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August 1966, Vol 76, No. 2 >
ARTICLE | August 1966

Dysthyroid Ocular Myopathy: Title and subTitle BreakAnatomy, Histology, and Electron Microscopy FREE

ARNOLD J. KROLL, MD; TOICHIRO KUWABARA, MD
[+] Author Affiliations

Submitted for publication Dec 8, 1965.

Reprint requests to Bascom Palmer Eye Institute, 1638 NW 10th Ave, Miami, Fla 33136 (Dr. Kroll).


Arch Ophthalmol. 1966;76(2):244-257. doi:10.1001/archopht.1966.03850010246017
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Article
References
Comments

The ocular myopathy associated with dysthyroid1 (endocrine) exophthalmos remains an intriguing problem. The gross and histologic findings are well-known.2-7 Grossly, the extraocular muscles are firm, rubbery, and very much enlarged. Histologically, there is interstitial edema, round cell infiltration, and, in some cases, degenerative change within muscle cells. Similar changes are found in the orbital tissues in experimentally produced exophthalmos in guinea pigs.6,8-15 The edema is believed to be due to an increased content of waterbinding mucopolysaccharide, probably hyaluronic acid.16-18 The round cell infiltrate in animals and man includes lymphocytes, plasma cells, macrophages, and mast cells.16,18-20

The fine structure characteristics of extraocular muscle in dysthyroid exophthalmos have not yet been reported.

Materials and Methods  Biopsy material was obtained at the time of Krönlein orbital decompression from 19 mucles of 17 eyes of ten patients with dysthyroid exophthalmos37 (Table). The patients' ages ranged from 41 to

