4. Hypothyroidism Flashcards
In the histology of the thyroid, what are the little white bits in the colloid?
Areas where stored thyroxine has been released into the blood stream
Summarise thyroid gland failure
- Autoimmune damage to thyroid
- 5% of population develop this
- Fall in thyroxine - start feeling cold and tired (basal metabolic rate falls)
- Pituitary detects this - produces more TSH
(biochemistry of primary hypothyroidism - myxoedema)
List the effects of primary hypothyroidism
- Tongue gets thick
- Slowed speech
- Deepened voice
- BMR falls
- Bradycardia
- General weakness
- Depression
- Cold intolerance
- Weight gain and reduced appetite
- Constipation
What does a healthy adult thyroid gland secrete?
- T4 (tetraiodothyronine/thyroxine) - a prohormone that gets converted to active T3 by deoiodinase
- 20% of T3 (80% comes from deiodination of T3)
- T3 provides almost all the thyroid hormone activity in the target cells
Describe the thyroid hormones’ mechanism of action in the target cell?
- T3 enters cell (+ T4 enters cell and is converted to T3 by deiodinase)
- T3 moves to the nucleus and binds to the thyroid hormone receptor
- Heterodimerises with a Retinoid X receptor
- This complex binds to the Thyroid Response Element => change in gene expression
What is used in thyroid hormone replacement therapy?
- Levothyroxine Sodium to replace thyroxine
* Liothyronine Sodium (rarely used - for T3 replacement)
What are the clinical uses of Levothyroxine Sodium?
- Autoimmune primary hypothyroidism
- Iatrogenic primary hypothyroidism e.g. post thyroidectomy or radioactive iodine
- Secondary hypothyroidism
How is Levothyroxine Sodium taken?
• One tablet a day, orally
• TSH levels used as guidance for thyroxine dose, so that it can be suppressed into reference range
- this can’t be used with secondary hypothyroidism
- adjust dose to achieve fT4 in the middle of the reference range, instead
What is secondary hypothyroidism?
- Problem with pituitary
- Thyroid gland is fine
- Low TSH produced, low T3/T4
What is Liothyronine clinically used for?
Myxoedema coma
• very rare complication of hypothyroidism
• IV liothyronine given as onset of action is faster than T4
• Oral thyroxine replacement then given if possible
Why would combined thyroid replacement sometimes be given and what are the problems with this?
- Some patients don’t feel better when given T4, even if TSH is normal
- They feel better when given a combination
- However, T3 is very potent - difficult for the right dose
- It will switch off TSH => symptoms of thyrotoxicosis: palpitations, tremor, anxiety
What are the adverse effects of thyroid hormone over-replacement?
• Usually associated with a low/suppressed TSH • Skeletal - increased bone turnover - reduction in bone mineral density - risk of osteoporosis • Cardiac - tachycardia - risk of dysrrhythmia • Metabolism - increased energy expenditure - weight loss • Increased β-adrenergic sensitivity - tremor - nervousness
What is the half-life of thyroid replacement drugs?
- T3 = 2-5 hours
* T4 = 6 days
Describe the relationship of the thyroid hormones and plasma proteins, and how can this change
• 99.97% of circulating T4 and 99.7% of circulating T3 bound to plasma proteins
• Mainly thyroxine binding globulin (TBG)
• Only the free, unbound hormones are available to tissues
• Plasma proteins increase in pregnancy and on prolonged treatment with oestrogens and phenothiazides
• Plasma proteins produced in liver ∴ liver disease or malnourishment => fall in TBG
• Certain drugs can compete for protein binding sites
(10x more T4 in plasma than T3)
Where and how quickly are the thyroid hormones cleared?
- Free and conjugated hormone is secreted into bile and urine
- T3 cleared in hours
- T4 cleared in around 6 days
