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Flashcards in Thyroid + cortisol Deck (18):

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