What are the two parts of the adrenal gland?
Adrenal cortex
Adrenal medulla
What are the three zones of the adrenal cortex?
Zona glomerulosa
Zona fasciculata
Zona reticularis
What hormone is produced in the zona glomerulosa of the adrenal cortex?
Mineralocorticoids
e.g aldosterone
What hormones are produced in the zona fasciculata of the adrenal cortex?
Glucocorticoids
cortisol
What hormones are produced in the zona reticularis of the adrenal cortex?
Androgens
Which cells, found in the adrenal medulla, secrete catecholamines?
Chromaffin cells
What is the precursor molecule for steroid hormones?
Cholesterol
Which axis regulates cortisol and androgen production by the adrenal cortex?
Hypothalamic-pituitary-adrenal axis
What regulates aldosterone secretion by the adrenal cortex?
Renin-angiotensin system
Which is regulated by blood pressure & renal perfusion
Corticosteroids bind to which kind of receptor?
Nuclear receptor
to alter transcription of protein
What are some
a) cardio
b) metabolic
c) bone and soft tissue
effects of cortisol?
a) Increased BP, cardiac output and renal perfusion
b) Increased blood glucose level, increased lipolysis and proteolysis, central redistribution of fat
c) Reduced serum calcium (inc. rate of onset of osteoporosis), reduced rate of wound healing
Cortisol (accelerates / dampens down) the immune response.
dampens down immune response
Which physiological processes are corticosteroids used to suppress?
Give examples of specific diseases.
Immune response
so allergic diseases like asthma, eczema and anaphylaxis
Inflammation
so inflammatory diseases like RA, UC and Crohn’s disease
In which diseases are exogenous corticosteroids used as a replacement for a deficiency in the body?
Adrenal insufficiency
e.g Addison’s disease (autoimmune reaction resulting in deficiency of cortisol), non-functioning adrenal tumours, non-functioning pituitary tumours
Aldosterone is a (glucocorticoid / mineralocorticoid) produced by the adrenal cortex.
What is its function?
mineralocorticoid
Stimulates Na+ reabsorption in the distal tubules and collecting ducts, therefore controlling sodium homeostasis and blood pressure via RAAS
What is the commonest cause of primary adrenal insufficiency?
Addison’s disease
Also consider Congenital adrenal hyperplasia
Apart from Addison’s disease, what else can cause primary adrenal insufficiency?
Congenital adrenal hyperplasia
TB
Malignancy
Adrenal insufficiency caused by a problem with the gland itself is (primary / secondary).
primary
Addison’s disease is an ___ disease.
autoimmune
What is destroyed by autoimmune reaction in Addison’s disease?
Adrenal cortex
70% of people with Addison’s disease are positive for what?
Autoantibodies
People with Addison’s disease are more likely to have other ___ diseases.
autoimmune
What are the features of Addison’s disease?
Anorexia
Weight loss
Pigmentation
Dizziness and hypotension
Abdominal pain, vomiting, diarrhoea
What kind of pigmentation is common in people with Addison’s disease?
Buccal pigmentation
What will be seen on biochemical tests of people with Addison’s disease?
Hyponatraemia
Hyperkalaemia
Hypoglycaemia
Which stimulation test is used to diagnose adrenal insufficiency?
Synacthen test
In primary adrenal insufficiency, ACTH levels will be very (high / low).
high
causing skin pigmentation
In secondary adrenal insufficiency, what will the patient’s ACTH be like?
Will they be pigmented?
Normal or low
No pigmentation
Why are aldosterone levels low in people with Addison’s?
Destruction of adrenal cortex
How should Addison’s disease be managed?
IV hydrocortisone (to replace cortisol)
Fludrocortisone (to replace aldosterone)
What is the maintenance dose of oral hydrocortisone in patients with Addison’s disease?
15-30mg
How many doses of hydrocortisone (15-30mg) in total are given to patients with Addison’s disease?
Two
to mimic diurnal rhythm
if you give after 6pm patient will be insomniac
What must be monitored in patients being treated for Addison’s disease?
Blood pressure
Potassium level
As in diabetes, patients with Addison’s disease must be educated on how to take their medication under which circumstance?
