addison disease Flashcards
also known as
primary adrenal insufficiency
what is addison disease
destruction of the adrenal cortex resulting in glucocorticoid (cortisol) and mineralocorticoid (aldosterone) deficiency
most common cause of addisons disease in developed countries
autoimmune destruction of the adrenal cortex
most common cause of addisons disease worldwide
tuberculosis
other causes of addisons disease
adrenal metastasis (e.g from lung, breast, renal cancer), opportunistic infections in people with HIV (CMV, mycobacterium avium), watterhouse freidrichson syndrome, congenital adrenal hyperplasia
adrenal cortex is made up of 3 layers
- zona glomerulosa
- zona fasciata
- zona reticularis
the zona glomerulosa secretes
aldosterone which is part of the renin angiotensin aldosterone system which acts to:
- decrease plasma potassium concentration
- increase plasma sodium concentration
- increase blood volume and pressure
aldosterone is secreted in response to elevated
levels of renin
how does aldosterone work
- it binds to receptors on the principal cells on the distal convoluted tubule which stimulate the Na+/K+ pump which drives potassium from the plasma into the cells which then flows down its concentration gradient to be excreted as urine
- at the same time it also drives sodium from the cell into the plasma allowing more sodium to flow from the tubule into the blood down its concentration gradient, water flows in the direction of sodium via osmosis so blood volume increases and blood pressure increases
aldosterone also stimulates
the proton ATPase in the alpha-intercalated cells causing more protons to be excreted into the urine meanwhile ion exchangers on the basal surface of the cell move the negatively charged bicarbonate ion into the extra-cellular space which increases the pH
the hypothalamus
secretes corticotrophin releasing hormones (CRH) which stimulates the anterior pituitary to secrete adrenocorticotrophin hormone (ACTH) which targets the cells of the bona fasciulata specifically causing its cells to release cortisol
cortisol main function is to
increase hepatic gluconeogenesis (glucose production from non-carbohydrate precursors) which increases the blood glucose levels
the bona reticualris cells secrete
androgens including dehydroepiandrosterone which is a precursor of testosterone, adrenal glands are involved in the production of testosterone in men and woman but in men they only contribute a tiny amount as most is produced by the testes
in males testosterone levels are
high and responsible for development of male reproductive tissue and secondary sex characteristics
in females testosterone levels are
low and responsible for growth spurt in development, underarm and pubic hair in puberty and increased sex drive during adulthood
in addisons disease
the adrenal cortex is destroyed so there is deficiency of cortisol and aldosterone so none of there processes can occur
reduction in aldosterone production
causes potassium retention and sodium and water excretion this causes
- low blood volume and blood pressure which causes a compensatory tachycardia
- hyperkalaemia and hyponatraemia
- hypoviolaemia and metabolic acidosis
reduction in cortisol
causes reduction in gluconoegensis so in times of stress can cause hypoglycaemia
why does addisons disease cause hyperpigmentation
loss of cortisol means that no negative feedback takes place so the hypothalamus produces much more CRH than normal, this stimulates the anterior pituitary to produces PROPIOMELANOCORTIN which is a precursor to ACTH and MSH (melanocyte stimulating hormone) which causes hyper pigmentation
loss of androgens (testosterone)
is not that symptomatic in males as they have enough produced from the testes out in females can cause loss of libido and sparse pubic and axillary hair
addison disease has an
insidious onset and is commonly not picked up until a major physiological stress (infection, injury, surgery) causing an ADDISONIAN crisis where there is a sudden requirement for glucocorticoids and mineralocorticoids (but mostly cortisol)
symptoms of addisons disease
- fatigue and weakness
- weight loss
- dizziness
- anorexia
- vomiting and diarrhoea
- abdominal pain
- hyper pigmentation
- postural hypotension
- sparse axially and pubic hair in females
- tachycardia
- depression
metabolic abnormalities
- ACTH levels are elevated, cortisol levels are low
- hyponatraemia and hyperkalaemia
- increased renin and low aldosterone
- hypoglycaemia
addisons is diagnosed using
the short synthacten test
measure plasma cortisol before and 30 minutes after an IV/IM injection of ACTH
- baseline >250 is normal
- post- ACTH >550 is normal
if the values are any less than these then this is abnormal
to check if addisons is caused by autoimmune destruction
adrenal autoantibodies
management of addisons disease
- hydrocortisone (to replace cortisol) 15-20mg daily
- fludrocortisone (to replace aldosterone)
hydrocortisone can cause
exogenous cushings syndrome however, STEROIDS SHOULD NEVER BE STOPPED SUDDENLY IN ANYONE AS IT CAN TRIGGER AN ADRENAL CRISIS
hydrocortisone and fludrocortisone can cause
secondary hypertension so blood pressure should be carefully monitored
acute adrenal insufficiency is also known as
adrenal crisis
acute adrenal insufficiency is
a life threatening condition where the body is acutely deprived of cortisol (and aldosterone)
causes of acute adrenal insufficiency
- patients with addisons disease who have suddenly stopped there steroids to get an acute illness infection or surgery
- patients with meningococcemia (waterhouse- fredreichsen- syndrome)
- withdrawal of exogenous steroids
- pituitary necrosis (pituitary apoplexy, sheehans syndrome)
- post- bilateral adrenalectomy
presentation
- severe vomiting and diarrhoea
- low blood pressure (hypotension)
- abdominal pain
- may have hyper pigmentation if they have addisons or a purpuric rash if caused by meningococcemia
if you suspect adrenal crisis what should you do
carry out investigations but do not wait for the results treat immediately!!
investigations of adrenal crisis
- hyponatraema and hyperkalaemia
- low cortisol and high ACTH
- hypoglycaemia
- blood urine and sputum culture is infection suspected
management of adrenal crisis
- 100mg hydrocortisone
- IV fluids
- IV glucose if they are hypoglycaemic
- IV antibiotics if you suspect meningococcaemia
waterhouse- friderichsen- syndrome
bilateral adrenal cortex haemorrhage most commonly caused by neisseria meningitidis (meningococcus)
waterhouse-friderichsen- syndrome causes
an adrenal crisis
symptoms of waterhouse- friderichsen- syndrome
- fever
- headache
- hypotension can cause shock
- purpuric rash
- abdominal pain
INVESTIGATIONS for waterhouse-friedrichsen- syndrome
treat before they come back!!
- blood cultures
- abdominal CT
- Low cortisol levels
- hypoglycaemia, hyperkalaemia, hyponotraemia
treatment of waterhouse-friedrichsen- syndrome
in ICU
- IV ceftriaxone
- IV hydrocortisone
- IV fluids
