Thyroid Gland PDF

First Part Thyroid gland Location: butterfly-shaped in the front of the neck Size: the larger endocrine gland in the body Secretions: metabolic hormones (T4 & T3), calcitonin (for calcium hemostasis) Thyroid Metabolic hormones (T & T3)  Function: 1. stimulate O2 consumption by body cells 2. Regu...

First Part Thyroid gland Location: butterfly-shaped in the front of the neck Size: the larger endocrine gland in the body Secretions: metabolic hormones (T4 & T3), calcitonin (for calcium hemostasis) Thyroid Metabolic hormones (T & T3)  Function: 1. stimulate O2 consumption by body cells 2. Regulate lipids and carbohydrate metabolism 3. Influence body mass and mentation Thyroid dysfunctions:  In fetal and neonatal life: absence or hypofunction cause severe mental retardation and dwarfism  In adult life: 1. Hypothyroidism: mental and physical slowing; poor resistance to cold (cold intolerance) 2. Hyperthyroidism: body wasting; nervousness, tachycardia; tremor; excess heat production Stimulus: TSH (that regulated by TRH) -ve Feedback control: direct (hypothalamic) & indirect (pituitary) inhibition by T4 Thyroid metabolic hormones  Are iodinated hormones (T4 – 4 iodides; T3 -3iodides)  T4 called Thyroxine & T3 called triiodothyronine  T4 is the main secreted hormone  T3 is the biologically active  T4 converted to T3 in peripheral tissues by deiodination  Synthesized from tyrosine amino acid Steps in thyroid hormone synthesis 1. Transport of iodine into colloid of the thyroid follicles (functional units) 2.Iodine oxidation in the colloid 3.Tyrosine iodination (tyrosine is in the thyroglobulin) 4.Endocytosis of thyroglobulin-thyroid hormone into thyrocytes 5.Thyroid hormone release by cleavage in lysosomes Thyroglobulin  Structure: glycoprotein contains 10% carbohydrate by weight and 123 tyrosine residues (4 -8 ONLY used for hormone synthesis)  Synthesis: in the thyrocytes  Secretion: by exocytosis into the colloid  Thyroid peroxidases (membrane-bound enzymes in the apical membrane of thyrocytes) mediate oxidation and reaction of iodine with thyroglobulin  The produced thyroid hormone remain part of thyroglobulin until needed (colloid represent reservoir of the hormone for at least 2 months)  When needed colloid is internalized by endocytosis into thyrocytes and the hormone released by lysosomal cleavage Thyroid peroxidases: involved in iodination and coupling of iodinated tyrosine residues Synthetic steps in thyroid hormone production: First step in synthesis: iodination of tyrosine to give MIT Next step in synthesis: iodination of MIT at C5 to give DIT Tow possibilities then operated: 1. Two DIT undergo oxidative condensation to form T4 2.One DIT condense with one MIT to form T3 (major) and reverse T3 (RT3 – trace) % Distribution in the thyroid follicle T4: 35% T3: 7% MIT: 3% DIT: 33% Secretion rate: T4: 80 g/day T3: 4 g/day RT3: 2 g/day DIT & MIT: null Remaining DIT & MIT are deiodinated by iodotyrosine deiodinase to recover iodine and tyrosine for next round of hormone synthesis Plasma levels: T4= 8ug/dL & T3= 0.15ug/dL Solubility: both are lipophilic In plasma: present as bound form (bind to the plasma protein Thyroxine-binding globulin) + free form (biologically active and) The bound form acts as a reservoir when needed The thyroid gland add the free form to the circulation Free hormone is biologically active and exerts an inhibitory feedback on pituitary TSH secretion Plasma proteins that bind thyroid hormones 1. Albumin (large capacity but bind only small amount); t1/2= 13days 2.Prealbumin (Transthyretin but bind only small amount); t1/2= 2days 3.Thyroxine binding globulin (TBG) (smallest capacity BUT bind most of T4; i.e.; TBG has higher affinity to T4 ; t1/2= 5days) T4 Plasma protein binding = 99.98% and the free form = 0.02% (2ng/dL) Urine conc. very little and t1/2 = 6-7days Metabolic pathway: T4 deiodinated into T3 (catabolism & 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