Hypothyroidism

Question 1

thyroxine store in thyroid

Answer 1

there is enough thyroxine stored in the colloid for a month

Question 2

what happens in the colloid?

Answer 2

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.

Question 3

what causes primary hypothyroidism/myxoedema?

Answer 3

autoimmune damage to the thyroid

Question 4

what are the plasma levels of TSH and thyroxine in primary?

Answer 4

high level of TSH

low levels of T4

Question 5

symptoms of hypothyroidism

Answer 5

• deepening of voice
• bradycardia
• weight gain
• decreased appetite
• cold intolerance
• low BMR
• constipation
• depression
• tiredness
• eventual myxoedema coma

Question 6

T4

Answer 6

tetraiodothyronine - prohormone

converted into the bioactive T3 form within tissue by deiodinase activity

Question 7

circulation of T3

Answer 7

80% made from the deionisation of T4

20% made from direct secretion from thyroid

Question 8

T3

Answer 8

all activity is caused by T3 (BIOACTIVE)

• travels into nucleus
• binds to heterodimer of TR and RXR
• bonds to TRE (thyroid response element)

Question 9

what thyroxine is given in hormone replace therapy

Answer 9

T4 (over T3) so the body can actively convert it to T3

Question 10

what form is the thyroxine given in, in therapy?

Answer 10

Levothyroxine sodium

Question 11

what cases is Levothyroxine given in ?

Answer 11

1) autoimmune primary
2) iatrogenic e.g. post thyroidectomy
3) secondary e.g. pit. tumour

Question 12

administration of Levothyroxine

Answer 12

oral form
dosage based on TSH level
aim is the suppress TSH into normal parameters

Question 13

problem of finding correct dosage in secondary hypothyroidism

Answer 13

TSH is low due to the failure of the pituitary
oral form is given but TSH is not used as the guide

aim to move fT4 into the middle of the reference range

Question 14

combination therapy

Answer 14

reported improvement in well being when T3 and T4 are given together

Question 15

problem with combined therapy

Answer 15

T3 is very potent and has a toxicity effect causing palpitations, tremors and anxiety

it feels like having excess thyroxine

Question 16

what are the adverse effect of over replacement of thyroid hormones

Answer 16

skeletal- increased bone turnover, reduction in bone density (osteoporosis)

cardiac- tachycardia, risk of dysrhythmia, atrial fibrillation

metabolism- increased energy expenditure, weight loss

increased beta-adrenergic activity- tremor, nervousness

Question 17

pharmokinetics of drugs levothyroxine and liothyronine

Answer 17

orally active

Question 18

T3 drug

Answer 18

liothyronine sodium

less common, used for rapid effect in a myxoedema coma due to potency

IV administration

Question 19

half life of levothyroxine

Answer 19

6 days

Question 20

half life of liothryonine

Answer 20

2.5 days

Question 21

binding of T4 and T3 to plasma proteins

Answer 21

T4 is 99.97% bound
T3 is 99.7% bound

mainly to thyroxine Binding Globulin

Question 22

changes in TBG : increase

Answer 22

increase in pregnancy

during prolonged treatment with oestrogen and phenothiazines

Question 23

changes in TBG: fall

Answer 23

with malnutrition
liver disease
certain drug treatments e.g. co-administered drugs phenytoin and salicylate compete for PPB binding sites

Question 24

relative numbers of T4 and T3 in plasma

Answer 24

10x more T4 than T3

Question 25

clearance of T4 and T3

Answer 25

T3 cleared in hours (active form needs quick remove)

T4 cleared in 6 days (inactive form to be used)

Question 26

what would a blood test for hypothyroidism show?

Answer 26

low thyroxine

high TSH

Question 27

give an example of secondary hypothyroidism

Answer 27

Sheehan’s syndrome

the pituitary is affected due to post-partum haemorrhage