hypothyroidism Flashcards
describe the hypathalamo-pituitary thyroid axis
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
draw the hypathalamo-pituitary thyroid axis
what is the general function of thyroid hormones
control every cell in the body determining the basal metabolic rate
what does TSH control in thyroid hormone production
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
where is thyroxine stored
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]
what is myxoedema *
primary thyroid failure
what are the causes of myxoedema *
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
signs of myxoedema *
thyroxine levels decline TSH rises because there is no -ve feedback
symptoms of myxoedema *
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
describe thyroid hormones
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
describe the mechanism of action of the thyroid hormones
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
how would you treat primary thyroidism *
thyroid replacement therapy
hormones used for thyroid replacement therapy *
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
describe the clinical use of levothyroxine *
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
causes of secondary hypothyroidism *
pituitary tumour
post-pit surgery
or radiotherapy
when would you replace T3 instead of T4 *
in myxoedema coma - severe hypothyroidism T3 given because it works quickly and is more potent given IV then switch to oral T4 when better
is combined hormone replacement better *
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
describe the pharmacokinetics of thyroid hormone replacement therapy *
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
what are the adverse effects of thyroid hormone over-replacement *
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
describe the production of thyroid hormones
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
What term is used to describe an individual who has irreversible brain damage caused by lack of thyroxine in foetal and neonatal life? *
cretin
Why is treatment of hypothyroidism essential?
patients will die otherwise
they will perform poorly
cholesterol goes up - causing death from heart attacks and strokes
features of cretinism *
slow mentation
slow growth
small height
how do you prevent cretinism *
screening
heel prick test
measure TSH
at the same time as Guthrie test for phenylketonuria
given thyroxine immediately if TSH high
