Hypothyroid disorders

Question 1

What does the thyroid gland secrete

Answer 1

Tetraiodothyronine (Thyroxine, T4), a pro hormone
Converted by deiodinase enzyme into
Tri-iodothyronine (T3), more active form

Question 2

What are the proportions of circulating T3

Answer 2

80% from iodination of T4

20% from direct thyroidal secretion

Question 3

Give the mechanism for conversion of T4 into T3

Answer 3

1. T4 enters the cell
2. Conversion to T3 via deiodinase enzyme
3. T3 binds to the TH receptor on the nucleus
4. Transcription of genes and proteins synthesis
5. T3 stimulated metabolic activity in the mitochondrion

Question 4

What is used for thyroid hormone replacement therapy

Answer 4

Levothyroxine sodium
T4, thyroxine sodium,

Liothyronine sodium
T3

Question 5

What is levothyroxine sodium used for

Answer 5

Primary hypothyroidism

Secondary hypothyroidism

Question 6

How is levothyroxine administrated for primary hypothyroidism and what is used to guide the dose

Answer 6

Autoimmune iatrogenic - post-thyroidectomy, post-radioactive iodine
Oral administration
TSH used as a guidance for the dose (aim to suppress TSH in the reference range)

Question 7

How is levothyroxine administrated for secondary hypothyroidism and what is used to guide the dose

Answer 7

pituitary tumour, post-pituitary surgery, radiotherapy
Oral administration
TSH low due to anterior pituitary failure so TSH cannot be used
Aim for free T4 to be in the middle of reference range

Question 8

What is liothyronine used for and how is it administered

Answer 8

Myxoedema coma (very rare)
IV initially, then orally

Question 9

What is combined thyroid hormone replacement and what are its complications

Answer 9

Mix of T3 and T4
Reported that it improved well being
Complicated by symptoms of toxicity - palpitations, tremor, anxiety - often combination treatment suppresses TSH

Question 10

What are the pharmacokinetics of thyroid hormone replacement drugs

Answer 10

Active oral 
Long half-life 
T3 - 2.5 days
T4 - 6 days
99% of T4 and T3 are bound to plasma proteins (TBG)

Question 11

What is myxoedema

Answer 11

Primary hypothyroidism
Autoimmune damage to the thyroid
Thyroxine levels decline
TSH levels increase

Question 12

What are the symptoms of primary hypothyroidism

Answer 12

Deepening voice
Depression and tiredness 
Cold intolerance
Weight gain and reduced appetite
Constipation
Bradycardia
Eventual myxoedema coma

Question 13

What are the actions of TH

Answer 13

Fetal growth and development
Untreated congenital hypothyroidism/cretinism
Increase basal metabolic rate
Protein, carb and fat metabolism
Potentiate actions of catecholamines
Effects on the GI, CNS, reproductive system

Question 14

How is thyroid hormone release regulated

Answer 14

TRH in the hypothalamus stimulates thyrotrophs to make TSH. T4/3 suppress the production of TSH.

Question 15

How many iodide affect thyroid hormone release

Answer 15

Inhibits release of thyroid hormones (wolff-chaikoff effect)

Question 16

What other factors may affect thyroid hormone release

Answer 16

Oestrogens (+)

Glucocorticoids (-)

Question 17

When may fT4 and fT3 proportions change

Answer 17

Plasma binding proteins increase in pregnancy and prolonged treatment with oestrogen and phenothiazines
TBG falls with malnutrition and liver disease
Certain co-administered drugs (e.g. phenytoin, salicylates) compete for protein binding sites