hypothyroidism

Question 1

describe the hypathalamo-pituitary thyroid axis

Answer 1

hypothalamus is at the top of the control chain - secretes TRH hormones these cause the ant pit to produce TSH these act on the thyroid gland causing it to release T3 and T4

Question 2

draw the hypathalamo-pituitary thyroid axis

Answer 2

Question 3

what is the general function of thyroid hormones

Answer 3

control every cell in the body determining the basal metabolic rate

Question 4

what does TSH control in thyroid hormone production

Answer 4

iodine entry into cells and the enzyme that releases thyroxine from the cell (if the thyroid gland is over active there is more enzyme that releases thyroxine from the cell)

stimulate the release of stored thyroxine

Question 5

where is thyroxine stored

Answer 5

in colloid which also contains thyroglobulin colloid is in the middle of the follicle, and is surrounded by cells there is enough stored thyroid for 1 month [IMAGE OF FOLLICLE]

Question 6

what is myxoedema *

Answer 6

primary thyroid failure

Question 7

what are the causes of myxoedema *

Answer 7

autoimmune damage - Ab attack thyroid and wipe it out - this is Hashimoto’s thyroiditis (chronic autoimmune thyroiditis which is characterised by lymphocytic invasion of the thyroid gland and anti-thyroid peroxidase (TPO) antibodies)

iatrogenic - post-thyroidectomy, post radioactive iodine

Question 8

signs of myxoedema *

Answer 8

thyroxine levels decline TSH rises because there is no -ve feedback

Question 9

symptoms of myxoedema *

Answer 9

hair dry and brittle LETHARGY memory impairment, slow cerebration oedema of face and eyelids thick tongue, slow speecg DEEP COURSE VOICE COLD diminished perspiration heart enlarged poor heart sounds pericardial pain hypertension skin course, dry, scaling PULSE SLOW BRADYCARDDIA ascites amenorrhoea weakness prolonged reflexes DEPRESSION TIREDNESS WEIGHT GAIN WITH REDUCED APPETITE CONSTIPATION EVENTUAL MYXOEDEMA COMA

Question 10

describe thyroid hormones

Answer 10

healthy adult thyroid secretes T4 and T3 T4 (tetraiodothyronine) is a prohormone - converted to T3 by deiodination enzymes in the target cell 80% T3 is from T4 deiodination 20% is from direct thyroidal secretion T3 is the most metabolically active and provides most of the activity in target cells

Question 11

describe the mechanism of action of the thyroid hormones

Answer 11

T4 and T3 enter target cell T4 converted to T3 by deiodination reaction T3 form heterodimer with RXR (retenoid x receptor) and TR (thyroid hormone receptor) heterodimer binds to part of DNA - thyroid response element (TRE) and alters gene expression

Question 12

how would you treat primary thyroidism *

Answer 12

thyroid replacement therapy

Question 13

hormones used for thyroid replacement therapy *

Answer 13

levothyroxine sodium, thyroxine Na, thyroxine - all mean salt of thyroxine (T4) - this will be converted to T3 to make the biological effects liothyronine Na, triiodothyronine - T3 less commonly used

Question 14

describe the clinical use of levothyroxine *

Answer 14

treats primary hypothyroidism oral admin the aim is to normalise TSH levels -the levothyroxine provides -ve feedback for TSH - TSH level is used for guidance for treatment, when it is in the normal range that is the correct levothyroxine dose for that patient it is converted to T3 to have an effect treats secondary hypothyroidism - TSH is low so free T4 (fT4) is used as the guidance for the dose - aim for middle of reference range for fT4 oral admin

Question 15

causes of secondary hypothyroidism *

Answer 15

pituitary tumour

post-pit surgery

or radiotherapy

Question 16

when would you replace T3 instead of T4 *

Answer 16

in myxoedema coma - severe hypothyroidism T3 given because it works quickly and is more potent given IV then switch to oral T4 when better

Question 17

is combined hormone replacement better *

Answer 17

no randomised control trial saying that T3 is better and it is more expensive NHS England wont support prescription for T3 anymore no reason because T4 is converted to T3 T3 is v potent - difficult to get dose right - end up having low TSH below reference range - have sympyoms of hyperthyroidism T3 use is complicated by symptoms of toxicity - palpitations, tremor, anxiety and irritability some patients have reported better psychological outcomes and psychometric tests on T3/4 combinations, better QOL on T3 replacements

Question 18

describe the pharmacokinetics of thyroid hormone replacement therapy *

Answer 18

active orally half life long T4 = 6 days, T3 = 2.5 days - so lack of compliance isn’t the end of the world 99.97% T4 and 99.7% T3 are bound to plasma proteins = mainly thyroxine binding globin (TBG), transthyretin and albumin - only free hormone is active this is what is measured, plasma binding proteins increase in pregnancyand on long term treatment with oestrogens and phenothiazines, fall with malnutrition (not getting proteins) and liver disease. some co-administered drugs eg salicylates compete for protein binding sites

Question 19

what are the adverse effects of thyroid hormone over-replacement *

Answer 19

usually associated with low TSH because of -ve feedback major targets of thyroid hormones are the skeleton, heart and metabolism skeletal - increased bone turnover because the osteoclastic resorption of bone is stimulated out of proportion to the osteoblastic remineralisation, also there is a reduction in bone mineral density and risk of development for osteoporosis cardiac- tachycardia, risk of dysrhythmia, particularly afib metabolism - increased energy expenditure, weight loss

increased B -adrenergic sensitivity caused by thyroxine - tremor, nervousness

Question 20

describe the production of thyroid hormones

Answer 20

TSHR on basolateral membrane stimulated by TSH

stimulates up take of iodide through the sodium iodide symporter

at the apical membrane the iodide enters the colloid

TSHRstimulate production of thyroglobulin protein

iodine is added to the AA with tyrosyl residues - iodination catalysed by TPO (thyroid peroxidase)

this forms monoiodotyrosine and diiodotyrosine

Question 21

What term is used to describe an individual who has irreversible brain damage caused by lack of thyroxine in foetal and neonatal life? *

Answer 21

cretin

Question 22

Why is treatment of hypothyroidism essential?

Answer 22

patients will die otherwise

they will perform poorly

cholesterol goes up - causing death from heart attacks and strokes

Question 23

features of cretinism *

Answer 23

slow mentation

slow growth

small height

Question 24

how do you prevent cretinism *

Answer 24

screening

heel prick test

measure TSH

at the same time as Guthrie test for phenylketonuria

given thyroxine immediately if TSH high

Question 25

what investigations would you do to diagnose hypothyroidism *

Answer 25

blood test - TSH, fT3/4 and thyroid peroxidase Ab (inhibit TPO)

TSH high

T3/4 low

Question 26

what is secondary hypothyroidism *

Answer 26

when the problem is wiyth the piuitary

the solution is to remove the pit gland

Question 27

why are females more susceptible to thyroid disease

Answer 27

the immune system attacks the thyroid - autoimmune

more mistakes like this occur in females because of response in pregnancy