Adrenal Insufficiency

Question 1

Definition

Answer 1

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

Question 2

Aetiology/Risk Factors

Answer 2

· Primary Adrenal Insufficiency
eg Addison’s disease (usually autoimmune)

· Secondary Adrenal Insufficiency
eg Pituitary or hypothalamic disease

· Infections
eg Tuberculosis, Meningococcal septicaemia (Waterhouse-Friderichsen Syndrome), CMV, Histoplasmosis

· Infiltration
eg Metastasis (mainly from lung, breast, melanoma), Lymphomas, Amyloidosis

· Infarction
eg Secondary to thrombophilia

· Inherited
eg Adrenoleukodystrophy, ACTH receptor mutation

· Surgical
eg After bilateral adrenalectomy

· Iatrogenic
eg Sudden cessation of long-term steroid therapy

Question 3

Epidemiology

Answer 3

Most common cause is IATROGENIC

Primary causes are rare

Question 4

Presenting Symptoms

Answer 4

Chronic presentation:
(symptoms tend to be vague and non-specific)
Dizziness
Anorexia
Weight loss
Diarrhoea and vomiting
Abdominal pain 
Lethargy
Weakness
Depression

Acute presentation:
(Addisonian Crisis)
Acute adrenal insufficiency
Major haemodynamic collapse
Precipitated by stress (eg infection, surgery)

Question 5

Signs on physical examination

Answer 5

· Postural hypotension
· Increased pigmentation (More noticeable on buccal mucosa, scars, skin creases, nails and pressure points)
· Loss of body hair in women (due to androgen deficiency)
· Associated autoimmune condition (e.g. vitiligo)

Addisonian crisis signs:
Hypotensive shock
Tachycardia
Pale
Cold
Clammy
Oliguria

Question 6

Investigations (confirm diagnosis)

Answer 6

o 9 am Serum Cortisol
· < 100 nmol/L is diagnostic of adrenal insufficiency
· > 550 nmol/L makes adrenal insufficiency unlikely

o Short Synacthen Test
· IM 250 mg tetrocosactrin (synthetic ACTH)
· Serum cortisol < 550 nmol/L at 30 mins indicates adrenal failure

Question 7

Investigations (level of defect in hypothalamo-pituitary-adrenal axis)

Answer 7

o HIGH in primary disease

o LOW in secondary

o Long Synacthen Test
· 1 mg synthetic ACTH administered
· Measure serum cortisol at 0, 30, 60, 90 and 120 minutes
· Then measure again at 4, 6, 8, 12 and 24 hours
· Patients with primary adrenal insufficiency show no increased after 6 hours

Question 8

Investigations (identify cause)

Answer 8

Autoantibodies (against 21-hydroxylase)
Abdominal CT or MRI
Other tests (adrenal biopsy, culture, PCR)

Question 9

Investigations (Addisonian crisis)

Answer 9

FBC (neutrophilia --> infection)
U&Es
· High urea
· Low sodium
· High potassium
CRP/ESR
Calcium (may be raised)
Glucose - low
Blood cultures
Urinalysis
Culture and sensitivity

Question 10

Management Plan (Addisonian crisis)

Answer 10

Rapid IV fluid rehydration
50 mL of 50% dextrose to correct hypoglycaemia
IV 200 mg hydrocortisone bolus
Followed by 100 mg 6 hourly hydrocortisone until BP is stable
Treat precipitating cause (e.g. antibiotics for infection)
Monitor

Question 11

Management Plan (chronic adrenal insufficiency)

Answer 11

Replacement of:
· Glucocorticoids with hydrocortisone (3/day)
· Mineralocorticoids with fludrocortisone

Hydrocortisone dosage needs to be increased during times of acute illness or stress

NOTE: if the patient also has hypothyroidism, give hydrocortisone BEFORE thyroxine (to prevent precipitating an Addisonian crisis)

Question 12

Management Plan (advice)

Answer 12

Have a steroid warning card
Wear a medic-alert bracelet
Emergency hydrocortisone on hand

Question 13

Possible Complications

Answer 13

HYPERKALAEMIA

Death during Addisonian crisis

Question 14

Prognosis

Answer 14

· Adrenal function rarely recovers
· Normal life expectancy if treated

· Autoimmune Polyendocrine Syndrome

o Type 1 - autosomal recessive disorder caused by mutations in the AIRE gene. Consists of the following diseases:
· Addison’s disease
· Chronic mucocutaneous candidiasis
· Hypoparathyroidism

o Type 2 - also known as Schmidt's Syndrome
· Addison's disease
· Type 1 Diabetes
· Hypothyroidism
· Hypogonadism