steroids Flashcards
3 main adrenal issues
Destruction of adrenal tissue
- Addison’s Disease
Excess adrenal action
- Cushings Disease
Therapeutic corticosteroids
- Suppression of adrenal action
- Steroid adverse effects
where is the adrenal gland
on kidney (cap)
2 parts of adrenal gland
medulla
cortex
what is the role of the medulla in the adrenal gland
secretes adrenaline
what is the role of the cortex in the adrenal gland
secretes other hormones
3 zones in the adrenal cortex
zona glomerulosa
zona fasicularis
zona reticularis
zona glomerulosa secretes
aldosterone
Renin/Angiotensin – angiotensin II triggers aldosterone release, salt and water reabsorption
what does ATII trigger
aldosterone release, salt and water reabsorption
what does the zona fasicularis secrete
cortisol
controlled by hypothalamus/pituitary
what does the zona reticularis secrete
adrenal androgens
what does pituitary release is lack cortisol
ACTH
triggered by CRH from hypothalamus
what are the variations in adrenal hormones
largely the same compound with small conformation changes
Synthetically close but variations fit into receptors
- Tend to all come from cholesterol
- Slightly different derivatives from same precursors
Some people lack certain metabolic enzymes
3 main groups of adrenal hormones
Mineralocorticoids
Glucocorticoids
Sex hormones
what tends to be the main starting factor for adrenal hormones
cholesterol
aldosterone effect
salt and water regulation
Enhances Na+ reabsorption and K+ loss
- End product of Renin-angiotensin system
Indirect effect on blood pressure
- Causes raise in BP
- Retention of salt and water
aldosterone effect on Na+
causes reabsorption
aldosterone effect on k+
causes loss
aldosterone effect on blood pressure
Indirect effect on blood pressure
- Causes raise in BP
- Retention of salt and water
what released aldosterone
adrenal gland
- zona glomerulosa in cortex
what 2 drugs inhibit aldosterone action
ACE inhibitors
AT2 Blockers
ACE inhibitors action on Aldosterone
inhibit aldosterone (Angiotensin Converting enzyme inhibitors)
Side effects related to the fact that they inhibit enzymes, some people more effected
Side effects –
side effects of ACE inhibitors for aldosterone inhibition
Cough
- Bradykinin
angio-oedema
- sudden onset of tissue fluid
- complement system fires when there is no damage/infection
triggers cascade
- get inflammation for hour or so before recession
Oral lichenoid drug reactions (tissue reaction and infection)
AT2 blockers action on aldosterone
Block angiotensin receptor
Stops the AT2 made from working
- Reduces amount of AT2 available to work
Very specific – effective against high BP
- But other health benefits from ACE inhibitors do not get from AT2 blockers
when would drugs acting on aldosterone be commonly used
first line in BP treatmetn in young
describe how aldosterone increase blood pressure
increases salt and water reabsorption, increasing circulating volume
what type of adrenal hormone is cortisol
natural glucocorticoid
where does cortisol work
Works in the nucleus
Doesn’t work through receptor on cell surface
Receptor takes cortisol into cell and leads to protein transcription reaction
- Change in expression of cell’s nucleic acid
- Can lead to another reaction by different protein
what is the level of effect cortisol has
physiological steroid effect
relative to physiological levels, small effect as natural low level but when add steroid more severe
4 physiological effects of cortisol
Antagonist to insulin
- Gluocneogenesis, fat & protein breakdown
Make it harder for insulin to work
- Move glucose into cells, prevent ketoacidosis
- Move glucose into storage
Lowers the immune reactivity
- Duller response
Raises blood pressure
Inhibits bone synthesis
release of cortisol
circadian
nocturnal peak (like growth hormone)
what is the effect of cortisol on insuline
antagonist
need to generate energy frm breakdown of other products (fat and protein)
what controls cortisol
Inhibit pituitary ACTH
Hypothalamic cortico-releasing hormone
what is a key difference in therapeutic steroids
different levels of potency
slight chemical differences can lead to more extreme responses
what can be the effect of taking steroid tablets for a long period
swamp natural hormone effect so hypothalamus/pituitary stop making ACTH (no more additonal steroid in blood)
May not be effective quickly if taking tablets for several months
- Can’t immediately kick back into action
- Starts to atrophy
what does adreanl suppression do
stop the release system of cortisol (ACTH production)
levels drop quickly
what are the 2 roles of therapeutic steroids
Enhanced Glucocorticoid effect
Enhanced Mineralcorticoid effect
- More than expected effect
- Salt and water retention
hypertension
therapeutic steroid action of prednisolone
More effect than cortisol
- At all cortisol effects
But also mimics aldosterone
