hypoadrenal disorders Flashcards
CRH =
ACTH =
POMC =
MSH =
CRH = Corticotrophin Releasing Hormone. ACTH = AdrenoCorticoTrophic Hormone. POMC = ProOpioMelanoCortin. MSH = Melanocyte Stimulating Hormone.
what is the main steroid precursor?
cholesterol
what are the three main pathways in synthesis?
cortisol
aldosterone
sex steroids
remember the steroid biosynthesis pathway
look at slide
17, 21, 11, 18 are the order of enzymes
Causes of Adrenocortical Failure
§ Adrenal glands destroyed.
o Tuberculosis Addison’s disease – most common worldwide.
o Autoimmune Addison’s disease – most common in the UK.
o Congenital adrenal hyperplasia – gland overgrows but does not function properly.
§ Enzymes in the steroid synthetic pathway not working.
consequences of adrenocortical failure?
Symptoms and signs include:
§ Hypotension.
§ Loss of salt in the urine, due to the loss of aldosterone!
§ Hyperkalaemia.
§ Hypoglycaemia – due to glucocorticoid deficiency.
§ High ACTH à hyperpigmentation.
o High ACTH due to loss of negative feedback by cortisol on the pituitary.
o POMC breaks down to ACTH + MSH (leading to hyperpigmentation).
§ Also breaks down into endorphins, enkephalins and other peptides.
§ Eventual death due to severe hypotension.
what are the tests for addisons?
§ An Addison’s suffering patient would have blood levels like this:
o 9am Cortisol = 100 (normal range: 270-900). LOW.
o ACTH = HIGH
§ Always high as no cortisol ever,
§ The test we then use is the Short synacthen test.
o Give 250mg of synacthen (synthetic ACTH) IM – this is a LARGE dose of ACTH and should induce a LARGE response in a healthy individual.
o Measure the cortisol response.
o If the cortisol response barely changes (e.g. goes from 100 to 150) they have Addison’s.
what are the 4 types of congenital adrenal hyperplasia?
§ Complete 21-hydroxylase deficiency.
§ Partial 21-hydroxylase deficiency.
§ 11-hyroxylase deficiency.
§ 17-hydroxylase deficiency
what happens in complete 21-hydroxylase deficiency?
Comes in complete and partial forms.
§ Leads to NO production of aldosterone or cortisol but EXCESS of sex steroids (no negative feedback).
what is the presentation for complete 21-hydroxylase deficiency?
§ Presentation:
o Children with this will present at 1 week-old.
§ This will usually be in the form of a salt losing Addisonian crisis.
§ In-utero the child will be fine as they receive steroids from the mother.
§ Girls present more obviously than boys due to ambiguous genitalia (virilisation) and may have clitoromegaly.
partial 21-Hydroxylase deficiency
What hormones are deficient?
What hormones are in excess?
Partial 21-Hydroxylase Deficiency § Hormones deficient: o Cortisol and aldosterone. § Hormones in excess: o Sex steroids & testosterone.
what are the signs and symptoms for partial 21-hydroxylase deficiency?
§ Age of presentation:
o Any age (as they survive).
o The main problem is in later life with hirsutism and virilisation in girls and precocious puberty in boys.
§ Symptoms and signs include:
o Acne, facial hirsutism, small breasts, clitoral enlargement, heavy arms/legs.
11-Hydroxylase Deficiency
-what is the mechanism behind the hypertension and hypokalaemia?
11-deoxycortisone behaves like aldosterone and so in excess (accumulation in zona glomerulosa) it can cause hypertension and hypokalaemia.
what are the hormones deficient and which are in excess in 11 hydroxylase deficiency?
Hormones deficient:
o Cortisol and aldosterone.
Hormones in excess:
o Sex steroids and testosterone and 11-deoxy corticosterone
Symptoms and signs of 11 hydroxylase deficiency?
Symptoms and signs:
o Virilisation, hypertension, hypokalaemia.
