Lecture 7 Thyroid

Question 1

SOM.1ai.BPM2.1.ER.1. PHYS.EN.0301. Describe the thyroid gland

Answer 1

• endocrine organ
• anterior portio of the neck
• cells/lumen
  
  • follicular cells
  • parafollicular cells
  • colloid

Question 2

SOM.1ai.BPM2.1.ER.1. PHYS.EN.0301. explain the role of TRH and TSH their chemical nature and their mechanism of action on their target organs.

Answer 2

Thyrotropin Releasing Hormone (TRH)

• synthesized: PVN
• tripetide
• half-life: 5 minutes
• secretion rate: constant
• target cell/organ: thyrotroph
• receptor: IP3 & DAG (Gq)

Question 3

SOM.1ai.BPM2.1.ER.1. PHYS.EN.0301. explain the role of TRH and TSH their chemical nature and their mechanism of action on their target organs.

Answer 3

Thyroid-Stimulating Hormone (TSH)

• synthesized: thyrotrophs in AP
• large glycoprotein
• half-life: 30 minutes
• target cell/organ: growth of thyroid gland (all steps of thyroid hormone synthesis)
• receptor: cAMP (Gs)

Question 4

SOM.1ai.BPM2.1.ER.1. PHYS.EN.0302. Describe the hormones synthesized in thyroid gland and their chemical structure

Answer 4

Thyroxine (T4) - 4 iodines

Triiodothyronine (T3) - 3 iodines, most potent

Reverse T3 (rT3) - 3 iodines

Question 5

SOM.1ai.BPM2.1.ER.1. PHYS.EN.0303. Describe the importance of iodine its absorption, uptake, distribution, and excretion.

Answer 5

• importance: thyroid hormone synthesis requires iodine
• uptake: from the diet in the form of iodide or iodate
• distribution: see picture
• excretion: see picture
• pregnant & lactating females have higher iodine requirements
• iodine deficiency decreases amount of hormone produced
  
  • compensates by increaseing TSH levels

Question 6

SOM.1ai.BPM2.1.ER.1. PHYS.EN.0304. Identify the steps in the biosynthesis, storage, and secretion of tri-iodothyronine (T3) and thyroxine (T4) and their regulation.

Answer 6

1. Synthesis & extrusion of TG into the lumen
   
   1. location: rER, golgi
2. Na/I co-transport (secondary active transport)
   
   1. location: basal membrane
   2. inhibitors: perchlorate, thyocyanate, ↑I-
3. Oxidation (I- to I2)
   
   1. location: apical membrane
   2. enzyme: TPO (thyroid peroxidase)
   3. inhibitor: PTU (propylthiouracil)
4. organification I2 to MIT (monoiodotyrosine) & DIT (di-iodotyrosine)
   
   1. location: apical membrane
   2. enzyme: TPO
   3. inhibitors: PTU, increased I-
5. Coupling DIT & MIT
   
   1. location: apical membrane
   2. enzyme: TPO
6. Endocytosis of TG
   
   1. location: apical membrane
7. Hydrolysis of T3, T4
   
   1. location: lysosome protease
   2. enzyme: proteolyase
8. Deiodination of MIT & DIT
   
   1. location: intracellular
   2. enzyme: deiodinase

Question 7

SOM.1ai.BPM2.1.ER.1. PHYS.EN.0305. Describe the physiologic effects and mechanisms of action of thyroid hormones and clinical applications.

Answer 7

• physiologic effects
  
  • brain maturation
  • bone growth
  • beta-adrenergic effects
  • basal metabolic rate increase (lipolysis, protein breakdown & synthesis, gluconeogenesis)
  • increase RR
  • increase CO via increase BMR -> vasodilation
  • increase urea, renal function
• intracellular effects
  
  • increase
    
    • mitochondria, repiratory enzymes, Na/K ATPase, O2 consumption
• MOA
  
  • T3 & T4 enter cell
  • T4 converted to T3 by 5’-deiodinase mainly in liver & kidneys
  • T3 induces downstram function
• TSH-R receptor (basolateral) target for antibodies
  
  • stimulated = Graves disease
  • blocked = Hashimoto’s disease

Question 8

SOM.1ai.BPM2.1.ER.1. PHYS.EN.0306. . Explain how thyroid hormone is transported, metabolized and regulated

Answer 8

1. transported
   
   1. mostly bound to thyroxine-binding globulin (TBG)
   2. some bound to albumin, lipoproteins, & transthyretin
2. metabolized
   
   1. increases glucose absorption in GIT
   2. increases use of glucose, fats & proteins for energy
   3. increase effects of other hormones that increase metabolic rate
   4. decreases body weight
3. regulated
   
   1. TRH stimulates thyrotroph in AP
   2. TSH stimulates thyroid gland
   3. T3 inhibits TRH (hypothalamus) & TSH (AP)

Question 9

SOM.1ai.BPM2.1.ER.1. PHYS.EN.0307. Understand the causes and consequences of a) over secretion and b) under secretion of thyroid hormones. Explain what conditions can cause an enlargement of the thyroid gland.

Answer 9

1. hypersecretion
   
   1. thyroid enlargement (Grave’s disease)
      
      1. mostly female
      2. TSH-R-Ab antibody
         
         1. stimulates thyroid gland to secrete Thyroid hormone
         2. exophthalmos (bug eyes)
         3. pretibial myexdema
   2. overactive lump (Plummer’s Disease)
   3. toxic multinodular goiter
2. hyposecretion
   
   1. Hashimoto’s thyroiditis
   2. thyroidectomy
   3. iodide deficiency
   4. insufficient pituitary action
   5. organ resistance to TH
   6. newborns
      
      1. iodine deficiency, placental transfer of TSH-Ab
   7. children
      
      1. growth & mental retardation
   8. adults
      
      1. puffiness due to accumulation of GAGs
      2. amenorrhea (no menstration)
      3. fatigue
3. thyroid gland enlargement
   
   1. due to increase stimulus of thyroid gland to grow via TSH or TSH-R-Ab