Adrenal disorders Flashcards
What is made in the adrenal cortex?
Corticosteroids
Mineralocorticoids (Aldosterone)
Glucocorticoids (Cortisol)
Sex steroids (Androgens, oestrogens)
What does angiotensin II do on the adrenals?
Bind to receptors on the zona glomorulosa
Activation of the following enzymes
Side Chain Cleavage
3 Hydroxysteroid dehydrogenase
21 hydroxylase
11 hydroxylase
18 hydroxylase
Makes aldosterone
What does aldosterone do?
Controls blood pressure, retains sodium and lower potassium
What does ACTH do on the adrenals? (During stress/ pneumonia…etc)
Binds to zona fasciculata
Activation of the following enzymes
Side Chain Cleavage
3 Hydroxysteroid dehydrogenase
17 hydroxylase
21 hydroxylase
11 hydroxylase
Makes cortisol
What rhythm does cortisol have
diurnal
What is Addison’s disease
Primary adrenal failure
Autoimmune disease where the immune system decides to destroy the adrenal cortex (UK)
Tuberculosis of the adrenal glands (commonest cause worldwide)
Pituitary starts secreting lots of ACTH and hence MSH
What happens in an adrenal crisis?
Fever
Syncope
Convulsions
Hypoglycaemia
Hyponatremia
Severe vomiting
Diarrhoea
What are some of the main symptoms of Addisons:
Weight loss
Increased pigmentation
Autoimmune vitiligo
No cortisol or aldosterone, so low blood pressure
Why do patients with Addison’s disease have a good tan?
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 2 causes of adrenal destruction?
Tuberculosis
Autoimmune disease
Congenital adrenal hyperplasia - born with huge adrenal glands as they were not making enough cortisol before you were born so pituitary made lots of ACTH but born with a missive enzyme
What are the consequences of adrenocortical failure?
Fall in blood pressure
Loss of salt in the urine
Increased plasma potassium
Fall in glucose due to glucocorticoid deficiency
High ACTH resulting in increased pigmentation - due to no negative feedback
Eventual death due to severe hypotension
What is POMC
Pro-opio melanocortin
Synthesised in pituitary and broken down to ACTH and MSH and endorphins and enkephalins and other peptides
What are the test for Addison’s?
9am cortisol = low
ACTH = high
Short synACTHen test
Give 250 ug synacthen IM
Measure cortisol response
What would cortisol be like in a typical Addison’s patient compared to normal?
Cortisol at 9am = 100 (270-900)
Administer injection IM of synacthen
Cortisol at 9.30 = 150 (>600)nM
How do you treat adrenal failure?
Fludrocortisone-50-100mcg daily
Fluorine does not exist in natural steroids, so its presence slows metabolism substantially.
Binds to both MR and GR
Fludrocortisone half life 3.5h and
effects seen for 18h.
Half life of aldosterone is too short for safe once daily administration
How do you increase cortisol?
Hydrocortisone by injections but half life too short - need to take it thrice a day
1-2 dehydro-hydrocortisone - longer half life - aka prednisolone - only need to take it once a day
2-4mg prednisolone = 15-25mg hydrocortisone
What is congenital adrenal hyperplasia
Usually caused by 21-hydroxylase deficiency
Either complete or partial deficiency
What hormones absent in complete 21-hydroxylase deficieny?
Aldosterone and cortisol
Can survive for less than 24 hours
Excess 17-OH progesterone in blood so excess sex steroids and testosterone
How does congenital adrenal hyperplasia present?
As a neonate with a salt losing Addisonian crisis
Before birth, (while in utero), foetus gets steroids across placenta
Girls might have ambiguous genitalia (virilised by adrenal testo)
What happens in partial 21 hydroxylase deficiency
What hormones are deficient
What hormones are in excess
What age will they present
There will be a bit of aldosterone and cortisol to get by with
Not enough cortisol to inhibit ACTH from pituitary
Cortisol and aldosterone
Sex steroids and testosterone
Any age as they survive
Main problem in later life is hirsutism and virilisation in girls and precocious puberty in boys due to adrenal testosterone
What happens with 11 hydroxylase deficiency?
There is an excess of 11 deoxycorticosterone
11 deoxycorticosterone behaves like aldosterone
In excess it can cause hypertension and hypokalaemia
What hormones are deficient in 11 hydroxylase deficiency?
What hormones are in excess
Associated problems?
Which hormones are deficient ?
Cortisol and aldosterone
Which hormones are in excess ?
Sex steroids and testosterone and 11-deoxycorticosterone
Problems :
Virilisation, hypertension and low K
What hormones are deficient in 17 hydroxylase deficiency?
What hormones are in excess
Associated problems?
Which hormones are deficient ?
Cortisol and sex steroids
Which hormones are in excess ?
11-deoxycorticosterone and aldosterone (mineralocorticoids)
Problems :
Hypertension, low K, sex steroid deficiency and glucocorticoid deficiency (low glucose).
