Clinical Biochemistry of Domestic Animals (Sixth Edition) - UMK ...

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Chapter 20 Thyroid Function J. Jerry Kaneko Department of Pathology, Microbiology, and Immunology School of Veterinary Medicine University of California, Davis Davis, California I. INTRODUCTION II. ANATOMICAL CONSIDERATIONS III. NUTRITIONAL REQUIREMENTS IV. IODINE METABOLISM V. FUNCTIONS OF THE THYROID GLAND A. Thyroid Hormones B. Hormonogenesis and Release VI. TRANSPORT OF HORMONE: PROTEIN BINDING VII. MECHANISM OF THYROID HORMONE ACTION A. General Effects of Thyroid Hormones B. Molecular Basis of Thyroid Hormone Action VIII. CATABOLISM AND EXCRETION OF THYROID HORMONES IX. REGULATION OF THE THYROID GLAND A. Production and Regulation of Thyroid-Stimulating Hormone B. Action of the Thyroid-Stimulating Hormone on the Thyroid Gland C. Action of the Thyroid-Stimulating Hormone on Hormonogenesis D. Long-Acting Thyroid Stimulators X. THYROID FUNCTION TESTS A. Indirect Tests of Thyroid Function B. Direct Tests of Thyroid Function C. Radionuclide Uptake Tests D. Thyroid Ultrasonography E. Trophic Hormone Response Tests XI. DISEASES OF THE THYROID A. Goiter B. Hypothyroidism C. Hyperthyroidism D. Tumors of the Thyroid Gland REFERENCES I . INTRODUCTION Disorders of the thyroid gland are the most common endocrine disorders in humans, and extensive historical and scientific literature is available. Among the domestic animals, thyroid function and its diseases are well known in companion animals but less so in other animals, domestic or wild. In livestock, nutritional iodine deficiencies have been of greater importance than thyroid gland diseases, particularly in the iodine-deficient areas of the world. The importance of thyroid function and its diseases has also become progressively more important as the longevity of companion animals such as the dog and the cat has increased. Advances in thyroid physiology, pathogenesis of its diseases, and the continued development and refinement of methods of testing thyroid function have added impetus to the study of thyroid disease in all animals. This chapter reviews the anatomy and physiology of the thyroid gland and its diseases as a corollary to the understanding of the pathophysiology of the thyroid gland in disease. Emphasis is placed on the physiological bases of a variety of thyroid function tests, most of which are now readily available to the veterinary clinician. II . ANATOMICAL CONSIDERATIONS The thyroid gland of animals is a bilobed structure that overlays the trachea at a point just below the larynx. Anatomical variations of the gland are marked between species and, to some extent, within a given species. The isthmus connecting the two lobes of the thyroid is the region that varies most markedly between species. Humans and pig have a large discrete isthmus, which forms a pyramidal lobe connecting the two lateral lobes. The cow has Clinical Biochemistry of Domestic Animals, 6th Edition 623 Copyright © 2008, Elsevier Inc. All rights reserved.
