Thyroid + cortisol Flashcards
Thyroid hormone synthesis
TSH binds to TSH R - activates thyroid follicular cell - causes iodine to enter via Na/I symporter - TPO binds iodine residues to thyroglobulin - T3/T4 stored in colloid + exocytosed into follicle + secreted when required
Thyroid pathway
Hypothalamus (TRH) - pituitary (TSH) - thyroid (T3/T4) - target tissue.
T4 gets iodinated in blood stream by deiodinase
Hypothyroidism symptoms + treatment
Bradycardia, HF, depression, psychosis, weight gain, vitiligo
Treatment - levothyroxine (synthetic T4)
Hyperthyroidism symptoms + treatment
Tachycardia, AF, anxiety, tremor, sore gritty staring eyes
Treatment - carbimazole = blocks action of TPO OR can have radioactive iodine therapy which is taken up by thyroid gland + destroys cells
Hypothyroidism pathophysiology
Worldwide - most common is iodine deficiency
UK - most common is autoantibodies to the TPO = Hashumitos thyroiditis (get inflammation + goitre then shrinkage + fibrosis)
Hyperthyroidism pathophysiology
60-80% due to Grave’s disease - have pathogenic AB for TSH R or long lasting AB that sits in TSH R - causes increased thyroid hormones
ABs can attach to tissue around eyes - lid retraction/conjunctival oedema/bulging + weakness of eye muscles
Cortisol pathway
Hypothalamus (CRH) - pituitary (ACTH) - adrenal glands (cortisol) - target tissues
Functions of cortisol
Dampens immune response + inflammation
Stimulates osteoclasts in bone
Increases blood glucose - increasing gluconeogenesis in liver, increasing insulin resistance, increasing breakdown of protein
Regulates BP - increases sensitivity of peripheral vessels to catecholamines
High cortisol symptoms
Cushing disease = pituitary tumour which releases too much ACTH
Cushing syndrome = elevated cortisol in the blood
Symptoms: protein breakdown in the body, central obesity as have increased insulin which makes central adipocytes activate lipoprotein lipase and take up glucose, buffalo hump, moonfaced, HTN, more infections
Causes of high cortisol
If pituitary origin - can be pituitary tumour releasing too much ACTH
If adrenal gland origin - can be adrenal gland carcinoma/adenoma which would show high levels of cortisol and low levels of ACTH
Could also have ectopic sites of ACTH production e.g. small cell lung cancer
Can be exogenous - comes from medications
OR endogenous - adrenal gland, pituitary problem etc
Diagnosis of high cortisol
Look at levels of free cortisol - in 24h urine sample or saliva samples at 11pm to demonstrate loss of diurnal variation
Do dexamethasone test - 1g given at 11pm and measure cortisol levels at 8am - should be low as dexamethasone blocks ACTH.
if levels are high, then need to find cause..
If have high ACTH - pituitary tumour
If have low ACTH - adrenal gland origin
High cortisol treatment
Stop meds that are causing high
Surgery to remove pituitary tumour
Metyrapone - blocks adrenal gland producing cortisol
Role of aldosterone
Activated by renin - works at the DCT:
On alpha-intercalated cells - causes H+ secretion + bicarbonate reabsorption to increase blood pH
On principal cells - causes Na-K pump to work harder so get absorption of Na + so h2o follows (K excreted)
Areas of the adrenal cortex
Zona glomerulosa - aldosterone
Zona fasiculata - cortisol
Zona reticularis - androgens
Addisons disease causes
In LEDC - from TB spreading to adrenal glands
In MEDC - autoimmune origin
Symptoms of addisons
Depends on layers damaged….
Zona glomerulosa - hyponatremia, hyperkalemia, hypovalemia, metabolic acidosis - crave salty food, dizzy
Zona fasciculata - low blood sugar so dizzy + weak, low blood pressure, also when cortisol levels are low - pituitary gland is overstimulated and produces proopriomelanocortin which is a precursor to melanocyte stimulating hormone so get bronzed skin
Zona reticularis - (rare) get reduced pubic hair + reduced sex drive (girls only as testes produce androgens)
Addisons disease treatment
Drugs - replacement aldosterone or cortisol
Addisons disease diagnosis
ACTH stimulation test - give ACTH IM and then measure cortisol. It should increase but it won’t in adrenal insufficiency
