Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P61278 (somatostatin)
22,083 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

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

We make a retrospective evaluation of clinical and radiologic features, treatment, and outcome of Erdheim-Chester disease, a rare non-Langerhans cell histiocytosis. We report a case of Erdheim-Chester disease and review 60 cases from the literature. These cases are consider to have Erdheim-Chester disease when they have either typical bone radiographs (symmetrical long bones osteosclerosis) and/or histologic criteria disclosing histiocytic infiltration with distinctive immunohistochemical phenotype of the non-Langerhans cell histiocytes with positive staining for CD68 and negative staining for S-100 protein and CD1a. Our patient undergoes chemiotherapy according to the LCH-II stratification and therapy plan (Vinblastine, Etoposide and Prednisone) and thereafter receives Carboplatin and Etoposide, and Somatostatin. She is alive and clinically well 33 months after onset of symptoms and the lesions don't appear to progress at imaging examinations. In conclusion, Erdheim-Chester disease may be confused with Langerhans cell histiocytosis as it sometimes shares the same clinical (exophthalmos, diabetes insipidus) or radiologic (osteolytic lesions) findings. However, the characteristics radiological pattern of Erdheim-Chester disease together the immunohistochemical phenotype of hystiocytic infiltration supports the theory that Erdheim-Chester disease is a unique disease entity distinct.
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PMID:[Erdheim-Chester disease: a non-Langerhans cell histiocytosis. A clinical-case and review of the literature]. 1534 69

There are few effective, safe modalities for the management of Graves' ophthalmopathy (GO), a cell-mediated immune comorbidity of thyroid disease. Somatostatin analogs inhibit lymphocyte proliferation and activation, and accumulate in the orbital tissue of patients with GO. A double-blind, placebo-controlled study of a long-acting somatostatin analog [16 wk of long-acting release formulation of octreotide (octreotide-LAR)] was conducted in 51 patients with mild active GO with the aim of preventing deterioration and precluding the need for more aggressive therapeutic modalities, such as glucocorticoids or radiotherapy. No treatment effect was observed for the primary end point (a composite parameter defining the outcome as either success or failure on the basis of changes in class/grade of the severity index and Clinical Activity Scale of GO). The Clinical Activity Scale score was reduced for patients treated with octreotide-LAR, but without any significant difference with respect to patients receiving placebo. However, octreotide-LAR significantly reduced proptosis (as measured by exophthalmometry). This was associated with nonsignificant differences in favor of octreotide-LAR in a series of proptosis-related parameters: class III grade, opening of the upper eyelid, the difference in ocular pressure between primary position and upgaze, and extraocular muscle involvement. By magnetic resonance imaging evaluation the extraocular muscle volumes appeared reduced, but nonsignificantly. No significant correlation between the initial uptake of the somatostatin analog indium-labeled and the response to treatment was observed. One patient in the octreotide-LAR group developed gallstones. In this study, octreotide-LAR did not seem suitable to mitigate activity in mild GO. Surprisingly, it significantly reduced proptosis, one of the most debilitating symptoms of GO. Additional studies are warranted to define the benefit to risk ratio of the somatostatin analogs in this indication.
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PMID:Octreotide (long-acting release formulation) treatment in patients with graves' orbitopathy: clinical results of a four-month, randomized, placebo-controlled, double-blind study. 1556 16

Ninety-three percent of symptomatic patients with small intestinal carcinoid tumours have metastases. The most common sites of metastases are lymph nodes and liver. Orbital metastases have rarely been described and the majority of them involve the choroid rather than extraocular orbital structures. We report a patient who developed proptosis, impairment of vision and reduced ocular motility on the left side, eighteen months after operation for primary intestinal carcinoid tumour with hepatic metastases. CT and MR studies revealed the tumour mass infiltrating the inferior rectus muscle. Biopsy examined by imprint and frozen section showed tumour consistent with metastatic carcinoid. The tumour was removed. HE and staining for cytokeratin, chromogranin, NSE, serotonin, somatostatin and gastrin showed that the tumour tissue corresponded to that of the primary intestinal carcinoid tumour. Intramuscular orbital metastasis from a carcinoid tumour is a rare occurrence. Diagnosis may be difficult, especially where no evidence of primary carcinoid tumour is present. Metastatic orbital carcinoid should be suspected in patients with a clinical history of carcinoid tumour and who develop ocular complaints and mass lesion in the orbit. Complete surgical removal of the tumour is important for optimal restitution of vision and eye movements.
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PMID:Carcinoid tumour metastatic to the orbit with infiltration to the extraocular orbital muscle. 1572 88

