Adrenal Disorders Flashcards
What hormones does the adrenal cortex produce?
Corticosteroids:
- Mineralocorticoids (Aldosterone)- zona glomerulosa
- Glucocorticoids (Cortisol)- zona fasciculata
- Sex steroids (Androgens, oestrogens)- zona reticularis
What is the effect of angiotensin II on the adrenals?
Activation of the following enzymes: 3 Hydroxysteroid dehydrogenase 21 hydroxylase 11 hydroxylase 18 hydroxylase.
Plus stimulates aldosterone synthase to make aldosterone
What is the function of aldosterone?
Controls blood pressure- increases water reabsorption so increased BP
Stimulates sodium reabsorption
Stimulates potassium excretion
How is aldosterone produced?
- Cholesterol
- progesterone (21 hydroxylase)
- 11-deoxycorticosterone (11 hydroxylase)
- corticosterone (18 hydroxylase)
- aldosterone
How is cortisol formed?
- Cholesterol
- Progesterone (17 hydroxylase)
- 17-hydroxy progesterone (21 hydroxylase)
- 11- deoxycortisol (11 hydroxylase)
- cortisol
How are sex steroids and oestrogen produced?
- Cholesterol
- Progesterone (17 hydroxylase)
- 17-hydroxy progesterone
- Sex steroids
- Androgens
- Oestrogen
How do levels of cortisol change throughout the day?
Cortisol has a diurnal rhythm
It peaks at 8:30am
Rise in cortisol begins at 5am
Lowest at midnight
What is addison’s disease?
Primary adrenal failure
Autoimmune disease where the immune system decides to destroy the adrenal cortex (commonest in UK)
Tuberculosis of the adrenal glands (commonest cause worldwide)
Pituitary starts secreting lots of ACTH and hence MSH
What are symptoms of addison’s disease?
Increased pigmentation Hyperkalaemia Autoimmune vitiligo may coexist Weakness Weight loss: anorexia, vomiting, diarrhoea Low BP: No cortisol or aldosterone
Why do people with addison’s disease have a tan?
Pro-opio-melanocortin (POMC) is a large precursor protein that is cleaved to form a number of smaller peptides, including ACTH, MSH and endorphins
Thus people who have pathologically high levels of ACTH may become tanned
What are causes of adrenocortical faliure?
Tuberculous Addison’s disease (commonest worldwide)
Autoimmune Addison’s disease (commonest in UK)
Congenital adrenal hyperplasia
What are consequences of adrenocortical failure?
Fall in BP
Loss of salt into urine (salty urine)
Increased plasma potassium
Fall in glucose due to glucocorticoid deficiency
High ACTH resulting in increased pigmentation (due to increase in MSH)
Eventual death due to severe hypotension
What are tests used to diagnose addison’s disease?
9am cortisol (should be high in a healthy patient) ACTH level
Short synACTHen test - give 250 ug synacthen IM (synATCHENen mimics ACTH and stimulates cortisol release. In healthy patient cortisol should increase)
What diagnostic results would we expect in someone with addison’s disease?
9am cortisol = low
ACTH = high
What measurements of cortisol would we approx. see after administration of synACTHen in an addison’s disease patient
Cortisol at 9am = 100 (270-900)
Administer injection IM of synacthen
Cortisol at 9.30 = 150 (>600)nM
What synthetic drug is used for Addison’s disease that mimics aldosterone?
Fludrocortisone (50-100 mcg daily)
Used to control amount of sodium and fluids in body
Half life of aldosterone is too short for safe daily administration se we use Fludrocortisone.
It has a half life of 3.5h so slows metabolism. (effects seen for 18h)
It binds to both MR and GR
Why can oral hydrocortisone not be administered for addison’s disease?
has a short half life: too short for once daily administration
Instead we use 1-2 dehydro-hydrocortisone or prednisolone. This has a longer half life and is more potent than cortisol (2.4x binding affinity than cortisol)
What is the recommended dose for prednisolone?
Replacement dose 3-4mg ONCE daily
What doses of prednisolone are available?
1mg, 2.5mg, 5mg
NOT enteric coated which
slows absorption
In some parts of the world they only give 5mg tablets which is too much so might need to break the pill
What drugs should be given to a patient with addison’s disease?
Hydrocortisone three times daily (10 (morning) + 5 (lunch) + 2.5 (dinner)) OR
Prednisolone 3mg daily
AND
Fludrocortisone 50 to 100 mcg daily
How does hydrocortisone compare to prednisolone?
2-4mg of prednisolone is equivalent to approx. 15-25mg hydrocortisone
What causes congenital Adrenal Hyperplasia?
Commonest cause is by 21-hydroxylase deficiency (missing gene)
Can be complete (complete loss of gene) or partial (mutation)
What hormones are affected in Congenital Adrenal Hyperplasia
Cortisol and aldosterone
How long can you live with untreated Congenital Adrenal Hyperplasia?
Less than 24 hours
At what age does complete Congenital Adrenal Hyperplasia cause symptoms?
At birth:
Before birth foetus gets steroid across placenta
After birth, baby has a salt losing addisonian crisis, BP falls and they become floppy and drowsy
To treta: saline given in hospital (replenish salts)
What hormones are in excess in complete Congenital Adrenal Hyperplasia and what are symptoms of this?
Sex steroids and testosterone
In a female this can cause ambiguous genitalia- viralised (development of male physical characteristics) by adrenal testosterone
What hormones are deficient in partial 21-hydroxylase deficiency?
Cortisol and aldosterone
What hormones are in excess in partial 21-hydroxylase deficiency?
Sex steroids and testosterone
At what age does partial 21-hydroxylase deficiency occur?
Any age as they survive birth
What are symptoms of partial 21-hydroxylase deficiency?
Main problem in later life is hirsutism (heavy growth of bodily hair) and virilisation in girls and precocious (early) puberty in boys due to adrenal testosterone
What happens if there is an 11- hydroxylase deficiency?
You get an excess buildup of 11-deoxycorticosterone which behaves like aldosterone
In excess it can cause hypertension and hypokalemia
You also get virilisation (due to excess testosterone)
In 11- hydroxylase deficiency what hormones are in excess and which are deficient?
Deficient: Cortisol and aldosterone
Excess: Sex steroids and testosterone and 11-deoxycorticosterone
In 17 hydroxylase deficient what hormones are deficient and which are in excess?
Deficient: cortisol and sex steroids
Excess: 11-deoxycorticosterone and aldosterone (mineralocorticoids)
What are symptoms of 17 hydroxylase deficiency?
Hypertension, low K, sex steroid deficiency and glucocorticoid deficiency (low glucose).
