Steroids Of The Adrenal Cortex Flashcards
What are the three types of steroids stimulated by the adrenal cortex?
Glucocorticoids, mineralocorticoids and androgens
What is the syndrome associated with excess cortisol?
Cushing’s syndrome
What is the disease associated with adrenal insufficiency?
Addison’s disease
How does functional zonation happen in the adrenal cortex?
Layer specific enzymes -> different hormones made in each layer
Where does the blood flow from/to in the adrenal cortex?
Outer cortex to inner medulla
What is the action of mineralocorticoids?
Salt and water balance
What are the actions of glucocorticoids?
Metabolism and immune action
What increases release of glucocorticoids?
Stress
What are the actions of androgens?
Weak sex steroids
What does aldosterone do?
Selectively increases sodium reabsorption in the distal tubule
What does aldosterone promote?
Potassium secretion
What is an aldosterone receptor?
Mineralocorticoid receptor
Why do you have to convert cortisol -> cortisone?
Mineralocorticoid receptor has equal affinity for cortisol and aldosterone, but cortisol is more ubiquitous so to get aldosterones effects you have to get rid of cortisol
What causes the syndrome of apparent mineralocorticoid excess (AME)?
Rare inactivating mutation of cortisol -> cortisone enzyme
What is the metabolic design of cortisol?
Store glucose
What does cortisol do to store glucose?
Promote lipolysis, gluconeogenesis, insulin resistance in muscles, proteolysis
Why does cortisol promote proteolysis?
So the amino acids are available as a substrate for gluconeogenesis
Why does cortisol promote lipolysis?
Stored fats being used as energy
Why does cortisol promote insulin resistance in muscles?
To stop muscle metabolising glucose and instead use fats
What can excess cortisol lead to (metabolically)?
Hyperglycaemia and lipogenesis
What gives rise to the alpha and beta isoforms of the glucocorticoid receptor?
Alternate splicing
What does the glucocorticoid do?
Transactivation and transrepression
What is transactivation?
Enhances transcription of the target gene
What does transrepression do?
Represses transcription of target gene
What is ACTH synthesised from?
Pro-opiomelanocortin prohormone
What type of receptor is the ACTH receptor?
Melanocortin
What is the function of ADH?
Maintain pure, solute free water
What does excess ADH cause?
Excess fluid retention -> dilution of ECF and hyponatremia
What may excess circulating ACTH cause (and why)?
Skin pigmentation because ACTH can also bind to other melanocortin receptors
What are the clinical features of addisons?
Low circulating adrenal steroids
high ACTH and plasma renin
plasma [Na+] normal -low
plasma [K+] normal to high
What is Addison’s disease caused by?
Primary adrenal failure due to autoimmune
What are the symptoms of Addison’s disease?
Anorexia, weakness, fatigue, hyperpigmentation, GI symptoms and hypotension
What may the clinical features of Addison’s disease be exposed by?
Significant stressors or illness
What is the treatment for Addison’s?
Cortisol replacement
What are the two causes of Cushing’s syndrome?
Excess cortisol or excess glucocorticoid drugs
What are the clinical features of Cushing’s syndrome?
Hypertension, hyperglycaemia, central obesity, fatigue, muscle weakness, virilisation and depression, mood or psychiatric disturbances
What are the two steps of Cushing’s syndrome diagnosis?
Confirm hypersecretion of cortisol, then determine the cause
How can you determine the cause of Cushing’s syndrome?
Plasma ACTH or dexamethasone suppression test
How can you confirm hypersecretion of cortisol?
24hr urinary cortisol, or measure the cortisol at lowest point of secretion (round midnight)
How do you distinguish between cushings disease and syndrome?
Disease has an identifiable cause, syndrome doesnt
