatively, plasma cortisol had fallen. The patient remained symptom-free one year later. The case presented here was regarded as a plurihormonal bronchial carcinoid associated with ectopic Cushing's syndrome. This unique plurihormonal bronchial carcinoid tumor produced three hormones, ACTH, CRH, and bombesin, that may have contributed to the patient's ectopic Cushing's syndrome.
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PMID:Plurihormonal Bronchial Carcinoid Associated with Ectopic Cushing's Syndrome. 1211 73

Cytoreductive therapy is effective in the management of metastatic neuroendocrine tumors to the liver, independent of their functioning status. In functioning tumors, clinical endocrinopathies are relieved in most patients and this response usually lasts for several months. Major morbidity and mortality are not greater than the average complication rate for resection for nonneuroendocrine metastatic tumors at major centers; therefore, surgical outcomes appear to justify operative intervention. Patients whose primary tumor can be controlled, whose metastases outside the liver are limited, and who have a reasonable performance status are candidates for resection. The authors' data support the previous statements. The current mortality rate of 1.2% and major morbidity rate of 15% clearly represent the success of the operative approach in such complex cases (54% of patients received a resection of at least one lobe) [9]. A symptomatic response in the 95% range with a median response of 45 months adds many months of symptom-free survival to the lives of most patients [9]. In the literature reviewed for this article, more than half of the patients also underwent a major hepatic resection and 40% of them had concurrent resection of the primary tumor. These data confirm that resection in selected patients is not more complicated or risky than resection for other metastatic tumors. Endocrinopathies have not increased anesthetic or operative risk in this population; however, these results are the product of managing these patients over time, becoming familiar with their clinical syndromes, and being active in the prevention of life-threatening endocrine complications (i.e., carcinoid crisis). The authors have learned over time that patients with valvular disease are not good candidates for surgery. These patients develop right-sided heart failure with an increase in the central venous pressure. This condition can result in massive hemorrhage during the liver resection because of the difficulty in controlling backbleeding from the hepatic veins [26]. Correction of valvular disease is warranted for safe liver resection. The authors' current policy is to rule out valvular disease in every patient with carcinoid tumors and repair the valves prior to hepatic resection when indicated [27]. This policy clearly has decreased the complication rate. Even though liver transplantation seems to be very attractive as a means of eradicating the disease, this has not been common in clinical practice because of the shortage of allografts, and the overall costs and complications of the procedure override its benefits, especially when compared with partial hepatectomy. Current methods to detect the spread of disease that were not readily available in the past, such as MRI and indium-111 pentetreotide (Octreoscan), may expand the applications of transplantation and allow for better selection of candidates. The option of transplantation is still open for improvement and is dependent on organ availability and better staging of the disease. Metastases from neuroendocrine tumors are hypervascular, favoring the application of MRI as the single imaging method; MRI not only evaluates the location and characteristics of the lesions but also determines the relationship with major vessels and bile ducts. Spiral CT scan has been used extensively in the past with acceptable results. Indium-111 pentetreotide functions on the base of somatostatin receptors present in these tumors, but its use has not been established definitely in the work-up of these patients. Perhaps the best use of indium-111 pentetreotide is in the evaluation of disease beyond the primary and liver locations, including bone metastases; its use therefore will likely affect the preoperative work-up of candidates for transplantation [28]. Once the patient has been deemed to have resectable disease by the preoperative work-up, several steps need to be completed prior to surgery to decrease the effect of specific endocrinopathies. For patients with symptoms related to carcinoid tumors, preoperative preparation with 150 to 500 micrograms of somatostatin decreases the chances of carcinoid crisis, which is manifested by hemodynamic instability [29]. The use of this medication intraoperatively should be kept in mind because a carcinoid crisis can occur despite anesthetic premedication. For islet cell tumors, treatment of underlying endocrinopathy has been initiated before referral for surgical treatment in most patients. Surgery is appropriate for patients with metastatic neuroendocrine tumors for the following two reasons: (1) many of them still have the primary tumor in place and resection should be undertaken to avoid acute complications and (2) the addition of adjunctive ablative therapies to surgical resection accomplishes the control of greater than or equal to 90% of the bulk of the tumor. If preoperative evaluation indicates that less than 90% of the tumor is treatable, surgical therapy is contraindicated. Last, even when complete resections are performed, the recurrence rate for these tumors is extremely high. In practical terms, patients with metastatic neuroendocrine tumors are seldom cured. The best hope physicians can offer these patients is an extended survival period with minimal endocrine symptoms and decreased requirements of somatostatin analogs.
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PMID:Hepatic surgery for metastases from neuroendocrine tumors. 1273 41

