Thyroid and Antithyroid Agents Flashcards
In which species is hypothyroidism most common?
Dog (and horse)
In which species is hyperthyroidism most common?
Cat
What is the most prevalent form of hypothyroidism?
Lymphocytic thyroiditis
What type of process is lymphocytic thyroiditis?
Autoimmune
What are the clinical signs associated with hypothyroidism?
Lethargy, weakness, coma, obesity, cold intolerance, skin lesions (myxedema), alopecia, infertility
What is the #2 underlying cause of demodicosis?
Hypothyroidism
What are the clinical signs associated with hyperthyroidism in a cat?
Weight loss, polyphagia, PU/PD, heat intolerance, tachycardia, tachypnea, hair loss, diarrhea, vomiting
1 MIT + 1 DIT = ?
T3
DIT + DIT = ?
T4
Where is thyroglobulin synthesized?
Follicular cells
In dogs, ____% of T4 and T3 are bound by plasma proteins.
99%
Plasma protein binding of T4 and T3 in the dog is greater than or less than that in the human?
Less than
What are the 3 plasma proteins that bind thyroid hormone?
- Thyroxin-binding globulin
- Transthyretin
- Albumin
In which species is thyroxin-binding globulin NOT found?
Cat
Rabbit
Rodent
Bird
Place the following in order of the most protein-bound T4 to the least: ruminants, horses, primates, dogs.
Primates > ruminants > horses > dogs
The more thyroid hormone bound to plasma protein, the longer its half life. What are the half lives of T4 and T3 in the dog?
T4 = 8 - 16 hours
T3 = 5 - 6 hours
What is the T4 dosage in a dog?
> 20 uL / kg / day
What is the T4 dosage in a human?
50 - 150 uL / day
How does estrogen affect TBG synthesis?
Increases TBG synthesis
How does liver/kidney disease affect thyroid hormone T1/2?
Decrease in plasma protein levels –> decreases T1/2
____% of T4 –> T3
30 - 40%
____% of T4 –> rT3
50%
How are the conjugates of the hormones excreted from the body?
Conjugates enter bile –> gut –> feces
What are the 3 enzymes involved in deiodination?
- Type 1 deiodinase
- Type 2 deiodinase
- Type 3 deiodinase
Which of the thyroid hormones are formed by Type 1 deiodinase?
T3 and rT3
Which of the thyroid hormones are formed by Type 2 deiodinase?
T3
Which of the thyroid hormones are formed by Type 3 deiodinase?
rT3
Where is Type 1 deiodinase found?
Liver and kidney
Where is Type 2 deiodinase found?
Brain (pituitary) and brown fat
Where is Type 3 deiodinase found?
Brain and placenta
Rate of T4 –> T3 increases or decreases with hypothyroidism?
Increases
Rate of T4 –> T3 increases or decreases with hyperthyroidism?
Decreases
____, a glycoprotein hormone, stimulates all steps involved in T4 synthesis.
TSH
TSH receptors are coupled to Gs, leading to ____ ____.
cAMP formation
cAMP –> ____ –> ____ –> increased protein
cAMP –> PKA-CREB –> increased mRNA –> increased protein
____ is needed for synthesis.
Iodide
T3 is ___ - ___ times as active as T4.
3 - 5X
What are the 3 main components of thyroid hormone’s calorigenic actions?
- Increased heat generation
- Increased O2 consumption
- Increased basal metabolic rate
Where is brown fat found within the body?
Between scapulas
Thorax
Abdomen
Brown fat cells contain large numbers of what?
Mitochondria
Brown fat cells contain large numbers of mitochondria with ____ ____ to generate heat.
Uncoupling proteins
Complete the pathway: Cold body temperature –> _____ –> ______ –> Increased T4
Cold body temperature –> Increased TRH –> Increased TSH –> Increased T4
Complete the pathway: Cold body temperature –> _____ –> ______ –> Increased T3 –> Increased thermogenin in mitochondria
Cold body temperature –> Increased Epi, NE –> Increased type II deiodinase –> increase T3 –> Increased thermogenin in mitochondria
What are the 4 cardiovascular effects of thyroid hormone?
- Increased CO
- Increased O2 consumption
- Increased expression of alpha-1 and beta receptors
- Increased expression of alpha-myosin heavy chain and Ca2+ channels in the myocardium
Would you expect a high or low cholesterol level in a hypothyroid patient? Why?
High cholesterol - thyroid hormones increase the conversion of cholesterol into bile acids
Thyroid hormone is needed for skin and hair turnover. What would be the dermatologic effects of hyperthyroidism?
Alopecia
Thyroid hormone is needed for skin and hair turnover. What would be the dermatologic effects of hypothyroidism?
Thickened skin (myxedema)
What is the effect of thyroid hormones on GH secretion?
Increases GH secretion & action
Thyroid hormones are critical for the development and maintenance of _____ tissue.
Neural
In which tissues do you see calorigenesis due to thyroid hormones?
- Heart
- Skeletal muscle
- Liver
- Kidney
Where is irisin found?
Within the skeletal muscle
What is the function of irisin?
Converts white fat cells (FCs) into brown fat cells (BFCs)
How would hypothyroidism affect keratin and sebum production?
Both would be increased
What are the neuromuscular effects of thyroid hormones?
Increase synthesis of proteins associated with neuromuscular activity
What are the neuromuscular consequences of hypothyroidism?
- Myopathy
- Cranial nerve VII paralysis
- Cranial nerve VIII paralysis
- CNS depression
What is the MOA of methimazole?
Blocks iodination and coupling reactions
Methimazole is 10x more potent than what?
Propylthiouracil (PTU)
Which of the following causes hemolytic anemia: Methimazole or Propylthiouracil?
Propylthiouracil (PTU)
Which of the following has less side effects: PTU or Methimazole?
Methimazole
What are the advantages of topical Methimazole?
- Convenience
2. Less GI disturbance (4%)
What are the disadvantages of topical Methimazole?
- Human hazard
2. Inconsistent absorption
What is the half-life of sodium idodide 131?
8 days