Classification of thyroid diseases

2. Classification of thyroid diseases • Enlargement of the gland • Goiters • Tumors • Hyperthyroidism • Graves disease • Toxic multinodular goiter • Toxic adenoma • Hypothyroidism • Hashimoto thyroiditis • Suabcute thyroiditis • Riedel thyroiditis • Congenital “Cretinism”

3. Enlargement of the gland • Goiters • Non toxic goiter • Diffuse non toxic goiter • Multinodular goiter • Thyroid cancer

4. Goiters • Goiter : an overgrown of the thyroid gland usually seen as a swelling in the neck. • The swelling may be linked to hyperthyroidism, hypothyroidism or normal levels of thyroid function • There are many types of goiters: • Non toxic goiter • Diffuse goiters • Multinodular non toxic goiters • Multinodular toxic goiter “included under hyperthyroidism”

5. A. Non toxic goiters • Non toxic goiters are also called simple, colloid or multinodular goiter. • It refers to an enlargement of the thyroid that is NOT associated with functional, inflammatory or neoplastic alterations  therefore, patients are euthyroid • More common in females • Diffuse form of goiters presents mostly in adolescents and pregnancy • Multinodular form presents in persons older than 50 years of age.

6. A. Non toxic goiters • Pathogenesis: • Patients are thought to have a subtle impairment of iodine utilization and to respond in an exaggerated fashion to normal TSH levels

7. A. Non toxic goiters • Pathology: • Diffuse non toxic goiter • Early stage of the disease • The gland is diffusely enlarge • Microscopically  it exhibits hypertrophy and hyperplasia of follicular epithelial cells

8. Non toxic goiters • Pathology: • Multinodular non toxic goiter • Evolves as the disease becomes more chronic • Many patients develop TOXIC multinodular goiters • The enlarged gland assumes an increasingly nodular configuration • Microscopically, • The nodules vary in size and shape.Some are distended with colloid and others are collapsed • Lining epithelial cells are flat to cuboidal and are arrayed as papillae that project into follicular lumen • Hemorrhagic, necrotic and cystic areas are common and fibrous band traverse the gland.

9. A. Non toxic goiters • Clinical features: • Patients are asymptomatic presenting with a mass in the neck • Large goiters  compress trachea and esophagus  cause inspiratory stridor or dysphagia • Hoarseness result from compression pf recurrent laryngeal nerve • Thyroid function test “TSH, T4, T3”= normal

10. A. Non toxic goiters • Treatment: • Administration of thyroid hormone to reduce TSH levels and stimulation to thyroid growth • In older patients, Radioactive iodine therapy is indicated • Surgery is contraindicated unless the local obstructive symptoms become troublesome.

11. B. Thyroid cancer • It is more common in females between the 30 – 70s years of age • Types: • Papillary • Follicular • Medullary • Anaplastic “undifferentatited”

12. B. Thyroid cancer • Papillary thyroid carcinoma • The most common thyroid cancer • Pathogenesis: • Iodine excess • Previous radiation to the neck • Genetic factors such as HLA DR7 • Pathology: • Orphan Annie nuclei • Eosinophilic pseudoinclusions • Nuclear grooves

13. Orphan Annie nucleus

14. B. Thyroid cancer • Follicular thyroid carcinoma • 15 – 25 % of all thyroid cancers • It could be minimally invasive or widely invasive  blood borne metastasis • Metastasis are directed to the bones of the shoulder, pelvis, sternum and skull • Some patients present with pathological fractures due to metastasis • Treatment = Radio labeled Iodine

15. B. Thyroid cancer • Medullary thyroid carcinoma • Tumor derived from parafollicular or C cells • Less than 5% of thyroid carcinomas • Patients having familial form of this carcinoma are afflicted with MEN type 2 that includes pheochromocytoma of the adrenal medulla and parathyroid hyperplasia • Pathology • Presence of stromal amyloid which represents the deposition of procalcitonin

16. B. Thyroid cancer • Anaplastic “Undifferentiated thyroid carcinoma • Rapidly fatal • History of long standing goiter • Invasion of the soft tissues of the neck • Pathology • Sarcoma like proliferation of spindles and giant cells with polyploid nuclei, necrosis and stromal fibrosis

17. Hyperthyroidism • Refers to the clinical consequences of excessive circulating thyroid hormone • Graves Disease • Toxic multinodular goiter • Toxic adenoma

18. 1. Graves Disease • Autoimmune disorder that is characterized by diffuse goiter, hyperthyroidism and exophthalmos • Most frequent cause of hyperthyroidism in patients younger than 40 years of age

19. 1. Graves Disease • Pathogenesis: • Immune mechanism: • Patients are hyperthyroid owing to the presence of IgG antibodies directed against components of the plasma membrane of the thyroid follicular epithelium presumably the TSH receptor • These antibodies function as an agonist “ they stimulate the TSH receptor  activate adenyl cyclase  increase in thyroid hormone secretion • Under continuous stimulation, the thyroid becomes diffusely hyperplastic and excessively vascular • Patients with Graves disease and their relatives both have a higher incidence of other autoimmune disease including pernicious anemia and Hashimotothyroiditis

20. 1. Graves Disease • Pathogenesis: • Sex : • More common in females than males • Emotional influences: • The onset of Graves disease often follows a period of emotional stress. • Opthalmopathy: • Exophthalmos is a common complication of Graves disease • T lymphocytes that are sensitized to antigens shared by thyroid follicular cells and orbital fibroblasts accumulate around the eye where they secrete cytokines that activate fibroblasts.