REFERENCES

1 +
Legends for electron micrographs: A, "A" band of muscle actomyosin; c, collagen fibrils; d, phagocytized debris within macrophage; g, specific granules of mast cell; gc, Golgi complex; gl, glycogen; i, nonspecific cytoplasmic inclusion; I, "I" band of muscle actomyosin; l, lipid or lipid-like inclusion in cytoplasm; lf, lipofuscin; m, mitochondrion; mc, intramitochondrial cristae; mu, muscle cell; n, nucleus; nl, nucleolus; r, ribosomes; s, sarcoplasmic reticulum; sl, sarcolemma (muscle cell membrane); t, triad of sarcoplasmic reticulum; v, cytoplasmic vacuole; vi, villosity of surface of mast cell; Z, "Z" band of muscle actomyosin.
2 +
Cogan, D.G.: Neurology of the Ocular Muscles , Springfield, Ill: Charles C Thomas, Publisher, 1956;, p 44-48.
3 +
Naffziger, H.C.:  Progressive Exophthalmos Following Thyroidectomy: Its Pathology and Treatment , Ann Surg 94:582-586, 1931;.
4 +
Naffziger, H.C.:  Pathologic Changes in the Orbit in Progressive Exophthalmos , Arch Ophthal 9:1-11, 1933;.
5 +
Wheeler, J.M.:  Principles of Modern Surgery in Ophthalmology , Amer J Ophthal 17:683-688, 1934;.
6 +
Reese, A.B.:  Dacryadenitis in Hyperthyroidism , Arch Ophthal 13:855-857, 1935;.
7 +
Smelser, G.K.:  A Comparative Study of Experimental and Clinical Exophthalmos , Amer J Ophthal 20:1189-1203, 1937;.
8 +
Hogan, M.J., and Zimmerman, L.E.: Ophthalmic Pathology—An Atlas and Textbook , Philadelphia: W. B. Saunders Co., 1962;, p 735-738.
9 +
Smelser, G.K.:  Experimental Production of Exophthalmos Resembling That Found in Graves' Disease , Proc Soc Exp Biol Med 35:128-130, 1936;.
10 +
Paulson, D.L.:  Experimental Exophthalmos in the Guinea Pig , Proc Soc Exp Biol Med 36:604-605, 1937;.
11 +
Smelser, G.K.:  The Histology of Orbital and Other Fat Tissue Deposits in Animals With Experimentally Produced Exophthalmos , Amer J Path 15:341-352, 1939;.
12 +
Aird, R.B.:  Experimental Exophthalmos and the Associated Myopathy Induced by the Thyrotropic Hormone , Arch Ophthal 24:1167-1174, 1940;.
13 +
Aird, R.B.:  Experimental Exophthalmos and the Associated Myopathy Induced by the Thyrotropic Hormone , Ann Intern Med 15:564-581, 1941;.
14 +
Dobyns, B.M.:  Studies on Exophthalmos Produced by Thyrotropic Hormone , Surg Gynec Obstet 82:609-617, 1946;.
15 +
Smelser, G.K., and Ozanics, V.:  Studies on the Nature of the Exophthalmos-Producing Principle in Pituitary Extracts , Amer J Ophthal 38:107-122, 1954;.
16 +
Tengroth, B.M.:  Endocrine Exophthalmos—Effects of Thyrotropin Preparations and the Thyroxin Isomers: Quantitative Evaluations in Guinea Pigs , Acta Ophthal , (suppl 65) , 1961;.
17 +
Ludwig, A.W.; Boas, N.F.; and Soffer, L.J.:  Role of Mucopolysaccharides in Pathogenesis of Experimental Exophthalmos , Proc Soc Exp Biol Med 73:137-140, 1950;.
18 +
Asboe-Hansen, G., and Iversen, K.:  Influence of Thyrotropic Hormone on Connective Tissue: Pathogenetic Significance of Mucopolysaccharides in Experimental Exophthalmos , Acta Endocr 8:90-96, 1951;.
19 +
Iversen, K., and Asboe-Hansen, G.:  Studies on the Fat-Mobilizing Factor of the Anterior Pituitary Gland , Acta Endocr 11:111-118, 1952;.
20 +
Asboe-Hansen, G.; Iverson, K.; and Wichmann, R.:  Malignant Exophthalmos: Muscular Changes and Thyrotropin Content in Serum , Acta Endocr 11: 376-399, 1952;.
21 +
Tengroth, B.M.:  Histological Studies of Orbital Tissues in a Case of Endocrine Exophthalmos Before and After Remission , Acta Ophthal 42:588-591, 1964;.
22 +
Asboe-Hansen, G.:  The Variability in the Hyaluronic Acid Content of the Dermal Connective Tissue Under the Influence of Thyroid Hormone , Acta Dermatovener 30:221-230, 1950;.
23 +
Luft, J.H.:  Improvements in Epoxy Resin Embedding Methods , J Biophys Biochem Cytol 9: 409-414, 1961;.
