Thyroid Gland Flashcards
Gestational deficiency of thyroid hormone will lead to what?
Cretinism (congenital hypothyroidism)
What is the functional unit of the thyroid?
Follicular cell
What cells releases calcitonin?
Parafollicular cells
Where are thyroid hormones stored?
Colloid
What is the precursor of thyroid hormones?
thyroglobin
Increased colloid will be found with HYPERthryoid or HYPOthyroid?
HYPOthyroid
Is more iodide found in stored in the thyroid or in plasma?
Thyroid storage (100:1)
*Protects against iodide deficiency
Iodide uptakes happens on the basal or apical membrane?
Basal membrane
What symporter brings iodide into the cell?
2Na/I symporter (NIS)
*Facilitated by Na/K-ATPase
What opens the anotamin-1/I channel?
TSH binding to receptor
Will NIS be up or down regulated w/ low iodide diet?
Unregulated
Loss of negative feedback due to no T3/T4 will cause what?
↑ TSH activity = goiter
With hypothyroidism, will there be increased or decreased uptake of radioactive iodide tracer?
decreased
A mutation NIS will lead to a defect in what?
Iodide transport
SX: hypothyroidism, goiter, and ↓ uptake of radio-iodide
Production of a thyroid stimulating immunoglobulin will stimulate or block the release of T3/T4?
Stimulate
Production of a thyroid stimulating immunoglobulin will ultimately lead to what with regards to the thyroid gland?
Hypertrophy and hyperplasia => goiter
In what tissues is NIS independent of TSH? (3)
- Gastric mucosa
- Placenta
- Lactating mammary glands
What are the pharmacologic inhibitors of iodide uptake? (2)
- Perchlorate
2. Thiocyanate
What are the 5 steps of thyroid hormone synthesis?
- Uptakes (basal membrane)
- Oxidation (apical membrane)
- Organification (follicular lumen)
- Coupling of iodinated tyrosines (apical membranes)
- Secretion (basal-lateral membrane)
What transports iodine to the apical membrane for it to be oxidized?
Pendrin
Goiter in childhood with progressive hearing loss is what syndrome?
Pendrin Syndrome
(due to mutation in pendrin gene)
hypothyroidism
What blocks TPO?
Propylthiouracil (PTU)
What oxidizes iodide to iodine?
Thyroid peroxidase (TPO) w/ H202 as oxidizing agent
Where does oxidation of iodine occur?
Apical membrane
Where does organification of iodine occur?
Follicular lumen
Tyrosine residues w/ TG (glycoprotein) are iodinated via TPO to form what?
Monoiodinated tyrosine (MIT) and Diiodinated tyrosine (DIT)
What is the name of the effect that temporarily blocks thyroid hormone production when plasma iodide levels are high?
Wolff-Chaikoff effect
Propylthiouracil blocks TPO in what three stages of TH synthesis?
Oxidation
Organification
Coupling
What couples MIT and DIT residues to form T3 and T4?
TPO
MIT + DIT is T3 or T4?
T3
DIT + DIT is T3 or T4?
T4
Where is T3/T4 stored until stimulated by TSH?
In colloid w/ TG
Where does coupling of iodinated tyrosines take place?
Apical membrane
Where does secretion of TH take place?
Basal lateral membrane
TSH stimulation leads to X induced endocytosis?
Megalin (folliculuar cells engulf colloid @ apical membrane)
What two substances allow T3/T4 to diffuse into the blood?
Lysosomes
Proteases
What enzymes deiodinates MIT and DIT allowing for free iodine to be recycled?
Intrathyroid deiodinase
What thyroid hormones is most abundant in the blood?
T4»_space;> T3, rT3
What transports bring TH into peripheral cells
NaTCp
Na independent OATP
LAT
MCT
Na independent OATP has a preference for T3 or T4?
T4
MCT transporter has a preference for T3 or T4?
