Endocrine - Thyroid Physiology Flashcards
What are the classic hormone groups?
Amine hormones (Tyrosine derivatives)
Steroids
Peptides
Proteins
Do thyroid hormones behave like amine hormones?
Do thyroid hormones have rapid enzymatic synthesis?
No
Thyroid hormones are slow
Do thyroid hormones behave like amine hormones?
Are thyroid hormones stored in secretory granules?
No
Thyroid hormones are stored outside the cell that synthesized it
Do thyroid hormones behave like amine hormones?
Are thyroid hormones water soluble?
No
Iodides present prevent water solubility
Do thyroid hormones behave like amine hormones?
Do thyroid hormones have a long or short half-life?
Long
Do thyroid hormones behave like amine hormones?
Do thyroid hormones have a membrane receptor?
No
Thyroid Hormones hve intracellular receptors
Where are Thyroid hormones made?
In thyroid follicular cells
Sphereical epithelial cells
Define:
Colloid
What is it?
Stored thyroid hormones in the center of follicular cells
What are the three major steps of thyroid hormone synthesis?
- uptake and concentration of iodide (I-) in the gland
- Oxidation and incorporation of I- in tyrosine’s phenol ring
- Coupling of two iodinated tyrosines to form T4 or T3
Thyroglobulin is secreted and iodinated by…
Thyroid epithelial cells
What is the effect of low iodine in the body?
Decreases the rate of thyroid synthesis
What is the effect of high levels of iodine on the body?
Suppresses thyroid synthesis
Wolff-Chaikoff effect
What is the purpose of storing iodine in the body?
It protects the body from iodinen deficiency for an extended period of time
Stored I= within the gland is 100x greater than daily need (80 ug)
TH synthesis: Step 1
How is I- transported into the thyroid gland?
vs its electrochemical gradient by a 2Na+-I- symporter in the basement membrane of thyroid epithelial cells
TH synthesis: Step 1
____ block active transport of I-
ClO4-
SCN-
TH Synthesis: Step 2
Thyroglobulin
Define
Scaffold to make Thyroid Hormone
TH Synthesis: Step 2
Tyrosine Iodination
I- is oxidized and incorporated into tyrosine both by the enzyme thyroid peroxidase (TPO)
Oxidize I-l Iodinize Tyrosine
TH Synthesis: Step 2
The residues of thyroglobulin form…
MIT or DIT
TH Synthesis: Step 3
2 DIT molecules couple to form…
T4
TH Synthesis: Step 3
1 MIT and 1 DIT couple to form…
T3
What is the ratio of T4 to T3 synthesized by the thyroid gland?
10-20 T4 : 1 T3
How is thyroid hormone secreted?
Thyroglobulin enter thyroid follicular cell via endocytosis
Lysosomal proteases hydrolyze the thyroglobulin
T4 and T3 are released
MITs and DITs aew deiondinated and I- recycles
_ is the active form of Thyroid Hormone
T3
4X more potent than T4
____% of thyroid hormone secreted is T4
90%
T4 is a prohormone
____% of thyroid hormone secreted is T3
9%
____% of thyroid hormone secreted is rT3
1%
What happens to T4?
Peripheral conversion of T4 to T3 through the action of specific deiondinases
_ thyroid hormone increases with cold temperature?
T3
_ thyroid hormone increases during starvation
rT3
What is the purpose of rT3?
To eat up energy to prevent T3 use
5’MD is highly active and converts T4 into…
T3
5MD is highly active and converts T4 into…
rT3
What occurs when there is a decrease in T4 to T3 conversion?
Fasting
Malnutrition
Physicalo Trauma
Drugs
Systemic Illness
Old Age
If starving and cold, which factor wins out?
Make more T3
How do T3 and T4 circulate the blood?
70% bound to thyroxine-binding globulin (TBG) bindingh protein
29.5% bound to prealbumin and albumin
Low levels of free hormone
What is the purpose of T4 and T3 as free hormones?
Binding proteins create a reservoir of hormone
protects from acute changes in thyroid gland function
If free T4 decreases suddenly…
What happens to bound T4?
The constant release and rebinding to binding proteins can replace lost free T4
What if the liver makes more binding protein?
This can happen during pregnancy
Alterations in RBG do not disturb biolgical function (if thyroid gland is normal)
What determined hyper/hypo thyroidism?
The concentration of free hormone
What is a major stimulator of thyroid hormone stimulation?
Thyroid - Stimulating Hormone (TSH)
TSH is under negative feedback control
What is the function of TSH?
Stimulates almost every step in the pathway of TH synthesis
Stimulates growth (goiter) and vascularity (Bruit) of thyroid gland
Feedback control of Thyroid Hormone is sensitive.
Explain
Changes in thyroidh ormone levels of only 10-30% are eno9ugh to change TSH in the opposite direction
What is the relationship between T3 and TSH?
↑T3 ↓TSH
What characteristic of T4 gives it a half life of 6 days?
T4 has a higher affinity for TBG
Why is T3 the biologically active hormone?
