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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)
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What is thyroid hormones backbone?
- 2 tyrosine molecules connected by an Ether Linkage.
- MIT has 1 iodide
- DIT has 2 iodides
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In relationship to MIT and DIT what linkages form T4, T3, and rT3?
- T3 = MIT + DIT
- rT3 = DIT + MIT
- T4 = DIT + DIT
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What is the main thyroid hormone secreted by the thyroid gland?
- T4
- (T3, to a lesser extent biologically active and Reverse T3 inactive)
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Which Thyroid hormones are active? Inactive?
- Active= T3
- Inactive = T4 & rT3
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T4 is a pro-hormone for T3? What enzyme catalyzes this reaction?
- T3 (T4 is de-iodinated to T3)
- Enzyme= Iodothyronine5’-deiodinase.
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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)
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What is the ½ life of T4 and T3 in humans and dogs?
- T4
- Humanes: 6 days
- Dogs: 8-16 hours
- T3
- Humans: 1 day
- Dogs: 5-6 hours
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Variable Thyroid ½ lives are due to…
Plasma protein binding
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What percent of T3 is from T4?
80% of T3 is derived from T4.
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Which Thyroid hormone has the greatest physiological activity? By how much?
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What factors increase Thyroid Levels (2)?
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What factors/Dz’s decrease thyroid levels (4)?
- Liver Dz
- Kidney Dz (Dec Plasma Prot)
- Glucocorticoids
- Androgens (Dec TBG)
- Some Drugs (Compete with ALB binding sites)
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Dogs require a Levothyroxin dosage of ____, while humans require _____. Why?
- Dogs: >20 ug/kg
- Humans: 50-150 ug/PERSON
- Increased Plasma Proteins & ½ Life
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What is the role of rT3?
Has no physiologic activity.
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What differentiates T3 and rT3?
The tyrosine linkage
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Why do thyroid hormones in humans have a longer half-life?
Bound to plasma proteins, which protects them from degradation.
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What are the three proteins that bind to thyroid hormones?
- TBG (thyroine binding globulin)
- Thyroxine-binding PreAlbumin
- Albumin
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What major plasma protein is bound to T4?
TBG (High Affinity, Low Capacity)
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What are the % of thyroid hormones protein bound in humans and dogs?
- T3/T4
- Human= 99.8%
- Dogs= 99%
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What is cretinism?
Thyroid deficiency during -> retardation.
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What are the Calorigenic effects of thyroid hormone?
- Increased Metabolism (Cell Activity)
- Increase T
- Increase O2 consumption
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How do thyroid hormones increase Metabolism?
- Increase Na+/K+ ATPase ->
- Increase ATP ->
- Increase Cell Activity
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What is thyroid hormones effect on the cardiovascular system?
- Increase HR
- Increase Contractility
- Increase BP (cats)
- Increase O2 consumption
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How does hyperthyroidism -> Tachycardia?
- Increase in B adrenergic receptor activity
- Increase Metabolic Rate.
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How can Tx cause a hyperthyroid cats have 2’ Cardiovascular Problems?
- Decrease thyroid hormone =>
- Decrease BP =>
- Decrease Renal Perfusion
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Would a hypothyroid dog have high or low serum cholesterol?
High
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Why would a hypothyroid dogs have Increased Chol (2)?
- Decreased Lipoysis
- Decreased Bile Secretion
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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)
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How would low thyroid levels affect reflexes?
Decreased conduction velocity in CNS.
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Could facial nerve paralysis be a result of a thyroid disorder? What type?
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What are the reproductive effects of thyroid hormone in males (4):
- Testicular atrophy
- Decrease lipido
- Decrease sperm production
- Infertility
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What are the reproductive effects of thyroid hormone in Females (4):
- Absent/Irregular cycles
- Infertility
- Abortion
- Poor litter survival rate.
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What causes Primary Hypothyroidism?
- Lymphocytic Thyroiditis
- Autoimmune
- Idiopathic atrophy of the thyroid gland
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What causes Secondary Hypothyroidism?
Destruction of thyrotrophs in the pituitary gland tumor.
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Which replacement thyroid hormone is used in dogs?
T4
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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.
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When giving Levothyroxine BID, when would you find peak T4 levels?
Middle of dose interval.
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What is the most common cause of hyperthyroidism in cats?
Thyroid adenoma is most common cause
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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.
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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.
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Can the body distinguish between 127I- and 131I-?
Thyroid follicles cannot distinguish between 127I and 131I.
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How does the use of 127I and 131I work?
NaI131 is sequestered by thyroid producing cells
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What are some concerns with surgical throidectomys?
- Possibility of Ectopic thyroid tissue
- Risk of parathyroid damage
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