Adrenal Pathway Dysfunction Flashcards
What hormones does the adrenal cortex produce?
Corticosteroids - aldosterone and cortisol (and sex steroids)
What is a steroid?
A molecule that comes from cholesterol
What are the effects of angiotensin II on the adrenal glands?
What are the effects of aldosterone?
Activation of 3 hydroxysteroid dehydrogenases: 21, 11 and 18 hydroxylases to form aldosterone
Aldosterone controls BP, retains sodium and lowers potassium
What are the effects of ACTH on the adrenal glands?
Activation of 3 hydroxysteroid dehydrogenases: 17, 21, 11 hydroxylases
What are the steroid synthetic pathways?
Cholesterol —> aldosterone
Cholesterol —> cortisol
Hydroxylase = H
Cholesterol –> progesterone –(21H)–> 11-deoxycorticosterone –(11H)–> corticosterone –(18H)–> aldosterone
Cholesterol –> progesterone –(17H)–> 17-OHprogesterone –(21H)–> 11-deoxycortisol –(18H)–> cortisol
Cholesterol –> progesterone –(17H)–> 17-OHprogesterone –> sex steroids –> androgens –? oestrogen
How does cortisol change over a day?
Has a dirunal rhythm, v. low at midnight, peaks at 8:30 before waking up, then declines throughout the day
Cortisol controls day and night - when we wake and sleep
What is Addison’s disease?
What are the possible causes?
Primary adrenal failure due to:
Autoimmune system destroys adrenal cortex (most common in the UK)
TB of the adrenal glands (most common worldwide cause esp. in Africa)
Congenital adrenal hyperplasia - adrenal glands are big when born but not working
Tumour of the adrenal glands
What are the clinical presentations of Addison’s disease and why?
Vitiligo may coexist
Increased pigmentation due to lack of cortisol = increased ACTH production = increased melanocyte stimulating hormone (MSH) production as they both come from the same precursor - POMC (which is cleaved to form ACTH and MSH)
No cortisol or aldosterone = low BP
What are the consequences of adrenocortical failure?
Fall in BP
Loss of Na+ in the urine (lack of aldosterone - main function is to retain Na+ as it stimulates Na+ reabsorption in the DCT and CD)
Increased plasma potassium
Fall in glucose due to glucosteroid deficiency
What is POMC?
Synthesised in pituitary, precursor to ACTH and MSH
What are clinical suspicions for Addison’s?
Low Na+
Hyperpigmentation
What are the tests for Addison’s disease?
Low 9am cortisol = 100 (270-900 normally) nM
High ACTH
Give them synthetic ACTH (synACTHen) 250ug via injection - then measure cortisol levels (in normal people it rises to more than 600nM, but cortisol levels in Addison’s barely change)
What is the treatment for Addison’s / adrenal failure?
Aldosterone and cortisol replacement:
Aldosterone = short half life, degrades too quickly to give daily
Put fluorine into the aldosterone to make fludrocortisone = more stable as fluorine does not exist in natural steroids
Cortisol = given hydrocortisone which has too short of a half life for once daily, so the doses are given 3 times a day - 10mg in the morning, 5mg in the afternoon, 2.5mg in the evening
How can cortisol be slowed down in degradation?
By adding a double bond in the stucture making 1-2 dehydro-hydrocortisone - has the right half life now
This is called Prednisolone - once daily, more potent (3-4mg)
Fludrocortisone 50 to 100 mcg daily
What is the most common cause of congenital adrenal hyperplasia? Which hormones are affected?
How is this treated?
Commonest cause = 21 hydroxylase (21H) deficiency
Missing 21H - no aldosterone and no cortisol production (as 21H is required for both pathways)
Same treatment as Addison’s - aldosterone and cortisol replacement
What are some side effects of congenital adrenal hyperplasia?
Due to the pathways of aldosterone and/or cortisol being blocked off - sex steroid pathway = more active
Girls = present more ambigious (harder to distinguish whether boy or girl due to increased testosterone)
Boys = more likely to miss increased testosterone levels
At what age do they present (congenital adrenal hyperplasia)?
After birth - babies may have Addisonian crisis at home. If not treated, survive less than 24 hours
What happens if the congenital adrenal hyperplasia is caused by partial 21H deficiency?
What age are they likely to present?
Some aldosterone and cortisol to get by
Issue is with excess sex steroids and testosterone
They can present at any age - early apparent puberty (e.g. when they are 4 or 5 years old, precocious puberty)
How may girls present clinically with partial 21H deficiency?
Some pigmentation - high ACTH Lots of facial hair Lack of breast Clitoralmegaly (i.e. developing into a penis) Heavy muscular appearance
What occurs if there is an 11H deficiency?
How does it present clinically?
Cortisol and aldosterone are deficient
11-deoxy corticosterone (11DCS) behaves like aldosterone
Presents as hypertension, low K, virilisation (development of physical male characteristics) as the 11DCS and sex steroid pathways are elevated
Also have too much testosterone as the sex steroid pathway is elevated
What occurs if there is a 17H deficiency?
How does it present clinically?
No sex steroid released, and no cortisol
Aldosterone pathway elevated = hypertension, low K
Males = produce no testosterone = feminised
Never go through puberty = no sex steroids
Always tired = no cortisol
What is the treatment for 21H deficiency?
How much more potent is prednisolone that hydroxycortisone?
Replacement of cortisol and adosterone (like in Addison’s)
Prednisolone = 6-8x more potent than the hydroxycortisone
What would be the treatment for 17H deficiency?
Only cortisol replacement
When they reach adolescence, they’re given sex steroid replacement
What would be the treatment for 11H deficiency?
Only cortisol replacement
