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 recent availability of the long-acting somatostatin analogue, octreotide, has allowed its therapeutical use in a wide variety of human diseases, including some digestive, neoplastic and autoimmune disorders. This review focuses on the treatment of some endocrine disorders with octreotide. Evidence is accumulating that octreotide treatment is effective in improving the cure rate of pituitary surgery in acromegaly by shrinking the tumour size, and in lowering GH and IGF-I levels in the vaste majority of patients. Octreotide is also effective in ameliorating TSH-induced hyperthyroidism in patients with TSH-secreting adenomas. Moreover, octreotide has proved useful in the management of endocrine tumours of the gastroenteropancreatic tract (vipomas, glucagonomas, gastrinomas, insulinomas, and carcinoids) by reducing hormone levels and in some instances the size of the primary and/or metastatic lesions. Besides the above well-established indications there are some other potential indications (non-secreting pituitary tumours, medullary thyroid carcinoma, ectopic Cushing's syndrome, diabete mellitus, Graves' ophthalmopathy, tall children and polycystic ovary syndrome) that still await further investigation. Side-effects of octreotide, particularly the formation of gallstones, should be carefully monitored.
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PMID:[Therapeutic use of somatostatin analogues in endocrinology]. 136 50

Since the identification of somatostatin receptors on lymphocytes, orbital infiltration with mononuclear cells in Graves' ophthalmopathy has provided a rationale for receptor imaging with the radiolabeled somatostatin analog Octreotide. In 40 patients with Graves' ophthalmopathy and 10 controls, 110 MBq indium-Octreotide were administered i.v., and scans were performed at 4 and 24 h after injection. An uptake ratio between the orbits and the brain was determined. In 20 ophthalmophathy patients, magnetic resonance imaging (MRI) of the orbits was performed and the T2 relaxation time was measured within the rectus muscles. Compared to controls (4 h Octreotide uptake: median 6.0 counts/pixel/MBq, orbit/brain ratio 5.6), ophthalmopathy patients showed a 2- to 3-fold increased uptake (15.8 counts/pixel/MBq vs controls p = 0.0032; ratio 12.6, vs controls p = 0.003). When considering patients with active disease only, a higher uptake was registered (16.8 counts/pixel/MBq vs controls p 0.0048, ratio 15.6 vs controls p = 0.0006). Untreated patients showed a markedly higher uptake (23 counts/pixel/MBq) compared to patients receiving steroid therapy (12.6, p = 0.001). MRI of the orbit revealed a correlation between T2 relaxation time of the eye muscles and orbital uptake of Octreotide (p < 0.001).
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PMID:Role of octreoscan and correlation with MR imaging in Graves' ophthalmopathy. 764 69

Thyroid Associated Ophthalmopathy (TAO) is an autoimmune disorder generally associated with Graves' disease (GD). The aim of our study was to evaluate the uptake of indium-111 Octreotide (111In-OCT), a somatostatin (SS) analogue able to bind specific SS receptors, at the level of the thyroid and orbits in patients with TAO. Seven patients with exophthalmos were investigated: six had GD while one was affected with a non small cell lung cancer (NSCLC). One patient with GD had undergone total thyroidectomy (TT) for a thyroid cancer. At the time of the study two patients were hyperthyroid, four were euthyroid and one was hypothyroid. 111 MBq of 111In-OCT were i.v. injected and two 30-minute scans were performed at 4 and 24 hours; 5 minute planar images were also obtained at 25, 60 and 120 minutes. A 180 degrees SPECT was carried out 5 hours after the injection in one patient. A qualitative analysis was performed, comparing these images with those obtained in 7 control patients without thyroid illness or exophthalmos. Moreover, in the TAO patients thyroid, orbit and brain counts were evaluated in comparison with background (BK) and blood activity (BA), measured at the level of the venous longitudinal sinus. In GD intense thyroid uptake was demonstrated independently of the functional state, with highest ratio compared to BK seen at 24 hours. Low uptake in the patient with NSCLC, no activity in the patient with GD that underwent TT, and slight or absent thyroid uptake in the controls were observed. Intense uptake was seen in the orbits of the patient who clinically had the most severe ophthalmopathy.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Indium-111 octreotide in Graves' disease and in the evaluation of active exophthalmos. 857 2