Sick days
What is the emergency presentation of Addison’s disease?
Addisonian crisis
What causes primary adrenal insufficiency?
Disease of adrenal gland itself
What causes secondary adrenal insufficiency?
Problems with hypothalamic-pituitary axis
Iatrogenic (surgery, radiotherapy)
WITHDRAWAL OF HIGH DOSE STEROID THERAPY
What is the most common cause of secondary adrenal insufficiency?
Withdrawal of high dose steroids
How does high dose steroid cessation cause secondary adrenal insufficiency?
As they are similar to cortisol, they inhibit CRH/ACTH release by negative feedback and the adrenal glands atrophy
So when you take the patient off them, their adrenal glands aren’t capable of producing enough cortisol
> Insufficiency
Are patients with secondary adrenal insufficiency pigmented?
No
normal / low ACTH
What happens to aldosterone secretion in secondary adrenal insufficiency?
Nothing
no adrenal cortex damage
How is secondary adrenal insufficiency treated?
Hydrocortisone (cortisol replacement)
Patients with central obesity, i.e lemon on matchsticks appearance, should tip you off to which adrenal disorder?
Cushing’s disease/syndrome
What causes Cushing’s syndrome?
Excess cortisol secretion by adrenal cortex
What are the features of Cushing’s syndrome?
Central obesity, abdominal striae
Acne
Moon face
Hypertension
Easy bruising
Proximal myopathy
i.e lots
Cushing’s syndrome is either ACTH ___ or ___.
dependent , independent
What causes 70% of Cushing’s disease?
Pituitary adenoma producing ACTH
As Cushing’s disease is caused by cortisol excess, how is it diagnosed?
Dexamethasone suppression test
If a patient passes a low dose dexamethasone suppression test, they don’t have Cushing’s.
If a patient fails the test, what is done next?
More tests
e.g overnight dexamethasone suppression test
What is the commonest cause of cortisol excess?
Prolonged high dose steroid therapy
causes atrophy of ACTH-producing cells and adrenal atrophy
must be weaned off steroids otherwise they will develop adrenal insufficiency
Patients presenting with hypertension under the age of 40 should always be checked for ___ adrenal disorders.
secondary
Which adrenal diseases produce
a) hypotension
b) hypertension with hyperglycaemia
c) hypertension with hypokalaemia?
a) Adrenal insufficiency
b) Cushing’s disease
c) Conn’s syndrome / primary aldosteronism
What is primary aldosteronism?
Excess aldosterone production unregulated by renin-angiotensin system
Why does primary aldosteronism cause hypokalaemia?
Loads of K+ excreted by kidneys
As it causes hypertension, many patients with Conn’s syndrome die of ___ disease.
cardiovascular
What are the main features of primary aldosteronism?
Hypertension
Hypokalaemia
Metabolic alkalosis (as H+ ions leave with potassium)
What are the two main causes of primary aldosteronism?
Adrenal adenoma - CONN’S SYNDROME
Bilateral adrenal hyperplasia
Primary aldosteronism can be caused by mutations for which channels?
Potassium channels
Which tests are used first and second-line to diagnose primary aldosteronism?
1. Aldosterone / renin ratio (A/R), abnormal if raised
2. Saline suppression test
give patient 2L saline IV, if aldosterone doesn’t drop by at least 50% then they have PA
Once you have confirmed that a patient has primary aldosteronism, how do you find out the cause?
Adrenal CT scan
Which scan shows the metabolic activity of cells and can be combined with a CT to confirm primary aldosteronism?
PET-CT scan
Gold-standard for diagnosing primary aldosteronism
If a PET-CT scan shows adrenal hyperplasia to be
a) unilateral (or an adrenal adenoma)
b) bilateral
how is it treated?
a) Unilateral adrenalectomy
b) Aldosterone antagonists
What is an aldosterone antagonist used to treat primary aldosteronism caused by bilateral adrenal hyperplasia?
Spironolactone
Apart from PET-CT, what test can be done to confirm if adrenal disease causing primary aldosteronism is unilateral or bilateral?
Adrenal vein sampling