21. 1. Graves Disease • Pathology: • The thyroid is symmetrically enlarged • Microscopically, • The thyroid is diffusely hyperplastic and highly vascular • The epithelial cells are tall and columnar and are often arranged as papillae that project into the lumen of the follicles • The colloid tends to be depleted and presents a scalloped “moth-eaten” appearance • Scattered lymphocytes and plasma cells infiltrate the interstitial tissue

22. Graves Disease • Clinical features: • gradual onset of nonspecific symptoms such as nervousness, emotional lability, tremor, weakness and weight loss • They are intolerant of heat, and tend to sweat profusely • Almost all patients exhibit tachycardia or palpitations • Physical examination reveals : • a symmetrically enlarged thyroid often with an audible bruit and palpable thrill • Protrusion of the eyeball and retraction of the eyelids expose the sclera • The skin is warm and moist • Some patients exhibit Graves dermopathy which is a peculiar pretibial edema caused by the accumulation of fluid and glycosaminoglycans

23. 1. Graves Disease • Treatment: • antithyroid drugs • Radioiodine • adjuvant therapy with corticosteroids • adrenergic anatagonist

24. 2. Toxic Multinodular Goiter • Many patients who are older than 50 years of age develop functional autonomy of the nodules and a toxic form of the disease • More frequent in women • Never develop exophthalmos • Patients complain of cardiac complications such as atrial fibrillation and congestive heart failure • Serum T4 & T3 are minimally elevated • Microscopic examination reveals groups of small hyperplasic follicles mixed with other nodules of varying size that appear to be inactive. • Treatment : radio labeled iodine

25. 3. Toxic adenoma • A solitary hyperfunctioning follicular neoplasm in a normal thyroid • Hyperfunctioning of the adenoma suppresses the remainder of the thyroid which then atrophies • Treatment: radiolabeled iodine and surgery for large nodules.

26. Hypothyroidism • Refers to the clinical manifestation of the thyroid hormone deficiency • It can be the consequence of 3 general processes: • Defective synthesis of the thyroid hormone • Inadequate function of the thyroid parenchyma • Inadequate secretion of TSH by the pituitary or TRH by the hypothalamus

27. 1. Hashimoto Thyroiditis • An autoimmune disease that is characterized by circulating antibodies to thyroid antigens and features that are suggestive of cell-mediated immunity to thyroid tissue • Arises most commonly in women during the 4th and 5th decades of life • in regions where supplies of Iodine are adequate  Hashimoto thyroiditis is the most common cause of goitrous hypothyroidism

28. 1. Hashimoto Thyroiditis • Pathogenesis: • Patients exhibit high titers of circulating autoantibodies directed against thyroid peroxidase, thyroglobulin and the TSH receptor • The intense filtration of the thyroid parenchyma by lymphocytes and plasma cells suggest cell-mediated destruction of the gland • Both patients of Hashimoto and their relatives have a higher incidence of other autoimmune diseases, such as Insulin dependent diabetes mellitus, pernicious anemia, Addison disease, and myasthenia gravis • Hashimoto is associated with an increased frequency of the HLA- B8, HLA-Dr3, and HLA-DR5 haplotypes

29. 1. Hashimoto Thyroidtis • Pathology: • The gland in Hashimoto is diffusely enlarged, firm and slightly lobular • Microscopically, the gland displays : • Infiltrate of lymphocytes and plasma cells • Destruction and atrophy of the follicles • Oxyphilic metaplasia of the follicular epithelial cells

30. 1. Hashimoto Thyroiditis • Clinical features : • The patient notes a gradual onset of a goiter • Majority of these patients are euthyroid, few are hypothyroid when they present for medical attention • Most cases progress to a hypothyroid state • Many patients require no treatment • Thyroid hormone is administered to alleviate hypothyroidism and to decrease the size of the gland

31. 2. Subacute Thyroiditis • It is also called (DeQuervain, Granulomatous, or Giant cell thyroiditis) • Infrequent self-limited viral infection of the thyroid that is characterized by granulomatous inflammation • The disease typically occurs after upper respiratory tract infections including those caused by Influenza Virus, adenovirus, echovirus, and coxsackievirus • Affect women between 30 & 50 years of age

32. 2. Subacute thyroiditis • Pathology: • The gland is enlarged and the cut surface is firm and pale • Microscopic examination reveals : • An acute inflammatory reaction often with micro abscesses • Appearance of a patchy infiltrate of lymphocytes, plasma cells and macrophages throughout the gland • Numerous multinucleated giant cell of the foreign body type often containing colloid

33. 2. Subacute Thyroiditis • Clinical features: • Pain in the anterior neck which is sometimes accompanied by fever • On physical examination, the thyroid is moderately enlarged and tender • Generally resolves within a few months and without clinical sequelae

34. 3. Riedel thyroiditis • Rare disease that is characterized by dense fibrosis of the thyroid • The disease involves extrathyroid soft tissues of the neck and is often associated with progressive fibrosis in other locations including the reroperitoneum, mediastinum, and orbit • A disease of middle age with a female: male ratio of 3:1 • Cause is unknown • Patients notice a gradual onset of painless goiter • Patients may suffer from the consequences of compression of the trachea, esophagus and recurrent laryngeal nerves • Treatment is primarily surgical to relieve compression of local organs