T3
Mutations in what peripheral cell transporter is associated w/ psychomotor retardation and TH resistance?
MCT
T4 will sequentially diodinate to T3 until levels are what in the cell?
T3/T4 levels are equal
TH binds to the thyroid hormone receptor on the promotor region of DNA regulating transcription. This leads to what general effects?
Genomic effect
Does the thyroid hormone receptor have greater affinity for T3 or T4?
T3 (making it more potent)
Do genomic or non-genomic effects of thyroid hormone exert more rapid effects?
Non-genomic (do not require gene transcription) => rapid effects on ion fluxes (T3 > T4)
Stimulation of
1. Ca-ATPase (SR - heart and skeletal muscles)
2. Na and K channel activation
3. L-type Ca channel
4. Na/H antiporter in muscle
5. Na/K-ATPase
6. Amino acid uptake (cell proliferation)
are genomic or non-genomic effects of TH?
Non-genomic
Calorigenic action of TH occurs in all tissues except? (3)
Brain
Gonads
Spleen
↑ O2 consumption → ↑ basal metabolic rate (BMR) and; ↑ body temp is regulated by TH stimulating what type of pump?
↑ Na/K-ATPase pump
What effects does TH have on CV system? (5)
↑ CO
↑ ventilation
↑ chronotropic
↑ inotropic
↓ vascular resistance
Is T3 or T4 responsible for CV effects of TH?
T3
TH ↑ glucose absorption, gluconeogenesis, glycogenolysis. What impact does this have on serum glucose? Increase, decreased or maintain normal?
Normal serum glucose
Lipolysis and protein catabolism are two effects of TH. Their byproducts (glycerol and amino acids) are essential for what process?
Gluconeogenesis
TH stimulates protein synthesis/breakdown.
T or F: This results in a net degradation of tissue protein => neg nitrogen balance.
TRUE
What effect does TH have on B-adrenergic receptors (SNS) in cardiac/ skeletal muscles and adipocytes?
Increased synthesis => up regulation => more sensitive to SNS effect
How does TH impact fetal development? (4)
- Required for normal growth
- Synergistic w/ GH → bone formation
- Protein synthesis (anabolic)
- CNS maturation, axonal growth, myelination
*Dysfunction/ low levels at birth can be reversed w/ early tx
What hormones regulate the secretion of TH? (5)
- TRH
- Dopamine
- Somatostatin
- TSH
- Peripheral T3/T4
T3/T4 have a positive or negative feedback effect?
Negative. Will down regulate TSH receptors on thyrotrophs
Hepatic sulfation and glucoronide conjugation result in what with regards to TH?
↑ solubility and biliary excretion
Does free T3/T3 generated from T4 or T4 have a greater effect on regulating secretion of TH?
T3/ T3 generated from T4
Do you have a faster or slower BMR with hypothyroidism?
Slower
Hyperthyroidism w/ fast BMR
Mutation to NIS gene, Hashimoto’s, low iodide diet and Thyroiditis are associated w/ Hyper or Hypothyroidism?
Hypothyroidism
T or F: Goiter can be seen with both hyper and hypothyroidism?
TRUE
Propylthiouricil (PTU), removal of part or entire thyroid gland, radioactive I and 𝛽-adrenergic antagonist are tx for hyper or hypothyroidism?
HYPERthyroidism
Hyperprolactimemia, cold intolerance, cramp and aches are associated w/ HYPER or HYPOthyroidism?
HYPOthyroidism
High glycoprotein TG levels, increased uptake of radioactive I tracer, heat intolerance, and muscle weakness are associated w/ HYPER or HYPOthyroidism?
HYPERthyroidism
Graves disease (immunoglobulin to TSH receptor) is associated w/ HYPER or HYPOthyroidism?
HYPERthyroidism
Pendrin syndrome (hearing loss and low iodide) is associated w/ HYPER or HYPOthyroidism?
HYPOthyroidism