• During embryonic development, thyroid starts at the base of the tongue and migrates along midline in thyroglossal duct
• Ectopic Thyroid – abnormal decent can lead to thyroid tissue at midline base of tongue, larynx, mediastinum, heart
• Thyroglossal Duct Cyst – remnants of thyroglossal duct that develop into cysts lined by epithelium in midline neck
• may contain thyroid tissue; rarely become malignant

• Acute Thyroiditis – via direct infection or migration of bacteria (esp. staph, strep, H.flu, Pseudomonas aeruginosa)
• Epidemiology – fairly rare, except in immunocompromised and undernourished patients
• Clinical Presentation – pain and swelling of thyroid
• Subacute Thyroiditis (a.k.a. DeQuervain’s, granulomatous, giant cell thyroiditis) – possibly a viral infection
• Clinical Presentation – pain and swelling of thyroid, also fever
• 50% of patients develop transient hyperthyroidism (from broken follicles) followed by hypothyroidism
• Histology – follicles are gone; granulomata and giant cells are apparent (classic sign of DeQuervain’s)
• Hashimoto’s Thyroiditis – autoimmune disease involving anti-thyroid antibodies (often against thyroglobulin)
• Epidemiology – very common – affects 3-4% of population, 5-10x as many females as males
• most common iodine-independent cause of hypothyroidism
• associated with HLA-DR5; also associated with increased risk of papillary carcinoma and lymphoma
• Clinical Presentation – early: diffuse, firm enlargement of gland; late: atrophic fibrous gland
• patients are usually hypothyroid, but can be euthyroid
• Histology – chronic inflammation; lymphoid follicles; destruction of architecture; parenchymal fibrosis
• epithelial cells undergo Hürthle change – become more oxyphilic, with lots of mitochondria

• Grave’s Disease (diffuse toxic goiter) – autoimmune disease involving antibodies that stimulate the TSH receptor
• Epidemiology – associated with HLA-DR3 and Hashimoto’s Thyroiditis; affects 5x as many females as males
• Clinical Presentation – diffuse thyroid enlargement, hyperthyroidism, ophthalmopathy
• exopthalmos – eyes pop out due to edema and inflammation in muscles and soft tissues behind the eye
• Histology – diffuse and marked epithelial hyperplasia
• Diffuse and Nodular Non-Toxic Goiter – involves undersecretion of thyroid hormone for a number of reasons
• endemic from iodine deficiency; sporadic from iodine deficiency, inborn error of metabolism, or "goiterogens"
• ß TH Þ Ý TSH Þ thyroid hyperplasia Þ involution and accumulation of colloid Þ more hyperplasia Þ nodules
• presence of thyroid hyperplasia and elevated TSH is diagnostic
• Epidemiology – most common thyroid disease
• Clinical Presentation – symmetric (diffuse) or asymmetric (nodular) enlargement; typical case is < 100g
• Histology – nodules and follicles of various sizes, some with large amounts of colloid; degenerative changes such as hemorrhage, scarring, and calcifications are commonly seen

• Follicular Adenoma – the only benign neoplasm that can arise in the thyroid gland
• most are solitary and circumscribed by a well-formed fibrous capsule; 1-5 cm in size; no evidence of invasion
• derived from follicular cells; clinically resemble malignant neoplasms

Malignant Neoplasms – relatively uncommon (1-2% of all cancer) – females > males

• Papillary Carcinoma – most common thyroid malignancy; derived from follicular epithelium
• risk factors include irradiation, Hashimoto’s thyroiditis, Grave’s disease
• often occult (not grossly evident), slow growing mass; lymphatic spread to cervical lymph nodes
• Histology – clear nuclei with grooving
• Prognosis – good; 10 year survival rate = 85-95%
• Follicular Carcinoma – 2^nd most common thyroid malignancy; from follicular epithelium; may resemble adenoma
• Prognosis – depends on invasion; 10 year survival 80-95% if minimally invasive, 30-45% if widely invasive
• minimally invasive type involves tumor invasion via vascular invasion or invasion of the tumor capsule
• widely invasive type often lacks capsule and disseminates directly through blood vessels
• Anaplastic Carcinoma – poorly differentiated; from follicular cells; can arise from papillary or follicular carcinoma
• Prognosis – very poor; 5 year survival rate = 0-10%
• Medullary Thyroid Carcinoma – derived from C-cells, which may still secrete calcitonin Þ ß blood [Ca⁺⁺]
• may be associated with Multiple Endocrine Neoplasia Syndrome, but most are sporadic
• Prognosis – 10 year survival rate = 40-70%
• Malignant Lymphoma – very rare; primary (usually associated with Hashimoto’s) or part of generalized lymphoma
• Hashimoto’s carries 80x increased risk of lymphoma (but papillary carcinoma is still more common)
• Prognosis – 5 year survival rate = 50%