Hyperthyroidism pathophysiology

Hyperthyroidism Microchapters
Patient Information
Overview
Classification
Differentiating hyperthyroidism from other diseases
Pathophysiology

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Farman Khan, MD, MRCP [2]

Pathophysiology

Thyroid hormone secretions are controlled by complex hypothalamic-pituitary-thyroid axis. Under normal circumstances thyrotropin-releasing hormone (TRH) from the hypothalamus stimulates the pituitary to release TSH. TSH in return acts on thyroid to produce T3 and T4. In turn, these hormones act on the hypothalamus to decrease TRH secretion and thus the synthesis of TSH. Iodine is essential for the synthesis of thyroid hormone. Dietary inorganic iodide is transported into the gland and then converted to iodine. Iodine binds to thyroglobulin with the help of thyroid peroxidase by process called organification. This forms monoiodotyrosine (MIT) and diiodotyrosine (DIT), which are coupled to form T3 and T4; these are then stored with thyroglobulin in the thyroid’s follicular lumen. More than 99% of T3 and T4 is bound to plasma proteins in the peripheral circulation and is inactive. Free T3 is 20-100 times more biologically active than free T4. Free T3 acts by binding to nuclear receptors and regulating the transcription of various cellular proteins. Any process that increases unbound thyroid hormone in peripheral circulation can cause hyperthyroidism. Disturbances of the thyroid axis can occur at the level of the hypothalamus, pituitary gland, thyroid gland, or in the periphery. Hyperthyroidism results in an increase in the transcription of cellular proteins, causing an increased basal metabolic rate.