Thyroid Gland and Its Functions

Thyroid Gland

• Location: Butterfly-shaped in the front of the neck
• Size: The largest endocrine gland in the body
• Secretions: Metabolic hormones (T4 and T3) and calcitonin (for calcium hemostasis)

Thyroid Metabolic Hormones (T4 and T3)

• Function: • Stimulate O2 consumption by body cells • Regulate lipids and carbohydrate metabolism • Influence body mass and mentation

Thyroid Dysfunctions

• In fetal and neonatal life: Absence or hypofunction causes severe mental retardation and dwarfism
• In adult life: • Hypothyroidism: Mental and physical slowing, poor resistance to cold (cold intolerance) • Hyperthyroidism: Body wasting, nervousness, tachycardia, tremor, excess heat production

Thyroid Hormone Synthesis

• Steps: • Transport of iodine into the colloid of thyroid follicles • Iodine oxidation in the colloid • Tyrosine iodination • Endocytosis of thyroglobulin-thyroid hormone into thyrocytes • Thyroid hormone release by cleavage in lysosomes
• T4 is the main secreted hormone, while T3 is the biologically active form
• T4 is converted to T3 in peripheral tissues by deiodination

Thyroglobulin

• Structure: Glycoprotein containing 10% carbohydrate by weight and 123 tyrosine residues
• Synthesis: In the thyrocytes
• Secretion: By exocytosis into the colloid
• Thyroid peroxidases mediate oxidation and reaction of iodine with thyroglobulin
• The produced thyroid hormone remains part of thyroglobulin until needed

Thyroid Peroxidases

• Involved in iodination and coupling of iodinated tyrosine residues

Synthetic Steps in Thyroid Hormone Production

• First step: Iodination of tyrosine to give MIT (monoiodotyrosine)
• Next step: Iodination of MIT at C5 to give DIT (diiodotyrosine)
• Two possibilities then occur: • Two DIT undergo oxidative condensation to form T4 • One DIT condenses with one MIT to form T3 (major) and reverse T3 (RT3 – trace)

Distribution and Secretion

• % Distribution in the thyroid follicle: • T4: 35% • T3: 7% • MIT: 3% • DIT: 33%
• Secretion rate: • T4: 80 μg/day • T3: 4 μg/day • RT3: 2 μg/day • DIT & MIT: null

Plasma Levels and Binding

• Plasma levels: T4 = 8 μg/dL, T3 = 0.15 μg/dL
• Solubility: Both are lipophilic
• In plasma: Present as bound form (bound to plasma protein) + free form (biologically active)
• Free hormone is biologically active and exerts an inhibitory feedback on pituitary TSH secretion
• Plasma proteins that bind thyroid hormones: • Albumin • Prealbumin (Transthyretin) • Thyroxine-binding globulin (TBG)

Metabolic Pathway

• T4 deiodinated into T3 (catabolism and activation)
• Site of metabolism: Liver, kidneys, and other tissues
• Metabolism of T4: 1/3 to T3, 45% to RT3
• T3 supply: 13% secreted by thyroid gland, 87% by deiodination