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
What is the half life of T3 and T4?
T3: 1 day
T4: 6 days
How does a T3 resin test work?
Indirectly assess circulating TBG
- TBG has an affinity for T4 and it out competes T3 for TBG
- More free T3 in the blood as a result
- Resin test can check how much T3 is in the blood, giving us an indirect idea for how much T4 there is
What can we expect from a resin test with an individual who has hyperthyroidism?
- Increased T3 resin uptake
- Increased T4
- TBG stays same
Since there is more total T4, there are even fewer spaces for T3 to bind to TBG –> more free T3 to bind to resin
What can we expect from a resin test with an individual who has hypothyroidism?
- Decreased T3 resin uptake
- Decreased T4
- TBG stays same
Since there is less total T4, there are more spaces for T3 to bind to TBG –> less T3 to bind to resin
What can we expect from a resin test with an individual who has increased TBG?
- Decreased T3 resin uptake
- Increased T4
Since there is more TBG, there will be an increase of binding to both T4 and T3 –> less T3 to bind to resin
What can we expect from a resin test with an individual who has decreased TBG?
- Increased T3 resin uptake
- Decreased T4
Since there is less TBG, there will be a decrease of binding to both T4 and T3 –> more T3 to bind to resin
What can we expect from a resin test with an individual who has hepatic failure?
- Increased T3 resin uptake
- Decreased TBG
Since there is less TBG, there will be a decrease of binding to T3 –> more T3 to bind to resin
What can we expect from a resin test with an individual who is pregnant?
- Decreased T3 resin uptake
- Increased TBG
Since there is more TBG, there will be an increase of binding to T3 –> less T3 to bind to resin
How does TSH compare to GH?
TSH is realeased at a steady state while GH is pulsatile
What are the general actions of TSH?
- Increased metabolic activity: BMR, CHO, lipid metabolism
- Growth
- Increased cardiac output
- CNS development and exciation
- GI motility
What actions does TSH have on the thyroid gland?
- Increases synthesis and secretion of thyroid hormone
- Trophic effect on thyroid gland
What important proteins do thyroid hormones help synthesize?
- Na+/K+ ATPases
- Structural proteins
- Metabolic enzymes
- Cardiac muscles cells:
- B1-adrenergic receptors
- Myosin
- Ca2+ ATPAse
How does the thyroid hormone affect metabolism?
Increased metabolic activity: BMR, CHO, lipid metabolism
- Increased oxygen consumption
- Increased activity of Na+/K+ ATPases
- Injection of T4 can increase BMR
Why are patients with hypothyroidism at risk for blindness?
Thyroid hormones stimulate lipid metabolism, which is needed for conversion of carotene to Vit A. Without lipid metabolism, hypothyroid patients can sufffer from blindess and yellowing of skin.
How do thyroid hormoes affect cardiovascular activity?
Increased Cardiac Output
- Decreased TPR/systemic resistance
- Increased blood volume/preload
- Increased contractility and force of contraction
- Increase of B1-adrenergic receptors
- more sensitive to sympathetic nervous system
How does thyroid hormone affect growth?
- Fetal development requires proper thyroid hormone levels
- Works with GH and somatomedins to promote bone formation
How does a defiencey in thyroid hormones affect CNS development?
- Abnormal synaptic development
- Decreased dendritic branching and myelination
What is cretinism?
Fetal hypothyroidism
- Feeding problems
- Respiratory difficulty
- Protruding tongue
- Curse facial features
- Growth and mental retardation
- Jaundice
- Dry skin
- Hypotonia
What are symptoms of hyperthyroidism?
- Weight loss
- Sweating
- Rapid heart rate
- High BP
- Heat Intolerance
What are symptoms of hypothyroidism?
- Body functin slows down
- Fatigue
- Weight gain
- Cold intolerance
What is Grave’s disease?
Primary hyperthyroidism
- TSH receptors are activate without TSH*
- TSH levels are low*
What are symptoms of Graves’ Disease?
- Exopthalmos: abnormal protrusion of eyebeall and periorbital edema
- Increased thyroid-stimulating immunoglobulins
- Increased T3 and T4
What can cause hypothyroidism?
Primary
- Gland destruction
- Hashimoto’s Thyroiditis: autoimmune disorder
- Inhibition of thyroid hormone syntehsis are release
- Iodine deficiency
- enzyme defects
Pituitary Disease
Hypothalamic Disease
What are treatments for hypothyroidism?
Replacement doses of T4
Higher doses in young patients
What is Hashimoto’s Thyroiditis?
- Autoimmune disorder: TPO antibodies
- low T3 and T4 secretion
- Trophic effect –> goiter
- TSH levels increase
What is Sheehan Syndrome?
Postpartum hypopituitarism due to necrosis of pituitary gland
- Difficulties with lactation
- Amenorrhea
- Endocrine dysfunction
What can lead to goiter?
Hyperthyroidism
- Grave’s Disease
- TSH-producting tumor
Hypothryoidism
- Lack of adequate iodine
- Chronic thyroiditis
