Normal histology	Histopathology	Pathological basis of disease	Clinical findings	
Tissue architecture:
•	The functional units of the thyroid gland are irregular spheroidal structures called thyroid follicles.
•	The thyroid gland is enveloped by an outer capsule of loose supporting tissue & an inner capsule of fibro-elastic tissue.
•	From the inner capsule, fine collagenous septa extend into the gland dividing the gland into lobules & conveying a rich blood supply together with lymphatics & nerves.

Cellular characteristics:
•	Thyroid follicles are lined by a simple cuboidal epithelium responsible for the synthesis of thyroid hormones.
•	Thyroid follicles are filled with a glycoprotein complex called thyroglobulin (colloid) which stores the thyroid hormones prior to secretion.
•	Parafollicular or ‘C’ cells are found in the thyroid gland interstitium as single cells scattered among follicular cells or as small clumps in the interfollicular spaces.
•	Parafollicular cells are identified by the immunoperoxidase stain with antibody to calcitonin.
•	Parafollicular cells synthesize the hormone calcitonin in direct response to raised blood calcium levels.	Abnormal histology:
•	The thyroid is abnormally enlarged, with an intact capsule.
•	The parenchyma is generally paler than normal.
•	Extensive heavy infiltrations of lymphocytes & plasma cells (small darkly staining cells) between the thyroid follicles.
•	In some areas, these inflammatory cells tend to aggregate & often form typical lymphoid follicles with germinal centers.
•	Thyroid follicle epithelial cells have abundant, eosinophilic granular cytoplasm with lots of mitochondria, leading to a red, eosinophilic appearance (Hurthle cell).
•	Areas of fibrosis in stroma.

Course:
•	When almost all the thyroid acini are destroyed, the lymphoid infiltrate becomes less obvious & fibrosis supervenes, with progressive atrophy of gland.

Differentiate from:
•	Lymph node	Incidence:
•	Most prevalent between 45 & 65 years of age.
•	Female predominance of 10:1 to 20:1.
•	Major cause of nonendemic goiter in children.

Pathogenesis:
•	Autoimmune disorder caused by a defect in the function of thyroid-specific suppressor T cells.
•	This defect results in the emergence of CD4+ helper T cells directed at the thyroid & production of autoantibodies to various components of the thyroid follicle, e.g. thyroglobulin, TSH receptor.
•	There may be a genetic component as some cases are associated with HLA-DR5 & HLA-DR3 (more severe cases).

Associated with:
•	Systemic lupus erythematosus
•	Sjogren syndrome
•	Rheumatoid arthritis
•	Pernicious anemia
•	Type II diabetes
•	Graves disease	Clinical course:
•	An insidiously developing condition.
•	Most common cause of hypothyroidism in areas of the world where iodine levels are sufficient.
•	Characterized by gradual thyroid failure due to an autoimmune-mediated destruction of gland.
•	Initially, the thyroid is enlarged and there may be transient hyperthyroidism, followed by a euthyroid state and then hypothyroidism with eventual atrophy years later.
•	Come to clinical attention as painless enlargement of the thyroid.
•	Small risk of subsequent lymphoma.

Clinical symptoms:
•	Slowing of physical & mental activity.
•	Fatigue, cold intolerance & apathy.
•	Periorbital edema
•	Coarsening of skin & facial features
•	Cardiomegaly
•	Pericardial effusion
•	Hair loss
•	Accumulation of mucopolysaccharide-rich ground substance within dermis & other tissues.