Endo 4: Hypothyroidism

Question 1

How is TSH release controlled

Answer 1

T3 (active) and T4 negatively feedback on the hypothalatmus which releases TRH and the pituitary which releases TSH

TSH levels are like a sin wave

Question 2

What is the cause of primary hypothyroidism

Answer 2

Autoimmune damage to thyroid (low thyroxine and high TSH),

iatrogenic, post thyroidectomy, post radioactive iodine.

Question 3

Symptoms of primary hypothyroidism

What is the worst thing that happens

Answer 3

Basal metabolic rate falls –> bradycardia, weight gain with REDUCED appetite, confused/slow cerebration, deep voice, cold intolerance, constipation, eventual myxoedema coma

Note that BP can be HIGH! Autonomic activation results in vasoconstriction! So low heart rate, increased BP frequently

EVENTUALLY WILL LEAD TO MYXOEDEMA COMA

Question 4

Why is T4 a prohormone

Answer 4

it’s converted to the biologically active form (T3) by deiodinase enzyme (T3 provides almost all thryoid hormone activity).

Note that this process is targeted by PTU

Question 5

Where does the T3 come from

Answer 5

80% converted from T4, 20% directly secreted from the thyroid gland

Question 6

Where does T3 bind

Answer 6

to the heterodimer of TR and RXR in the nucleus which then binds to the TRE (thyroid response element) part of the DNA

Question 7

Which drug is given for hypothyroid patients

Answer 7

Levothyroxine sodium/thryoxine sodium= T4 replacement

Liothyronine sodium is T3 (not really used)

Question 8

Clinical use of levothyroxine

Answer 8

1. Primary hypothyroidism e.g autoimmune, iatrogenic, post thyroidectomy, post radioactive iodine.
2. Secondary hypothyroidism e.g pituitary tumour, post pituitary surgery of radiotherapy

Question 9

What is used as guidance for thryoxine dose

Answer 9

Aim to supress TSH into the reference range

Question 10

Why can’t TSH be used as a guidance for the dose of levothyroxine in secondary hypothyroidism

Answer 10

Because TSH is low due to anterior pit. failure so aim for T4 in middle of reference range

Question 11

When woud liothyronine be used and why

Answer 11

Myxoedema coma- rare complication of hypothyroidism (iv initially- onset of action faster than t4 –> then oral)

Question 12

Outline combined thyroid hormone replacement

Answer 12

Combined t3/t4- some reported improvement in well-being.

BUT complicated by symptoms of toxicity- palpitations, tremor, anxiety (combination treatment can supress TSH) i.e. showed signs of hyper!

Question 13

Half life of levothyroxine and liothyronine

Answer 13

levothyroxine- 6 days
lio- 2.5 days
(active orally but with lio you would give T3 IV for myxoedema coma)

Question 14

The vast majority of T3 and T4 is bound to which protein

Answer 14

Thyroxine binding globulin 99.97 of T4 and 99.7% is T3

Question 15

What can increase plasma binding proteins

Answer 15

increase in pregnancy and on prolonged treatment with oestrogens, phenothiazines (have to make sure you measure the free, unbound T3 or T4)

Question 16

When can thyroid binding globulin fall (or the amount of T3/T4 bound to it)

Answer 16

Malnutrition, liver disease decrease TBG

Some co-administered drugs (phenytoin and salicyclates) compete for protein binding sites.

Question 17

How would TSH plasma levels look if plotted on a graph

Answer 17

Sin wave- increase a bit, stimulating release of T3/T4 which then inhibits TSH, so level will decrease etc. etc.

Question 18

What is the small white area on the micrograph which projects into the colloid?

Answer 18

This is area of proteolytic enzyme

Question 19

What does myxoedema refer to

Answer 19

primary hypothyroidism

Question 20

What is a myxoedema coma?

Answer 20

Myxedema coma is a loss of brain function as a result of severe, longstanding low level of thyroid hormone in the blood

Question 21

What do TSH and t3/4 levels look like in primary hypo

Answer 21

TSH- high (trying to stimulate release of t3/4) t3/4- low