Hypothyroidism Flashcards
09.10.2019
Draw the thyroid - hypothalamus - pituitary axis.
TRH, TSH, T3+T4
What is Myxoedema?
Primary hypoparathyroidism
- high TSH
- low T4
- autoimmune damage to the thyroid
What are some symptoms of primary hypothyroidism?
- Deepening voice
- Depression
- tiredness
- Cold intolerance
- Weight gain with reduced appetite
- Constipation
- Bradycardia
- Eventual myxoedema coma
How are thyroid hormones made?
- TSH binds to TSHR on follicular cells.
- this has multiple effects
a) I- enters cell via NIS and then colloid via pending pump
b) TPO moves to the colloid
c) TG moves to the colloid
d) reaction 1: iodination (I- -> I* + TG -> TG bound to MIT and DIT)
e) reaction 2: coupling reaction (DIT-TG-MIT -> TG bound to T3 and T4)
(both reactions via TPO and H2O2)
e) TG-T3-T4 packaged into a lysosome and then broken down into T3 and T4 g) packaged hormones are released into bloodstream
What are other names for T4?
Tetraiodothyronine, Thyroxine
Is T3 or T4 more active?
- T3 is more active
- T4 is a prohormone -> converted to T4 in the cell via deiodination
- T3 provides almost all the thyroid hormone activity in target cells.
How much of circulating T3 is due to deiodination of T4?
80% (other 20% was produced as T3)
What does T3 do inside the cell?
It binds to TRE (thyroid response element) and alters gene expression.
(RXR (retinoid x receptor) and TR (thyroid hormone receptor) also bind to TRE to produce effects)
What is thyroid hormone replacement therapy?
- Give oral thyroxine to replace the missing hormone
other names: thyroxine sodium; thyroxine;
Tetraiodothyronine; T4
Less commonly used: Liothyronine sodium
triiodothyronine; T3
Clinical use of levothyroxine sodium
Primary hypothyroidism:
- eg autoimmune, iatrogenic - post-thyroidectomy, post-radioactive iodine
- Oral administration
- TSH used as guidance for thyroxine dose - aim to suppress TSH into the reference range
Secondary hypothyroidism:
- eg pituitary tumour, post-pituitary surgery or radiotherapy
- Oral administration.
- TSH low due to anterior pituitary failure, so can’t use TSH as a guide to dose.
- Aim for fT4 middle of reference range
Clinical use of triiodothyronine
Myxoedema coma - a VERY RARE complication of hypothyroidism
-> iv initially – as onset of action faster than T4, then oral when possible
=> no clinical evidence that T3 is better, but it is more expensive!
Combined Thyroid hormone replacement
- Combination T4/T3 – some reported improvement in well-being
- Complicated by symptoms of ‘toxicity’ – palpitations, tremor, anxiety - often combination treatment suppresses TSH
Pharmacokinetics of Thyroid hormone replacement therapy
- orally active
- long plasma half life: T3=2.5d; T4: 6d;
- majority of hormone is ppb (tbg)
- only free fraction of hormones is available to tissues
What is the half life of T3?
2.5d plasma half life
What is the half life of T4?
6d plasma half life