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)

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

Alzheimer's disease (AD) is a progressive neurodegenerative disorder, the pathology of which becomes irreversible as it proceeds downstream of the disease cascade. Therefore, overcoming AD primarily requires early (presymptomatic) diagnosis, followed by preventive treatment. Since accumulation of amyloid beta peptide (A beta) in brain seems to play a central role AD pathogenesis, we established a new imaging technique to visualize A beta plaques in a mouse model of A beta amyloidosis in a non-invasive manner using a high-power MRI. This will open a new avenue to search for biochemical markers that correlate with the pathological parameters. We also found that a dimeric form of A beta, the quantity of which can be metabolically regulated by neprilysin, impairs in vivo neuronal plasticity, i.e. hippocampal long term potentiation. This suggests that reducing A beta dimers by upregulating neprilysin activity is likely to contribute to alleviation of memory-associated symptoms. Finally, we discovered that a neuropeptide, somatostatin, upregulates neuronal neprilysin activity. Because brain somatostatin expression is known to decline during aging, the finding indicates that the aging-induced downregulation of somatostatin may be a trigger for A beta accumulation leading to late-onset sporadic AD development and that somatostatin receptor(s) now emerge as pharmacological target candidates for the prevention and treatment of AD.
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PMID:[Towards presymptomatic diagnosis, prevention and treatment of Alzheimer's disease]. 1565 Dec 88

To assess the role of scintigraphy with 111In-DTPA-D-Phe-octreotide (111In-octreotide) in the diagnosis of pituitary adenomas and in the evaluation of post-surgical recurrent or residual tumours, we performed scintigraphy with 111In-DTPA-D-Phe-octreotide (SRS) in 35 patients: 14 patients with confirmed pituitary tumours and 15 with confirmed recurrent tumours. Clinical, biochemical and histological analyses, conventional images (CT/MRI), and follow-up assessments during a period of 1 year to 4 years were recorded in all patients. In the present study, scintigraphy with 111In-octreotide showed positive uptake in 10 out of 14 patients with confirmed pituitary tumour and in 13 out of 15 patients with confirmed recurrent tumour, with an overall sensitivity of 79%. SRS showed better results in growth hormone (GH)- and prolactin (PRL)-secreting tumours (7/8 patients correctly identified) than in other adenomas (3/9). SRS detected recurrence of adenocorticotrophic hormone (ACTH)-secreting tumours (4/5 patients correctly identified) and non-secreting tumours (5/7 patients correctly identified). 111In-octreotide scintigraphy, in combination with other imaging modalities, is useful in the diagnosis and follow-up of pituitary tumours. It allows scar tissue to be differentiated from tumour recurrence after surgical treatment and ensures better selection of patients who will benefit from medical treatment with somatostatin analogues.
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PMID:The role of somatostatin receptor scintigraphy in patients with pituitary adenoma or post-surgical recurrent tumours. 1568 21

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.
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PMID:Diagnosis and treatment of pituitary adenomas. 1576 32

Multiple endocrine neoplasia syndrome type II-A (MEN-IIA) is a rare endocrinological disorder occurring in 0.04% of the general population. The combination of papillary thyroid carcinoma with MEN-IIA appears even less frequently. We describe the case of a 21-year-old woman with pheochromocytoma of the left adrenal gland, medullary thyroid carcinoma, hyperplasia of the parathyroid glands and papillary thyroid carcinoma. MEN II-A syndrome resulted from de novo mutation of the RET proto-oncogene, which was detected in the DNA of peripheral blood leucocytes. Three months postoperatively calcitonin levels were normal, whilst increased serum thyroglobulin values prompted the need for further investigation. Whole body scanning with (131)I and with (99m)Tc-sestamibi and also US test of cervical lymph nodes, were negative. The synthetic analogue of somatostatin (99m)Tc-depreotide was used for whole body scintigraphy, cervical and thoracic tomographic scanning and revealed anterior cervical, upper mediastinal and right hilar foci of pathological uptake[Fig.1 and Table 1: see text]. These findings were compatible with findings from CT and MRI that followed in order to complete the diagnostic evaluation. The patient underwent surgical resection of the metastatic foci with uneventful postoperative course. Histology showed lymph node metastases originating from the papillary thyroid carcinoma. Ratio values >2 were abnormal (Fig. 2). Computer processing of the corresponding ROIs on healthy tissues produced the following normal values: Th/Arm: 1.874,, Med/Arm: 1.699, Hi/Arm: 1.141 (Fig. 3).
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PMID:[A patient with MEN-IIA syndrome due to de novo mutation and papillary thyroid carcinoma; the role of 99m Tc-depreotide in diagnosing metastases and brief review of the literature]. 1584 Dec 92

