PATHOLOGY
It should be noted that only the abnormalities of the thyroid, orbital contents, lymphatic system, and skin can be considered specific for Graves' disease; the other lesions probably could be caused by thyrotoxicosis of any cause.
It is known from observations made before the introduction of iodide or antithyroid drugs that the essential lesion of Graves' disease is parenchymatous hypertrophy and hyperplasia (Figure 10-2). The central features are increased height of the epithelium from cuboidal to columnar; and redundancy of the follicular wall, giving on section the picture of papillary infoldings, cytologic evidence of increased activity, hypertrophy of the Golgi apparatus, increased number of mitochondria, and increased vacuolization of colloid. There is probably nothing specific about the hyperplasia. Any stimulus that calls for sustained hyperfunction produces this picture, such as antithyroid drugs. There is also a characteristic lymphocyte and plasma cell infiltrate. This infiltrate may be mild and diffuse throughout the gland, but more typically occurs as aggregates of mononuclear cells and even lymphoid germinal centers, referred to as focal thyroiditis. Occasionally the histologic pattern completely overlaps that of Hashimoto's thyroidits.
| Figure 10-2 Extreme
thyroid hyperplasia in Graves' Disease, with tall cells, small follicles, scant and
"scalloped" colloid. Figure kindly provided by Dr. Francis Straus. |
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Fine structure examination discloses a rather widely varying size and shape of the follicles, with columnar cells and reduced homogeneous colloid. 136,137 The basement membrane is well demarcated and is 400 - 1,000 A thick. Between the follicles is a large array of capillaries, together with lymphocytes and fibrocytes. The apical end of the follicular cell often bulges into the lumen, and cuplike villi extend into the lumen. Vesicles and free ribosomes may be found in these villi. These microvilli vary in size and shape; some may enclose colloid. The nucleus is near the basal part of the cell. The mitochondria are numerous; they are mostly large, elongated structures, and some are branched. The endoplasmic reticulum is usually well developed. Ribosomes occur in great numbers. The Golgi apparatus is well developed. Vesicles are present in abundance, but vary in size and number from cell to cell. Multivesicular bodies are occasionally found near the Golgi apparatus. Droplets, globules, and dense bodies appear. Phagolysosomes are common. All these changes are quite like those of the normal thyroid chronically stimulated by TSH.
There are some data on the thyroid in persons who have recovered from Graves' disease. 136 Autopsy material from seven patients who had recovered from exophthalmic goiter and died later of other causes showed complete regression of the hyperplastic changes.
The ophthalmologic problem and pretibial myxedema, which are unique to Graves' disease, are described in Chapter 11.
Abnormalities in striated muscle may be a part of Graves' disease 138-140. Decades ago Askanazy and Rutishauser (140) studied four patients with hyperthyroidism on whom autopsies were performed. They found a diffuse process in all striated muscles, including the extrinsic muscles of the eyeball, consisting of degenerative atrophy of muscle cells, fatty infiltration, loss of striation and uniform appearance, vacuolization, and proliferation or degeneration of nuclei. Cardiac and smooth muscle were not involved in this process. Not all muscle groups were equally involved, nor were the same muscles involved in different patients.
Dudgeon and Urquhart, 142 in studies of the muscles in nine postmortem cases of Graves' disease, found in various skeletal muscles interstitial myositis characterized by plasma cells, tissue macrophages, and atrophy of fibers. Ocular muscles were more affected and cardiac muscle less affected than skeletal muscle. The lesions were spotty and were observed in only a small fraction of the sections. On the other hand, Naffziger 143 examined biopsy muscle specimens from other parts of the body in patients with the ophthalmopathy of Graves' disease and found no abnormalities. The fat content of skeletal muscle may be increased, just as it is in the extraocular muscles.144 Myocardial degenerative lesions have been reported in thyrotoxicosis, with foci of cell necrosis, mononuclear infiltrates, and mucopolysaccharide deposits similar to those described in extraocular and skeletal muscles, 144 and severe damage has been found in patients dying of thyrotoxicosis 146 (Figure 10-3).
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Figure 10-3 Myocardial tissue from a patient that died of cardiac failure with extreme thyrotoxicosis, showing degeneration of myocardial cells, mononuclear and polymorphonuclear infiltration, and edema. |
The extraocular muscle lesions are probably specific for Graves' disease, whereas the remainder of the abnormalities may reflect the action of excess hormone.
The anterior pituitary demonstrates, not surprisingly, a dramatic decrease in identifiable thyrotropin containing cells in patients dying in thyroid storm. This loss is found entirely reversed in patients who come to autopsy after treatment to euthyroidism.148-149
Lesions specific for Graves' disease do not appear in the parathyroids, gonads, or pancreas.
Studies based on autopsies of patients with Graves' disease made years ago demonstrated focal and even diffuse liver cell necrosis,150 atrophy, and cirrhosis, including a kind of peripheral fibrosis that was believed to be peculiar to this disease -- cirrhosis basedowiana. In more contemporary series of liver biopsy specimens obtained from thyrotoxic persons, the deviations from normal were minimal.151,152 Some decrease in glycogen and increase in fat, and some round cell infiltrates were noted. The differences among these studies are at least superficially explicable on the basis of lesser severity and duration of the disease in those patients studied during life.
Hyperplastic changes may be found in the spleen, thymus, and lymph nodes in Graves' disease. The thymus occasionally presents as an anterior mediastinal mass153 and has been inadvertently resected. Persistence or enlargement of the thymus was once believed to be significant in Graves' disease, and early in the century thymectomies were performed for its treatment, with apparent benefit. The TSH-R is expressed in thymic tissue, suggesting that it might be the target of auto-immunity inducing hyperplasia.
Prolonged hyperthyroidism is known to produce the histologic picture of osteoporosis.154,189 but osteitis fibrosa also occurs 156 . Histomorphometric studies show clear evidence of excess bone formation and resorption. The high degree of exchangeability of calcium in the bones of patients with thyrotoxicosis and the high rate of loss of calcium in the urine are discussed later in this chapter. Serum 1,25dihydroxychole-calciferol is decreased, probably in response to increased bone turnover. 202
Cytologic investigations of mitochondria using the electron microscope have revealed anatomic lesions not visible by the ordinary light microscope. Schulz et al.157 reported that the mitochondria from tissues of T4-treated animals appeared to be swollen.
