Thyroid Basics

Question 1

Embryology + 2 Remnants

Answer 1

• Endodermal epithelium from foregut (medial thyroid analage) thickens at day 16-17 –> form pit next to myocardial cells –> both descend into neck thru outpouched diverticulum –> stops anterior to trachea (around wk 5-7) –> contacts ultimobranchial glands (lateral analage) to incorporate parafollicular C cells which secrete calcitonin

1- Foramen cecum - remnant of the thyroid at the base of the tongue

2- Thyroglossal duct - remnant of descent; connect thyroid to base of tongue but usually atrophies at birth

Question 2

Which lobe is bigger?

Answer 2

Right

Question 3

5 Poss Abnormal Anatomies

Answer 3

• Under migration - lingual thyroid (iodine uptake test)
• Over migration - into mediastinum
• Hemi-agenesis (1 lobe does not develop)
• Complete agenesis (both lobes)
• Thyroglossal duct cysts

Question 4

Role and Sources of Iodine

Answer 4

• Need iodine (100 ug of iodine per day) for synthesis
• Iodine added by peroxidases and removed by de-iodinases or halogenases
• Iodine sources = soil (dairy from cows that eat from soil), water, seafood, seaweed OR fortified iodized salt, iodized bread OR medications (vitamins, amiodarone, tablets), betadyne can be iodine load
• Def more common inland - Midwest US, Andes, Alps, Middle East, Africa

Question 5

TBG (what is it? what inc and dec it?)

Answer 5

• TH is hydrophobic so needs proteins carrier in blood (99% bound) = thyroid binding globulin (made by liver)

DEC- Cirrhosis, nephrotic syndrome, androgen use, congenital deficiency

INC- Hepatitis, estrogen, oral contraceptives, pregnancy

Question 6

8 Steps TH Synthesis

Answer 6

• 1- iodide uptake - sodium-iodide symporter on basolateral membrane
• 2- iodide export to colloid - iodide-chloride transporter named “pendrin”
• 3- oxidation of iodide to iodine - “thyroid peroxidase” (TPO)
• 4- spontaneous attachment of iodine molecules to the phenyl rings on tyrosines in TG (“organification”) –> TG-DIT and TG-MIT
• 5- coupling - thyroglobulin folds on self so N and C termini come together and transfer iodo-phenyl groups
  
  • MIT + DIT = T3
  • DIT + DIT = T4
• 6- pinocytosis - colloid engulfed by apical pseudopods; then fuse w/ lysosomes to free hormones by degradation of thyroglobulin by proteases
• 7- hormones now free to exit basolateral side
• 8- dehalogenation to recycle iodine from DIT and MIT (otherwise they would leave thyroid - net loss of iodine)

Question 7

T3 and T4 Metabolism

Answer 7

-T4 > T3 in secretion from thyroid but T3 is active form that binds receptor w/ greater affinity

• T4 –> T3 by deiodinase (resp for 80% T3)
  
  • D1 - liver and other peripheral tissues
  • D2 - intracellular (w/in pituitary, brain and brown fat)
• D3 inactivates T3 and T4 (T4 –> reverse T3 which is inactive)
• Sulfation expediates breakdown by D3
• Glucouronidation –> excretion in bile (may be partially reabsorbed after de-glucouronidation in intestine)

Question 8

Role of TH at Cell

Answer 8

• Enters cell via MCT8
• T3 passes thru nuclear envelope and binds to specific thyroid hormone receptor (act as transcription factors - inc or dec transcription)

Question 9

Thyroid and Pregnancy

Answer 9

• Inc demand for thyroid hormone / inc iodine requirements (cont into breast feeding)
• Beta-hcg shares beta homology w/ TSH so binds TSH receptor –> stimulation of thyroid gland (causes TSH to dec in first trimester)
• Estrogen –> inc liver production of thyroxine binding globulin
• If mom has underlying hypothyroid it can be exacerbated by fetal D2 and D3 breaking down and using up mom’s thyroid hormone she does have –> goiter –> maternal hypothyroid –> fetal hypothyroid
• Embryonic thyroid can concentrate iodide and synthesize T4 in about 11th week so need moms T4 before that (T4 crosses placenta while T3 does not)
• Do not give mom radioactive iodine after 10 wks gestation b/c fetus then has own thyroid that can take it up –> thyroid destruction
• Thyroid hormone essential for fetal development; cretinism if low (mental retardation); on newborn screen

Question 10

Clinical Thyroid Eval (Steps and Tests)

Answer 10

1 - Serum TSH - most accurate/ best test UNLESS…

 - Hypothalamic or pituitary disease (cannot trust TSH level), ACUTE change in thyroid function (TSH lags by wks), thyroid hormone resistance, interference by meds/illness
- Technique - noncompetitive immunoassay; good for small conc

2 - Total T3 and T4 - used to confirm or validate TSH
- Use competitive assay b/c larger conc of T4

3- Free T3 and T4 (very low conc - most is bound)
- Can use immunoassay OR FTI (use if binding proteins are affected - ill pts in hospital)

Question 11

FTI / T3 Resin Uptake

Answer 11

• FTI - estimate of conc of free thyroid hormone
• Calc: FTI = total T4 X T3RU
• T3RU - estimates # unoccupied binding sites in pt serum and compare to normal (so corrects for diff in binding capacity, binding protein conc and altered affinity for thyroid hormone to bind TBG)
• High T3RU if pt has dec # unoccupied binding sites (AKA there were few spots for labeled T3 to go so more was trapped by resin)
• Low T3RU if pt has inc # unoccupied binding sites (AKA there were a lot of spots for labeled T3 to go and less trapped by resin)
• Process
  - Fixed labeled T3 added to assay w/ pt serum + insoluble resin binder
  - T3 binds the TBG in pt serum; any unbound T3 is trapped by resin; report % bound to resin
• Hypothyroid - low T4 so not as many sites occupied –> low T3RU –> low FTI
• Hyperthyroid - high T4 so more sites occupied –> more T3RU –> high FTI