Paragangliomas are tumours that arise within the sympathetic nervous system originating from the neural crest. These tumours can be found anywhere from the neck to the pelvis in locations of sympathetic ganglions. Although in the majority of paragangliomas the diagnosis is based on measuring catecholamines and metabolites in plasma or urine, imaging plays an important preoperative role. Today, there are several morphological and radionuclide imaging methods available that predict tumour localisation and tumour extent and give anatomic information to the surgeon. MRI is the morphological imaging modality of choice in localising pheochromocytomas and extra-adrenal paragangliomas. It provides excellent anatomic detail and has the advantage of lacking ionising radiation. The overall accuracy of computed tomography (CT) in detecting primary adrenal pheochromocytomas is very high, but CT lacks in specificity as difficulties may occur in distinguishing between paragangliomas and other tumour entities. The major advantages of radionuclide imaging are very high specificity and routinely performed whole-body scanning. Furthermore, metabolic imaging is not influenced by artifacts like scar tissue or metallic clips in post-surgical follow-up. Currently, a reported specificity of 99% and a cumulative sensitivity of about 90% in paragangliomas make (123)I-MIBG the most important nuclear imaging method. However, (18)F-DOPA-PET seems to be a very promising procedure which offers higher accuracy. The higher spatial resolution of PET-scanners enables the detection of small lesions not visualised with (123)I-MIBG. Both use of radiolabelled somatostatin analogue like (111)In-pentetreotide and (18)F-FDG is limited due to low specificity of the tracers and should be restricted to MIBG- and F-DOPA-negative cases.
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PMID:Imaging of pheochromocytoma and paraganglioma. 1588 12

Malignant melanomas are characterized by a high intrinsic resistance to chemotherapy. Multiple drug resistance (MDR) can be mediated by transport proteins such as MDR-1, multidrug resistance-associated protein (MRP) or lung resistance protein (LRP). The cytotoxic analogue of somatostatin AN-238 consisting of 2-pyrrolinodoxorubicin (AN-201) linked to a somatostatin analogue RC-121 binds to receptors for somatostatin and is targeted to tumors expressing these receptors. We evaluated the expression of somatostatin receptors on human malignant melanoma tumor lines MRI-H255 and MRI-H187 and examined the effects of the targeted analogue AN-238 and its cytotoxic radical AN-201 on growth of these tumors in nude mice. We also studied the effects of AN-238 and AN-201 on the expression of MDR-1, MRP-1 and LRP by real-time PCR. AN-238 inhibited the growth of MRI-H255 and MRI-H187 tumors while AN-201 was ineffective. Blockade of somatostatin receptors by somatostatin analogue RC-121 abolished the effects of AN-238. Targeted therapy with AN-238 did not produce an induction of mRNA of MDR-1, MRP-1 or LRP. Our findings show that targeted chemotherapy with cytotoxic somatostatin analogue AN-238 inhibits the growth of malignant melanomas. AN-238 could provide a novel treatment approach for advanced malignant melanomas.
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PMID:Effective therapy of experimental human malignant melanomas with a targeted cytotoxic somatostatin analogue without induction of multi-drug resistance proteins. 1668 51

We describe the first case of a 36 year-old male patient with a somatotropin and thyreotropin secreting pituitary adenoma, co-treated by a long-acting releasing somatostatin analog (Octreotide) and a GH receptor antagonist (Pegvisomant). The patient normalized his biological disease activity reflected by hormone levels but his tumor size remained unchanged as measured by MRI. The co-treatment was well tolerated and induced a synergic effect on IGF1 levels that allowed us to use low doses of both therapies.
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PMID:An unusual somatotropin and thyreotropin secreting pituitary adenoma efficiently controlled by Octreotide and Pegvisomant. 1684 Sep 17

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.
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PMID:Neuroendocrine tumors secreting growth hormone-releasing hormone: Pathophysiological and clinical aspects. 1703 95

Gastrin receptor scintigraphy (GRS) is a new imaging method primarily developed for the detection of metastases of medullary thyroid carcinoma (MTC). As gastrin-binding CCK(2) receptors are also expressed on a variety of other neuroendocrine tumours (NET), we compared GRS to somatostatin receptor scintigraphy (SRS) in patients with NET. SRS and GRS were performed within 21 days in a series of 60 consecutive patients with NET. GRS was directly compared with SRS. If lesions were visible on GRS but not detectable by SRS, other imaging modalities (MRI, CT) and follow-up were used for verification. Of the 60 evaluable patients, 51 had carcinoid tumours, 3 gastrinomas, 2 glucagonomas, 1 insulinoma and 3 paragangliomas. The overall tumour-detection rate was 73.7% for GRS and 82.1% for SRS. In the 11 patients with negative SRS, GRS was positive in 6 (54.5%). Based on the number of tumour sites detected and the degree of uptake, GRS performed better than SRS in 13 patients (21.7%), equivalent images were obtained in 18 cases (30.0%) and SRS performed better in 24 (40.0%) cases. In six of the SRS positive patients, 18 additional sites of tumour involvement could be detected. Overall, GRS detected additional tumour sites in 20% of the patients. Localisation of the primary tumours or their functional status had no influence on the outcome of imaging. GRS should be performed in selected patients as it may provide additional information in patients with NET with equivocal or absent somatostatin uptake.
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PMID:Added value of gastrin receptor scintigraphy in comparison to somatostatin receptor scintigraphy in patients with carcinoids and other neuroendocrine tumours. 1715 65


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