Thyroid Gland Hormones and Iodide

Thyroid Gland Hormones

• Iodide is necessary for the synthesis of thyroid hormones, and can be obtained from sources such as iodized salt, iodated bread, and dairy products, with a daily requirement of 75 micrograms (about 10g of iodized salt)

Thyroid Hormone Synthesis

• The oxidation, iodination, and coupling reactions are catalyzed by iodine or thyroid peroxidase enzyme
• Lysosomal enzymes hydrolyze thyroglobulin, releasing T4 and T3
• Most of the released T4 is converted to T3 by deiodinase enzyme in peripheral tissues

Thyroid Hormone Characteristics

• Thyroxine (T4) and triiodothyronine (T3) are the two main thyroid hormones
• T4 is more abundant in the thyroid gland, with a ratio of T4:T3 of 4:1
• T3 is more potent than T4, with a potency ratio of 3-5:1
• Both T4 and T3 are bound to thyroxine-binding globulin (TBG) in the blood, with T4 being more highly bound (99.97%) than T3 (99.5%)
• The half-life of T4 is 1 week, while that of T3 is 1 day

Mechanism of Action of Thyroid Hormones

• Thyroid hormones travel in the blood bound to TBG and are transported to target cells
• T4 is converted to T3 in target cells, and only T3 enters the nucleus and binds to nuclear receptor protein
• The hormone-receptor protein complex binds to specific response elements on DNA, leading to a direct effect on transcription
• The resulting mRNA codes for specific proteins that mediate the effects of thyroid hormones

Effects of Thyroid Hormones

• Thyroid hormones promote growth and development, and are essential for growth in childhood
• They have a calorigenic effect, increasing BMR, O2 consumption, and general metabolism, as well as CHO metabolism
• They also increase lipolysis and lipid breakdown, decrease cholesterol blood levels, and increase β-adrenergic receptors in most tissues

Disorders Affecting the Thyroid Gland

• Hypothyroidism can occur in children (cretinism) and adults (myxedema)
• Causes of hypothyroidism include surgical removal of the thyroid, thyroiditis, deficiency or excess of iodine, and pituitary or hypothalamic dysfunction
• Symptoms of hypothyroidism include cold intolerance, lethargy, constipation, slowing of mental function and motor activity, weight gain, and dry/thick skin
• Treatment of hypothyroidism involves hormone replacement therapy (HRT)

Thyroid Hormone Preparations and Clinical Uses

• Thyroid hormone preparations include thyroid USP, thyroid extract, levothyroxine sodium, liothyronine sodium, and liotrix
• Clinical uses of thyroid hormones include hypothyroidism, thyroid cancer, and weight reduction
• Side effects of thyroid hormone preparations include hyperthyroidism and allergic reactions

Hyperthyroidism

• Hyperthyroidism can be caused by Grave's disease, hyperplasia of the thyroid, and exophthalmos
• Symptoms of hyperthyroidism include heat intolerance, nervousness, fatigue, weight loss, increased bowel movements, and abnormal menses
• Treatment of hyperthyroidism includes propranolol, antithyroid drugs, and surgery
• Antithyroid drugs include thiourea derivatives (thionamides) such as methimazole, carbimazole, and propylthiouracil
• Side effects of antithyroid drugs include allergy, hepatic dysfunction, agranulocytosis, and teratogenicity

Iodine Therapy

• Iodine can be used to treat hyperthyroidism and thyroid cancer
• Iodine therapy can cause allergy and has a high relapse rate
• Radioactive iodine (RAI) can be used to treat hyperthyroidism and thyroid cancer

Lithium Carbonate

• Lithium carbonate has a similar mechanism of action to iodide
• It has a narrow therapeutic window and can cause side effects such as nausea, diarrhea, and blurred vision