Endo - Adrenal Disorders Flashcards
What is a steroid?
a chemical that comes from cholesterol
What enzymes are needed for the synthesis of aldosterone?
angiotensin II activates: → side chain cleavage → 3 hydroxysteroid dehydrogenase → 21 hydroxylase → 11 hydroxylase → 18 hydroxylase
What enzymes are needed for the synthesis of cortisol?
ACTH activates: → side chain cleavage → 3 hydroxysteroid dehydrogenase → 17 hydroxylase → 21 hydroxylase → 11 hydroxylase
What are the actions of aldosterone?
→ controls BP
→ controls sodium
→ lowers potassium
When is the best time to measure cortisol?
early in the morning
What is Addison’s disease?
primary adrenal failure
→ adrenal glands don’t produce sufficient hormones
→ pituitary produces too much ACTH + MSH
What is the world’s no.1 common cause of Addison’s?
tuberculosis of adrenal glands
What are the symptoms of Addison’s disease?
→ hyperpigmentation → hypotension → weakness → weight loss → vitiligo → gastrointestinal issues (nausea, diarrhoea, vomiting, constipation, ab pain)
Why do Addison’s disease patients have hyperpigmentation?
→ POMC is precursor for ACTH
→ when cleaved to produce ACTH, MSH is also produced
What are the 2 main mechanisms that cause adrenal failure generally?
→ enzymes in steroid synthetic pathway not working
→ adrenal glands destroyed
What is the most common cause of Addison’s Disease in the UK?
autoimmune Addison’s disease
What are 3 causes of adrenocortical failure?
→ TB Addison’s disease
→ autoimmune Addison’s disease
→ congenital adrenal hyperplasia
What are clinical consequences of adrenocortical failure?
→ fall in BP
→ loss of salt (sodium) in urine
→ increased plasma potassium
→ fall in glucose due to glucocorticoid deficiency
How can you test for Addison’s?
→ 9 am cortisol = low
→ ACTH = high
→ short synACTHen test (give 250 ug synacthen IM + measure cortical response)
Why can’t you treat Addison’s with pure aldosterone?
→ half life of aldosterone too short for safe once daily administration
→ has to be done through IV
What can you treat Addison’s disease with for aldosterone replacement?
fludrocortisone
→ aldosterone + fluorine
→ does not exist naturally
→ non-biodegradable
Why can’t you treat Addison’s with pure cortisol?
→ too short of a high life
→ too short for daily administration - has to be given thrice but causes late peaks of cortisol
→ late peaks in cortisol are harmful
Why can you treat Addison’s with for cortisol replacement?
hydrocortisone → longer half life → more potent than cortisol → 2.3 x binding affinity prednisolone → longer half life (more accurate for cortisol diurnal rhythm) → more potent than cortisol → 2.3 x binding affinity
What is a major cause of congenital adrenal hyperplasia?
21-hydroxylase deficiency
→ can be complete or partial
What hormones are deficient in congenital adrenal hyperplasia?
aldosterone + cortisol
How long can a baby survive with complete 21 hydroxylase deficiency?
less than 24 hrs
Which hormones are in excess in 21 hydroxylase deficiency?
sex steroid + testosterone
How will the baby present with 21 hydroxylase deficiency?
→ salt-losing Addisonian crisis (the placenta would’ve been feeding it nutrients)
→ girls may have ambiguous genitalia (excess of sex steroids causes virilisation of genitlia)
At what age do patients with partial 21 hydroxylase deficiency present?
any age after survival
What are the symptoms of partial 21 hydroxylase deficiency?
→ usually has enough cortisol + aldosterone to get by
→ excess sex steroids cause hirsutism + virilisation in girls
→ causes precocious puberty in boys
What hormones are deficient in 11 hydroxylase deficiency?
cortisol + aldosterone
Which hormones are in excess in 11 hydroxylase deficiency?
→ 11-deoxycorticosterone
→ sex steroids + testosterone
What are the consequences of 11-hydroxylase deficiency?
→ virilisation
→ hypertension
→ low potassium
What hormones are deficient in 17-hydroxylase deficiency?
→ cortisol
→ sex steroids
Which hormones are in excess in 17 hydroxylase deficiency?
→ 11-deoxycorticosterone
→ aldosterone (mineralcorticoids)
What are the consequences of 17-hydroxylase deficiency?
→ hypertension
→ low potassium
→ sex steroid deficiency
→ glucocorticoid deficiency