The aim of this study was to examine patients with long-standing Graves' ophthalmopathy using 111In-octreotide scintigraphy. Sixteen patients with inactive ophthalmopathy of up to 114 months duration and 14 normals were investigated for 48 h following an injection of 200 MBq 111In-octreotide. No significant tracer accumulation in the orbital region could be identified in any of the patients with long-standing Graves' ophthalmopathy. The orbit to brain (O/B) ratios after 24 and 48 h were 2.39 +/- 0.36 and 2.15 +/- 0.44 versus 2.17 +/- 0.33 and 2.20 +/- 0.37 for the patients and normals, respectively (N.S.). 111In-octreotide accumulation in ophthalmopathy described in the literature may thus be a passing event limited to its active stage, which is consistent with the concept of imaging a lymphocytic infiltration. In this study, the lack of accumulation of 111In-octreotide in the orbital region during the inactive stage demonstrates an absence of somatostatin receptors in orbital tissue itself. Thus, in patients with inactive Graves' ophthalmopathy, there is no basis for a diagnostic approach with somatostatin.
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PMID:111In-octreotide imaging in patients with long-standing Graves' ophthalmopathy. 858 56

Uncontrolled study has demonstrated the usefulness of somatostatin in the treatment of mild Graves' ophthalmopathy (GO). We performed a prospective study to evaluate the usefulness of somatostatin as compared to corticosteroid in the treatment of moderately severe GO. All patients were rendered euthyroid and observed for 3 months to exclude spontaneous improvement without active treatment. They were randomized to receive either somatostatin (SS, octreotide 200 micrograms q8h subcutaneously, n = 8) or corticosteroid (CS, prednisone 1 mg/kg/day in decreasing doses, n = 10). Assessments of soft tissue inflammation, exophthalmos, palpebral aperture, intraocular pressure, diplopia, cornea, and visual acuity were made every 4 weeks for 3 months. MRI of the orbit was performed before and after treatment. Both SS and CS therapy decreased the palpebral aperture and activity score after 3 months (p < 0.05), but those treated with CS had a lower activity score after treatment when compared to SS [2.5 (1-7) v.s. 3.5 (0-4), median (range), p < 0.05]. Only CS, but not SS, was able to reduce intraocular pressure and muscle size as documented by MRI, but no significant reduction in proptosis was observed in either group. Also, patients' self-assessments of the eye changes after treatment were similar between the two groups. Both groups showed significant elevation of urinary glycosaminoglycan (GAG) excretion before therapy (SS 24.6 +/- 10.8; CS 27.8 +/- 11.4 mg/24 h), which was reduced after treatment (SS 12.5 +/- 7.3; CS 10.8 +/- 6.3 mg/24 h, p < 0.05). However, no significant correlation could be observed between the degree of GAG reduction and the clinical outcome of the patients. In conclusion, the long acting SS octreotide was effective in reducing soft tissue inflammation and providing symptomatic relief in GO but not as effective as corticosteroid in reducing muscle size. In view of the minimal side-effects and similar efficacy as compared to corticosteroid in patients with minimal extraocular muscle enlargement, it is suggested that a trial of SS may be considered in selected patients with GO.
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PMID:The effect of somatostatin versus corticosteroid in the treatment of Graves' ophthalmopathy. 922 22

Most patients with Graves' disease have some evidence of ocular involvement, but this is commonly mild, requiring only local measures. A minority of patients (3-5%) have severe Graves' ophthalmopathy, for which the three main treatment procedures are represented by high-dose glucocorticoids, orbital radiotherapy and orbital decompression. Favourable results with medical treatment have been reported in approximately 60% of patients, with particular regard to inflammatory changes, newly developed eye muscle dysfunction and optic neuropathy. Orbital decompression is indicated in severe eye disease not responsive to glucocorticoids and/or irradiation, particularly in the presence of marked proptosis and optic neuropathy. Not conclusive or unsatisfactory results have been obtained with other medical treatment procedures, including immunosuppressive drugs, intravenous immunoglobulins and plasmapheresis. Recently favourable responses have been reported with somatostatin analogues. Rehabilitative surgery involving either the eye muscles or the eyelids is not infrequently required after medical treatment or decompression. Permanent control of thyroid hyperfunction by radioiodine or thyroidectomy is advisable when severe ophthalmopathy is present. Exacerbation of ophthalmopathy following radioiodine may occur but can be prevented by concomitant administration of glucocorticoids. Smoking deleteriously influences the course of ophthalmopathy and its response to treatment.
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PMID:Treating severe Graves' ophthalmopathy. 953 37

