Hypothyroidism Flashcards
What can you see in a histological sample of the thyroid?
White chunks in the colloid where colloid has been taken up to have the thyroxine liberated to then pass into the blood
What happens inside the colloid
[1] Iodide ions in the presence of TPO and H2O2, are converted to a reactive iodine form. [2] 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. [3] TPO and H2O2 then catalyse a coupling reaction to create tri-iodothyronines (T3) or tetra-iodothyronines (T4) – Again, forms of TG. [4] Lysosomes then uptake clumps of colloid which is broken down to liberate T3 and T4 -> moves to the blood.
What causes primary hypothyroidism? (myxoedema)
Autoimmune damage to the thyroid
What are the thyroxine and TSH levels in myxoedema?
Thyroxine LOW
TSH HIGH
What are the symptoms of primary hypothyroidism?
Deepening voice Depression and tiredness Cold intolerance Weight gain, reduced appetite Constipation Bradycardia Eventual myxoedema coma EVERYTHING SLOWS DOWN
What does the thyroid gland secrete?
T3 and T4
What is circulating T3 made up of?
80% from de-iodination of T4
20% from direct thyroidal secretion
What happens to T3 when it travels to the nucleus?
It binds to a heterodimer of TR and RXR, which then bonds onto the DNA part called the thyroid response element which causes effects
What happens to T4 in the body
It is a prohormone that is converted into the most bioactive molecule T3 within tissues by deiodinase enzyme activity
What is the thyroxine given to hypothyroid patients - thyroid hormone replacement therapy
Levothyroxine sodium
It is a T4 hormone that is converted by the body into T3
What are the three scenarios that levothyroxine sodium is used?
Autoimmune primary hypothyroidism
Iatrogenic primary hypothyroidism eg post thyroidectomy
Secondary hypothyroidism eg pituitary tumour
What is the T3 drug that is given sometimes and why is it used? How is it given?
Called Iiothyronine sodium and is used when you want a rapid effect eg in a myxoedema coma and is given intravenously
What is combined thyroid hormone therapy and why is it asked for and why is it not used?
Some people reported an improvement in well being when patients are given a combination of T4 and T3 but T3 is so potent that you often get effects of excess hormones and a ‘toxicity’ effect - palpitations, tremours, anxiety etc from low TSH also NHS doesn’t agree with using T3 when T4 just as effective so its hard to get away with giving T3
What are the adverse effects of thyroid hormone over replacement?
Low or supressed TSH leads to
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.
What are the half lives of Levothyroxine and Liothyronine?
Levothyroxine (T4) – 6 days.
Liothyronine (T3) – 2.5 days
