Thyroid

• Thyroid gland


  Butterfly shaped gland
• Thyroid gland


  • Consists of two lobes located in the lower part of the neck, just below the larynx
  • Lobes are connected by a narrow band called the isthmus
  • Begins to produce measurable hormones by 11 weeks of gestation
• Thyroid gland regulation


  Regulated by secretion of thyroid-stimulating hormone (TSH) from the anterior pituitary gland
• Thyroid hormone synthesis


  1. Iodide reaches the thyroid

  2. Oxidized

  3. Combine with tyrosine residues in the thyroglobulin molecule forming MIT and DIT

  4. MIT and DIT coupled to form T3 and T4
• Follicle


  Fundamental structural unit of thyroid gland (tiny bags or tiny sacs)
• Follicular cells


  • Responsible for secreting T3 and T4
• Parafollicular or C cells

  • Secrete/produce calcitonin (calcium regulation)
• Physiologic effects of thyroid hormones

  • Growth, maturation, and sexual development
  • Heat production & energy expenditure
  • Influence carbohydrate, protein and lipid metabolism
  • Increased oxygen consumption
  • Increased heart rate
  • Increased blood volume
• Thyroglobulin


  Performed matrix containing tyrosyl groups
• Thyroglobulin


  • Acts as a storage form of thyroid hormones
  • Stored in the follicular colloid of the thyroid gland
  • Weighs about 15-25 g
  • Divided into lobules each of which is composed of 20-40 follicles
• Thyroid follicles


  • Ring-shaped structures, in which a single cell band of follicular cells surrounds a closed cavity containing colloid
  • Follicular cells rest on a basement membrane that is rich in glycoprotein that separates the cells from surrounding capillaries
  • Apex of the follicular cells has microvilli that extend into the colloid, where iodination, exocytosis, and the initial phase of hormone secretion occur
  • Follicles are sites of thyroid hormone synthesis
• Thyroid gland also contains parafollicular cells, or C cells, which are responsible for the synthesis and secretion of calcitonin, a hormone important in calcium metabolism
• Hypothalamic-pituitary-thyroid axis


  1. Hypothalamus secretes TRH which stimulates anterior pituitary to secrete TSH

  2. TSH stimulates thyroid hormone synthesis and secretion by the thyroid gland

  3. Negative feedback on hypothalamus and pituitary gland
• Sources of T3


  • 80% enzymatic T3 outside thyroid
  • 20% of T4 converted to T3
  • 10% of T4 converted to T3
• Protein bound thyroid hormones


  Bound to thyroid binding globulin, transthyretin (pre-albumin), and albumin
• Free thyroid hormones


  Physiologically active form of thyroid hormone, mediated by T3 receptors in nucleus
• Reverse T3


  Biologically inactive form of T3
• Hypothalamic-pituitary-thyroid axis


  1. Hypothalamic hormone: TRH

  2. Action: Stimulates anterior pituitary to secrete TSH

  3. Pituitary hormone: TSH

  4. Thyroid hormone: T4
• Thyroxine (Total T4)


  Primary secretory product of the thyroid gland
• T4 measurements are often used along with TSH and can be important in interpreting TSH results
• Total T4 reference range

  1. 12 μg/dL
• Distribution of total T4


  • 70% bound to thyroid binding globulin
  • 20% bound to transthyretin (pre-albumin)
  • 10% bound to albumin
• Primary hypothyroidism


  Decreased total T4
• Symptoms of primary hypothyroidism: Hoarseness, cold sensitivity, dry skin, constipation, bradycardia, muscle weakness, goiter
• Hyperthyroidism


  Increased total T4
• Symptoms of hyperthyroidism: Thyrotoxicosis (decreased weight and normal appetite), eyelid retraction, tremors, thyroid storm (hyperpyrexia)
• T4 thyrotoxicosis


  Increased total T4
• Low T3 and low T4 syndrome

  Decreased total T4 and T3
• T3 uptake test


  Classical method of adjusting a total T4 measurement for alterations in binding protein
• Free thyroxine


  Biologically active fraction of total T4
• Free thyroxine measurement


  Reference method is equilibrium dialysis
• T4 thyrotoxicosis


  Hyperthyroidism with elevated T4 levels
• Low T3 and low T4 syndrome


  Non-thyroidal illness, with associated decrease in T3 and T4
• Reference Interval


  1. 12.5 ug/dL or 71-161 nmol/L (adult), 11.8 – 22.6 ug/dL or 152-292 nmol/L (neonate)
• T3 uptake test


  Saturating available binding sites with radiolabeled T3, then measuring the unbound T3 by adsorbing it onto a resin
• Free thyroxine (FT4)


  Biologically active fraction of T4
• Reference method of measurement for FT4

  Equilibrium dialysis
• FT4 has been used alone or in conjunction with TSH to diagnose thyroid dysfunction because of its advantage in states of altered protein binding
• Hyperthyroidism and FT4


  FT4 increased
• Hypothyroidism and FT4


  FT4 decreased