Patients with Endocrine Ophthalmopathy not Associated with Overt Thyroid Disease Have Multiple Thyroid Immunological Abnormalities*

Abstract

Twenty-two apparently euthyroid patients with endocrine ophthalmopathy not associated with goiter, antithyroid microsomal or antithyroglobulin antibodies, or overt thyroid disease (so-called ophthalmic Graves' disease) were tested for subclinical hyperthyroidism or hypothyroidism. We measured 131I uptake and scan, serum T3 (by RIA), and serum TSH using a sensitive (by immunoradiometric assay) assay. Three patients were found to be hyperthyroid, and 1 was hypothyroid. The remaining 18 patients, who remained euthyroid throughout the study period, were investigated for evidence for antibody-mediated immunity against thyroid antigens. We measured antibody-dependent cell-mediated cytotoxicity against fresh thyroid cells using a 51chromium release assay, thyroid membrane-reactive antibodies in an enzyme-linked immunosorbent assay incorporating solubilized thyroid membranes, and TSH receptor-binding antibodies using a RRA and carried out sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and Western blotting with patient sera for antibodies reactive with 64 and 110 kDa (thyroid peroxidase) membrane proteins. Bands were demonstrated, on SDS-PAGE, at 64 or 110 kDa in 13 patients, antibody-dependent cell-mediated cytotoxicity tests were positive in 7 patients, and enzyme-linked immunosorbent assay was positive in 4 of the 17 patients tested. In addition, TSH receptor antibody tests were positive in 5 patients, none of whom had other evidence for hyperthyroidism. Finally, significant lymphocyte infiltration was demonstrated on aspiration biopsy in 3 patients. All 18 patients had positive tests in at least 1 of the immunological assays. We believe that these data support the hypothesis that endocrine ophthalmopathy always occurs in patients with overt or subclinical Graves' hyperthyroidism, Hashimoto's thyroiditis, or thyroid immunological abnormalities. Those patients previously described as having euthyroid Graves' disease should, thus, be considered to have associated thyroid immunological abnormalities even though histological confirmation (from aspiration needle biopsy) may be obtained in only a minority of the patients. The possibility that the mechanism for this close association is cross-reactivity of cytotoxic antibodies against a thyroid/eye muscle cell surface shared antigen is discussed in the context of recent evidence from the authors' laboratory.

Significance of Thyroid Stimulating Antibody and Long Term Follow Up in Patients with Euthyroid Graves' Disease.

“…Almost all the patients with euthyroid Graves' disease suspected ophthalmologically had abnormalities in thyroid function and/or in antithyroid auto-antibodies [26]. In combination with TRH test, T3-suppression test, TBII, TGHA and MCHA, we found abnormalities in the thyroid in 10 patients (77%), and more in 12 patients (92%) when TSAb was examined.…”

Keeping an Eye on Crohn’s Disease: Orbital Myositis as the Presenting Symptom

“…Approximately 10% of patients with ophthalmopathy do not have hyperthyroidism. The majority of these patients have laboratory evidence of thyroid immune disease including antibodies to thyroid peroxidase or thyrotropin receptors (9). The negative test for thyroid-stimulating immunuglobulin in our patient made Graves' ophthalmopathy much less likely.…”

Factors associated with outcome after combined steroid and orbital radiotherapy on Graves’ ophthalmopathy

“…The onset of TAO is in most cases concomitant with the onset of hyperthyroidism, but TAO may precede or follow hyperthyroidism. 18 As the factors concerning the onset, severity, and drug responsiveness of TAO are yet uncertain and the role that hyperthyroidism management may play on TAO's emergence and development are also unclear, TAO management remains a key research topic. 19 In this review, we found therapeutic indication for TAO in 53 out of 167 patients.…”