Hypothyroidism Flashcards
Describe the steps of the mechanism for thyroxine (T3/T4) release and their effects on other parts of the mechanism.
- Hypothalamus releases TRH
- Ant. pituitary releases TSH in response to TRH
- Thyroid releases T3/T4 in response to TSH
- T3/T4 have NEGATIVE FEEDBACK on hypothalamic release of TRH and pituitary release of TSH
Which of T3 and T4 is inactive and which is active, and what does the active hormone control?
T3 active
T4 inactive
- Control basal metabolic rate (body temperature)
What is the process of T3/T4 generation and where does it take place? (diagram in notes)
- I- moves into thyroid cells surrounding colloid where it is oxidised to I2
- I2 allows creation of mono-iodo-tyrosine
- MIT is either used to form DIT (di-iodo-tyrosine) or is fed to a coupling enzyme
- The coupling enzyme catalyses the reaction between an MIT/DIT (makes T3) or DIT/DIT (makes T4)
- T3 (tri-iodo-thyronine) and T4 (thyroxine) enter bloodstream and then move to their target tissues (warms you up)
Thyroid follicular cell colloid stores thyroxine
What happens in primary hypothyroidism?
Primary - problem is the gland itself
- Autoimmune damage to the thyroid
- Thyroxine production, and thus levels, decline
- TSH levels climb (attempting to raise thyroxine levels)
What are the general effects of hypothyroidism?
Everything slows down
- Pulse slow (bradycardia)
- Feel cold/cold intolerance
- Deepness of voice
- Depression
- Tiredness/fatigue
- Weight gain w/ reduced appetite
- Sluggishness, lac of alertness
- Constipation
- Confusion (sometimes)
Eventual myxoedema coma - should never really get to this stage with today’s medicine
Two questions that may come up in the exam
1) What happens to TSH in primary hypothyroidism?
2) Give one clinical problem that such a patient might complain of.
1) Goes up - trying to revive the thyroxine levels
2) Tiredness, depression, bradycardia, weight gain, deepness of voice
A healthy adult thyroid gland secretes which hormones?
T3 - trio-iodothyronine
T4 - tetra-iodothyronine (thyroxine)
How do T3 and T4 interact and which is the more active hormone?
- T4 is a prohormone for T3, is converted by deiodinase enzyme into T3
- T3 is the more active hormone, provides almost all the thyroid hormone activity in target cells (hence the mechanism for conversion of T3 to T4)
What is the distribution of circulating T3 origin, and which hormone is released in larger quantities by the thyroid gland?
- 80% circulating T3 comes from deiodination of T4
- 20% from direct thyroidal secretion
T4 is actually the more-released hormone
How do T3/T4 cause their effect on the target cell and what part of the DNA does T3 bind to in order to alter gene expression?
Enter target cell through membrane
- T3 acts directly on DNA
- T4 is converted to T3 via deiodinase and then has its effect
TRE - Thyroid Response Element
What is the treatment method for primary hypothyroidism?
Thyroid hormone replacement therapy
What are some examples of thyroid hormone replacement drugs and which drug is usually the drug of choice?
Levothyroxine sodium aka Thyroxine sodium aka Thyroxine (T4) Liothyronine sodium (T3 replacement) - much less commonly used
T4 (levothyroxine sodium) usually the drug of choice
What is the clinical use of levothyroxine sodium (synthetic thyroxine), how is it administered and what is the dose adjusted to?
Treatment of primary hypothyroidism (since T4 isn’t being made, problem with gland)
- Oral administration (tablet)
- TSH used as a guidance for thyroxine dose - aim to suppress TSH into reference range
How is levothyroxine used to treat secondary hypothyroidism including administration and what the dose is adjusted to?
- Oral administration (tablet)
- TSH low due to ant. pituitary failure so can’t be used for reference
- Have to aim for T4 level in the middle of the reference range, little more tricky than primary hypothyroidism
What is the clinical use of Liothyronine (T3 replacement), what is the administration route, and why is it instead of T4?
Myxoedema coma - very rare complication of hypothyroidism
- IV administration as onset of action faster than T4 then given orally where possible