624 Chapter | 20 Thyroid Function a fairly wide band of glandular tissue, which forms the connecting isthmus. In the horse, sheep, goat, cat, and dog, the isthmus is a narrow remnant of tissue and may be nonexistent. The size of the gland relative to body weight is extremely small in all animals, approximating 0.20% of body weight. The size of the gland varies and may be enlarged when iodine deficiency, ingestion of goitrogenic toxins, tumors, or hyperactivity is present. In primary hypothyroidism, the gland may be reduced to fibrotic and inactive remnants of thyroid tissue. Accessory or extrathyroidal tissue is commonly observed in the dog, particularly near the thoracic inlet though they may be found anywhere along the esophagus. This accessory tissue is fully functional physiologically, synthesizes hormone, and can be located by its uptake of radionuclides. This is a particularly important consideration for the dog when thinking about surgical intervention for treatment of hyperthyroidism resulting from a thyroid tumor. The thyroid gland is a highly vascularized tissue with a large blood flow. The functional unit of the thyroid gland is the thyroid follicle, which can be envisioned as a spherical structure composed of an outer monolayer of follicular cells surrounding an inner core of colloid. Colloid is a thyroglobulin-hormone complex that is the storage reservoir of thyroid hormone in the thyroid gland. The colloid stored in the lumen is a clear, viscus fluid. The individual follicular cells vary from 5 to 10 μ m in height, and the entire follicle may vary from 25 to 250 μ m in diameter. The size of the follicles and the height of their follicular cells vary according to the functional state of the gland. The cells may vary from an inactive squamous cell to the highly active, tall columnar cell. Interspersed between the follicles are the thyroid “ C ” cells, the source of calcitonin, the hypocalcemic hormone associated with calcium metabolism. A third type of hormonal tissue, the parathyroid, is imbedded within the thyroid or located in close proximity to it. The parathyroids are the source of parathormone, the hypercalcemic hormone. Removal of the parathyroids is virtually unavoidable during surgical thyroidectomies so that postsurgical hypocalcemias are important consequences to be considered. III . NUTRITIONAL REQUIREMENTS The thyroid gland is unique among the endocrine glands in that an integral part of its hormone, L-thyroxine (T 4 ), is a trace mineral, iodine, which is available to the animal in only limited amounts. Marine plants are known to be good sources of iodine, but on land, iodine is limited and many regions of the world are known to be iodine deficient. The recommended daily requirement is 35μg/kg bw (276nmol/kg bw) for the adult dog and 70 μg/kg bw (551.6nmol/kg bw) for the growing puppy. For most animals, nutrient requirements are given in mg/Kg dry diet or ppm and range from 0.1 to 1.0 mg, including cats and horses. Milk is a poor source of hormonal iodide contributing only about 4% to 7% of the maintenance requirements for hormone ( Akasha and Anderson, 1984 ). The small requirements are compensated for by an efficient intestinal absorption mechanism and conservation and recycling of internal iodine. Little iodine is lost from the body by the various excretory routes such as urine, saliva, tears, milk, sweat, and feces. Also, whereas most endocrine glands store little of their hormones, the thyroid manages to store large quantities of hormone sufficient for 1 to 3 weeks depending on the species. The thyroid gland contains about 20% of the total body iodine. Its iodine content and size vary with iodine intake and the state of thyroid function, but it usually contains 10 to 40mg (78.8 to 315.2μmol) iodine/100 gm tissue or 4 to 16mg (31.5 to 126.1μmol) iodine in a 20-kg dog. IV . IODINE METABOLISM Iodine can be absorbed in any of its soluble chemical forms, but in the intestines it is usually absorbed in the form of iodides (I ), iodates (IO 4 ), or as the hormonal forms. Iodides may be absorbed from any moist body surface, including the mucus membranes, and it is absorbed easily through broken epithelia. Normally, the chief route of entry into the general circulation is by absorption through the mucosal cells of the small intestine. The I in the circulation is trapped almost exclusively by the thyroid gland, with small amounts being trapped by the salivary gland and minimal amounts by the gastric mucosa, placenta, and mammary gland. In the ruminant, 70% to 80% of an oral dose is absorbed in the rumen and 10% in the omasum. The main route of excretion of I is by the kidneys through which almost all the I that was not trapped by the thyroid is lost in the urine. A small but significant amount is lost in the saliva, and minimal amounts are lost in tears, feces, sweat, and milk. A minute amount of free hormone, that fraction not bound to serum proteins, is also lost in the urine. These routes of excretion are especially important considerations when patients are being treated with radioiodine. V . FUNCTIONS OF THE THYROID GLAND The main functions of the thyroid gland are the trapping of I and the synthesis, storage, and release of thyroid hormones ( Fig. 20-1 ), and these activities are under the control of the thyrotropin or the thyroid-stimulating hormone (TSH). Although TSH stimulates all steps in hormonogenesis, the trapping of I and the release of hormone are the two major sites of its action.
