Hypoadrenal disorders

Question 1

What can cause adrenocortical failure?

Answer 1

• destruction of the adrenal glands

- enzymes in the steroid synthetic pathway not working

Question 2

What are specific causes of adrenocortical failure?

Answer 2

• tuberculous Addison’s disease (commonest worldwide)
• AI Addison’s disease (commonest in the UK)
• congenital adrenal hyperplasia

Question 3

What are signs and symptoms of adrenocortical failure?

Answer 3

• 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
• AI vitiligo may coexist
• tired, extreme fatigue
• postural hypotension
• eventual death due to hypotension (Addisonian Crisis)

Question 4

POMC

Answer 4

• pro-opio melanocortin

- POMC -> ACTH + MSH + endorphins, enkephalins and other peptides

Question 5

How does the adrenal gland change in adrenocortical failure?

Answer 5

• medulla: unaffected

- cortex: (entire) adrenal cortex destroyed or atrophied

Question 6

What happens to the adrenal gland itself in TB and AI adrenocortical failure?

Answer 6

• TB: medulla unaffected, cortex destroyed

- AI: medulla unaffected, cortex atrophied

Question 7

How do you test for Addison’s disease?

Answer 7

• 9 am cortisol: low
• ACTH: high
• short synACTHen test:
  - give 250 ug synACTH i.m.
  - measure the cortisol response

Question 8

What are typical blood test results of a patient with Addison’s?

Answer 8

• Cortisol at 9am = 100 (270-900)
  - >Administer injection IM of synacthen
• Cortisol at 9.30 = 150 (>600)
• low Na+, high K+ (not enough aldosterone)

Question 9

What is the commonest cause of congenital adrenal hyperplasia?

Answer 9

21-hydroxylase deficiency

Question 10

Complete 21-hydroxylase deficiency

Answer 10

• aldosterone and cortisol totally absent
• can survive less than 24h
• excess sex steroids and testosterone

Question 11

Age of presentation in complete 21-hydroxylase deficiency

Answer 11

• as a neonate with a salt losing Addisonian crisis
• before birth (in utero) foetus gets steroids across the placenta
• girls might have ambiguous genitalia (virilised by adrenal testosterone) -> might have to karyotype

Question 12

Partial 21-hydroxylase deficiency

Answer 12

• aldosterone and cortisol deficient
• too many sex steroids and testosterone
• may present at any age as they survive

Question 13

What are the main problems with partial 21-hydroxylase deficiency?

Answer 13

• in later life hirsutism and virilisation in girls

- precocious puberty in boys due to adrenal testosterone

Question 14

What is congenital adrenal hyperplasia associated with?

Answer 14

hyperplasia of the adrenal glands.

Question 15

Important fact about 11-deoxycorticosterone

Answer 15

• behaves like aldosterone

- can cause hypertension and hypokalaemia

Question 16

11-hydroxylase deficiency

Answer 16

• cortisol and aldosterone are deficient
• excess sex steroids, aldosterone and 11-deoxycorticosterone
• problems: virilisation, low K+, hypertension

Question 17

17-hydroxylase deficiency

Answer 17

• cortisol and sex hormones are deficient
• excess aldosterone and 11-deoxycorticosterone (mineralocorticoids)
• Problems: hypertension, low K+, sex steroid deficiency, low glucose possible