Evaluation of Immunological Mechanisms Mediating Thyroid-Associated Ophthalmopathy by Radionuclide Imaging Using the Somatostatin Analog¹¹¹In-Octreotide

Abstract

Thyroid associated ophthalmopathy (TAO) is a disorder involving the soft tissues and extraocular muscles of the orbit seen mainly in cases of Graves' disease. Although an immunogenic pathogenesis has been proposed, the actual mechanisms of the in vivo retrobulbar involvement are not well defined. The recent introduction of the mInlabeled somatostatin analog, octreotide, which can bind in vivo to the cell membrane of activated lymphocytes expressing somatostatin receptors, has provided a new investigational tool for diseases with a presumed immunological background. Based on this property, octreotide scans can be expected to be positive in cases of immunological disease showing tracer accumulation within affected sites. The aim of this study was to evaluate the utility of scintigraphic imaging with octreotide of the retrobulbar space in cases of TAO, including sequential studies of patients undergoing immunosuppressive therapy. We studied a series of 51 patients who had Graves' disease with varying degrees of TAO. Nine patients had received immunosuppressive therapy. The degree of orbital inflammation was classified according to the clinical activity score of Mourits. Both planar and tomographic imaging of the orbit were carried out using 111 MBq of the mIn-labeled octreotide (OctreoScan®) 2 h after tracer injection. A significant tracer accumulation in the retrobulbar space was seen in all 20 patients with a high activity score, in 8 of 16 cases with a negative score, and in 11 of 20 cases with an intermediate Mourits' score. In cases of persistent eye disease in spite of immunosuppressive therapy, the octreotide scan remained positive. Successful therapy either with prednisolone, external radiation, or iv immunoglobulins showed a significant diminution of tracer uptake after finishing the therapeutic regime. Three-dimensional reconstruction of the images also revealed a significant tracer accumulation in the areas of the lacrimal gland, the nasal region, and the pituitary. Controls cases (n = 30) showed no uptake in the orbital region. We conclude that mIn octreotide scintigraphy is an objective method that identifies patients with active inflammatory eye disease, i.e., having significant tracer uptake in the retrobulbar space. This uptake appears to reflect an immunological process, since immunosuppressive therapy will significantly decrease tracer accumulation.

Clinical implications of somatostatin-receptor scintigraphy in ophthalmic Graves' disease

“…The identification of patients with Graves' ophthalmopathy is based primarily on clinical signs and symptoms affecting one or both eyes (4). Additional information can be obtained from conventional imaging methods such as magnetic resonance imaging (MRI) or computed tomography (CT), which allow gross changes in the retrobulbar space (e.g.…”

Topical cyclosporine A for the dry eye findings of thyroid orbitopathy patients

“…5 This is not caused by lacrimal gland obstruction or dysfunction, as one may expect to find in TO. [16][17][18][19] Lacrimal proteins of acinar and extra-acinar origin, such as secretory IgA could be demonstrated at normal levels in such patients. 5,20 Unfortunately, the analysis of lacrimal content could not be carried out in this study because of technical reasons.…”

Novel Approaches to the Management of Graves` Ophthalmopathy

“…These promising results must, however, be weighed against the following considerations: i) The number of patients so far treated is too small (Table 3); ii) Most published studies are nonrandomized or uncontrolled; iii) A selection bias was probably applied in some stud- treotide and lanreotide) for the management of severe and active GO derives from the observation that SMS receptors can be visualized in vivo in the orbital tissue of GO patients by 111 In-DTPA-D-Phe-octreotide scintigraphy (octreoscan) 10 . Octreoscan positivity is higher in Graves' patients with than in those without ophthalmopathy 11 ; in patients with active than in those with inactive GO [11][12][13] ; in patients with recent-onset than in those with longstanding eye disease 12 . Octreoscan positivity correlates with other indicators of activity of the ophthalmopathy, such as high CAS 10 or T2-relaxation time of the extraocular muscles at magnetic resonance imaging 14 .…”