8 adrenal disease Flashcards
define stress
a state of threatened homeostasis or dysharmony;
how does the body respond to stress to re establish homeostasis?
- arousal, alertness, vigilance
- Redirection of energy:
- Increased CV tone, ventilation
- Increase glucose availability
- Decrease energy consuming activities (digestion and reproduction)
what is a stressor?
stimulus that induces state of stress
- psychological / emotional – anxiety, fear
- physiological - pain, fever, hypoglycaemia, injury, fluid deprivation, heavy exercise, etc.
stress response system of SNS
intergrated response
- ↑ cardiac output and ventilation
- Diversion of blood flow to muscles and heart
- Mobilisation of glycogen and fat stores
“fight or flight”
synergistic with CRH-ACTH-cortisol
stress response system of CRH-ACTH-cortisol
- Shift from protein & fat stores in favour of expanded glycogen stores and plasma glucose availability
- Amino acids available for tissue repair if physical damage
cortisol has permissive action on adrenaline and noradrenaline
synergistic with SNS & adrenaline
stress response system of RAS, ADH, GH
decreased thyroid hormones
how does cortisol have a protective function in stress activated immune responses
cortisol has an anti inflammatory effect to prevent over activation of immune defence mechanisms
effects of chronic stress with prolonged elevated cortisol levels (4)
- muscle wasting
- hyperglycaemia
- GI ulcers (increased susceptibility) : decreased production of prostaglandins in gut, responsible for mucus secretion that protect from gastric acid secretions - less protection
- impaired immune response
what is cushing’s syndrome?
excess glucocorticoid activity
what is cushing’s disease?
ACTH- secreting anterior pituitary tumour
cushing’s syndrome
why are both ACTH and cortisol levels high in an ectopic tumour of ACTH- producing cells
ectopic tumour cells lack feedback mechanism
why do ACTH levels stay high in cushing’s syndrome?
tumour cells have impaired responsiveness to negative feedback from high cortisol levels
what are the levels of CRH in cushing’s syndrome and why?
decreased due to negative feedback from increased ACTH levels
what are signs and symptoms of cushing’s syndrome?
- altered fat distribution- truncal obesity, buffalo hump, red round face
- excess adrenal androgens - acne, female frontal balding and hirtuism, menstrual irregularities, testicular atrophy
- breakdown of protein, muscle wasting, loss of collagen- thin arms and legs, muscle weakness, thin skin, purple striae
- immunosuppressant- poor wound healing, easy bruising, infections
- mental changes- cognitive difficulties, emotional instability, depression, sleep disturbances
- altered bone metabolism- osteoporosis
- hypertension (excess mineralocorticoid actiivty- sodium retention hypokalemia)
- diabetes
what is cushing syndrome’s effect on parathyroid hormone?
increased secretion due to decreased bone formation, intestinal calcium formation and increased urinary calcium excretion
what does excess glucocorticoids in childhood cause?
growth retardation
what is the diagnosis of cushing’s syndrome?
elevated plasma cortisol levels confirm diagnosis
loss of diurnal cortisol rhythm
- 24h urine free cortisol
- ACTH measurements
- dynamic tests- dexamethasone and CRH tests
explain the diagnosis of CS using DEX tests
- Low dose: confirms cushing’s syndrome (cortisol remains high or in normal range suggests CS as low dose should cause suppression)
- 2nd test High dose test to confirm the cause of cushing’s syndrome
- Cushing’ disease low cortisol (supression of ACTH)
- Adrenal gland tumour low ACTH and high/ normal cortisol
- Ectopic ACTH tumour- high ACTH and high/ normal cortisol
what are the cortisol levels of serum cortisol 9am, midnight and 24h urine cortisol tests in CS?
serum 9am: N or increased
serum midnight: increased
24h urine: increased
what is CRH stimulation test used for?
determine pituitary- dependent Cushing’s and ectopic source of ACTH
in adrenal or ectopic ACTH syndrome- no response to CRH- cortisol and ACTH levels are flat
pituitary- dependent: N or increased cortisol
how would you locate these tumours?
- ant pituitary
- adrenal
- bronchial
- ACTH secreting tumour
- MRI
- abdominal x ray
- chest x ray
- octrescan
what are some treatments of cushing’s syndrome?
surgery or radiotherapy
drugs to inhibit steroidogenesis (pre-operative or pallative, not long term therapy)
what is Conn’s syndrome?
what is the common cause?
primary hyperaldosteronism
tumour
what are the clinical findings of conn’s syndrome?
hypokalemia and weakness
chronic hypokalemia- rena; dysfunction-> polyuria
hypertension is main clinical finding
what is the treatment of Conn’s syndrome?
surgery, aldosterone receptor antagonist e.g. spironolactone
what is addison’s disease?
what type of condition is this?
primary adrenal insufficiency
(apparent when 90% of adrenal cortex is destroyed)
rare and chronic condition- failure of adrenal glands
What are some causes of destruction of adrenal tissue in Addison’s?
autoimmune, HIV or TB
what are the levels of alosterone, cortisol, androgens and ACTH in Addison’s?
low except high ACTH due to minimal negative feedback loops
what are some symptoms of Addison’s?
- postural hypotension
- muscle weakness, fatigue, lethargy
- hyponatraemia, hyperkalaemia
- increased pigmentation
- ACTH production increased, and MSH melanocyte stimulating hormone: share same POMC precursor as ACTH
- Increased melanin content in skin
- Hyperpigmentation in skin creases, old scars, gums and inside of the cheek
- weight loss, anorexia
- nausea and vomitting
what are some tests of addison’s/ adrenal failure?
- cortisol (decreased) and ACTH levels (increased)
- ACTH stimulation test
- adrenal auto-antibodies (if suspect auto-immune disease)
treatment of addison’s
life- long hormone replacement
Glucocorticoid hydrocortisone to mimic diurnal variation (two doses, AM and PM)
Mineralocorticoid fludrocortisone (daily)
Higher doses of glucocorticoids during times of illness or major stress (e.g. surgery)
what is secondary adrenal insufficiency?
what are the clinical findings?
lack of ACTH production
low cortisol, normal aldosterone (RAAS intact)
what are the causes of adrenal insufficiency?
- tumour, damage to pituitary
- secondary adrenal suppression-> exogenous glucocorticoid use
- supression of ACTH levels-> supression atrophy of adrenal cortex
when should you suspect excess glucocorticoid use?
cushingoid apperance
what happens if there is a sudden withdrawal of glucocorticoid use?
symptoms of acute adrenal insufficiency - lack of cortisol activity (weight loss, fatigue, N&V)
what is an adrenal crisis?
= Acute adrenal insufficiency expressed when patient is under stress (e.g. infection)
→ hypotension, circulatory failure, death
Urgent treatment (iv fluids, hydrocortisone, (iv then oral))
medical emergency
what is congenital adrenal hyperplasia?
inherited defect in an enzyme involved in the production of cortisol and aldosterone
>90% of CAH due to deficiency of 21β-hydroxylase
what happens in severe and less severe cases of CAH?
severe: females born with ambiguous genitalia- incorrect gender assignment
less severe: children- precocious puberty
females: virilisation (male characteristics)
what are some clinical findings of CAH?
low cortisol and aldosterone
build up of androgens
decreased negative feedback inhibition-> excess ACTH
Prolonged ACTH hyperstimulation results in hyperplasia of the adrenals
treatment of CAH
hormone replacement
plastic surgery (androgens)
