Adrenal pathway dysfunction Flashcards
What does the adrenal gland produce
Aldosterone
Cortisol
Androgens, oestrogen
Why are the numbers on cholesterol important?
We name the enzymes based on which carbon atoms on cholesterol they affect
What are the main actions of aldosterone?
Controls blood pressure
Retains sodium
Lowers potassium
What hydroxylases are involved in making aldosterone?
21, 11 and 18
What hydroxylases are involved in making cortisol?
17, 21,11
What rhythm does Cortisol have?
Diurnal
What is Addison’s disease?
Primary adrenal failure
Autoimmune
TB of the adrenal glands is the most common cause worldwide
What are the symptoms of Addison’s?
Increase pigmentations
Autoimmune viitiligo
No cortisol or aldosterone so low blood pressure
What are the three causes of Adrenocortical failure?
Congenital adrenal hyperplasia
TB Addison’s
Autoimmune Addison’s
What is POMC?
Pro-opio-melanocortin
Why does Addison’s cause a 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
How does Addison’s present acutely?
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
What are other symptoms of Addison’s?
Darkening of hair Weight loss - anorexia, diarrhoea, vomiting Muscular weakness Pigment accentuation at nipples Vitiligo Freckling Mucous membrane pigmentation
What is the treatment for Addison’s?
IV hydrocortisone
Oral steroid replacement
What are the tests for Addison’s?
9am cortisol = low
ACTH = high
Short synACTHen test
What is the Short synACTHen test?
Give 250 ug synACTHen
IM
Measure cortisol response
What cortisol levels are seen on a typical Addison’s patient?
Cortisol at 9am = 100 (270-900)
Administer injection IM of synacthen
Cortisol at 9.30 = 150 (>600)nM
Levels will eventually go to 0 if left untreated
Why can you not give a aldosterone tablet?
Half life of aldosterone is too short (20 mins) for safe once daily administration
What do we give to replace aldosterone?
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.
50-100mcg once daily
How do we replace cortisol?
Oral hydrocortisone
Has a short half life: too short for once daily administration
8am
12pm
5pm
Why is oral hydrocortisone problematic?
Peaks are too high and harmful
Disrupts sleep
What is used more commonly now to replace cortisol?
3-4mg of prednisolone once daily
What is the problem with prednisolone?
Cannot get a 3mg tabled of predisonlone
Have to take 1mg x3
3 1/4 of a 5mg tablet
Summaries the treatment of adrenal failure
Hydrocortisone three times daily (10 + 5 + 2.5)
OR
Prednisolone 3mg daily
Fludrocortisone 50 to 100 mcg daily
What is congenital adrenal hyperplasia?
Commonest is caused by
21-hydroxylase deficiency
(missing gene)
Can be complete or partial
Born without aldosterone and cortisol
Survive in utero because mother gives steroids via placenta
What happens before birth?
Huge adrenal glands
High ACTH production
How do you treat congenital adrenal hyperplasia?
Replacement
What also happens in congenital adrenal hyperplasia?
Make huge amount of sex steroids
In females
Virilised by adrenal testosterone
- labial fusion
- ambiguous genitalia
In males
Missed as there is no obvious visual presentation
How long can you survive with complete 21 hydroxyls deficiency?
Less than 24 hours without treatment
What does partial 21 hydroxylase deficiency mean?
Partial 21 hydroxylase deficiency means that there will be a bit of aldosterone and cortisol to get by with
Large excess of testosterone
When do patients with partial 21 hydroxylase present?
At any age
Go through precocious puberty
What are the main features of partial 21 hydroxylase deficiency in later life?
Main problem in later life is hirsutism and virilisation in girls and precocious puberty in boys due to adrenal testosterone
What are features of females with partial 21 hydroxylase deficiency?
Small breasts Facial hirsutism Receding hair line baldness Male escutcheon Heavy muscular appearance
What happens with 11 hydroxylase deficiency?
11 deoxycorticosterone behaves like aldosterone
In excess it can cause hypertension and hypokalaemia
What hormones are in excess with 11 hydroxylase deficiency?
Sex steroids and testosterone and 11-deoxycorticosterone
What are the problems with 11 hydroxylase deficiency?
Virilisation, hypertension and low K
What happens with 17 hydroxylase deficiency?
11-deoxycorticosterone and aldosterone (mineralocorticoids)
What are the problems with 17 hydroxylase deficiency?
Hypertension, low K, sex steroid deficiency (no puberty) and glucocorticoid deficiency (low glucose).
What are the treatments for congenital adrenal hyperplasia?
Single morning does of prednisolone 3mg is the equivalent dose to 20mg of hydrocortisone