Today, positron emission tomography (PET) using F-18 Fluoro-deoxyglucose (FDG) is, when available, the most important nuclear medicine procedure applied to oncology. Nevertheless, 2 main reasons for the clinical use of somatostatin analogues labeled with single photon emitting radionuclides are: a) the low accuracy of PET-FDG in neuroendocrine tumors (NET); b) the expression of somatostatin receptors (sstr) in most cells deriving from so-called neuroendocrine dispersed cells. The latter forms the premise for the use of radiolabeled somatostatin analogues, and (111)In pentetreotide (Octreo-scan) in particular, in the diagnosis of NET and other pathological conditions, including some benign diseases. Alongside diagnosis, staging and follow-up of NET, somatostatin analogues, whether radiolabeled or not, can have a role in evaluating prognosis and predicting therapeutic efficacy in cancer patients. Interesting indications have emerged with radioguided surgery and in diagnosing the activity of disease in patients with Graves' disease (exophthalmos), sarcoidosis, and rheumatoid arthritis. The pathophysiological premises to imaging, starting from an analysis of cells expressing sstr, binding affinity of octreotide for sstr, in vivo uptake of Octreoscan in lesions expressing or not sstr are discussed, as is the possible role of quantitative receptor scintigraphy in improving diagnostic accuracy based on tumor expression of sstr.
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PMID:The present and future role of (111)In pentetreotide in the PET era. 1617 68

Graves' orbitopathy or thyroid associated orbitopathy is the most frequent extrathyroidal manifestation of Graves' disease with autoimmune mechanism which is still incompletely understood. The epidemiologic data provided evidence that severe, infiltrative orbitopathy is present in 3-5% of patients, and the quality of life is impaired even in individuals with mild form of this disease. The anti-TSH receptor and anti-eye muscle autoantibodies have been proved to be involved into pathomechanism of orbitopathy. The accumulation of glucose-aminoglycan and proinflammatory cytokines in retro-orbital fibroblasts are responsible for enlargement of eye muscle and the retro-orbital tissues resulting in inflammation of periorbital tissues and proptosis. Management of orbitopathy can be either medical and surgical. The medical therapy relies on the use of high dose systemic glucocorticoids or retro-orbital irradiation, either alone or in combination. Recent randomized clinical trials have confirmed that glucocorticoids are more effective in intravenous than oral use. Retro-orbital radiotherapy is an effective and safe therapy for orbitopathy and the side effects are avoidable. Somatostatin analogs are not so effective as it has been waited in previous studies. The high dose intravenous immunoglobulins and pentoxifylline therapy are favorable, however, prospective randomized trials have been not yet made. The manifestation of orbitopathy includes both unavoidable (genetic background) and avoidable (smoking, cytokine therapy, iodine exposure, radioiodine therapy) risk factors. Cigarette smoking must be given up by all patients with Graves' disease. Pentoxifylline therapy is advisable for all patients with Graves'diseases, especially for those who have genetic susceptibility to autoimmune disorders and not able to give up cigarette smoking.
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PMID:[Graves' orbitopathy]. 1691 90

Thyroid eye disease (TED), which affects the majority of patients with Grave's disease, is associated with significant ophthalmic morbidity. In patients with mild disease, supportive treatment with lubricating medication can be sufficient. However, in patients with severe TED and disfiguring proptosis or sight-threatening neuropathy, more aggressive medical or surgical interventions are necessary. Corticosteroids remain the preferred pharmacological treatment modality in the majority of patients with an active inflammatory component. Other immunosuppressive drugs in combination with corticosteroids may be helpful in patients with corticosteroid-resistant TED. Newer agents such as somatostatin analogues have not shown to be of significant clinical benefit; however, initial studies on the use of antioxidants and cytokine antagonists are encouraging.
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PMID:Pharmacological treatments for thyroid eye disease. 1697 34


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