3.10 - Adrenal disorders 1/2 Flashcards
What hormones does the adrenal cortex produce and from which zones?
Corticosteroids
- mineralocorticoids (aldosterone) - zona glomerulosa
- glucocorticoids (cortisol) - zona fasciculata and zona reticularis
- small amount of sex steroids (androgens, oestrogens) - zona fasciculata and zona reticularis
What is the precursor to steroid hormones?
Cholesterol
What is an enzyme?
- protein that catalyses a specific reaction
- various enzymes are present in cells
- specific enzymes catalyse the synthesis of particular alterations to the molecule (cholesterol)
What are the key steps in the synthesis of aldosterone?
- cholesterol side chain cleavage produces pregnenolone
- 3-beta-hydroxysteroid dehydrogenase oxidises C3 to form progesterone
- 21 hydroxylase adds OH to C21 to form 11-deoxycorticosterone
- 11 hydroxylase adds OH to C11 to form corticosterone
- 18 hydroxylase adds OH to C18 to form aldosterone
What are the key steps in the synthesis of cortisol?
- cholesterol side chain cleavage produces pregnenolone
- 3-beta-hydroxysteroid dehydrogenase oxidises C3 to form progesterone
- 17 hydroxylase adds OH to C17 to form 17-hydroxyprogesterone
- 21 hydroxylase adds OH to C21 to form 11-deoxycortisol
- 11 hydroxylase adds OH to C11 to form cortisol
What are the key steps in the synthesis of androgens/oestrogens?
- cholesterol side chain cleavage produces pregnenolone
- 3-beta-hydroxysteroid dehydrogenase oxidises C3 to form progesterone
- 17 hydroxylase adds OH to C17 to form 17-hydroxyprogesterone
- sex steroids
- androgens
- oestrogen
What are the effects of angiotensin II on the adrenals?
- side chain cleavage
- 3 beta hydroxysteroid dehydrogenase
- 21 hydroxylase
- 11 hydroxylase
- 18 hydroxylase
- = cause aldosterone release
What is a summary of the function of aldosterone?
Controls blood pressure, increases sodium and lowers potassium
What are the effects of ACTH on the adrenals?
- side chain cleavage
- 3 beta hydroxysteroid dehydrogenase
- 17 hydroxylase
- 21 hydroxylase
- 11 hydroxylase
- = cortisol release
What kind of rhythm does cortisol have?
Diurnal rhythm - increase starts early morning, peaks around 8:30/9, decreases again
What is Addison’s disease?
Primary adrenal failure (lose aldosterone and cortisol - salt loss and eventual death due to low BP)
What is the commonest cause of Addison’s disease in the UK?
Autoimmune disease where the immune system decides to destroy the adrenal gland
What is the commonest cause of Addison’s disease worldwide?
Tuberculosis of the adrenal glands
What does the pituitary do in response to low cortisol and aldosterone due to Addison’s disease?
Pituitary starts secreting lots of ACTH and hence MSH (melanocyte stimulating hormone)
What are the features of Addison’s disease? (3)
- 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?
- pro-opio-melanocortin (POMC) is a large precursor protein that is cleaved to form a number of smaller peptides including ACTH, MSH and endorphins
- people with Addison’s increase ACTH to try and increase cortisol/aldosterone
- since ACTH comes from POMC, pathologically high ACTH = increased MSH = increased melanin –> tanned
What are two types of dysfunction in adrenocortical failure?
- adrenal glands destroyed
- enzymes in the steroid synthetic pathway not working - congenital adrenal hyperplasia
What are three causes of adrenocortical failure?
- tuberculous Addison’s disease (commonest worldwide)
- autoimmune Addison’s disease (commonest in UK)
- congenital adrenal hyperplasia
What are the consequences of adrenocortical failure? (6)
- fall in BP (postural hypotension)
- loss of salt in urine (low sodium in plasma = hyponatraemia)
- increased plasma potassium (less K+ excreted in urine = hyperkalaemia)
- low glucose due to glucocorticoid deficiency
- high ACTH = increased pigmentation
- eventual death due to severe hypotension
What are the tests for Addison’s disease?
- clinical suspicion - fatigue, low Na+, high K+
- 9am cortisol (low) and ACTH (high)
- short synACTHen test where you do a cortisol blood test then give 250ug synACTHen IM and measure cortisol response - if little response we know it is Addison’s
What is an example of cortisol levels in a typical Addison’s patient before and after synACTHen?
- cortisol at 9am = 100 (270-900)
- administer injection IM synACTHen
- cortisol at 9:30am = 150 (>600)nM
- ie NO response to synACTHen
How do we treat primary adrenocortical failure?
- patient needs replacement of cortisol and aldosterone
- no need to replace adrenal sex steroids (gonads)
What is the problem with replacing aldosterone in Addison’s disease?
- problem with aldosterone is half-life is too short for safe once daily administration
- fludrocortisone (50-100mcg daily) - longer acting than aldosterone
- fludrocortisone is an agonist for the MR (mineralocorticoid) receptors
What specific drugs do we give to treat primary adrenocortical failure?
- fludrocortisone 50-100mcg daily (aldosterone replacement)
- EITHER hydrocortisone three times daily (10mg + 5mg + 2.5mg) OR prednisolone 3mg daily - (cortisol replacement)
