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12/26/200 THYROID OXIDASE DEFICIENCY – 2A Marc E. Tischler, PhD; University of Arizona THYROID OXIDASE DEFICIENCY – 2A • thyroid hormones (T4,T3) are made by the follicular cells of the thyroid gland (Figure 1) • the key enzyme in the processing (oxidation) of iodine and formation of thyroid hormones is peroxidase • lack ac of o peroxidase pe o dase in thee ddisease sease means ea s that a iodine od e cannot ca o be oxidized o d ed nor o attached a ac ed for o making thyroid hormone • lack of thyroid hormone in the blood causes the brain to send out unabated signals for the gland to make more thyroid hormone, which of course is not possible (Figure 2) • lack of thyroid hormone production in the disease requires hormone replacement therapy • thyroid hormone functions: o growth o maintaining body’s basal metabolic rate (BMR) o heat production o promoting sweating • consequences of hypothyroidism (low blood thyroid concentration) o low BMR weight gain o sluggishness, decreased heart rate o intolerance to cold o dry skin 12/26/200 THYROID FOLLICULAR CELL COLLOID SPACE IT IT T3 IT IT T4 Tgb IT T3 IT Tgb IT + T4 I Tgb T4 IT IT Iodination Hormone T4 Oxidation I- I- Formation Peroxidase Peroxidase T X T DISEASE S t d tto C ll id Secreted Colloid T T T3 Peroxidase In Golgi T T4 Thyroglobulin (Tgb) I- T3 Tgb T4 T Golgi T4 T4 Thyroglobulin (Tgb) Hormone release I- NORMAL I- I- Thyroid hormones T4, T3 BLOOD NORMAL Figure 1. Iodine from the blood is oxidized and then attached to tyrosine (T) on Tgb in the colloid. Thyroid hormones are then formed on the modified Tgb. These events all are regulated by peroxidase. Thyroid hormone is then released from Tgb inside the cell and from there moves to the blood. In thyroid oxidase deficiency the peroxidase is lacking (X) and none of these events can occur. Patients require hormone replacement therapy. Hypothalamus Inhibitory signals by thyroid hormone Hypothalamus Thyrotropin releasing hormone (TRH) Anterior pituitary gland X DISEASE Loss of inhibitory signals Anterior pituitary gland X Thyroid stimulating hormone (TSH) Thyroid Th id hormones T4, T3 Thyroid gland: hormone secretion and cell growth Thyroid gland: enhanced cell growth only X Figure 2. TRH from hypothalamus region of the brain signals anterior pituitary to release TSH. TSH signals thyroid gland to make and release thyroid hormones. Abundant thyroid hormone signals the hypothalamus and anterior pituitary to stop releasing their stimulatory factors. In thyroid oxidase deficiency, the lack of thyroid hormones causes the stimulatory factors to be overproduced due to loss of inhibitory signals (X) and leads to growth (enlargement) of the thyroid gland.