Hypothyroidism Flashcards
Draw the hypothalamus pituitay thyroid axis
See diagram - only T4/T3 have a negative feedback effect. TSH does not have a negative feedback effect.
What is the difference between T3 and T4?
T3 is active and T4 is inactive. T3 controls basal metabolic rate. Most of T4 is converted in the liver to T3. T4 is a prohormone
What is the colloid?
The colloid stores thyroxine and is the site where thyroxine is produced - can last a month. It is also a store of thyroglobulin where it remains associated to the apical membrane.
What is primary hypothyrodism?
Myxoedema - Autoimmune damage to the thyroid meaning thyroxine levels decline but TSH levels climb.
Everything slows down
What are the symptoms of primary hypothyroidism?
Deepening of voice Depression and tiredness Cold intolerance Weight gain with reduced appetite Constipation Bradycardia Eventual myxoedema coma
Describe the thyroid hormones
T3 and T4
See notes
How does T3 have its biological effect?
T4 that gets into the cell is converted to T3 by a deiodination enzyme. T3 gets into the nucleus and binds to the heterodimer of the thyroid receptor TR and RXR. This binds to specific part of the DNA called the thyroid response element (TRE) which alters gene expression.
What is used as thyroid hormone replacement?
Thyroxine (T4) or a thyroxine salt. Because this is its inactive form it will be broken down into T3 anyway. Levothyroxine sodium (synthetic thyroxine)
Less commonly T3 can be given in the form of liothyronine sodium
Levothyroxine sodium is used to treat primary hypothyroidism. Given orally and TSH is used an guidance for the thyroxine dose. The aim is to supress the TSH to the reference range.
In patients with secondary hypothyroidism can’t use the TSH as a guide for the dose (not making much TSH). So you aim for a fT4 in the middle of the reference range.
Liothyronine sodium is only used during myxoedema coma and IV initially. This ensures active forms of the thyroxine are reaching the blood stream quickly and effectively. Then orally when possible.
You can use a combination of T4/T3
Describe the pharmacokinetics of levothyroxine and liothyronine
Active orally
Levothyroxine - plasma half life of 6 days
Liothyronine - plasma half life of 2.5 days
99.97% of T4 and 99.7% of T3 in the plasma is bound to TBG. The levels of TBG can change too.
How can the levels of TBG change in the blood plasma?
Plasma binding proteins increase in pregnancy and on prolonged treatment with oestrogens and phenothiazines
TBG falls with malnutrition, liver disease
Certain co-administered drugs (phenytoin, salicylates) compete for protein binding sites