- Not same shape but similar enough to trigger aldosterone in kidney actions
- Saves top much salt and water leads to hypertension
11 possible adverse effects of therapeutic steroids
Hypertension
Type 2 diabetes
- Antagonist effect on insulin
- Raise secretion – need more insulin to keep normal
- Faster using it up the shorter time have left to use it
- More insulin needed to keep blood level constant
- Quicker progress to diabetes
Osteoporosis
- Inhibit bone synthesis
Increased infection risk
Peptic ulceration
- Changed mucosa production
Thinning of the skin
Easy bruising
Cataracts & Glaucoma
Hyperlipidaemia (atherosclerosis)
Increased cancer risk
Psychiatric disturbance
how can taking steroids for a disease cause adverse effects
given too much of a substance which naturally controls body system
what are 2 factors to take into consideration when giving steroid tablets
amount of steroid is important
- Steroid skin cream might tip into this
- Most adults with inhaled steroids (asthma)and skin cream not issue
- Children on high steroid cream
length of prescription
- few weeks some changed but return to normal
glucocorticoid hyperfunction of adrenal gland
cushings syndrome
adrenal tumour - primary
pituitary tumour - secondary (site of making ACTH)
cushings syndrome caused by
adrenal hyperfunction of glucocorticoid
aldosrerone hyperfunction of adrenal gland
Conn’s syndrome
adrenal tumour
- high level of cortisol in blood
- lots of aldosterone leads to hypertension by salt and water retention
primary hypofunction of adrenal gland
addison’s disease
- gland itself damaged or destroyed
secondary hypofuntion of adrenal gland
pituitary failure
- tumour squashed cells that make ACTH
2 casues of Conn’s syndrome
excess aldosterone/ adrenal hyperfunction
adrenal tumour adrenal hyperplasia (rare)
causes of cushing’s syndrome (4)
excess glucocorticoid
CUSHINGS DISEASE
- pituitary tumour
- then leads to high level of ACTH
- 70% spontaneous Cushing’s patients
Adrenal adenoma or hyperplasia
- Syndrome is tumour in pituitary/ adrenal or taken tablets in larger physiological need
- Symptoms and signs of excess glucocorticoid
Ectopic ACTH production
- Some Lung tumours – excess cortisol made due to ACTH in excess
excess steroid tablets for disease treatment
5 cushing’s syndrome signs
centripetal obesity
- moon face
- buffalo hump
- Fat collection at back of neck
hypertension
thin skin & purpura
muscle weakness
Osteoporotic changes & fractures
8 cushing’s syndrome symptoms
diabetes mellitus’ features
- thirst, peeing, tiredness
poor resistance to infections
- less ability to fight of fungal and candida
osteoporotic changes
- back pain & bone fractures
psychiatric disorders
- depression
- emotional lability
- psychosis
hirsuitism
skin and mucosal pigmentation
amenorrhoea, impotence & infertility
- all related to adrenal androgens and these are similar to corticosteroids
Abdominal striae
- thinning of skin
- stretch marks – purple marks where torn and bleeding into surface
MSH
melanocyte stimulating hormone
alpha MSH in ACTH seqeunce
what effect can be seen in melanocytes of excess ACTH
ACTH in excess will have noticeable effect on melanocytes
- Develop pigmentation of skin and mucosa
- Can show in the mouth more than skin as a response to high ACTH levels
2 causes of adrenal hypofunction
gland failure
pituitary failure
3 possible causes for adrenal gland failure in hypofunction
autoimmune gland destruction In Western World
- adrenal failure from adrenal antibodies
infection
- more globally
- especially Tuberculosis
infarction
2 possible causes of pituitary failure in adrenal hypofunction
compression from other adenoma
Sheehan’s syndrome
- Sudden drop in BP causes sudden drop in adrenal secretions
- E.g. bleeding at birth
- Recover drop in BP but pituitary gland no longer functioning
what is the biggest worldwide cause of Addison’s disease
TB
addison’s disease
primary hypofunction of adrenal gland
describe the onset for addison’s disease usually
slow
months
what are potential causes of addison’s disease
Previously TB a major cause in UK
- TB still the biggest worldwide cause
Autoimmune adrenalitis - (90%)
- Organ-specific Autoimmune disease
- thyroid, diabetes mellitus, Pernicious anaemia
outcome of addison’s disease
death
not enough adrenal hormones
need to have hormone replacement to keep them alive
4 signs of addison’s disease
postural hypotension
- salt and water depletion
- absence of ALDOSTERONE and aldosterone effects of GLUCOCORTICOIDS
- standing up and feel faint
- not enough capacity in blood stream to pump to head
weight loss & lethargy
- not retaining fluid
- loss fluid = loss weight
- losing fat too (energy)
hyperpigmentation (not in secondary hypofunction)
- - scars, mouth, skin creases
pigmentation effect of increased ACTH secretion by pituitary
—–in attempt to try and trigger cortisol but not functioning
causes excess MSH