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Preface It has been more than a dec
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viii Contributors Björn P. Meij (5
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2 Chapter | 1 Concepts of Normality
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10 Chapter | 1 Concepts of Normalit
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Chapter 2 Comparative Medical Genet
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I. Introduction 29 Green Red Green
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I. Introduction 31 A1 genetic map d
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I. Introduction 33 of genomes of va
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36 Chapter | 2 Comparative Medical
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46 Chapter | 3 Carbohydrate Metabol
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IX. Disorders of Carbohydrate Metab
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X. Disorders of Ruminants Associate
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X. Disorders of Ruminants Associate
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References 79 Kaneko , J. J. , Luic
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Chapter 4 Lipids and Ketones Michae
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II. Long Chain Fatty Acids 83 FIGUR
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II. Long Chain Fatty Acids 85 Plasm
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IV. Phospholipids 87 The regulation
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V. Cholesterol 89 V. CHOLESTEROL A.
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VI. Lipoproteins 91 TABLE 4-1 Compo
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VI. Lipoproteins 93 TABLE 4-2 Apoli
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96 Chapter | 4 Lipids and Ketones B
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98 Chapter | 4 Lipids and Ketones
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Chapter 5 Proteins, Proteomics, and
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III. Metabolism of Proteins 119 C .
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IV. Plasma Proteins 121 NH 4 HCO
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V. Methodology 123 molecule. The gl
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V. Methodology 125 has occurred wil
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V. Methodology 127 Although attempt
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V. Methodology 129 kD 94 67 43 2 2
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V. Methodology 131 D . Specific Pro
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VI. Normal Plasma and Serum Protein
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VII. Interpretation of Serum Protei
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References 149 Andersson , M. , Ste
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References 151 response of haptoglo
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References 153 dogs with metastasiz
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References 155 Watson , T. D. G. (
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158 Chapter | 6 Clinical Veterinary
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V. Methods for Evaluation of the Im
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VI. Laboratory Diagnosis of Disease
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Chapter 7 The Erythrocyte: Physiolo
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II. Hematopoiesis 175 progenitor ce
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III. Developing Erythroid Cells 177
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IV. Mature RBC 185 immune-mediated
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IV. Mature RBC 187 TABLE 7-3 Erythr
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IV. Mature RBC 189 TABLE 7.5 Erythr
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IV. Mature RBC 191 Echinocyte forma
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IV. Mature RBC 193 Pig RBC isoantig
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IV. Mature RBC 195 occurs in chicke
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IV. Mature RBC 197 inorganic phosph
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IV. Mature RBC 199 (a) FIGURE 7-6 T
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IV. Mature RBC 201 RBC 2,3DPG incre
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IV. Mature RBC 203 mechanisms would
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IV. Mature RBC 205 released during
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IV. Mature RBC 207 reduced by ascor
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V. Determinants of RBC Survival 209
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V. Determinants of RBC Survival 211
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VI. Inherited Disorders of RBCs 213
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described in people. They include a
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References 221 Boas , F. E. , Forma
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References 223 Della Rovere , F. ,
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References 225 Gedde , M. M. , Davi
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References 227 phosphofructokinase-
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References 229 Knight , A. P. , Las
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References 231 Martinovich , D. , a
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References 235 Shadduck , R. K. ( 1
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References 237 Tennant , B. , Dill
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References 239 Williams , D. M. , L
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Chapter 8 Porphyrins and the Porphy
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II. Porphyrins 243 two vinyl groups
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II. Porphyrins 245 TABLE 8-2 Nomenc
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IV. Porphyrias 247 6. Uroporphyrins
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IV. Porphyrias 249 i . Urine It is
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IV. Porphyrias 251 to localize the
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IV. Porphyrias 253 FIGURE 8-6 Metab
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IV. Porphyrias 255 estrogens. The d
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References 257 and hexachlorobenzen
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Chapter 9 Iron Metabolism and Its D
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II. Iron Distribution 261 plasma of
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IV. Plasma Iron Transport 263 pathw
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VI. Iron Metabolism in Cells 265 of
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VI. Iron Metabolism in Cells 267 in
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VII. Tests for Evaluating Iron Meta
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VII. Tests for Evaluating Iron Meta
