Hypothyroidism

Question 1

What happens inside the colloid?

Answer 1

Iodide ions in the presence of TPO and H2O2, are converted to a reactive iodine form.

I* then iodinates one (MIT) or two (DIT) positions on TG to create mono-iodotyrosines (MIT) or di-iodotyrosines (DIT) – Both are forms of TG.

TPO and H2O2 then catalyse a coupling reaction to create tri-iodothyronines (T3) or tetra-iodothyronines (T4) – Again, forms of TG.

Lysosomes then uptake clumps of colloid which is broken down to liberate T3 and T4 -> moves to the blood.

Question 2

What are the features of primary hypothyroidism?

Answer 2

myxoedema - autoimmune damage to the thyroid

Thyroxine (T4) levels low, TSH levels high.

Symptoms

• Deepening voice.
• Depression and tiredness.
• Cold intolerance.
• Weight gain, reduced appetite.
• Constipation.
• Bradycardia.
• Eventual myxoedema coma
• hypotension
• thick tongue , slow speech

Question 3

What are the thyroid hormones?

Answer 3

Thyroid gland secretes T3 and T4.

T4 – tetraiodothyronine/thyroxine/T4 = a prohormone.
- Converted into the most bioactive molecule T3 within tissues by deiodinase enzyme activity.

Circulating T3 is made up of;

• 80% from de-iodination of T4.
• 20% from direct thyroidal secretion.
• Almost ALL activity within cells is from T3.

Question 4

Describe the action of T3

Answer 4

T3 travels to the nucleus and binds to a heterodimer of TR and RXR -> then bonds onto the DNA part called the TRE -> effects!

Question 5

What is the common hormone used in thyroid hormone replacement therapy?

Answer 5

T4 - levothyroxine sodium.

Used in 3 scenarios:

• Autoimmune primary hypothyroidism.
• Iatrogenic primary hypothyroidism – e.g. post-thyroidectomy -Oral form and the dosage is based off the high TSH levels (aim to supress the TSH into reference ranges.
• Secondary hypothyroidism – e.g. pituitary tumour - Oral form BUT TSH is low due to adenohypophysial failure so you can’t use it as a guide so you aim to move the fT4 to the middle of reference range.

Question 6

When would you give T3?

Answer 6

rapid effect e.g myxodema coma

liothyronin sodium given intravenously

Question 7

What happens in thyroid hormone over-replacement?

Answer 7

Low/supressed TSH.

Adverse effects of thyroid hormone over-replacement are:

• Skeletal – increased bone turnover, reduction in bone density (osteoporosis).
• Cardiac – tachycardia, risk of dysrhythmia and atrial fibrillation.
• Metabolism – increased energy expenditure, weight loss.
• Increased beta-adrenergic sensitivity – tremor, nervousness.

Question 8

What are the half-lives of T3 and T4?

Answer 8

both long

Levothyroxine (T4) – 6 days.
Liothyronine (T3) – 2.5 days

Question 9

What percentage of T3 and T4 are bound to plasma proteins? What alters the amount of plasma protein?

Answer 9

Approx. 99.97% (T4) and 99.7% (T3) are bound to plasma proteins (PPB) (mainly TBG – Thyroxine Binding Globulin).

PPBs increase during pregnancy and during prolonged treatment with oestrogens and phenothiazines.

TBG falls with malnutrition, liver disease and certain drug treatments.

Certain co-administered drugs (phenytoin and salicylates) compete for PPB binding sites.