thyroid

Question 1

what 2 things does the healthy adult thyroid gland secrete

Answer 1

T3 and T4

Question 2

what is T4 (thyroxine; tetraiodothyronine) and what is its fate

Answer 2

prohormone converted by deiodinase enzyme into more active metabolite tri-iodothyronine (T3)

Question 3

relative proportions of T3 in circulation

Answer 3

80% from T4 deiodination, 20% from direct thyroidal secretion

Question 4

what does T3 provide in target cells compared to other thyroid secretions

Answer 4

almost all thyroid hormone activity which increased basal metabolic rate

Question 5

how do T3 and T4 cause altered gene expression in target cells

Answer 5

T3 and T4 enter target cells via channels -> any T4 that has entered is converted to T3 by deiodinase -> T3 binds to a retinoid x receptor (RXR) and thyroid hormone receptor (TR) -> this complex binds to a thyroid response element (TRE) on DNA -> altered gene expression

Question 6

2 drugs used in thyroid hormone replacement therapy

Answer 6

levothyroxine sodium, liothyronine sodium

Question 7

what does levothyroxine sodium mimic

Answer 7

T4 (drug of choice); converted in target cells to T3

Question 8

what does liothyronine sodium mimic

Answer 8

T3 (less commonly used)

Question 9

when is levothyroxine sodium (T4) used clinically

Answer 9

primary hypothyroidism, secondary hypothyroidism

Question 10

when treating primary hypothyroidism, how is levothyroxine sodium (T4) administered and and what is used as a dose guide

Answer 10

by oral administration, suppressing TSH into reference range through negative feedback (TSH used as guidance for dose)

Question 11

2 causes of primary hypothyroidism (myxoedema), and effect on thyroxine and TSH levels

Answer 11

autoimmune damage to thyroid or iatrogenic (post-thyroidectomy, post-radioactive iodine); thyroxine levels decline, TSH levels climb (used to diagnose)

Question 12

hypothalamic pituitary thyroid axis

Answer 12

TRH released from hypothalamus -> TSH released from anterior pituitary -> causes thyroid to make T3 and T4 -> both have direct negative feedback on pituitary and indirect negative feedback on hypothalamus

Question 13

3 causes of secondary hypothyroidism and effect on TSH

Answer 13

pituitary tumour, post-pituitary surgery, radiotherapy; low TSH as effect upstream of thryoid

Question 14

when treating secondary hypothyroidism, how is levothyroxine sodium (T4) administered and what is used as a dose guide

Answer 14

by oral administration; as TSH is low to due anterior pituitary failure, can’t use TSH as dose guide so must aim for fT4 (free T4) in middle of reference range

Question 15

what is a very rare complication of hypothyroidism

Answer 15

myxoedema coma

Question 16

what is used to treat myxoedema coma

Answer 16

initially i.v. liothyronine sodium (T3) as onset of action is much faster than T4, then oral when possible

Question 17

significance of T3 replacement vs T4 replacement

Answer 17

T4 converted to T3 by deiodinase enzyme which then has effect, so T4 administered normally as less expensive and same effect

Question 18

outcomes of combined thyroid hormone replacement (combination of T4 and T3; very expensive)

Answer 18

some reported improvement in well-being, but complicated by symptoms of ‘toxicity’ as too much thyroid hormone: palpitations, tremor, anxiety (often combination treatment suppresses TSH)

Question 19

2 pharmacokinetic features of thyroid hormone replacement therapy drugs

Answer 19

active orally, long half-life

Question 20

plasma half-life of levothyroxine (T4) and liothyronine (T3)

Answer 20

levothyroxine (T4): 6 days; liothyronine (T3): 2.5 days

Question 21

what is 99.97% of circulating T4 and 99.7% of circulating T3 bound to

Answer 21

plasma proteins, mainly thyroxine binding globulin (TBG)

Question 22

what version of thyroid hormone is available to tissues (biologically active)

Answer 22

free, unbound fraction

Question 23

when do plasma binding proteins increase (3)

Answer 23

in pregnancy, on prolonged treatment with oestrogens and phenothiazines

Question 24

when does thyroxine binding globulin fall (2)

Answer 24

malnutrition and liver disease

Question 25

what co-administered drugs compete with thyroid hormone replacement therapy drugs for protein binding sites, increasing concentration of fT4

Answer 25

phenytoin, salicylates

Question 26

T3 and T4 synthesis pathway: what 3 things does TSH stimulate thyroid follicles to do

Answer 26

synthesis and release of protein hormone thyroglobulin and enzyme thyroporoxidase into the colloid from apical membrane; iodide uptake from blood and release into colloid; uptake and transport of T3 and T4 by lysozymes from the colloid into the blood (appears as a white dot in colloid in histology)

Question 27

T3 and T4 synthesis pathway: how is iodide taken up from blood into follicular cells

Answer 27

through NIS (sodium/iodide active cotransporter), then oxidated to I2

Question 28

T3 and T4 synthesis pathway: in the nucleus what is incorporated into thyroglobulin

Answer 28

tyrosyl residues

Question 29

T3 and T4 synthesis pathway: what happens within the colloid

Answer 29

iodination of tyrosine in thyroglobulin to form mono/di-iodotyrosine, catalysed by thyroporoxidase and H2O2

Question 30

T3 and T4 synthesis pathway: what is the coupling reaction

Answer 30

where mono/di-iodotyrosine are coupled to form T3/T4, catalysed by thyroporoxidase and H2O2

Question 31

clinical signs and symptoms of hypothyroidism

Answer 31

dry and brittle hair; lethargy and depression; memory impairment; oedema of face and eyelids; thick tongue and slow speech; deep coarse voice; feel cold; diminished perspiration; enlarged heart (cardiomegaly) so poor heart sounds and precordial pain; bradycardia; hypertension; coarse, dry, scalin, cold, yellowish skin; slow pulse; ascites; menorrhagia; weight gain with reduced appetite; constipation; eventual myxoedema coma