Endocrine System: Anatomy, physiology and pathology of the thyroid

1. Endocrine System:Anatomy, physiology and pathology of the thyroid Lecture 42 Thursday, April 12, 2007 Refs. Moore and Agur Chapter 9, Ross Chapter 21, Wheater’s Chapter 17, Medical Physiology Chapters 46 and 48, Basic Pathology Chapter 20, Ganong Chapter 18

2. Thyroid gland (anterolateral view of left side) Moore and Agur 9.13a

3. Thyroid gland (transection of neck at level of thyroid isthmus, superior view) M&A 9.1b

4. Thyroid gland 12x WFH 17.6Septa (S) divide gland into lobules.F = colloid-filled follicles

5. Thyroid gland 480 x W 17.7bFollicles are filled with eosinophilic thyroglobulin and lined by cuboidal epithelial cells

6. Thyroid gland 480 x W 17.7c C= Parafollicular or C (clear) cells.C cells secrete calcitonin.

7. Thyroid gland 6800 x W 17.8F, follicular cell; C, C cell, Mv, microvilli

8. Production of thyroid hormones • Epithelial cells of follicle secrete thyroglobulin. • Thyroglobulin (colloid) is stored within the follicle. • When the gland is inactive, the follicle is large and the epithelial cells are flattened. • When activated by TSH, the apical membrane takes up thyroglobulin by endocytosis. • Lysosomes fuse with the endosome. • Thyroglobulin is cleaved. • Thyroxine (T4) and triiodothyronine (T3) are secreted from the basolateral surface of the follicular epithelium.

9. Thyroid cellLeft: resting Right: after TSH stimulationGanong 18-3

10. Structure of secreted thyroid hormones Ganong

11. Iodination • Dietary iodine is required for thyroid hormone formation. • Ingested iodine is converted to iodide and absorbed. • Iodide is transported across the epithelial cell. • Iodination occurs at the apical surface of the cell while the tyrosine residues are bound to thyroglobulin. • T3 is more active than T4, and reverse T3 (RT3) is inactive.

12. Thyroid hormone biosynthesis Ganong 18-6

13. Thyroid hormones Normal daily secretion amount in tissues • T4 80 µg • T3 4 µg 31 µg • RT3 2 µg 38 µg • Difference between amounts of T3 and RT3 secreted and amounts in tissues is the deiodination of T4 in the tissues.

14. Plasma protein binding of thyroid hormones • Most of the circulating T3 and T4 is bound to plasma proteins • 3 binding proteins: • Thyroxine-binding globulin (TBG) • Transthyretin • Albumin • TBG has the greatest affinity and binds the majority of the plasma T4 and about half the plasma T3.

15. Free T3 and T4 • The unbound or free T3 and T4 are the physiologically active molecules. • Normal plasma concentrations in µg/dl: • T4 total 8 free 0.002 • T3 total 0.15 free 0.003 • In other words, the percent protein bound is very high. • T4 is 99.98% bound • T3 is 99.8% bound

16. Homeostasis • Euthyroid state can be maintained when the concentration of thyroid hormone-binding proteins changes. • If the concentration of binding proteins increases, free thyroid hormones will decrease, but low free T3 and T4 levels stimulate both the hypothalamus and pituitary to increase TSH production. The thyroid responds to TSH by secreting more thyroid hormones and free levels return to normal despite higher than normal total plasma levels. • Measuring free levels is more diagnostic of the clinical state than measuring total levels.

17. Control of thyroid secretion. Solid arrows are stimulatory effects. Dashed arrows show inhibition. Ganong 18-12

18. Summary of the effects of thyroid hormones Ganong

19. Effects of thyroid hormones • Overall, the many of the effects of thyroid hormones are secondary to stimulation of oxygen consumption. • This is called a calorigenic action. • Exceptions are brain, testis, uterus, lymph nodes, spleen, and anterior pituitary. • T3 is 3-5 times more potent than T4 because it is less tightly bound to plasma proteins. • RT3 is inactive.

20. Effects of thyroid hormones on growth • Thyroid hormones are essential for normal growth and skeletal development. • See lecture 41. Hypothyroidism prevents growth and mental development in infants and young children. • Cretinism is hypothyroidism from birth or in utero. • Cretins are dwarfed and mentally retarded. • Thyroid hormones cannot replace growth hormone, but are permissive for the action of growth hormone.

21. Goiter • Presently refers to any enlargement of the thyroid. • Goitrogens are substances that inhibit the function of the thyroid gland. • Although iodine is necessary for the synthesis of thyroid hormones, excess iodine and deficiency of iodine both inhibit thyroid function.

22. Clinical signs of hypothyroidism in adults • Weight gain. • Intolerance to cold • Myxedema (puffiness due to water retention because proteins and polysaccharides accumulate in skin) • High serum cholesterol and atherosclerosis. • Poor memory and sometimes more serious mental disturbances. • Hair is coarse and sparse; skin is dry

23. Causes of hypothyroidism • Hypothalamic failure to secret TRH • Pituitary- lack of TSH secretion • Primary diseases of thyroid gland • Iodine deficiency • Autoimmune destruction of thyroid gland • Hashimoto’s thyroiditis-most common cause • Lymphocytic, plasmacytic infiltration of thyroid gland • End-stage thyroid- shrunken, fibrotic, residual inflammatory infiltrate

24. Clinical signs of hyperthyroidism • Weight loss • increased basal metabolic rate, lipolysis, increased protein breakdown • Nervousness • Polyphagia • Heat intolerance • Increased pulse pressure

25. Causes of hyperthyroidism • Hypothalamic • Pituitary hypersecretion of TSH • Primary thyroid lesion • Most common cause is Graves’ disease • More common in women than men. • exophthalmos • Antibodies stimulate TSH receptor --LATS (long acting thyroid stimulator) • Plasma TSH is low.

26. Diffuse thyroid hyperplasia in Graves Disease BP 20-8

27. Neoplasia of the thyroid gland • Adenoma-usually solitary; most are nonfunctional • Carcinoma/adenocarcinoma - 4 types • Follicular- may invade blood vessels and often metastasizes to lung or bone. • Papillary- may spread by lymphatics to local lymph nodes; best prognosis. • Anaplastic-small cells, no follicles, rapid growth, locally invasive. • Medullary- a tumor of parafollicular or C cells, often secretes calcitonin or other polypeptide hormones and tumor often contains amyloid.