Addison's disease

Question 1

Addison’s disease aka primary adrenal insufficiency = rare but can be fatal.

What is Addison’s disease and its underlying pathology?

Answer 1

Addison’s disease = destruction of the entire adrenal cortex

=> reduced production of glucocorticoids (cortisol) ; mineralocorticoids (aldosterone) ; sex steroids

=> reduced cortisol level leads to increased CRH and ACTH production

Question 2

Who does Addison’s most commonly affect?

Answer 2

Females > males

HIV/AIDS & TB

Question 3

What causes Addison’s disease - primary adrenal insufficiency?

Answer 3

1. Autoimmune disease >90% in UK
2. Tuberculosis - commonest cause worldwide especially in high HIV/AIDS area

Others:

Adrenal metastases from lung, breast, renal cancer

Lymphoma

Opportunistic infections in HIV i.e. CMV, mycobacterium avium

Adrenal haemorrhage (Waterhouse Friderichsen syndrome, antiphospholipid syndrome)

Congenital adrenal hyperplasia

Question 4

What is the underlying pathology behind autoimmune adrenalitis (Addison’s)?

Answer 4

Autoimmune adrenalitis => destruction of adrenal cortex by organ specific auto-antibodies

=> assoc. with other autoimmune conditions i.e. type 1 diabetes, pernicious anaemia, thyroiditis, hypoparathyroidism

Question 5

What’s the most common cause of adrenal insufficiency in childhood?

Answer 5

Congenital adrenal hyperplasia

Question 6

Symptoms of Addison’s are very non-specific => Addison’s often diagnosed late

What are the symptoms of Addison’s disease?

Answer 6

Weight loss ; Malaise ; Weakness ; Fever

Anorexia ; Nausea & Vomiting ; Diarrhoea

Abdominal pain ; Constipation

Depression ; Confusion

Myalgia ; Joint or Back pain

Impotence / Amenorrhoea

Syncope from postural hypotension

Question 7

What are the signs of Addison’s disease?

Answer 7

General signs: Weight loss* ; General wasting*

Pigmentation especially of new scars and palmar creases*

Buccal pigmentation

Postural hypotension*

Loss of body hair (vitiligo)

Dehydration

• Signs of higher discriminant value
• Think of Addison’s in all unexplained abdo pain or vomiting

Question 8

What causes hyperpigmentation?

Answer 8

Increased ACTH production responsible for hyperpigmentation (dull, slaty, grey-brown)

ACTH cross-reacts with melanin receptors

=> sign present in >90%

Question 9

What causes postural systolic hypotension?

Answer 9

Postural systolic hypotension due to hypovolaemia and sodium loss caused by mineralocorticoid deficiency

=> sign present in 80-90%

Question 10

What investigations are carried out to confirm suspected Addison’s disease?

Answer 10

I) Bloods:
=> low sodium; high potassium due to low mineralocorticoids
=> low glucose due to low cortisol
=> Uraemia, calcium, eosinophilia, anaemia

II) Short ACTH stimulation test (synacthen test)
=> Measure plasma cortisol before and 30 mins after administering synathen 250mcg IM
=> Addison’s excluded if 30min cortisol >550nmol/L
=> Absent or impaired cortisol response confirms hypoadrenalism but doesn’t differentiate between Addison’s or ACTH deficiency

III) 9am plasma ACTH level
=> high level ACTH and low level cortisol confirms primary adrenal insufficiency

IV) 21-hydroxylase adrenal auto-antibodies
=> +ve in autoimmune disease >80% of patients

V) Plasma renin & aldosterone to assess mineralocorticoid status
=> High plasma renin due to low aldosterone

VI) Chest/abdo X-ray
=> Past TB?
=> Adrenal calcifications?

Question 11

How do you treat Addison’s disease?

Answer 11

Long term treatment:

Glucocorticoid and mineralocorticoid replacement

TB treated

Patient advice:

=> know how to increase steroid replacement by doubling dose during any illnesses

=> Wear a MedicAlert bracelet - provides details of their condition so emergency replacement therapy can be initiated if found unconscious

=> Carry a steroid card

=> Keep hydrocortisone ampoule at home in case of emergency

Question 12

What is Addisonian crisis?

Answer 12

Patient can present in shock 
=> high heart rate, 
=> vasoconstriction, 
=> postural hypotension, 
=> oliguria, 
=> weak, 
=> confused, 
=> comatose

Commonly in patients with Addison’s e.g. when oral steroid has not been increased during high stress e.g. pneumonia

Question 13

What are the precipitating factors for Addisonian crisis?

Answer 13

Infection

Trauma

Surgery

Missed medications

Question 14

Clinical context of acute hypoadrenalism:
=> Hypotension
=> Hyponatraemia ; hyperkalaemia
=> Hypoglycaemia
=> Dehydration
=> Pigmentation
=> Often precipitating infection, infarction, trauma, operation

Major deficiencies: salt, steroid, glucose

How do you manage Addisonian crisis?

Answer 14

If Addisonian crisis suspected, treat before biochemical results.

=> Bloods for cortisol and ACTH, U&E
=> ECG if high K+

Treat:
=> IV Hydrocortisone 100mg stat
=> IV fluid bolus 500ml 0.9% saline to support BP
=> Glucose IV if hypoglycaemic
=> High K+ give calcium gluconate 

Salt depletion improves with fluid rehydration and steroids

Question 15

What causes secondary hypoadrenalism?

Answer 15

Hypothalamic-pituitary disease => low ACTH production

=> Panhypopituitarism common in hypothalamic-pituitary disease - likely to need T4 replacement too

Long term steroid therapy leading to ACTH suppression
=> long term steroid use for non-endocrine condition most common cause

=> hypothalamic-pituitary axis and adrenal glands may both be suppressed

ACTH levels are low in secondary hypoadnrealism

Weaning of steroids difficult & long process