Adrenal Disease Flashcards
What are the layers of the adrenal gland?
Zona glomerulosa - produces aldosterone Zona fasciculata - produces cortisol Zona reticularis - produces androgens Adrenal medulla - chromograffin cells produce catecholamines
What is the mechanism that leads to aldosterone production?
Blood pressure falls, and is detected by the macula dense
This causes a release of renin, which catalyses the conversion of angiotensinogen to angiotensin I
ACE then converts angiotensin 1 to angiotensin 2
Angiotensin 2 acts on the adrenals to produce aldosterone
- this causes salt retention and an increase in BP
Describe the action of aldosterone.
Aldosterone binds to a mineralocorticoid receptor in the kidney tubules
This causes an increase in the action of ENaC channels (sodium from urine into the cell) and NaK pump (potassium from the blood, into the cell and sodium from the cell, into the blood). Both these things lead to increase in sodium in the blood, and water tends to follow sodium.
There is also an increase in potassium excretion into the urine
Describe the hypothalamic-pituitary-adrenal axis.
Stress, illness and the time of day act on the hypothalamus to cause release of CRH (corticotrophic releasing hormone)
CRH acts on the pituitary to increase ACTH (adrenocorticotrophic hormone) production/secretion
ACTH acts on the adrenal cortex to produce cortisol
Cortisol negatively inhibits both ACTH and CRH
In what group of people are the action of the zona reticularis important?
Children (pre-puberty)
- they don’t have any other source of androgens
What biochemical signs would you expect to see in someone with primary aldosteronism?
Hypertension Hypokalaemia Hypernatraemia Hyperaldosterone Decreased renin (being suppressed by the large amounts of aldosterone present)
What is the most common cause of secondary hypertension?
Primary aldosteronism
What is the best screening tool for primary aldosteronism?
Aldosterone-renin-ratio (ARR)
- if increased, suggests further testing
How do you confirm aldosterone excess?
Stop medications if possible, as some can affect the ARR
- beta-blockers
- MRA antagonists
Saline suppression test
Describe the saline suppression test.
Saline load (2L over 4 hours) causes volume expansion, and normally causes a decrease in aldosterone levels Suspicion arises if after four hours the aldosterone is >270pmol/l
How is the primary aldosteronism subtype identified?
CT scan
- bilateral hyperplasia
VS
- adrenal adenoma
How is primary aldosteronism managed?
Surgical
- only if adrenal adenoma
- unilateral laparoscopic adrenalectomy
- cures hypokalaemia and hypertension (in 30-70% of cases)
Medical
- MR antagonists (spironolactone or eplerenone)
- amiloride (blocks Na reabsorption by the kidney)
What are the clinical features of Cushing’s syndrome?
Weight gain Hirsutism Psychiatric Proximal myopathy Obesity (central) Plethora Moon face Hypertension Bruising Striae (red/purple)
How is Cushing’s syndrome screened for?
Two of the following
- urinary free cortisol (x3 cortisol:creatinine ratio or 24 hours urine collection for cortisol)
- dexamethasone suppression test
- late night salivary cortisol (should be undetectable/very small amounts)
Describe the dexamethosone suppression test.
A large steroid dose is given to the patient, and they are left overnight
The steroids act as a cortisol substitute and should suppress the production of ACTH and therefore cortisol
By the morning, the plasma cortisol levels should be undetectable