T3 has a higher affinity for thyroid receptor
When treating hypothyroidism, why do we give synthetic T4 (Levothyroxine) instead of synthetic T3 (Liothyronine)?
Levoythroxine - mimics true physiology, low cost, lacks allergens, easy lab measurements, long half-life (↑ compliance), more stable
Liothyronine - shorter half life (multiple doses/day), expensive, harder to monitor, higher activity (dangerous)
What is the function of T3?
Brain maturation
Bone growth
β - adrenergic effects
BMR increases
4 B’s
Actions of Thyroid Hormones
Pathway
T4 → 5’-iodinase →T3 →T3 binds nuclear receptor → DNA transcription → mRNA translation → synthesis of new proteins → 4B’a functions
T3’s function in bone growth:
Growth formation
Bone maturation
T3 stimulates secretion of GH and remodeling of mineralized bone
TH accelerates shedding of skin and hair
T3’s function in BMR:
↑Na-K ATPase
↑O2 Consumption
↑Heat production
↑# and size of mitochondria
Regulates BMR
T3’s function in metabolism:
↑Glucose absorption
↑Glycogenolysis
↑Gluconeogenosis
↑Lipolysis
↑Protein synthesis and degredation
T3’s function in cardiovascular:
↑CO
↑HR, SV, contractility, SBP, ↓DBP, vasodilation, ↓ SVR
Define
Synpathomimetic
What is it? What does it do?
Many actions of high thyroid hormone levels resemble ↑ed SNS activity
reinforces CV resoponses to Epi and NE
Permissive effect for Epi and NE on lipolysis, glyconeolysis, and GNEO
Symptoms of Hyperthryoidism:
Nervousness
Insomnia
Anxiety
Restlessness
Sweating
Heat intolerance
Tremor
Weight Loss
Palpitations
Tachycardia
T3’s effect in CNS development:
T3 receptor is expressed in the brain throughout fetal life
Activity of 5’ deiodinase is augmented
Degredation of T3 is diminished
TH enhances a variety of neurally controlled functions:
↑speed and amplitude of reflexes, wakefulness, alertness, responsiveness to various stimuli, awareness of hunger, memory and learning capacity
Normal emotional tone
What happens to a fetus if a. mother has hypothyroidism and T3 is defificent in utero?
Impaired growth of the cerebal and cerebellar cortex
Imparied proliferation of axons and branching dendrites
Impaired myelinization
Irreversible brain damage if not treated immediately after birth
Biochemically: ↓RNA and protein content, protein synthesis, enzymes for DNA synthesis, NT receptors, NT synthesis
Symptoms of Congenital Hypothyroidism:
Short stature
Malformed legs
Dull expression
Intellectual disabilities
delayed puberty
muscle weakness
Define
Hypothyroidism
A deficiency of thyroid hormones
Under active thyroid
Symptoms of Hypothyroidism
Fatigue, lethargy
Weight Gain
Cold intolerance (↓BMR)
Muscle aches, stiffness
Somnolence (drowsiness)
Thinning hair
Dry Skin
Prolonged reflex times
Depression
Mental Slowness
Constipation
Amenorrhea (heavy/irregular periods)
Puffy face (myxedema)
Goiter
Water retention
Primary causes of hypothyroidism
Thyroid failure
Iodine insufficiency
↓T4&T3
↑TSH
Hashimoto’s Thyroiditis
Autoimmune, thyroid antibodies damage thyroid
Feedback works
Secondary Causes of Hypothyroidism
Pituitary or hypothalamic failure
↓T4 &T3
↓TSH
Feedback wont work
No goiter, not a problem with thyroid
Define:
Hyperthyroidism
Excess thyroid hormones
Symptoms of Hyperthyroidism:
Heat intolerant (↑ BMR)
Weight loss
Palpitations
Nervousness, anxiety, irritability
Tremor
Moist, warm skin
↑defecation frequency
Goiter
Bruit over thyroid
Pretibial myxedema (Grave’s Disease)
Fatigure
Exopthalamos, lid retraction
Forward siaplacement of eyeballs
Primary causes of Hyperthyroidism
Graves Disease
↑T4 and T3
↓TSH
Thyroid Stimulating Immunoglobulins (TSI)
Hypersecreting thyroid tumor (Toxic adenoma)
Define
Graves Disease
Autoimmune disease in which antibodies target thyroid receptor activating thyroid hormone synthesis
Stimulate gland, Goiter
Secondary Causes of Hyperthyroidism
Excess TSH or TRH
Feedback isnt working
↑T4&T3
↑TSH
What happens if you have low TSH and T3/T4?
Tropic Hormone Deficiency
Secondary Hypothyroidism
What happens if you have High TSH and Low T3/T4?
Primary failure of target endocrine organ
Primary Hypothyroidism
What happens if you have High TSH and High T3/T4?
Seecondary hyperthyroidism
Autonomous secretion of tropic hormone
TSH-secreting tumor
No feedback
What happens if you have Low TSH and High T3/T4?
Primary Hyperthyroidism
Autonomous secretion of target endocrine organ
Graves Disease; goiter
