Adrenal insufficiency

Question 1

What is adrenal insufficiency?

Answer 1

Deficiency of the adrenal cortical hormones (e.g. mineralocorticoids, glucocorticoids and androgens)

Question 2

What is the aetiology of adrenal insufficiency?

Answer 2

• Primary (Addison’s disease): Autoimmune
• Infections: Tuberculosis, meningococcal septicaemia (Waterhouse-Friderischen syndrome), CMV (HIV patients), histoplasmosis
• Infiltration: Metastasis (e.g. lung, breast, melanoma), lymphoma, amyloidosis
• Infarction: Secondary to thrombophilia
• Inherited: Adrenoleukodystrophy, ACTH receptor mutation
• Surgical: After bilateral adrenalectomy
• Secondary: Pituitary or hypothalamic disease

- Iatrogenic: Sudden cessation of long-term steroid therapy

Question 3

What is the epidemiology of adrenal insufficiency?

Answer 3

Most common cause is iatrogenic

• Primary causes are rare

Question 4

What are the presenting symptoms of adrenal insufficiency?

Answer 4

- Chronic presentation:

Non-specific symptoms such as

• dizziness
• anorexia
• weight loss
• diarrhoea
• vomiting
• abdominal pain
• lethargy
• weakness
• depression
• Acute presentation (Addisonian crisis):

Acute adrenal insufficiency with major haemodynamic collapse often precipitated by stress (e.g. infection or surgery)

Question 5

What are the signs of adrenal insufficiency on examination?

Answer 5

• Postural hypotension
• Increased pigmentation: Generalised but more noticeable on buccal mucosa, scars, skin creases, nail, pressure points (resulting from melanocytes being stimulated by raised ACTH level)
• Loss of body hair in women (androgen deficiency)
• Associated autoimmune conditions: e.g. vitiligo
• Addisonian crisis: Hypotensive shock, tachycardia, pale, cold, clammy, oliguria

Question 6

What are the investigations for adrenal insufficiency?

Answer 6

• Confirm the diagnosis: 9am serum cortisol less than 100nmol/L is diagnostic of adrenal insufficiency.
• Identify the level of defect ACTH: Raised in primary disease, decreased in secondary. Long Synacthen test
• Identify the cause: Autoantibodies (against 21-hydroxylase). Abdominal CT or MRI. Other tests e.g. adrenal biopsy for microscopy, culture, PCR, depending on the suspected causes Check TFTs
• Investigations in ‘Addisonian crisis’: FBC

Question 7

How is adrenal insufficiency managed?

Answer 7

- Addisonian crisis:

• Rapid IV fluid rehydration.
• 50ml of 50% dextrose to correct hypoglycaemia.
• IV 200mg hydrocortisone bolus followed by 100mg 6 hourly (until BP stable).
• Treat the precipitating cause (e.g. antibiotics for infection).
• Monitor temperature, pulse, respiratory rate, BP, sat 02 and urine output

- Chronic:

• Replacement of glucocorticoids with hydrocortisone (three times/day) and mineralocorticoids with fludrocortisone.
• Hydrocortisone dosage needs to be increased during acute illness or stress.
• If associated with hypothyroidism, give hydrocortisone before thyroxine (to avoid precipitating Addisonian crisis)
• Advice: Steroid warning card, Medic-alert bracelet, emergency hydrocortisone ampoule, patient education

Question 8

What are the possible complications of adrenal insufficiency?

Answer 8

• Hyperkaelaemia
• Death during Addisonian crisis

Question 9

What is the prognosis of adrenal insufficiency?

Answer 9

• Adrenal function rarely recovers, but normal life expectancy can be expected if treated
• Type I (autosomal recessive disorder caused by mutation in the AIRE gene which encodes a nuclear transcription factor): Addison’s disease, chronic mucocutaneous candidiasis, hypoparathyroidism
• Type II: Addison’s disease, diabetes mellitus Type I, hypothyroidism, hypogonadism