Corticosteroid treatment is successfully used in Graves' ophthalmopathy, and its effect varies according to the phase of the disease. The infiltration of the orbit by activated lymphocytes may explain the effectiveness of corticosteroid therapy. Scintigraphy with [111In-DTPA-D-Phe1]-octreotide was recently used to reveal the presence of activated lymphocytes in foci of autoimmune diseases, because elevated amounts of somatostatin receptors are expressed in the surface of these cells. The aim of the current study was to evaluate whether the degree of orbital [111In-DTPA-D-Phe1]-octreotide uptake is able to predict the response to corticosteroid therapy in patients with Graves' ophthalmopathy. Ten patients with Graves' ophthalmopathy entered the study. In all patients scintigraphy was performed, and subsequently, corticosteroid therapy (methylprednisolone, 1 g i.v. for 2 consecutive days a week for 6 weeks) was given. Clinical activity of Graves' ophthalmopathy was evaluated before and after treatment by calculating the ophthalmopathy index (OI). Planar and single photon emission computed tomography (SPECT) images of the head were obtained 24 h after the i.v. injection of 120-190 MBq of [111In-DTPA-D-Phe1]-octreotide. Radioligand uptake within each orbit (O) and brain (B) was measured using the region of interests (ROI) method and the O-to-B ratio was determined. According to the O-to-B ratio, the images were classified using the following three points score: 0 = O-to-B ratio < or =1; 1 = O-to-B ratio between 1 and 2.5; 2 = O-to-B ratio > or =2.5. The value of OI, measured before and after corticosteroid treatment, was correlated to the scintigraphic score. A significant change of OI was observed between posttreatment and pretreatment evaluation both in orbits with score 2 (OI: 15.4 +/- 1.5 vs. 9.6 +/- 0.5, P < 0.005) and in those with score 1 or 0 (OI: 12.9 +/- 1.5 vs. 11.5 +/- 1.4, P < 0.05) at the scintigraphy. However, when the OI was calculated excluding the changes in the soft tissue, which generally occur in all patients independently from the phase of the disease, a significant change of OI was observed only in the orbits with score 2 (OI: 12.9 +/- 1.3 vs. 8.3 +/- 0.5, P < 0.01) but not in those with score 0 or 1 (OI: 11.2 +/- 1.3 vs. 10.4 +/- 1.3). In particular, 6 weeks after corticosteroid treatment, the patients with orbital score 2 at the scintigraphy had a significant improvement of soft tissue changes, proptosis, lagophthalmos, extraocular muscle movements impairment, and diplopia, whereas patients with score 0 or 1 had only a significant improvement of the soft tissue inflammation. In conclusion, the current preliminary data suggested that [111In-DTPA-D-Phe1]-octreotide scintigraphy is able to predict the clinical response to corticosteroid treatment in patients with Graves' ophthalmopathy, and may be considered an useful approach to select the patients for the proper treatment.
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PMID:Orbital scintigraphy with [111In-diethylenetriamine pentaacetic acid-D-phe1]-octreotide predicts the clinical response to corticosteroid therapy in patients with Graves' ophthalmopathy. 981 48

Graves' ophthalmopathy is an debilitating disease impairing the quality of life of affected individuals. Despite recent progress in the understanding of its pathogenesis, treatment is often not satisfactory. In mild cases, local therapeutic measures (artificial tears and ointments, sunglasses, nocturnal taping of the eyes, prisms) can control symptoms and signs. In severe forms of the disease (3-5%), aggressive measures are required. If the disease is active, high-dose glucocorticoids and/or orbital radiotherapy, or orbital decompression represent the mainstay of treatment. If the disease is severe but inactive, orbital decompression is preferred. Novel treatments such as somatostatin analogs or intravenous immunoglobulins are under evaluation. Rehabilitative (extraocular muscle or eyelid) surgery is often needed after treatment and inactivation of eye disease. Correction of both hyper- and hypothyroidism is crucial for the ophthalmopathy. Antithyroid drugs and thyroidectomy do not influence the course of the ophthalmopathy, whereas radioiodine treatment may cause the progression of preexisting ophthalmopathy, especially in smokers. The exacerbation, however, is prevented by glucocorticoids. In addition, thyroid ablation may prove beneficial for the ophthalmopathy in view of the pathogenetic model relating eye disease to autoimmune reactions directed against antigens shared by the thyroid and the orbit.
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PMID:Management of Graves' ophthalmopathy: reality and perspectives. 1078 63

