Therapeutic Use of Adrenal Steroids Flashcards
Name the 3 parts of the adrenal cortex and the steroids that each produces.
Zona Glomerulosa: Aldosterone
Zona Fasciculata: Cortisol
Zona Reticularis: Sex Steroids
What hormone controls the production of adrenal sex steroids and cortisol?
ACTH
What controls the production of aldosterone?
Angiotensin II
State 4 triggers of aldosterone release
Hyperkalaemia
Hyponatraemia
Drop in renal blood flow
Beta-1 adrenoceptor stimulation
What is the principle action of aldosterone?
Increases Na+ reabsorption
Increases K+ excretion
State 3 differences between glucocorticoid receptors and mineralocorticoid receptors.
GRs are widely distributed, MRs have a discrete distribution (kidney)
GRs are selective for glucocorticoids, MRs can’t distinguish between cortisol + aldosterone
GRs have a low affinity for cortisol, MRs have a high affinity for cortisol
Describe how MRs are protected from cortisol stimulation.
11-beta hydroxysteroid dehydrogenase-2 converts cortisol to the inactive cortisone to prevent it from interacting with MRs
Why do you get hypokalaemia in Cushing’s syndrome?
Excess cortisol overloads the 11-beta-HSD-2 system so the cortisol binds to MRs + has mineralocorticoid effects.
Name 3 glucocorticoid drugs in order of decreasing mineralocorticoid activity.
Hydrocortisone (highest mineralocorticoid activity)
Prednisolone
Dexamethasone (no mineralocorticoid activity)
What does prednisolone tend to be used for?
Immunosuppression
Used in asthma, RA + other inflammatory diseases
What does dexamethasone tend to be used for?
Acute anti-oedema
E.g. used clinically for brain metastases where there is a lot of oedema
Name an aldosterone analogue.
Fludrocortisone
How are the steroid drugs administered?
Orally
Hydrocortisone + Dexamethasone can be administered parenterally (IV or IM) in high doses
Describe the extent of plasma protein binding in each of the 4 steroid drugs.
They bind to plasma proteins: corticosteroid binding globulin + albumin
Hydrocortisone is extremely plasma protein bound ~90-95%
Prednisolone is less bound
Dexamethasone + fludrocortisone are even less bound
Fludrocortisone only binds to albumin
Where are the corticosteroid drugs metabolised and how are they excreted?
Hepatic metabolism
Excreted in the bile + urine
Describe the half-lives of the 3 glucocorticoid drugs in order of increasing half-life (shortest half-life first):
Hydrocortisone (8 hours)
Prednisolone (12 hours)
Dexamethasone (40 hours)
State 4 reasons for giving corticosteroid replacement therapy
Primary adrenocortical failure (Addison’s)
Secondary adrenocortical failure (ACTH deficiency)
Acute adrenocortical failure (Addisonian crisis)
Congenital adrenal hyperplasia (CAH)
State 2 causes of primary adrenocortical failure.
Addison’s disease
Chronic adrenal insufficiency
What is the usual treatment for primary adrenocortical failure?
Lack of cortisol + aldosterone so need to give:
Hydrocortisone
Fludrocortisone
What is secondary adrenocortical failure?
Adrenal gland itself is fine but there is a problem with the pituitary gland (ACTH deficiency)
There is NORMAL aldosterone production (because aldosterone isn’t dependent on ACTH)
So only cortisol needs to be replaced
Describe the treatment of secondary adrenocortical failure.
HYDROCORTISONE (titrate dose to mimic normal physiology)
What is the treatment for acute adrenocortical failure (Addisonian Crisis)?
IV saline (0.9% sodium chloride) (suffering from a salt losing crisis) High dose hydrocortisone (IV): binds GR + overwhelms 11B HSD 2 thus binds to MR 5% Dextrose (if hypoglycaemic)
What is the most common cause of congenital adrenal hyperplasia?
21-hydroxylase deficiency
Describe the ACTH levels in CAH and explain the effect this has on steroid synthesis.
High ACTH: because no cortisol is being produced so there is no negative feedback on the hypothalamo-pituitary axis
High ACTH means that the sex steroid synthesis pathway is turned on + there is an increase in adrenal sex steroids
What are the consequences of CAH in childhood?
CAH caused by partial enzyme deficiency can result in virilisation + precocious puberty
How do you treat CAH?
Replace cortisol with high dose hydrocortisone (2-3/day) or dexamethasone (1/day)
Replace aldosterone with fludrocortisone
To replace cortisol + to suppress the ACTH axis to reduce adrenal sex steroid production
How do you monitor/ diagnose CAH?
Measure 17a-hydroxyprogesterone levels
Monitor them clinically – are they complaining of hirsuitism/acne (GC dose too low) or cushingoid (GC dose too high) symptoms?
When would you change the dose of hydrocortisone in CAH?
Minor illness
Surgery
How does cortisol production change when placed under stress e.g. when ill?
We make 10X more to aid recovery
What should patients with adrenocortical failure do to prevent a crisis?
Wear a MedicAlert bracelet + carry a steroid alert card