24 +
Reynolds, E.S.:  The Use of Lead Citrate at High pH as an Electron-Opaque Stain in Electron Microscopy , J Cell Biol 17:208-212, 1963;.
25 +
Naffziger, H.C., and Jones, O.W., Jr.:  The Surgical Treatment of Progressive Exophthalmos Following Thyroidectomy , JAMA 99:638-642, 1932;.
26 +
Rundle, F.F.; Finlay-Jones, L.R.; and Noad, K.B.:  Malignant Exophthalmos: A Quantitative Analysis of the Orbital Tissues , Aust Ann Med 2: 128-135, 1953;.
27 +
Wegelius, O.; Asboe-Hansen, G.; and Lamberg, B.A.:  Retrobulbar Connective Tissue Changes in Malignant Exophthalmos , Acta Endocr 25:452-456, 1957;.
28 +
Selye, H.: The Mast Cells , Washington, DC: Butterworths, 1965;.
29 +
Yoffey, J.M.:  The Lymphocyte , Ann Rev Med 15:125-148, 1964;.
30 +
Roitt, I.M., and Doniach, D.:  Thyroid Autoimmunity , Brit Med Bull 16:152-158, 1960;.
31 +
Hales, LB., et al:  Relation of Eye Signs in Graves' Disease to Circulating Antibodies to Thyroglobulin , Lancet 1:468, 1961;.
32 +
McGill, D.A., and Asper, S.P.:  Endocrine Exophthalmos , New Eng J Med 267:133-140, 188-193, 1962;.
33 +
Pellegrino, C., and Franzini, C.:  An Electron Microscope Study of Denervation Atrophy in Red and White Skeletal Muscle Fibers , J Cell Biol 17: 327-349, 1963;.
34 +
Gustafsson, R., et al:  The Relationship Between the Structure and Activity of Rat Skeletal Muscle Mitochondria After Thyroidectomy and Thyroid Hormone Treatment , J Cell Biol 26:555-578, 1965;.
35 +
Stenger, R.J., et al:  Ultrastructural and Physiologic Alterations in Ischemic Skeletal Muscle , Amer J Path 40:1-20, 1962;.
36 +
Van Breemen, V.L.:  Ultrastructure of Human Muscle: II. Observations on Dystrophic Striated Muscle Fibers , Amer J Path 37:333-341, 1960;.
37 +
Aleu, F.P., and Afifi, A.K.:  Ultrastructure of Muscle in Myotonic Dystrophy , Amer J Path 45: 221-231, 1964;.
38 +
Kroll, A.J., and Casten, V.G.: Dysthyroid Exophthalmus: Palliation by Lateral Orbital Decompression, Arch Ophthal, to be published.
39 +
Fagraeus, A.:  Den plasmacellulära reaktionen vid antikroppsbildning , Nord Med 30:1381-1385, 1946;.
40 +
Fagraeus, A.:  The Plasma Cellular Reaction and Its Relation to the Formation of Antibodies in Vitro , J Immunol 58:1-13, 1948;.
41 +
Fagraeus, A.:  Antibody Production in Relation to the Development of Plasma Cells: In Vivo and in Vitro Experiments , Acta Med Scand 130 ( (suppl 204) ):1-122, 1948;.
42 +
Fagraeus, A.:  La corrélation entre la réaction reticuloplasmocytaire et la formation des anticorps , Sangre 21:480-483, 1950;.
43 +
Nossal, G.J.:  Antibody Production by Single Cells: IV. Further Studies on Multiply Immunized Animals , Brit J Exper Path 41:89-96, 1960;.
44 +
Bing, J., and Plum, P.:  Serum Proteins in Leukopenia , Acta Med Scand 92:415-428, 1937;.
45 +
Adams, D.D., and Purves, H.D.:  Abnormal Responses in the Assay of Thyrotrophin , Proc Univ Otago Med School 34: No. (1) , 1956;.
46 +
McKenzie, J.M.:  The Pituitary and Graves' Disease , Proc Roy Soc Med 55:539-540, 1962;.
47 +
Kriss, J.P.; Pleshakov, V.; and Chien, J.R.:  Isolation and Identification of the Long-Acting Thyroid Stimulator and Its Relation to Hyperthyroidism and Circumscribed Pretibial Myxedema , J Clin Endocr 24:1005-1028, 1964;.
48 +
Kriss, J.P.; Pleshakov, V.; and Koblin, R.:  Long-Acting Thyroid Stimulator (LATS) and Circumscribed Pre-tibial Myxedema: An Auto-immune Phenomenon? , Clin Res 12:116, 1964;.
49 +
Purves, H.D., and Adams, D.D.:  Thyroid-Stimulating Hormone , Brit Med Bull 16:128-132, 1960;.
50 +
Werner, S.C., and Platman, S.R.:  Remission of Hyperthyroidism (Graves' Disease) and Altered Pattern of Serum-Thyroxine Binding Induced by Prednisone , Lancet 2:751-756, 1965;.