—–often in areas of skin trauma as melanocytes overreact
vitiligo associated
3 symptoms of addison’s disease
weakness
anorexia
loss of body hair (females)
3 investigations for cushing’s syndrome
high 24hr urinary cortisol excretion
abnormal dexamethasone suppression tests
- feedback suppression of cortisol via ACTH
CRH test
- cushings disease show rise in ACTH with CRH
2 investigations for Addison’s disease
high ACTH level
negative synACTHen tests
- No plasma cortisol rise in response to ACTH injection
what hormone is high in cushing’s disease
cortisol
hyperfunction of adrenal due to pituitary adenoma or ectopic ACTH production causes
high ACTH
high cortisol
hyperfunction of adrenal due to gland adenoma causes
low ACTH
high cortisol
hypofunction of adrenal due to pituitary failure causes
low ACTH
low cortisol
and will have positive synACTHen test
(gland is OK but pituitary failure, inject synACTHen and should rise)
hypofunction of adrenal due to gland destruction causes
high ACTH
low cortisol
and will have negative synACTHen test
(nothing to response to ACTH)
how to treat adrenal hyperdunction
detect cause
- pituitary
- adrenal
- ectopic (lung)
surgery
- pituitary (transsphenoidal surgery)
- adrenal - partial/complete adrenalectomy
what is a severe outcome of addison’s disease
crisis
- hypotension
- vomiting
- eventual coma/collapse
Absence of MINERALOCORTICOID and mineralocorticoid effects of GLUCOCORTICOIDS
- CRISIS takes time to develop
- hypopvolaemic shock
- Hyponatraemia low sodium
what are the symptoms of addison’s crisis
low BP
collapse
low Na
treat with salty water
replace cortisol and aldosterone to maintain health
2 drugs used to manage addison’s disease
cortisol
fludrocortisone - mimics aldosterone
how does addison disease treatment need to vary with environment
cortisol dose varies
- increased by physical/psychological stress
- increased by infection
treatment for persistent vomiting
IV steroids and hospital admission
treatment of significant infection in Addison’s disease
Double oral cortisol dose during illness
Acute infections e.g. ‘herpes’
not for ‘mild cold’ ‘stressful day at work’
physiological stresses cause increase work on body
- not defined – need to be aware of potential problems and enquire
preoperative cortisol management of Addison’s disease
for GA need 100mg hydrocortisone on induction (BNF)
- repeat every 8hrs
- halve every 24hrs until day 5 - then normal dose
what is steroid prophylaxis
increase the steroid dose when increased physiological requirement anticipated:
- infection
- Surgery
- Physiological stress
e.g. mandible surgery, 3 molars extracted
Not psychological stress
influence of addison’s disease in pregnancy
NO routine increase in hydrocortisone dose
- seek advice
LABOUR
- DOUBLE oral dose for 24hrs
increase dose for a ‘few days’
Is having a tooth out worse than childbirth?
- Decide each case on merit for steroid cover!
- Art rather than a science!
steroid cover in Addison’s Disease for routine restorative treatment
no cover needed
steroid cover in Addison’s Disease for simple dental extractions
no cover usually needed
steroid cover in Addison’s Disease for minor oral surgery
give steroid prophylaxis
steroid cover in Addison’s Disease for spreading dental or facial infection
give steroid prophylaxis
do patients on therapeutic steroids have a tendency for hyper or hypotension
hypertension
do pt with addison’s disease have a tendency for hyper or hypotension
hypotension
type of steroid replacement in addison’s disease pt
physiological replacement
20-30mg hydrocortisone
type of steroid replacement in therapeutic steroid pt
supra-physiological
10mg Prednisolone = 40mg hydrocortisone
is there need for increase dose/cover for above 15mg Prednisolone at treatment
no case for increase dose/cover
is there need for increase dose/cover for 1-15mg Prednisolone at treatment
cover with double oral dose if required
perioperative’ period -
surgery day + 2days
- NO evidence base!
Low risk - have exogenous + endogenous steroids
is there need for increase dose/cover for pt who have stopped prolonged systemic steroids in last 3 months
cover with 100mg IM dose if required
highest risk?
preoperative period
surgery day and 2 days
how to manage addisonian crisis
Treat the problem
- hypovolaemia, hyponatraemia, hyperkalaemia
FLUID RESUSCITATION
- SALINE infusions
- —–Volume expansion with colloid if shock present
- corticosteroids IV
- ——100mg hydrocortisone every 6hrs
- correct hypoglycaemia
- ——present in CRISIS only
- treat precipitating event
- ——infection
dental aspects with steroids
steroid precautions
liase with physician for infections/illness
?diabetes or CV disease
Candidiasis in Cushings
Oral pigmentation in Addison’s/Cushings
9 causes of oral pigmentation
Racial
SMOKING
Melanotic Macule
Drugs
- Oral Contraceptive pill
- Minocycline
- Antimalarials
- AZT
Pigmented Naevus
Pregnancy
Chronic
Trauma
Melanoma
