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In the hypothalamic-pituitary-thyroid axis what is secreted by each?
- Hypothalamus: TRH
- Anterior Pituitary: TSH
- Thyroid Gland secretes Thyroid Hormone (T4 and T3)
What is thyroid hormones backbone?
- 2 tyrosine molecules connected by an Ether Linkage.
- MIT has 1 iodide
- DIT has 2 iodides
In relationship to MIT and DIT what linkages form T4, T3, and rT3?
- T3 = MIT + DIT
- rT3 = DIT + MIT
- T4 = DIT + DIT
What is the main thyroid hormone secreted by the thyroid gland?
- (T3, to a lesser extent biologically active and Reverse T3 inactive)
Which Thyroid hormones are active? Inactive?
- Active= T3
- Inactive = T4 & rT3
T4 is a pro-hormone for T3? What enzyme catalyzes this reaction?
- T3 (T4 is de-iodinated to T3)
- Enzyme= Iodothyronine5’-deiodinase.
What & where are the 3 types of enzyme that catalyze T4 -> T3?
- Type 1: 5’-deiodinase→ converts T4 to T3 in the serum. Located in liver and kidneys.
- Type 2: 5’-deiodinase→ converts T4 to T3 intracellularly (local). Located in pituitary, brain and brown fat.
- Type 3: 5’-deiodinase→ converts T4 to reverse T3 (inactive)
What is the ½ life of T4 and T3 in humans and dogs?
- Humanes: 6 days
- Dogs: 8-16 hours
- Humans: 1 day
- Dogs: 5-6 hours
Variable Thyroid ½ lives are due to…
Plasma protein binding
What percent of T3 is from T4?
80% of T3 is derived from T4.
Which Thyroid hormone has the greatest physiological activity? By how much?
What factors increase Thyroid Levels (2)?
What factors/Dz’s decrease thyroid levels (4)?
- Liver Dz
- Kidney Dz (Dec Plasma Prot)
- Androgens (Dec TBG)
- Some Drugs (Compete with ALB binding sites)
Dogs require a Levothyroxin dosage of ____, while humans require _____. Why?
- Dogs: >20 ug/kg
- Humans: 50-150 ug/PERSON
- Increased Plasma Proteins & ½ Life
What is the role of rT3?
Has no physiologic activity.
What differentiates T3 and rT3?
The tyrosine linkage
Why do thyroid hormones in humans have a longer half-life?
Bound to plasma proteins, which protects them from degradation.
What are the three proteins that bind to thyroid hormones?
- TBG (thyroine binding globulin)
- Thyroxine-binding PreAlbumin
What major plasma protein is bound to T4?
TBG (High Affinity, Low Capacity)
What are the % of thyroid hormones protein bound in humans and dogs?
- Human= 99.8%
- Dogs= 99%
What is cretinism?
Thyroid deficiency during -> retardation.
What are the Calorigenic effects of thyroid hormone?
- Increased Metabolism (Cell Activity)
- Increase T
- Increase O2 consumption
How do thyroid hormones increase Metabolism?
- Increase Na+/K+ ATPase ->
- Increase ATP ->
- Increase Cell Activity
What is thyroid hormones effect on the cardiovascular system?
- Increase HR
- Increase Contractility
- Increase BP (cats)
- Increase O2 consumption
How does hyperthyroidism -> Tachycardia?
- Increase in B adrenergic receptor activity
- Increase Metabolic Rate.
How can Tx cause a hyperthyroid cats have 2’ Cardiovascular Problems?
- Decrease thyroid hormone =>
- Decrease BP =>
- Decrease Renal Perfusion
Would a hypothyroid dog have high or low serum cholesterol?
Why would a hypothyroid dogs have Increased Chol (2)?
- Decreased Lipoysis
- Decreased Bile Secretion
How would low thyroid levels affect the skin?
- Follicle atrophy=>
- Bilateral alopecia
- Myxedema (puffy appearance and thickened skin folds above the eyes, tragic facial expression in some dogs sue to upper eyelids drooping)
How would low thyroid levels affect reflexes?
Decreased conduction velocity in CNS.
Could facial nerve paralysis be a result of a thyroid disorder? What type?
What are the reproductive effects of thyroid hormone in males (4):
- Testicular atrophy
- Decrease lipido
- Decrease sperm production
What are the reproductive effects of thyroid hormone in Females (4):
- Absent/Irregular cycles
- Poor litter survival rate.
What causes Primary Hypothyroidism?
- Lymphocytic Thyroiditis
- Idiopathic atrophy of the thyroid gland
What causes Secondary Hypothyroidism?
Destruction of thyrotrophs in the pituitary gland tumor.
Which replacement thyroid hormone is used in dogs?
When giving Levothyroxine SID, when would you find peak T4 serum levels? Low to Normal T4 level?
- Peak: 4-6 hours after dose
- Low normal to normal: 24 hours after dose.
When giving Levothyroxine BID, when would you find peak T4 levels?
Middle of dose interval.
What is the most common cause of hyperthyroidism in cats?
Thyroid adenoma is most common cause
How does methimazole decrease thyroid synthesis?
Is a Thioureylene drug. Is a reversible anti-thyroid agent. Inhibits the iodination and coupling of thyroglobin. Metabolized by oxidation and conjugation.
Why would it be a good idea to reversibly treat hyperthyroidism initially?
It is a good idea to reversibly treat Hyperthyroidism before treating irreversibly as the kidney’s function can be compromised by the decrease in blood pressure when the thyroid levels return to normal.
Can the body distinguish between 127I- and 131I-?
Thyroid follicles cannot distinguish between 127I and 131I.
How does the use of 127I and 131I work?
NaI131 is sequestered by thyroid producing cells
What are some concerns with surgical throidectomys?
- Possibility of Ectopic thyroid tissue
- Risk of parathyroid damage