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Country-Specific Mortality and Growth Failure in Infancy and Yound Children and Association With Material Stature

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1 +
Legends for electron micrographs: A, "A" band of muscle actomyosin; c, collagen fibrils; d, phagocytized debris within macrophage; g, specific granules of mast cell; gc, Golgi complex; gl, glycogen; i, nonspecific cytoplasmic inclusion; I, "I" band of muscle actomyosin; l, lipid or lipid-like inclusion in cytoplasm; lf, lipofuscin; m, mitochondrion; mc, intramitochondrial cristae; mu, muscle cell; n, nucleus; nl, nucleolus; r, ribosomes; s, sarcoplasmic reticulum; sl, sarcolemma (muscle cell membrane); t, triad of sarcoplasmic reticulum; v, cytoplasmic vacuole; vi, villosity of surface of mast cell; Z, "Z" band of muscle actomyosin.
2 +
Cogan, D.G.: Neurology of the Ocular Muscles , Springfield, Ill: Charles C Thomas, Publisher, 1956;, p 44-48.
3 +
Naffziger, H.C.:  Progressive Exophthalmos Following Thyroidectomy: Its Pathology and Treatment , Ann Surg 94:582-586, 1931;.
4 +
Naffziger, H.C.:  Pathologic Changes in the Orbit in Progressive Exophthalmos , Arch Ophthal 9:1-11, 1933;.
5 +
Wheeler, J.M.:  Principles of Modern Surgery in Ophthalmology , Amer J Ophthal 17:683-688, 1934;.
6 +
Reese, A.B.:  Dacryadenitis in Hyperthyroidism , Arch Ophthal 13:855-857, 1935;.
7 +
Smelser, G.K.:  A Comparative Study of Experimental and Clinical Exophthalmos , Amer J Ophthal 20:1189-1203, 1937;.
8 +
Hogan, M.J., and Zimmerman, L.E.: Ophthalmic Pathology—An Atlas and Textbook , Philadelphia: W. B. Saunders Co., 1962;, p 735-738.
9 +
Smelser, G.K.:  Experimental Production of Exophthalmos Resembling That Found in Graves' Disease , Proc Soc Exp Biol Med 35:128-130, 1936;.
10 +
Paulson, D.L.:  Experimental Exophthalmos in the Guinea Pig , Proc Soc Exp Biol Med 36:604-605, 1937;.
11 +
Smelser, G.K.:  The Histology of Orbital and Other Fat Tissue Deposits in Animals With Experimentally Produced Exophthalmos , Amer J Path 15:341-352, 1939;.
12 +
Aird, R.B.:  Experimental Exophthalmos and the Associated Myopathy Induced by the Thyrotropic Hormone , Arch Ophthal 24:1167-1174, 1940;.
13 +
Aird, R.B.:  Experimental Exophthalmos and the Associated Myopathy Induced by the Thyrotropic Hormone , Ann Intern Med 15:564-581, 1941;.
14 +
Dobyns, B.M.:  Studies on Exophthalmos Produced by Thyrotropic Hormone , Surg Gynec Obstet 82:609-617, 1946;.
15 +
Smelser, G.K., and Ozanics, V.:  Studies on the Nature of the Exophthalmos-Producing Principle in Pituitary Extracts , Amer J Ophthal 38:107-122, 1954;.
16 +
Tengroth, B.M.:  Endocrine Exophthalmos—Effects of Thyrotropin Preparations and the Thyroxin Isomers: Quantitative Evaluations in Guinea Pigs , Acta Ophthal , (suppl 65) , 1961;.
17 +
Ludwig, A.W.; Boas, N.F.; and Soffer, L.J.:  Role of Mucopolysaccharides in Pathogenesis of Experimental Exophthalmos , Proc Soc Exp Biol Med 73:137-140, 1950;.
18 +
Asboe-Hansen, G., and Iversen, K.:  Influence of Thyrotropic Hormone on Connective Tissue: Pathogenetic Significance of Mucopolysaccharides in Experimental Exophthalmos , Acta Endocr 8:90-96, 1951;.
19 +
Iversen, K., and Asboe-Hansen, G.:  Studies on the Fat-Mobilizing Factor of the Anterior Pituitary Gland , Acta Endocr 11:111-118, 1952;.
20 +
Asboe-Hansen, G.; Iverson, K.; and Wichmann, R.:  Malignant Exophthalmos: Muscular Changes and Thyrotropin Content in Serum , Acta Endocr 11: 376-399, 1952;.
21 +
Tengroth, B.M.:  Histological Studies of Orbital Tissues in a Case of Endocrine Exophthalmos Before and After Remission , Acta Ophthal 42:588-591, 1964;.
22 +
Asboe-Hansen, G.:  The Variability in the Hyaluronic Acid Content of the Dermal Connective Tissue Under the Influence of Thyroid Hormone , Acta Dermatovener 30:221-230, 1950;.
