Addison's

Question 1

What is Addison’s?

Answer 1

Endocrine disorder in which the adrenal gland can’t produce enough of the hormones needed by the body

Primary adrenal insufficiency - decrease in adrenal cortex hormones

Question 2

What does the adrenal cortex produce?

Answer 2

1. Mineralocorticoids: zona glomerulosa
2. Glucocorticoids (cortisol): zona fasciculata
3. Androgens: zona reticulans

Question 3

What are the functions of mineralocorticoids?

Answer 3

Mineralocorticoids are a type of corticosteroid involved in salt and water balance

Aldosterone is a mineralocorticoid, it increases Na+ and water retention in at the kidneys and increases BP

Question 4

What are glucocorticoids?

Answer 4

Type of corticosteroid involved in the metabolism of carbohydrates, proteins and fats

Anti-inflammatory

Example: cortisol - causes immunosuppression, anti-inflammatory, weight gain, inculin resistance, skin thinning and increases osteoporosis

Question 5

What is the most common cause of Addison’s in developed countries?

Answer 5

Autoimmune destruction of the adrenal glands

*In underdeveloped countries it is TB

Question 6

Why is Addison’s called PRIMARY adrenal insufficiency?

Answer 6

Because the problem lies within the adrenal gland itself rather than any other area of the HPA axis

Question 7

Zona glomerulosa

Answer 7

Outermost layer of the cortex of the adrenal gland

Full of cells that produce mineralocorticoids/ aldosterone

Question 8

Function of aldosterone

Answer 8

Part of the RAAS - decreases potassium levels, increases Na+ retention and thus increases water retetion

1. Works on Na/K+ pumps in the DCT - drives K+ from blood into lumen of nephron in exchange for Na+
2. Works on alpha intercalated cells, stimulated H+ pumps and causes more H+ to be excreted in the urine

Question 9

Zona fasciculata

Answer 9

Middle layer of the cortex of the adrenal gland

Produces cortisol and other glucocorticoids

Question 10

Function of cortisol

Answer 10

Main role is increasing blood glucose levels by promoting gluconeogeneis in the liver - provides energy for times of fight/ flight

Needed in times of stress

Stress - hypothalamus releases corticotropin releasing hormone (CRH)

The pituitary, in response to CRH then releases adrenocorticotropic hormone (ACTH)

The ACTH travels through the blood to the zona fasciculata and causes the cells in this zone to release cortisol

Cortisol (because it is fat soluble) then enters cells and exerts its effects

Question 11

Zona reticularis

Answer 11

Innermost area of the adrenal cortex

Contains cells that produce andorgens (relatively small amounts, the testes produce +++ in men)

Mechanism of androgen production isn’t well understood but may be in response to ACTH release from the pituitary gland

Question 12

Why does it take a while before atrophy of the adrenal gland produces symptoms?

Answer 12

It has a high functional reserve - when symptoms do appear it suggests that 90% of the gland is gone

Question 13

What are the symptoms of Addison’s?

Answer 13

Depends on which layer have been destroyed:

a) Zona glomerulosa: fall in aldosterone which cause hyperkalaemia and hyponatremia, also causes hypovolemia and acidosis because H+ ions aren’t excreted by action of aldosterone: presenting as craving for salty food, nausea, vomiting, fatigue and dizziness
b) Zona fasciculata: low cortisol production so not enough gluconeogenesis during times of stress, causes weakness/ tiredness

*Low cortisol = no feedback to tell pituitary to calm down and so the pituitary produces a substance similar to melanocyte stimulating hormone and the poor patients end up yellow

c) Zona reticularis: only in extreme cases does this layer get affected, this doesn’t really affect men but women have a loss of armpit and pubic hair and a decreased sex drive

Question 14

What causes symptoms of Addison’s to become severe?

Answer 14

Injury, surgery and infection

The body needs cortisol but the adrenal gland can’t supply it

= ADDISONIAN CRISIS

Sudden pain in back, abdomen and legs, low blood pressure and confusion, diarrhoea and vomiting

Can be fatal

Question 15

What is Waterhouse Friderichsen syndrome?

Answer 15

Sudden increase in BP causes blood vessels in adrenal gland to rupture, glands fill up with blood and tissue ischaemia leads to adrenal insufficiency and an Addisonian crisis

Question 16

Investigations for Addison’s

Answer 16

Morning serum cortisol: <83nm/L suggests Addison’s

>497nm/L excludes Addison’s

ACTH stimulation test: if cortisol is <497nm/L 30-60mins after ACTH stimulation test, Addison’s highly likely

Abnormal ACTH test warrants further testing - measure serum ACTH, if high it suggests primary adrenal insufficiency because there is no negative feedback to tell the pituitary to calm down

Question 17

How do we differentiate between primary and secondary adrenal insufficiency?

Answer 17

Measure serum ACTH

Primary adrenal insufficiency = high ACTH because no negative feedback from cortisol

Secondary adrenal insufficiency = low ACTH

Question 18

Discuss the ACTH stimulation test

Answer 18

Small amount of synthetic ACTH (synacthen) is given and the amount of cortisol and aldosterone is measured

Measurement 1: baseline cortisol

Measurement 2: 30 mins after ACTH given

Measurement 3: 60 mins after ACTH given

What should happen? Cortisol levels should be 2x higher following ACTH

No increase = primary adrenal insufficiency

Question 19

What is secondary adrenal insufficiency?

Answer 19

Lack of stimulation of the adrenal glands due to lack of ACTH - usually due to damage of pituitary

Question 20

Initial investigations for Addison’s

Answer 20

Serum electrolytes: low Na+ and high K+

Urea: elevated

FBC: anaemia present in 40%

Morning serum cortisol: in below 100nm/L admit as Addison’s likely

Question 21

Management of Addison’s

Answer 21

Mineralocorticoid replacement: Fludrocortisone

Glucocorticoid replacement: Hydrocortisone 15-30mg in divided doses

Androgen replacement is not generally given in the UK but if it is DHEA is given

Question 22

Advice to give to patients with Addison’s

Answer 22

• Medication is lifelong
• Adjusting medication on sick days: double hydrocortisone dose, if vomiting use emergency hydrocortisone injection
• Carry identification relating to condition
• Medication is free of charge

Question 23

Management of an adrenal crisis

Answer 23

Admit to hospital

Give IV or IM hydrocortisone (use of emergency fludrocortisone isn’t necessary because high dose hydrocortisone has mineralocorticoid activity)

Question 24

HPA axis

Answer 24

CRH

ACTH

Cortisol

CAC - absolute cac comes from the person I know who has Addison’s