Chp 77

• Thyroid hormone


  Endocrine gland that secretes two major hormones: thyroxine (T4) and triiodothyronine (T3)
• Thyroxine (T4)


  • Has four iodines connected to it
  • Major thyroid hormone transported in the blood (93% of thyroid hormones)
• Triiodothyronine (T3)


  • Has three iodines connected to it
  • More potent than T4 at producing effects of increased metabolism
• Thyroid hormone secretion


  Stimulated by thyroid stimulating hormone (TSH) from the anterior pituitary gland
• Thyroid gland also secretes calcitonin, which is involved in calcium metabolism
• Protein binding of thyroid hormones

  Increases the store of thyroid hormones in the blood and slows their removal
• Thyroid gland


  • Located just below the chin, hugging the trachea
  • Contains cuboidal epithelial cells forming follicles filled with colloid solution high in thyroglobulin
  • Contains C cells that secrete calcitonin
• Iodine uptake by thyroid gland

  1. Iodine enters cuboidal epithelial cells via sodium-iodide symporter

  2. Iodine is then transported into the follicle and oxidized by peroxidase enzyme

  3. Oxidized iodine attaches to tyrosine amino acids within thyroglobulin to form T4 and T3
• Thyroglobulin


  Protein molecule produced by thyroid epithelial cells that stores T4, T3, and other iodinated products
• Thyroid hormone release


  1. TSH stimulates: increased iodide trapping, peroxidase activity, thyroglobulin transport and breakdown

  2. Thyroglobulin is broken down, releasing T4 and T3 which are secreted into the bloodstream
• Thyroid hormone effects


  • Increase metabolic rate of virtually every cell in the body
  • Increase growth, development, cardiovascular output, glucose/lipid metabolism, heat production
  • Necessary for normal brain development in early life
• Increased thyroid hormone


  Increases skeletal growth rate but leads to early fusion of bone plates, limiting final height
• Decreased thyroid hormone


  Leads to mental depression, increased cholesterol, triglycerides, and phospholipids
• Thyroid hormone


  • Causes excessive skeletal growth, but bone plates fuse early so duration of growth is too fast
  • Important for brain development during early fetal life
• Too much thyroid hormone


  • Increased glucose production and utilization
  • Reduced cholesterol, phospholipids, and triglycerides
• Low thyroid/hypothyroidism


  Increased cholesterol and increased risk for atherosclerosis
• Thyroid hormone


  • Increases almost all bodily enzyme reactions
  • Increases vitamin usage, leading to relative vitamin deficiency
  • Decreases body weight due to protein cannibalism and increased fat utilization
  • Increases cardiovascular system (increased cardiac output, heart rate, contractility)
  • Increases respiration and GI motility
  • Excites central nervous system (more anxiety, difficulty sleeping)
  • Increases production of other endocrine glands
• Thyroid stimulating hormone (TSH)


  Increases proteolysis of thyroglobulin, activity of sodium iodide pump, iodination of tyrosine, size and secretory function of thyroid cells, and number of thyroid cells
• How TSH increases thyroid hormone release

  1. Increases cyclic AMP in thyroid cells

  2. Activates protein kinases

  3. Phosphorylates multiple enzymes

  4. Increases activity of various components
• Thyrotropin releasing hormone (TRH)


  Released from hypothalamus, stimulates secretion of TSH from anterior pituitary
• Stimuli for TRH and TSH secretion


  • Cold (increases)
  • Emotional stimuli, high metabolism (decreases)
• T4


  Has negative feedback on TSH secretion in anterior pituitary
• Anti-thyroid drugs


  • Thiocyanate (decreases iodide trapping)
  • Propylthiouracil (reduces thyroid hormone formation)
  • Methimazole, carbimazole (block peroxidase, prevent iodination)
  • High iodide (reduces thyroid hormone production, paralyzes endocytosis of colloid)
• Anti-thyroid drugs


  Decrease thyroid hormone production, leading to increased TSH and enlarged thyroid (goiter)
• Hyperthyroidism


  Can be caused by Graves' disease (autoimmune stimulation of TSH receptors) or thyroid adenomas
• Hyperthyroidism


  • High state of excitability, tolerance to heat, increased sweating, weight loss, muscle weakness, nervousness, diarrhea, fatigue, tremor of hands, exophthalmos (with Graves')
• Hypothyroidism


  Can be caused by autoimmune destruction of thyroid, low dietary iodine, or goitrogenic substances
• Hypothyroidism


  • Fatigue, increased sleepiness, sluggishness, muscular weakness, slow heart rate, reduced cardiac output, increased body weight, constipation, decreased hair growth, scaly skin, myxedema, increased cholesterol
• Cretinism


  Extreme form of hypothyroidism occurring early in life, leading to failure of body growth and mental depression