12/26/2008

THYROID OXIDASE DEFICIENCY – 2A Marc E. Tischler, PhD; University of Arizona

THYROID OXIDASE DEFICIENCY – 2A

• (T4,T3) are made by the follicular cells of the thyroid gland (Figure 1) •the key enzyme in the processing (oxidation) of and formation of thyroid hormones is peroxidase •lack o f pe ro xidase in th e di sease m eans th at iod ine ca nno t be o xid ized no r a ttac hed fo r 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

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THYROID FOLLICULAR CELL COLLOID SPACE T IT IT IT T3 IT T T IT Tgb IT 3 4 T Oxidation + IT Tgb I Tgb IT T4 - IT T4 I Iodination Hormone I- T4 X Formation Peroxidase Peroxidase DISEASE SStdtCllidecreted to Colloid T T

T3 T T 3 4 Golgi T T Tgb Peroxidase T4 T4 In Golgi T 4 (Tgb) Thyroglobulin (Tgb) Hormone release I- I- NORMAL

I- I- 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. Thyroid These events all are regulated by peroxidase. Thyroid hormone is then released hormones from Tgb inside the cell and from there moves to the blood. In thyroid oxidase BLOOD deficiency the peroxidase is lacking (X) and none of these events can occur. T4, T3 Patients require hormone replacement therapy.

NORMAL DISEASE Hypothalamus X Inhibitory signals by Loss of thyroid Thyrotropin releasing hormone (TRH) inhibitory hormone signals

Anterior gland X

Thyroid stimulating hormone (TSH)

Thyroid hormones Thyroid gland: Thyroid gland: hormone secretion enhanced T4, T3 and cell growth 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.

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