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”. Enlargement of the gland. Goiters
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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”
Enlargement of the gland • Goiters • Non toxic goiter • Diffuse non toxic goiter • Multinodular goiter • Thyroid cancer
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”
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.
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
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
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.
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
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.
B. Thyroid cancer • It is more common in females between the 30 – 70s years of age • Types: • Papillary • Follicular • Medullary • Anaplastic “undifferentatited”
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
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
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
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
Hyperthyroidism • Refers to the clinical consequences of excessive circulating thyroid hormone • Graves Disease • Toxic multinodular goiter • Toxic adenoma
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
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
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.
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
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
1. Graves Disease • Treatment: • antithyroid drugs • Radioiodine • adjuvant therapy with corticosteroids • adrenergic anatagonist
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
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.
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
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
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
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
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
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
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
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
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