Morphology The functional unit of the thyroid gland is the follicle It is composed of epithelial cells arranged as hollow vesicles of various shapes ranging in size from 0.02 to 0.3 mm in diameter It is filled with a glycoprotein colloid called thyroglobulin Groups of densely packed follicles are bound together by connective tissue septa to form lobules Single layer of epithelial cells (red arrow) Parafollicular cell (white arrow) Connective tissue septum separating two lobules (green arrow)

Secretory cells of the thyroid gland are of two types: Follicular cells, which produce the classical thyroid hormones, thyroxine and triiodothyronine Parafollicular, or C cells, are located between the follicles and produce the polypeptide hormone calcitonin

Thyroid Hormones The thyroid hormones are α-amino acid derivatives of tyrosine Thyroxine & Triiodothyronine are exceptionally rich in iodine, which comprises more than half of their molecular weight Thyroxine contains four atoms of iodine and is abbreviated as T4 Triiodothyronine, which has three atoms of iodine, is abbreviated as T3 Alpha amino acids having both the amine and the carboxylic acid groups attached to the first carbon

Feedback Regulation of Thyroid Hormone Secretion Measurement of relative concentrations of TSH and thyroid hormones in the blood provide important information for diagnosing thyroid disease. For instance, low blood concentrations of free T3 and T4 in the presence of elevated levels of TSH signal a primary defect in the thyroid gland while high concentrations of free T3 and T4 accompanied by high concentrations of TSH reflect a defect in the pituitary or hypothalamus

Hypothyroidism Etiology of hypothyroidism Hypothyroidism may be classified as Primary thyroid failure (most common) Etiology Hashimoto’s thyroiditis: Radioactive iodine therapy for Graves’ disease Subtotal thyroidectomy for Graves’ disease Excessive iodide intake Iodide deficiency Inborn errors of thyroid hormone synthesis Drugs (Lithium) Removal of majority of both lobes leaving behind 4-5 grams (equivalent to the size of a normal thyroid gland) of thyroid tissue on one or both sides The mechanism by which lithium inhibits thyroid hormone release is not well understood. In vitro, lithium decreases colloid droplet formation within thyroid follicular cells, a reflection of decreased pinocytosis of colloid from the follicular lumen

Peripheral resistance to the action of thyroid hormones Secondary due to pituitary TSH deficiency Tertiary due to hypothalamic deficiency of TRH Peripheral resistance to the action of thyroid hormones

Graves’ Disease Graves’ disease is the most common form of thyrotoxicosis Females are involved about five times more commonly than males Autoimmune disease of unknown cause The syndrome consists of one or more of the following features: thyrotoxicosis goiter ophthalmopathy dermopathy inflammation of the eyes and bulging eyes.

Treatment of Graves’ Disease Although autoimmune mechanisms are responsible for the syndrome of Graves’ disease, management has been largely directed toward controlling the hyperthyroidism Three good methods are available: Antithyroid Drug therapy inhibiting TPO-mediated iodination of thyroglobulin Surgery Partial or total thyroidectomy and radioactive iodine therapy (131I) destroys thyroid cells A dangerous and short lived fission product. Iodine 131 is a radioisotope with a very short half-life of 8.02 days, making it highly radioactive