Thyroid Physiology Flashcards
What are the three major steps of thyroid hormone synthesis?
- Uptake & concentration of iodide (I-) in the thyroid gland
- Oxidation & incorporation of I- onto tyrosine’s phenol ring
- Coupling of two iodinated tyrosines to form T4 or T3
What is the minimum daily requirement of iodine? What is the US daily average intake?
Min: 80 μg
Avg: 300-400 μg
What are some sources for iodine in the diet (8)? Best (*)?
Seaweed*
Iodized table salt (since 1924)
Tuna
Cod
Shrimp
Dairy
Eggs
Lima beans
Describe the Wolff-Chaikoff effect?
When iodine intake exceeds 2 mg/day, TH synthesis is suppressed for about 10 days. Synthesis resumes via the “escape phenomenon”
How does iodine enter the cells of the thyroid gland?
Active transport down electrochemical gradient by 2Na+/ I- symporter
What is the function of thyroglobulin?
Scaffolding glycoprotein that TH grows from; contains lots of tyrosine residues
What enzyme catalyzes the oxidation and incorporation of I- onto tyrosine, as well as coupling iodinated tyrosines together?
Thyroid peroxidase (TPO)
What are MIT and DIT?
Thyroid hormone (T4 & T3) precursors
MIT: 3-monoiodotyrosine
DIT: 3,5-diiodotyrosine
What are the compositions of T3 and T4?
T3: one DIT coupled to one MIT
T4: Two DITs coupled together
______ makes up 90% of total TH secreted, _____ makes up 9%, and _____ makes up 1%.
90% T4
9% T3
1% rT3
What are the functions of T4, T3, and rT3?
T4: prohormone
T3: biologically active TH
rT3: biologic dud; made for regulation
What enzymes convert T4 into T3 vs T4 into rT3?
T4 –> T3: 5’-monodeiodinase
T4 –> rT3: 5-monodeiodinase
When temperature decrease, T3 production ______. During fasting, T3 production _______. If you are starving and cold, which factor wins out?
Decrease temp: increase T3
Fasting: decreased T3 (more rT3)
Cold wins and 5’MD is activated
Does thyroxine-binding globulin (TBG) have a greater affinity for T3 or T4?
T4
How are T3 and T4 transported in the blood?
70% bound to TBG
- 5% bound to prealbumin or albumin
- 03% free T4
- 3% free T3
True or false: alterations in TBG do not disturb biological function if the thyroid gland is normal.
True
What is the major stimulator of thyroid hormone secretion? What does it stimulate exactly?
Thyroid-stimulating hormone (TSH)
Virtually every step in TH synthesis
Growth and vascularity of the thyroid gland
What are the effects of feedback of T3 on the anterior pituitary? (3)
Represses transcription of TSH gene
Suppresses TSH release
Down-regulates TRH
Does the TH receptor have a greater affinity for T3 or T4?
T3
Why is levothyroxine chosen over liothyronine in the treatment of hypothyroidism?
Levothyroxine (synthetic T4) mimics a true physiological response
Lower cost
More stable (2yrs in dark bottle)
Lack of allergens
Easy lab measurement
Long half-life
Taken once daily
What are T3’s major functions? (4)
Brain maturation
Bone growth
β-adrenergic effects
BMR increases
How many thyroid hormone transporter proteins have been identified and how many are proven to have clinical significance?
16 identified
2 have clinical significance
How does TH regulate basal metabolic rate (BMR)? (4)
- Increase number and size of mitochondria
- Increase O2 consumption
- Increase substrate use (synthesis & oxidation of fatty acids and glucose)
- Increased Na-K ATPase activity
What does it mean for TH to be sympathomimetic?
Many actions of high thyroid hormone levels resemble increased SNS activity
How does TH reinforce cardiovascular responses to Epi and NE?
Increases the number of β- and α1-adrenergic receptors
Describe the permissive effect TH has for Epi and NE?
Increases lipolysis, glycogenolysis, and gluconeogenesis
T3 stimulates the _____ growth, development, and maturation of bone. T3 also stimulates secretion of _____.
Linear
Growth hormone
T3 is essential for the fetal development of the CNS. What is its function in the CNS in children and adults? (7)
Enhances speed and amplitude of reflexes
Wakefulness
Alertness
Responsiveness to stimuli
Awareness of hunger
Memory and learning capacity
Normal emotional tone
Describe congenital hypothyroidism. What causes it? What are its symptoms?
Cause:
Deficient TH in utero
Symptoms:
Impaired growth of cerebellar and cerebral cortices, proliferation of axons and dendrites, and myelination
Irreversible brain damage if not treated immediately after birth
Decreases all metabolic processes
What are some of the symptoms of hypothyroidism (there are a lot, but the (*) ones are most important)?
*Fatigue, lethargy
*Weight gain
Cold intolerance
Drowsiness
Thinning hair
*Dry skin
Prolonged reflex time
Depression
Mental slowness
Conspitation
Amenorrhea (heavy/irregular periods)
*Puffy face (myxedema)
*Goiter
What is the difference between primary and secondary hypothyroidism?
Primary: thyroid failure
Secondary: pituitary or hypothalamic failure
Describe Hashimoto’s thyroiditis.
Autoimmune; antibodies attack thyroid peroxidase, thyroid gland, or TSH receptors
Most common cause of hypothyroidism
How are T4, T3, and TSH levels affected in primary hypothyroidism? Can a goiter present itself?
Decreased T4 and T3
Increased TSH
Goiter possible
How are T4, T3, and TSH levels affected in secondary hypothyroidism? Can a goiter present itself?
Decreased T4 & T3
Decreased TSH
No goiter
How are T4, T3, and TSH levels affected in iodine insufficiency? Can a goiter present itself?
Decreased T4 & T3
Increased TSH
Goiters HIGHLY likely
What are some of the symptoms of hyperthyroidism (there are a lot, but ones marked (*) are most important)?
*Pretibial myxedema (Graves’ disease)
*Exophthalmos, lid retraction (Graves’ disease)
Heat intolerance (increased BMR)
Weight loss
*Nervousness/anxiety/irritability
Tremors
*Moist/warm skin
Increased defecation frequency
*Goiter
Bruit over thyroid
Fatigue
What is the difference between primary and secondary hyperthyroidism?
Primary: Graves’ disease (autoimmune)
Secondary: Excess TSH or TRH
What is the cause of Graves’ disease?
Autoimmune disease in which antibodies target thyroid receptors activate thyroid hormone synthesis (thyroid stimulating immunoglobulins or TSI)
How are T4, T3, and TSH levels affected in Graves’ disease? Can a goiter present itself?
T3 & T4 increase
TSH decreases (TSI increases)
Goiter possible
How are T4, T3, and TSH levels affected in secondary hyperthyroidism? Can a goiter present itself?
Increased T3 & T4
Increased TSH
Goiter possible
How are T4, T3, and TSH levels affected by a hypersecreting thyroid tumor (toxic adenoma). Can a goiter present itself?
Increased T4 & T3
Decreased TSH
No goiter