A 52-yr-old woman presented with hypertension, elevated urinary vanillylmandelic acid, metanephrines, normetanephrines, and plasma chromogranin A (CgA), but normal urinary catecholamine levels. Abdominal ultrasonography and subsequent MRI imaging showed a 3 cm nodular lesion of the right adrenal gland also visualized by 123I-meta-iodobenzylguanidine scintigraphy consistent with a pheochromocytoma (PC). Her OctreoScan was negative. The patient underwent right adrenalectomy and histological examination showed a PC. The adrenal medulla tissue was examined for somatostatin (SRIH) receptor subtypes 1 to 5 (SSTR1 to 5) expression by RT-PCR. Cultured tumor cells were treated with either SRIH, Lanreotide (Lan), or an SSTR2 (BIM-23 120) or SSTR5 (BIM-23 206) selective agonist. CgA secretion was measured in the medium by ELISA and catecholamine levels by HPLC after 6h. Cell viability was assessed after 48h. RT-PCR analysis showed that SSTR1, 2, 3 and 4 were expressed. CgA secretion was significantly reduced by SRIH (- 80 %), Lan (- 35 %), and the SSTR2 selective agonist (- 65 %). Norepinephrine secretion was reduced by SRIH (- 66 %), Lan (- 40 %), and BIM-23 120 (- 70 %). Epinephrine and dopamine secretion was also inhibited by treatment with SRIH (- 90 % and - 93 %, respectively) and BIM-23 120 (- 33 % and - 75 %, respectively) but not by Lan. Cell viability was also significantly reduced by SRIH (- 30 %), Lan (- 10 %), and the SSTR2 selective agonist (- 20 %). The SSTR5 selective agonist did not modify either CgA and catecholamine secretion or cell viability. Our data show that SSTRs may be present in a PC although OctreoScan is negative in vivo, and that SRIH and its analogs may reduce both differentiated and proliferative functions in chromaffin cells in vitro. These findings suggest that SRIH analogs with enhanced SSTR2 affinity might be useful in the medical therapy of PC, even when an OctreoScan is negative.
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PMID:An in vivo OctreoScan-negative adrenal pheochromocytoma expresses somatostatin receptors and responds to somatostatin analogs treatment in vitro. 1292 Jun 56

In this paper, we evaluate nuclear medicine tests used for the diagnosis of breast carcinoma. Breast carcinoma is the most common carcinoma in women in Europe and its early diagnosis and treatment is important for the overall survival of the patients. Scintimammography technique, indications, contraindications and diagnostic procedures for the identification of the sentinel node and the axillary nodes infiltrated by tumour are described. Also, the use of the radiopharmaceuticals, radioactive thallium chloride-201, methylene diphosphonate labelled with technetium-99m, somatostatin receptors labelled with indium-111, diagnostic procedures with the PET camera, the labelled antibodies to CEA with technetium-99m and also the importance of the MRI and the US techniques are mentioned. These tests have greater diagnostic accuracy as compared to X-ray mammography, clinical examination, MRI and the US technique. Tumour markers in vitro are recommended for the follow- up of metastatic breast carcinoma.
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PMID:Evaluation of nuclear medicine tests for the diagnosis of breast carcinoma. 1460 Aug 79

A rare case of mucinous adenocarcinoma with neuroendocrine differentiation of the mandibular ramus is presented. The patient, an 80-year-old man, was referred to our hospital with chief complaint of swelling and pain in the left buccal mucosa. CT and MRI examination showed an osteolytic tumor mass occupying the upper region of the left mandibular ramus. Macroscopically, the excised tumor was a relatively well-defined, solid mass with diffuse bone resorption, measuring 3 cm x 3.2 cm x 3 cm. Microscopical examination showed that the tumor forming glandular structures with abundant mucous production and high cellular atypia. Immunohistochemical studies demonstrated the positive reactivities for pan-keratin, cytokeratin 7, vimentin,alpha-amylase, alpha-smooth muscle actin, neuron-specific enolase, glial fibrillary acid protein, calcitonin, and somatostatin in tumor cells. These findings suggested that the tumor was originated from heterotopic or misplaced salivary gland in the mandible.
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PMID:Mucinous adenocarcinoma with neuroendocrine differentiation of the mandibular ramus: report of a case. 1467 43

The most widely used diagnostic nuclear medicine technique in well-differentiated thyroid cancer (DTC) is radioiodine scintigraphy, either diagnostic or post-therapeutic, together with serum thyroglobulin (Tg) measurement; this combination is usually able to determine the presence or absence of cancer. FDG-PET has shown less sensitivity in DTC that retains the ability to trap 131I. Several alternative procedures with single photon emitting radiopharmaceuticals have been evaluated including whole body scan with 201Tl, 99mTc-sestamibi or tetrofosmin scan, with different sensitivity and specificity. The main advantage of these tests is that their results are not influenced by the levels of TSH, therefore they do not require a hypothyroid state in the patient. Recently positron emission tomography (PET) with FDG has been demonstrated to be highly useful in thyroid cancer patients with a negative 131I whole body scan but measurable Tg. According to reports in the literature FDG-PET in the follow-up of operated patients has a sensitivity ranging from 70% to 90% in identifying the source of Tg. The demonstration of lesions can lead to a change in treatment including surgery or external radiation instead of radioiodine treatment. In Europe, medullary thyroid cancer (MTC) is currently visualized by 99mTc pentavalent dimercaptosuccinic acid (DMSA) and 99mTc-sestamibi or tetrofosmin. Metaiodobenzylguanidine (MIBG) radiolabeled with 123I or 131I is another reliable radiopharmaceutical for medullary tumors. (111)In-pentetreotide scan is positive in a high percentage of patients because MTC expresses somatostatin receptors. FDG-PET has an interesting role to play in calcitonin-positive patients, where PET has been shown to correctly identify lesions in cervical and mediastinal lymph nodes as well as at distant sites. Furthermore, calcitonin-guided PET has been found to be superior to CT and MRI in many patients. Recent reports indicated that 18F-DOPA scan in MTC seems to be more accurate than FDG-PET.
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PMID:FDG-PET in thyroid cancer. 1487 Jul 81


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