How is the production of adrenal steroids controlled?
Hyperkalaemia and hyponatraemia, reduced RBF and b1 stimulation causes angiotensinogen release into aldosterone secretion
What are the principal physiological actions of adrenal steroids?
Cortisol- essential for life, aldosterone - promotes Na retention and K loss, androgens/oestrogens - main source from gonads
What are the 2 types of corticosteroid receptors?
Glucocorticoid receptor (cortisol) and mineralocorticoid receptor (Aldosterone)
How do the glucocorticoid and mineralocorticoid receptors compare?
How are the mineralocorticoid receptors protected from cortisol?
By 11 beta-hydroxysteroid dehydrogenase which converts cortisol into cortisone -> cortisol can activate both GR and MR in HEALTH -> explains why hypokalaemia can occur in cushing's syndrome, as when cortisol is very high it overwhelms 11bHSD, so activates MR = also explains why they're hypertensive
Which receptor is hydrocortisone selective to?
GR/MR; Glucocorticoid with mineralocorticoid activity (overwhelmed 11bHSD) at high doses
Which receptor is prednisolone selective to?
GR, weak MR; Glucocorticoid with weak mineralocorticoid activity
Which receptor is dexamethosone selective to?
GR; Synthetic glucocorticoid with no mineralocortiod activity
Which receptor is fludrocortisone selective to?
MR; Aldosterone analogue used as aldosterone substitute
Which corticosteroid drugs are administered orally?
Hydrocortisone, prednisolone, dexamethasone and fludrocortisone
Which corticosteroid drugs are administered parenterally (IV, IM)?
Hydrocortisone and dexamethasone -> when quick administration is needed
How are corticosteroid drugs distributed?
They bind to CBG and albumin as circulating cortisol does
How long do hydrocortisone, prednisolone and dexamethasone act for?
Hydrocortisone = 8h; prednisolone = 12h; dexamethasone = 40h
Which conditions need corticosteroid replacement therapy?
Primary adrenocortical failure (Addison's disease); secondary adrenocortical failure (ACTH deficiency); Acute adrenocortical failure (Addisonian crisis); congenital adrenal hyperplasia
How is Addison's disease treated and what symptoms do they have?
Patients lack cortisol and adosterone -> treat with hydrocortisone and fludrocortisone by mouth
How do you treat the symptoms of ACTH deficiency?
Patients lack cortisol but have normal aldosterone -> treat with hydrocortisone
How would you treat an Addisonian crisis?
IV saline (0.9% NaCl) to rehydrate patient (due to lack of retention) and high dose hydrocortisone -> IV infusion/IM every 6h (overwhelming 11betaHSD so don't need to wrry about aldosterone replacement as it will continue to activate MR until enzyme is less overwhelmed); 5% dextrose if hypoglycaemic
What is congenital adrenal hyperplasia?
Congenital lack of enzymes needed for adrenal steroid synthesis -> majority due to 21 hydroxylase deficiency
What is the objective of therapy for congenital adrenal hyperplasia?
Replace cortisol, suppress ACTH suppressing adrenal androgen production, replace aldosterone in salt wasting forms
What drugs are needed for congenital adrenal hyperplasia?
Dexamethasone (1/d pm) or hydrocortisone (2-3/day, high dose pm) to try and reduce ACTH which will reduce the amount of adrenal androgens and aldosterone made and fludrocortisone which replaces aldosterone
How do you monitor corticosteroid replacement therapy in congenital adrenal hyperplasia?
17OH progesterone, clinical assessment, BUT cushingoid (GC dose too high) and hirsuitism (GC dose too low, hence ACTH has risen) can occur
What additional measures can be taken in subjects with adrenocortical failure?
Normal cortisol production = 20mg/day and in stress 200-300 mg/day -> increase glucocorticoid dosage when patients are vulnerable to stress or has an illness (needs to double dose)
When do you increase glucocorticoid dosage in corticosteroid replacement therapy?
In minor illness (2x normal dose), after surgery -> hydrocortisone, IM, with pre-med and at 6-8h intervals, oral once eating and drinking
How does the pituitary-gonadal axis work in men?
How does the pituitary-gonadal axis work in women?
Different as it is a 28-day menstrual cycle with follicular phase, ovulation, luteal phase
How does the pituitary-gonadal axis work in women during folllicular phase?
How does the pituitary-gonadal axis work in women during ovulation?
What happens during the luteal phase in women?
If implantation doesn't occur then endometrium is shed; otherwise pregnancy occurs
What is infertility?
Inability to concieve after 1y of regular unprotected sex -> 1:6 couples caused by abnormalities in males(30%), females (45%), or unknown (25%)
What is primary gonadal failure?
No testosterone/oestradiol so no negative feedback