To explore the mechanism underlying the effects of the somatostatin (SST) analogue octreotide in Graves' ophthalmopathy (GO), we investigated the expression of SST and of SST receptor (sst(1-5)) genes in primary cultures of fibroblasts established from retroorbital tissue of GO patients and of control subjects. We determined also SST specific binding sites by competitive binding of [(125)ITyr(11)]SST-14 and the effect of octreotide on cell growth, cAMP accumulation, Bcl-2 intracellular levels and apoptosis in GO fibroblast primary cultures. All primary cultures expressed the SST gene transcript and one or more ssts that have a high affinity for the two analogues (class 1 sst. The sst(2) transcript was found in nine, sst(3) in five and sst(5) in eight out of ten GO cell cultures. Sst(2) was detected in all six, and sst(3) in four out of the six control cell cultures. Sst(4) was absent from all samples, and sst(1) was found only in six out of the ten GO samples. SST-14 and octreotide inhibited the binding of [(125)I-Tyr(11)]SST-14 with a half-maximal inhibition of binding (IC(50)) of 0.80+/-0.37 and 33. 7+/- 33.1 nmol/l respectively in GO cell cultures, and with an IC(50) of 0.9 and 1.5 nmol/l in control cultures. Octreotide (10(-6) and 10(-7) M) significantly decreased (P<0.001) forskolin-induced but not basal cAMP accumulation; at both doses for 72 h it inhibited cell growth (20 and 55% respectively), and induced apoptosis (20 and 40%), and abolished Bcl-2 protein in cell lysates. In conclusion, SST and sst transcripts are expressed and functional in cultured retroorbital fibroblasts. The presence of class 1 sst in GO tissue and the inhibition exerted by octreotide on retroorbital cell growth and activity in vitro may account for the effects of SST analogue administration in vivo in GO.
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PMID:Somatostatin receptor gene expression and inhibitory effects of octreotide on primary cultures of orbital fibroblasts from Graves' ophthalmopathy. 1091 19

Somatostatin-receptor (SSTR) scintigraphy using the single photon emission computed tomography (SPECT) technique allows the assessment of orbital inflammation in patients with Graves' disease. Previous studies showed differences in orbital octreotide uptake already 4 hr after injection. In this study, analysis of inter-/intra-observer variance and reproducibility in the evaluation of orbital SPECT images was performed. First, SPECT data of one representative female patient with clinically active Graves' ophthalmopathy (GO), obtained 4 hr after intravenous injection of 110 MBq 111In-pentetreotide and processed by filtered backprojection, were analyzed. Transverse SPECT images were reconstructed, an optimal orbital image was selected and predetermined regions of interests (ROIs) for both orbits were positioned by three independent observers 15 to 19 times each. In a second step, SPECT data of 8 different patients with GO were evaluated in the same manner by four independent observers 3 to 4 times each. Variance component partitioning was used to compare the order of intra- and inter-observer variation. For the right and the left orbit, the inter-observer variance proportion was 90% and 79%, whereas intra-observer variance partition was 10% and 21%, respectively. The corresponding ratios 0.11 and 0.27 summarize the comparison of sources of variance. The overall reliability was 84%, representing the patients influence on the total variance. Intra-observer reliability for both orbits was 88%, 89%, 97% and 98% (mean over orbits), respectively for observers I to IV. Using the Spearman Brown prophecy formula it follows that two replications per patient are sufficient to ensure a minimum reproducibility of 90%, which is also confirmed by the low intra-observer variation. Furthermore, intra-class correlation as a measure of (multiple) observer reproducibility was 94%. In conclusion, due to the increased inter-observer variance proportion and the high variation in intra-observer reliability, evaluations of orbital SSTR scintigraphy have to be done by the same and experienced observer leading to comparable data. But an automatic and quantitative computerized technique for evaluation of these SPECT data should be exactly reproducible and probably lead to more accurate and representative results.
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PMID:Somatostatin-receptor scintigraphy in Graves' disease: reproducibility and variance of orbital activity. 1115 23


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