Lecture 12: Thyroid Gland Flashcards
What hormones are produced from the thyroid gland?
Tetraiodothyronine (T4)
Triiodothyronine (T3)
Calcitonin
Which one is more common, T3 or T4?
Which one is the active form?
T4: more common
T3: active
What is the functional unit of the thyroid gland?
Thyroid follicle
What is the thyroid follicular lumen filled with?
What is it composed of?
Colloid
Newly synthesized thyroid hormones attached to thyroglobulin
What lines the thyroid follicle?
What is its function?
Cuboidal epithelial cells
Takes up iodine
What is a key enzyme for peripheral converion of T4 to T3?
Deiodinase
What can cause reduced conversion of T4 to T3?
Fasting
Medical and surgical stress
Catabolic disease
What are the eight steps of thyroid hormone synthesis?
- Thyroglobulin (which has a lot of tyrosine) is synthezied in follicular epithelial cell and pushed into the follicular lumen, awaiting iodization.
- Iodide enters follicular epithelial cell via Na+/I- symporter.
- Iodide moves to apical membrane of the follicular epithelial cell via pendrin where it meets thyroid peroxidase. Iodide is converted to iodine.
- Iodine passes through apical membrane and meets thryoglobulin in follicle.
- I2 + Thryoglobulin —-> MIT/DIT via thyroid peroxidase
- MIT/DIT remains attached to thyroglobulin in follicle until thyroid gland is stimulated to make hormones.
- MIT/DIT —-> T3/T4 via thyroid peroxidase
- When thyroid gland is stimulated, MIT/DIT + T3/T4 are endocytosed back in to follicular epithelial cell.
- Cell lysosmal membranes fuse with thryoglobulin and lysosmal proteases hydrolze peptide bonds to release MIT/DIT and T3/T4.
- T3/T4 are transported across basal membrane into blood stream. MIT/DIT remain in follicular epithelial cell and are deionated via thyroid deiodinase.
What can inhibit the Na+/I- symporter?
Perchlorate
What is pendrin?
Cl-/I- counter transporter on apical membrane of follicular epithelial cell
What happens if there is a mutation in pendrin?
- Defects in transporter across apical membrane
- Can affect cochlea –> snsorineural hearing loss
- Pendred Syndrome: hypothryoidism with goiter
What oxidizes iodide to make iodine?
Thyroid Peroxidase
Why is there more T4 produced than T3?
DIT is made much faster than MIT
What happens if there is a intrathyroid deiodinase deficiency?
Mimics dietary iodine deficiency
-can’t recycle MIT and DIT
What does PTU do?
Treat hyperthyroidism (including Grave’s)
-inhibits thyroid peroxidase in steps 3-5
What is the Wolff-Chaikoff effect?
High levels of iodine inhibits organification in step 4
(Slows down production of MIT/DIT)
How is activity of thyroid gland assessed?
What would we see for patient’s with hyperthyroidism, Grave’s, and hypothryoidism?
Assessed by radioactive iodine uptake: amount of iodine absorbed over time differs for various conditions and diseases
- Hyperthyroidism: Absorbs 75% iodine over 24 hours
- Grave’s Disease: Absorbs 70% iodine in first six hours
- Normal: Absorbs 25% of iodine over 24 hours
- Hypothyroidism: Absorbs very little over 24 hours
What is the main binding protein of T3 and T4?
What does it prefer?
Thyroxin-binding protein (TBG)
-has affinity for T4