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VIII. Disorders of Iron Metabolism
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References 279 ( Norrdin et al ., 2
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References 281 Fresco , R. ( 1981 )
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References 283 Moore , C. V. , Duba
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References 285 Weiden , P. L. , Hac
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288 Chapter | 10 Hemostasis TABLE 1
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292 Chapter | 10 Hemostasis The pro
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294 Chapter | 10 Hemostasis exhibit
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298 Chapter | 10 Hemostasis that is
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302 Chapter | 10 Hemostasis However
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304 Chapter | 10 Hemostasis 2. Comp
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306 Chapter | 10 Hemostasis is a re
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308 Chapter | 10 Hemostasis 2. Asse
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310 Chapter | 10 Hemostasis necessi
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312 Chapter | 10 Hemostasis disease
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314 Chapter | 10 Hemostasis concent
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316 Chapter | 10 Hemostasis the rol
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318 Chapter | 10 Hemostasis proport
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320 Chapter | 10 Hemostasis a consi
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322 Chapter | 10 Hemostasis Bakhtia
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324 Chapter | 10 Hemostasis Dowd ,
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326 Chapter | 10 Hemostasis Kier ,
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328 Chapter | 10 Hemostasis Nielsen
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330 Chapter | 10 Hemostasis Tablin
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332 Chapter | 11 Neutrophil Functio
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352 Chapter | 12 Diagnostic Enzymol
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380 Chapter | 13 Hepatic Function L
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382 Chapter | 13 Hepatic Function e
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384 Chapter | 13 Hepatic Function p
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386 Chapter | 13 Hepatic Function m
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388 Chapter | 13 Hepatic Function s
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390 Chapter | 13 Hepatic Function f
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392 Chapter | 13 Hepatic Function T
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394 Chapter | 13 Hepatic Function 2
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396 Chapter | 13 Hepatic Function u
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398 Chapter | 13 Hepatic Function 2
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400 Chapter | 13 Hepatic Function c
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402 Chapter | 13 Hepatic Function F
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404 Chapter | 13 Hepatic Function A
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406 Chapter | 13 Hepatic Function E
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408 Chapter | 13 Hepatic Function K
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410 Chapter | 13 Hepatic Function R
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412 Chapter | 13 Hepatic Function W
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414 Chapter | 14 Gastrointestinal F
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Chapter 15 Skeletal Muscle Function
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II. Specialization of the Sarcolemm
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II. Specialization of the Sarcolemm
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III. Heterogeneity of Skeletal Musc
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III. Heterogeneity of Skeletal Musc
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V. Exercise and Adaptations to Trai
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VI. Diagnostic Laboratory Methods f
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VI. Diagnostic Laboratory Methods f
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IX. Selected Neuromuscular Disorder
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IX. Selected Neuromuscular Disorder
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References 479 and, recently, there
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References 481 Engel , A. G. ( 2004
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Chapter 16 Kidney Function and Dama
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II. Kidney Morphology and Function
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II. Kidney Morphology and Function
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III. Tests of Kidney Function 491 (
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III. Tests of Kidney Function 493 T
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III. Tests of Kidney Function 495 B
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6 5 4 3 2 1 0 Dog Cat Equine Cattle
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III. Tests of Kidney Function 499 d
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IV. Tests of Kidney Damage 501 1000
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IV. Tests of Kidney Damage 503 and
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IV. Tests of Kidney Damage 505 Enzy
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V. Biochemical Changes in Kidney Di
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V. Biochemical Changes in Kidney Di
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References 511 were reported to occ
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References 513 Bovee , K. C. ( 1969
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References 515 Deguchi , E. , and A
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References 519 Harvey , D. G. ( 197
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References 521 Kühl , S. , Mischke
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References 523 creatinine measureme
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References 525 Reusch , C. , Vochez
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Chapter 17 Fluid, Electrolyte, and
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532 Chapter | 17 Fluid, Electrolyte
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VIII. Clinicopathological Indicator
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References 555 plasma water, electr
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References 557 Krzywanek , H. ( 197
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References 559 Strombeck , D. R. (1
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562 Chapter | 18 Pituitary Function
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674 Chapter | 22 Trace Minerals 2 .
