| Affiliation |
(AGL) Chairman, Department of Ophthalmology, The Methodist Hospital, Houston, Texas; Professor of Ophthalmology, Weill Cornell Medicine, New York City, New York; (ZF) Class of 2020, Baylor College of Medicine, Houston, Texas |
| Transcript |
[Transcript of video] Today we're going to be talking about thyroid and thyroid eye disease, in relation to the immunology: and if we understand the immunology will understand the clinical features of thyroid eye disease. As with all immunologic processes, there's an antigen. In thyroid eye disease we really don't know what the stimulating antigen is, but that antigen is presented to an antigen presenting cell, and then some sort of MHC class interaction where the T cell leads to the recruitment of B cells, and that B cell then produces an antibody. This antibody - immunoglobulin - cross reacts with the thyroid-stimulating receptor on the thyroid gland. But there are other autoantibodies that attack the thyroid, including thyroid peroxidase antibody. And there are other thyroid antibodies that we're not going to cover. We'll just use these two as the prototype. So if the thyroid stimulating immunoglobulin binds to the receptor on the thyroid gland, because it's the stimulating immunoglobulin, this will stimulate the thyroid to produce thyroid hormone, and the patient will be hyper thyroid - and that disease we call Graves autoimmune hyperthyroidism. If however the antibody is a destructive antibody like thyroid peroxidase and it attacks the thyroid colloid, the thyroid will be damaged and that will cause the thyroid hormones to go down. And as opposed to Graves disease, we call that disease Hashimoto's thyroiditis. However sometimes you have the antibodies, but you don't have any abnormality in your thyroid hormone status, and that has no eponym: we just call that euthyroid. So you can be euthyroid, hyperthyroid, or hypothyroid and still have autoimmune thyroid disease. These antibodies cross-react, because of molecular mimicry, with the orbital fibroblasts, and when the antibody binds to the orbital fibroblasts it stimulates differentiation of the fibroblasts into adipocyte and myocyte. It also causes the production, by the fibroblasts, of glycosaminoglycans, also known as mucopolysaccharides, and those are very hydrophilic and will bring water to the muscle or the tissue, so you'll have an increase in water and that we call edema. So you need to know this immunology to convert what we're talking about here in immunology land into the clinical findings. So from an eye standpoint, what we see when we have binding to the fibroblasts: (1) increase adipocytes that's going to increase the fat and the muscles from edema as well as (2) differentiation of the fibroblasts that will cause big muscles. And when muscles get big, they don't work well, and that will cause the symptom of diplopia. And the sign of ophthalmoplegia. It will cause lid retraction, lid edema, lid lag in down gaze, and proptosis. The most common cause of proptosis, or lid retraction, or lid lag, in an adult is thyroid eye disease. So those are the clinical findings based on the immunologic findings. And if the muscles get big enough, they press on the optic nerve in the orbital apex, causing a compressive optic neuropathy. So in summary, all of the features of thyroid disease can be explained by the immunology. The antibody TSig stimulates the thyroid and causes Graves hyperthyroidism, or destructive antibody causing low thyroid - Hashimoto's thyroiditis. Both antibodies cross-react with orbital fibroblast, stimulating it to produce glycosaminoglycans and causing edema, which leads to big fat and big muscles. And so if you just know the immunology of thyroid you pretty much know how this comes to us in the clinic. |