23 +
Luft, J.H.:  Improvements in Epoxy Resin Embedding Methods , J Biophys Biochem Cytol 9: 409-414, 1961;.
24 +
Reynolds, E.S.:  The Use of Lead Citrate at High pH as an Electron-Opaque Stain in Electron Microscopy , J Cell Biol 17:208-212, 1963;.
25 +
Naffziger, H.C., and Jones, O.W., Jr.:  The Surgical Treatment of Progressive Exophthalmos Following Thyroidectomy , JAMA 99:638-642, 1932;.
26 +
Rundle, F.F.; Finlay-Jones, L.R.; and Noad, K.B.:  Malignant Exophthalmos: A Quantitative Analysis of the Orbital Tissues , Aust Ann Med 2: 128-135, 1953;.
27 +
Wegelius, O.; Asboe-Hansen, G.; and Lamberg, B.A.:  Retrobulbar Connective Tissue Changes in Malignant Exophthalmos , Acta Endocr 25:452-456, 1957;.
28 +
Selye, H.: The Mast Cells , Washington, DC: Butterworths, 1965;.
29 +
Yoffey, J.M.:  The Lymphocyte , Ann Rev Med 15:125-148, 1964;.
30 +
Roitt, I.M., and Doniach, D.:  Thyroid Autoimmunity , Brit Med Bull 16:152-158, 1960;.
31 +
Hales, LB., et al:  Relation of Eye Signs in Graves' Disease to Circulating Antibodies to Thyroglobulin , Lancet 1:468, 1961;.
32 +
McGill, D.A., and Asper, S.P.:  Endocrine Exophthalmos , New Eng J Med 267:133-140, 188-193, 1962;.
33 +
Pellegrino, C., and Franzini, C.:  An Electron Microscope Study of Denervation Atrophy in Red and White Skeletal Muscle Fibers , J Cell Biol 17: 327-349, 1963;.
34 +
Gustafsson, R., et al:  The Relationship Between the Structure and Activity of Rat Skeletal Muscle Mitochondria After Thyroidectomy and Thyroid Hormone Treatment , J Cell Biol 26:555-578, 1965;.
35 +
Stenger, R.J., et al:  Ultrastructural and Physiologic Alterations in Ischemic Skeletal Muscle , Amer J Path 40:1-20, 1962;.
36 +
Van Breemen, V.L.:  Ultrastructure of Human Muscle: II. Observations on Dystrophic Striated Muscle Fibers , Amer J Path 37:333-341, 1960;.
37 +
Aleu, F.P., and Afifi, A.K.:  Ultrastructure of Muscle in Myotonic Dystrophy , Amer J Path 45: 221-231, 1964;.
38 +
Kroll, A.J., and Casten, V.G.: Dysthyroid Exophthalmus: Palliation by Lateral Orbital Decompression, Arch Ophthal, to be published.
39 +
Fagraeus, A.:  Den plasmacellulära reaktionen vid antikroppsbildning , Nord Med 30:1381-1385, 1946;.
40 +
Fagraeus, A.:  The Plasma Cellular Reaction and Its Relation to the Formation of Antibodies in Vitro , J Immunol 58:1-13, 1948;.
41 +
Fagraeus, A.:  Antibody Production in Relation to the Development of Plasma Cells: In Vivo and in Vitro Experiments , Acta Med Scand 130 ( (suppl 204) ):1-122, 1948;.
42 +
Fagraeus, A.:  La corrélation entre la réaction reticuloplasmocytaire et la formation des anticorps , Sangre 21:480-483, 1950;.
43 +
Nossal, G.J.:  Antibody Production by Single Cells: IV. Further Studies on Multiply Immunized Animals , Brit J Exper Path 41:89-96, 1960;.
44 +
Bing, J., and Plum, P.:  Serum Proteins in Leukopenia , Acta Med Scand 92:415-428, 1937;.
45 +
Adams, D.D., and Purves, H.D.:  Abnormal Responses in the Assay of Thyrotrophin , Proc Univ Otago Med School 34: No. (1) , 1956;.
46 +
McKenzie, J.M.:  The Pituitary and Graves' Disease , Proc Roy Soc Med 55:539-540, 1962;.
47 +
Kriss, J.P.; Pleshakov, V.; and Chien, J.R.:  Isolation and Identification of the Long-Acting Thyroid Stimulator and Its Relation to Hyperthyroidism and Circumscribed Pretibial Myxedema , J Clin Endocr 24:1005-1028, 1964;.
48 +
Kriss, J.P.; Pleshakov, V.; and Koblin, R.:  Long-Acting Thyroid Stimulator (LATS) and Circumscribed Pre-tibial Myxedema: An Auto-immune Phenomenon? , Clin Res 12:116, 1964;.
49 +
Purves, H.D., and Adams, D.D.:  Thyroid-Stimulating Hormone , Brit Med Bull 16:128-132, 1960;.
50 +
Werner, S.C., and Platman, S.R.:  Remission of Hyperthyroidism (Graves' Disease) and Altered Pattern of Serum-Thyroxine Binding Induced by Prednisone , Lancet 2:751-756, 1965;.

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