Simple (Nontoxic) Goiter: Diffuse and Multinodular

1. Simple (Nontoxic) Goiter: Diffuse and Multinodular M.Nakhjavani,M.D.

3. Goiter Goiter refers to an enlarged thyroid gland

4. NONTOXIC GOITER • Endemic goiter: when it affects >5% of the population • Sporadic goiter: in nonendemic regions

5. Introduction • Several thyroid disorders exist: • Non-toxic goiter: Diffuse and multinodular • Hyperthyroidism • Hypothyroidism • Thyroid nodules • Malignancies • Thyroiditis

6. Benign Thyroid Disease • Benign Nontoxic Conditions • Diffuse and Nodular Goiter • Benign Toxic Conditions • Toxic Multinodular Goiter • Graves’ Disease • Toxic Adenoma • Inflammatory Conditions • Chronic (Hashimoto’s) Thyroiditis • Subacute (De Quervain’s) Thyroiditis • Riedel’s Thyroiditis

7. Thyroid Disease Spectrum Overt Hypothyroidism TSH >20IU/mL, Free T4 Low Mild Thyroid Failure TSH >4.0 IU/mL, Free T4Normal Euthyroid TSH 0.4-4.0 IU/mL, Free T4 Normal Thyrotoxicosis TSH <0.4 IU/mL, Free T3/T4Normal or Elevated 10 0 5 TSH, IU/mL Braverman LE, et al. Werner & Ingbar’s The Thyroid. A Fundamental and Clinical Text. 8th ed. 2000. Canaris GJ, et al. Arch Intern Med. 2000;160:526-534. Vanderpump MP, et al. Clin Endocrinol (Oxf). 1995;43:55-68.

11. Multinodular Goiter He is a 21-year-old man with a 2-year history of a visible goiter. He is clinically asymptomatic. FT4 and TSH are within normal range. FT4 = 1.4 ng/dl (0.8-2), TSH = 1 mU/L. What is your interpretation?

12. Multinodular Goiter She is a 48-year-old woman with a long history of slowly growing goiter. FT4 and T3 are within normal range. TSH = 0.1 mU/L. What is your next step?

20. Cervical Map

21. Thyroid Gland Describe your observation in A, B, C, and D.

22. Simple Goiter: Diffuse and Multinodular • Definition • Pathogenesis and Pathophysiology • Pathology • Clinical Picture • Laboratory Tests • Imaging in Goiter Evaluation • Differential Diagnosis • Treatment

23. NONTOXIC GOITER: Diffuse and NodularDefinition May be defined as any thyroid enlargement characterized by uniform or selective (i.e., restricted to one or more areas) growth of the thyroid tissue►

24. NONTOXIC GOITER: Diffuse and NodularDefinition ► that is not associated with overt hyperthyroidism or hypothyroidism and that does not result from inflammation or neoplasia.

25. NONTOXIC GOITER: Diffuse and NodularDefinition A thyroid nodule is defined as a discrete lesion within the thyroid gland that is due to an abnormal local growth of thyroid cells.

26. Etiology and Pathophysiology • Goiter has been traditionally regarded as the adaptive response of the thyroid follicular cell to any factor that impairs thyroid hormone synthesis. This classic concept no longer appears to encompass the many aspects of goiters.

27. Etiology and Pathophysiology • . Also, iodine deficiency as the sole factor responsible for goiter appears to be an oversimplification. Not all inhabitants in an iodine-deficient region develop goiter

28. Etiology and Pathophysiology • Moreover, endemic goiter has been observed in countries with no iodine deficiency, and even in some regions with iodine excess, and has not been observed in some regions with severe iodine deficiency.

29. Etiology and Pathophysiology • These findings suggest that other factors, both genetic and environmental, may play a role in the genesis of diffuse and nodular goiter, and some of these factors may act synergistically.

30. Etiology and Pathophysiology • Environmental factors include cigarette smoking, infections, drugs, and goitrogens

31. Etiology and Pathophysiology • Environmental factors include cigarette smoking, infections, drugs, and goitrogens

32. Etiology and Pathophysiology • TSH has long been considered the major agent determining thyroid growth in response to any factor that impairs thyroid hormone synthesis.

33. Etiology and Pathophysiology • Indeed, in the rare clinical setting of a functioning TSH-secreting pituitary tumor, the increased blood TSH levels typically cause enlargement of the thyroid gland

34. Etiology and Pathophysiology • Similarly, goiter is also a typical feature of Graves’ disease, in which a stimulatory growth effect on thyroid tissue is induced by TSHR-stimulating antibody through TSHR activation.

35. Etiology and Pathophysiology • ] Moreover, thyroid enlargement may appear during the course of Graves’ disease when increased TSH levels result from overtreatment with antithyroid drugs.

36. Etiology and Pathophysiology • The serum TSH concentration is normal in most patients with nontoxic goiter.Experimentally, it has been demonstrated in rats that iodine depletion enhances the promotion of thyroid growth despite normal levels of TSH.

37. Etiology and Pathophysiology • Hence, any factor that impairs intrathyroidal iodine levels may lead to gradual development of goiter in response to normal concentrations of TSH.

38. Etiology and Pathophysiology • Indeed, a complex network of both TSH-dependent and TSH-independent pathways directs thyroid follicular cell growth and function and plays a role in the goitrogenic process.

39. Etiology and Pathophysiology • A variety of growth factors, derived from the bloodstream or through autocrine or paracrine secretion, may serve to regulate thyroid cell proliferation and differentiation processes.

40. Etiology and Pathophysiology • Early in the course of goiter formation, areas of microheterogeneity of structure and function are intermixed and include areas of functional autonomy and areas of focal hemorrhage.

41. Etiology and Pathophysiology • Analysis of hyperplastic nodules by rigid criteria have indicated that morphologically indistinguishable hyperplastic thyroid nodules may be either monoclonal or polyclonal.

42. Etiology and Pathophysiology • Monoclonal adenomas within hyperplastic thyroid glands may reflect a stage in progression along the hyperplasia-neoplasia spectrum; accumulation of multiple somatic mutations may subsequently confer a selective growth advantage to this single-cell clone.

43. Natural History • .

44. Natural History However, as evidenced by sonographic measurement of thyroid volume in women living in an area of moderate iodine intake, normal pregnancy is goitrogenic, especially in women with preexisting thyroid disorders. • .

45. Natural History The increased thyroid volume during pregnancy is associated with biochemical features of thyroid stimulation (i.e., an increased ratio of triiodothyronine [T3] to thyroxine [T4]) owing to slightly elevated serum TSH levels at delivery or a high concentration of human chorionic gonadotropin (hCG) during the first trimester. • .

46. Natural History Repeated pregnancies may play a role in the development of later thyroid disorders, and this relation might explain the higher prevalence of thyroid disorders in women. • .

47. Natural History The natural outcome of nontoxic nodular goiter was examined in an adult population with two main findings. • .

48. Natural History (1) benign thyroid nodules are likely to grow (although slowly) over time, and (2) as a consequence, the concept that growing nodules are malignant whereas stable ones are benign should be discarded. • .

49. Natural History • .

50. NONTOXIC GOITERNatural History • Thyroid growth • Nodule formation • Development of functional autonomy • Increasing functional heterogeneity within the thyroid gland