Primary Adrenal Failure Flashcards
What is a steroid?
Comes from Cholesterol
What is the effect of Angiotensin 2?
Stimulates production of Aldosterone in the Adrenal gland. Controls blood pressure, sodium and potassium.
What is the mechanism of action of Angiotensin 2?
Activation of the following enzymes in the zona glomerulosa Side Chain Cleavage 3 Hydroxysteroid dehydrogenase 21 hydroxylase 11 hydroxylase 18 hydroxylase
What is the mechanism of action of ACTH on the Adrenal glands?
Activation of the following enzymes in the zona fesiculata Side Chain Cleavage 3 Hydroxysteroid dehydrogenase 21 hydroxylase 11 hydroxylase 17 hydroxylase
What is cortisols rhythm?
Diurnal, best time to test in in the morning when it should be the highest.
What is Primary adrenal failure?
Autoimmune disease where the immune system decides to destroy the adrenal cortex (UK)
TB is still the commonest cause worldwise.
What happens in Primary adrenal failure?
Not enough steroids produced
Not enough cortisol or aldosterone
How does Addison’s present?
Increased pigmentation
Autoimmune vitiligo may coexist
No cortisol or aldosterone, so low blood pressure
Why do patients with Addison’s disease have a good tan?
High MSH due to Pro-opio-melanocortin POMC cleaved to form many smaller peptides, including ACTH, MSH.
High ACTH means high MSH.
What is the third possible cause of Primary Adrenal failure?
Congenital adrenal hyperplasia
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
Eventual death due to severe hypotension
What are the tests for Addison’s disease?
9am cortisol = low ACTH = high Short synACTHen test Give 250 ug synacthen IM Measure cortisol response
Why is Fludrocortisone 50-100mcg daily used instead of Aldosterone?
Aldosterone has a very short half life, not safe for once daily administration. Fluorine takes longer to be metabolised as it is not present naturally. It has a longer half life and binds to both MR & GR.
What is the problem with giving aldosterone multiple times a day?
Multiple peaks can be harmful.
Why is 2-4mg of prednisolone once daily used instead of 12-15mg of hydrocortisone split throughout the day?
Prednisolone has a longer half life and is more potent than cortisol
2.3x binding affinity than cortisol
Replacement dose 3-4mg ONCE daily
What is the problem with higher doses of Prednisolone?
Increased mortality due to adrenal insufficiency, steroid exposure.
What is the treatment for a patient with Adrenal failure?
Hydrocortisone three times daily (10 + 5 + 2.5)
Prednisolone 3mg daily
Fludrocortisone 50 to 100 mcg daily
What happens in complete Congenital Adrenal Hyperplasia?
21-hydroxylase deficiency. Aldosterone and Cortisol will be absent. You cannot survive more than a few hours. you can have a salt losing adddisonian crisis when you’re less than a day old. Can be treated with saline + hydrocortisone as a neonate. In utero foetus gets steroids across the placenta.
Enlarged Adrenal glands
Why do you have increased sex steroids & testosterone in utero in Congenital Adrenal Hyperplasia?
Increased ACTH production. Girls might have ambiguous gentialia.
What happens in partial Congenital Adrenal Hyperplasia?
Partial 21 hydroxylase deficiency means that there will be a bit of aldosterone and cortisol to get by with. Low in aldosterone and cortisol. High testosterone. Can present at any age, but may have facial hair as a child.
Enlarged Adrenal glands
What is the main problem later on in life for someone with partial congenital adrenal hyperplasia?
Main problem in later life is hirsutism and virilisation in girls and precocious puberty in boys due to adrenal testosterone
What is the most common defficiency?
21 - 90%
11 - 10%
17
What happens if you have 11-hydroxylase deficiency ?
11 deoxycorticosterone behaves like aldosterone
In excess it can cause hypertension and hypokalaemia
What are the features of 11-hydroxylase deficiency?
Cortisol and Aldosterone deficient.
Sex steroids, testosterone & 11-deoxycorticosterone are in excess.
Main problems are virilisation, hypertension and low Potassium
What happens in 17-hydroxylase deficiency?
Deficiency of cortisol and sex steroids, but an excess of aldosterone and 11-deoxycorticosterone.
Hypertension, low K, sex steroid deficiency means they will not go through puberty, and glucocorticoid deficiency (low glucose).