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676 Chapter | 22 Trace Minerals Cor
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678 Chapter | 22 Trace Minerals inf
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680 Chapter | 22 Trace Minerals tis
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682 Chapter | 22 Trace Minerals VI
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684 Chapter | 22 Trace Minerals red
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686 Chapter | 22 Trace Minerals of
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688 Chapter | 22 Trace Minerals Per
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690 Chapter | 22 Trace Minerals In
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692 Chapter | 22 Trace Minerals Liu
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Chapter 23 Vitamins Robert B. Rucke
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III. Fat-Soluble Vitamins 697 TABLE
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III. Fat-Soluble Vitamins 699 Carot
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III. Fat-Soluble Vitamins 701 Major
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III. Fat-Soluble Vitamins 703 doses
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III. Fat-Soluble Vitamins 705 Diet
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III. Fat-Soluble Vitamins 707 conta
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III. Fat-Soluble Vitamins 709 immun
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IV. Water-Soluble Vitamins 711 are
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IV. Water-Soluble Vitamins 713 abil
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IV. Water-Soluble Vitamins 715 5’
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IV. Water-Soluble Vitamins 717 H 2
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IV. Water-Soluble Vitamins 719 Enzy
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722 Chapter | 23 Vitamins When biot
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724 Chapter | 23 Vitamins Cyanocoba
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726 Chapter | 23 Vitamins V . VITAM
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728 Chapter | 23 Vitamins nature, r
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730 Chapter | 23 Vitamins Stites ,
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732 Chapter | 24 Lysosomal Storage
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Chapter 25 Tumor Markers Michael D.
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II. Serum Tumor Markers 753 also be
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III. Flow Cytometry 755 cancer of t
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V. Immunohistochemistry/Immunocytoc
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V. Immunohistochemistry/Immunocytoc
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References 761 analysis will facili
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References 763 Fernandez , N. J. ,
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References 765 Meinecke , B. , and
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References 767 Walter , J. ( 2000 )
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770 Chapter | 26 Cerebrospinal Flui
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TABLE 26-7 Continued Constituent Ro
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Chapter 27 Clinical Biochemistry in
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II. Hepatotoxicity 823 Therefore, A
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III. Nephrotoxicity 825 suggested a
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IV. Toxins Affecting Skeletal and C
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VII. Toxins Affecting Erythrocytes
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VIII. Toxins Affecting Hemoglobin a
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IX. Toxins Affecting the Nervous Sy
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References 835 Plants classified as
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References 837 Solaiman , S. G. , M
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840 Chapter | 28 Avian Clinical Bio
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Budgerigar ALAT (IU/g tissue) Budge
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874 Appendix | I SI Units TABLE E S
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Appendix II Conversion Factors of S
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Appendix IV Stability of Serum Enzy
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Appendix VI Nomogram for Computing
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t0100 Appendix VIII Blood Analyte R
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884 Appendix | VIII Blood Analyte R
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890 Appendix | IX Blood Analyte Ref
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Appendix X Blood Analyte Reference
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Appendix XI Blood Analyte Reference
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Appendix XII Urine Analyte Referenc
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902 Appendix | XIII Cerebrospinal F
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904 Appendix | XIV Cerebrospinal Fl
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