Hypoadrenal disorders

Question 1

Causes of adrenocortical failure

Answer 1

• Adrenal gland destruction (happens to previously normally functioning adrenal cortex)
• Enzymes in the steroid synthetic pathway not working (missing or not working at full capacity)-> present from birth

Question 2

Complete 21-hydroxylase deficiency

Answer 2

Totally absent hormones: aldosterone and cortisol
Length of survival if these hormones are totally absent: less than 24 hours
Hormones in excess: sex steroids and testosterone
Age of presentation:
-neonate with salt losing Addisonian crisis
Problem presentation:

Question 3

Partial 21-hydroxylase deficiency

Answer 3

Deficient hormones: cortisol and aldosterone
Hormones in excess: sex steroids and testosterone
Age of presentation: any age as they survive
Problem presentation:
-hirsutism and virilisation in girls
-precocious puberty in boys (adrenal testosterone cause)

Question 4

11-hydroxylase deficiency

Answer 4

Deficient hormones: cortisol and aldosterone
Hormones in excess: sex steroids, testosterone and 11-deoxycorticosterone
Problem presentation:
-virilisation
-hypertension
-low potassium (hypokalaemia)

Question 5

17-hydroxylase deficiency

Answer 5

Deficient hormones: cortisol and sex steroids
Hormones in excess: 11-deoxycorticosterone and aldosterone (mineralocorticoids)
Problem presentation:
-hypertension
-low potassium (hypokalaemia)
-sex steroid deficiency
-glucocorticoid deficiency (low glucose levels)

Question 6

Investigations for Addison’s disease

Answer 6

• 9am serum cortisol concentration

- short synACTHen test

Question 7

11-deoxycorticosterone

Answer 7

• behaves like aldosterone
• 11-deoxycorticosterone levels high in 11-hydroxylase deficiency patients->excess results in hypertension and hypokalaemia

Question 8

Congenital adrenal hyperplasia

Answer 8

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Question 9

Consequences of adrenocortical failure

Answer 9

• Fall in blood pressure (hypotension)
• Loss of salt in urine
• Increased plasma potassium
• Fall in glucose due to glucocorticoid deficiency
• High ACTH resulting in increased pigmentation

EVENTUAL DEATH DUE TO SEVERE HYPOTENSION

Question 10

POMC

Answer 10

• Pro-opio melanocortin
• synthesised in pituitary gland
• broken down to ACTH, MSH, endorphins, enkephalins and other peptides
• precursor of ACTH
• Rise in ACTH due to low cortisol leads to more POMC being broken down to liberate more of the byproduct MSH->MSH leads to melanocyte stimulation and hence the production of more melanin

Question 11

Short Synacthen Test

Answer 11

• synthetic ACTH is used to stimulate cortisol secretion from adrenal cortex
• usually starts at 9am to capture early morning peak of cortisol
  1) blood sample taken to measure serum cortisol concentration at baseline
  2) intravenous or intramuscular injection of 250 micrograms of Synacthen
  3) blood samples taken 30 mins and 60 mins later to measure cortisol response (serum cortisol concentration)

Question 12

Adrenal gland destruction

Answer 12

• Most common cause worldwide is Tuberculous Addison’s disease (microbacteria destroy adrenal cortex in TB)
• Most common cause in the UK is Autoimmune Addison’s disease