what are corticosteroids derived from?
cholesterol
what is aldosterone regulated by?
renin-angiotensin system and plasma potassium
describe the renin-angiotensin system?
when blood pressure fall, kidneys release renin.
renin converts angiotensinogen into angiotensin 1
ACE then converts angiotensin 1 into angiotensin 2
angiotensin 2 causes BP to increase
angiotensin 2 also causes adrenals to release aldosterone which causes salt retention and also increase BP
what are the main clinical actions of corticosteroids
anti-inflammatory]
immunosuppressant
vascoconstrictive
replacement treatment
metabolic effects of cortisol
increase blood glucose
increase lipolysis
increase proteolysis
circulatory effects of cortisol
increase cardiac output
increase BP
increase renal flow
CNS effects of cortisol
mood lability
decrease libido
euphoria
bone/connect tissue effects of cortisol
decrease collagen formation
decrease wound healing
increase osteoporosis
decrease serum calcium
most common cause of primary adrenal insufficiency
Addison’s disease
autoimmune destruction of adrenal cortex
Addison’s disease
anorexia , weight loss fatigue, lethargy dizzy low BP abdo pain D+V hyperpigmented skin tanned
Addison’s disease
what can cause primary adrenal insufficiency?
Addisons
congenital adrenal hyperplasia
adrenal TB
malignancy
best test to diagnose Addison’s?
short Synacthen test (ACTH levels will be high)
Addison’s management?
hydrocortisone and fludrocortisone
what does the hydrocortisone replace in addisons?
cortisol
what does the fludrocortisone replace in addisons?
aldosterone
in addisons what will the levels of renin and aldosterone be like?
high renin
low aldosterone
in addisons what will Na and K be like?
decreased Na
increased K
what causes secondary adrenal insufficiency?
lack of CRH or ACTH
what is the most common cause of secondary adrenal insufficiency?
exogenous steroid use
high dose prednisolone, inhaled corticosteroid etc
what is clinically different between primary and secondary adrenal insufficiency?
primary -tanned skin
secondary-pale skin as no increase in ACTH
excess cortisol
cushings
easy brusing osteoporosis increase appetite increase risk infection proximal myoptahy buffalo hump moon face central obesity
cushings
what are the ACTH dependent causes of cushings
pituitary adenoma
ectopic ACTH
ectopic CRH
what are the ACTH independent causes of cushings
adrenal adenoma
adrenal carcinoma
nodular hyperplasia
definitive test for cushings
low dose dexamethsone suppression test
what is the most common cause of cortisol excess?
Iatrogenic cause- due to prolonged high does steroid therapy
this causes chronic suppression of pituitary ACTH production and adrenal atrophy
what is conn’s syndrome?
primary aldosteronism
what the sub types of primary aldosteronism?
adrenal adenoma (conns)
bilateral adrenal hyperplasia (most common)
unilateral hyperplasia
genetic causes
how do diagnose primary aldosteronism?
- confirm aldosterone excess-do aldosteronee/renin ratio
2. confirm subtype- adrenal CT
how do you treat adrenal adenoma?
surgically
how do you treat bilateral adrenal hyperplasia?
MR antagonists- spironolactone
what is the most common congenital adrenal hyperplasia?
21 alpha hydroxylase deficiency
how do you diagnose 21 alpha hydroxylase deficiency?
basal or stimulated 17-OH progesterone
clues for phaeochromocytoma?
labile hypertension postural hypotension paroxysmal sweating, headache pallor tachycardia
nothing sometimes
the classic triad:
hypertension
headache
sweating
phaeochromocytoma
biochem abnormalities for phaeochromocytoma?
hyperglycaemia
may have low K+
lactic acidosis
the 10% tumour
phaeochromocytoma
10% maligant 10% extra adrenal 10% bilateral 10% associated hyperglycaemia 10% in children 10% familial (more like 25%)
diagnosis of phaeochromocytoma
confirm catecholamine excess- urine/ plasma
identify source- MRI abdo, whole body, PET scan
treatment for phaeochromocytoma
full alpha and beta blockade
fluid and or blood replacement
surgery-total excision where possible
chemo if malignant
can catecholamines be high in heart failure?
yes