Addisonian Crisis

Crisis occurs when the physiological demand for these hormones exceeds the ability of adrenal glands to produce them i.e. in patients with chronic adrenal insufficiency when subject to an intercurrent illness or stress:

• Major or minor infections
• Injury
• Surgery
• Burns
• Pregnancy
• General anaesthesia
• Hypermetabolic states

Commonest cause is abrupt withdrawal of steroids; secondary adrenocortical insufficiency occurs when steroids given as therapy have suppressed the hypothalamic-pituitary-adrenal axis.

Bilateral adrenal gland haemorrhage can produce adrenal crisis due to severe physiological stressors such as myocardial infarction, septic shock or complicated pregnancy, or with concomitant coagulopathy or thromboembolic disorders.

Other causes include autoimmune Addison's disease, tuberculosis, HIV, adrenoleukodystrophy, congenital adrenal hypoplasia and syndromes including Triple A (Allgrove syndrome) and IMAGe (see 'further reading' below for more detail on these).

• Long term steroids:
  • There have been a few cases associated with high dose inhaled fluticasone and it may cause suppression at lower doses also.¹
  • A case has been documented following intra-articular steroid injection.²
• There have also been cases after ketoconazole,³ phenytoin and rifampicin.

• Patient is acutely ill with hypotension, especially postural. They may also be very weak and confused.
• Circulatory collapse may be severe with feeble rapid pulse and soft heart sounds.
• Pyrexia is common and may be due to underlying infection.
• Anorexia, nausea, vomiting and severe abdominal pain occurs very frequently. This may be severe and present as an apparent acute abdomen.
• The patient may show increased motor activity progressing to delirium or seizures.

• Sodium usually moderately decreased, but may be normal.
• Potassium usually slightly increased or normal, rarely markedly increased (risk of arrhythmias).
• Hypoglycaemia, possibly severe, characteristic.
• Serum cortisol of less than 20 mcg/dL in severe stress or after ACTH stimulation indicates adrenal insufficiency.
• ACTH test is diagnostic:
  • Determine the baseline serum cortisol, then administer ACTH 250 mcg intravenously.
  • Serum cortisol are taken at 30 and 60 minutes after ACTH administration.
  • An increase of less than 9 mcg/dL is considered diagnostic of adrenal insufficiency.
• ECG may show prolonged QT interval:
  • This may induce ventricular arrhythmias.
  • Deep negative T waves have been described in acute adrenal crisis.⁴

General principles

• Start treatment immediately based on clinical features and not delayed for confirmation of adrenal function.
• Administration of glucocorticoids in supraphysiological or stress doses is the only definitive therapy.
• Dexamethasone does not interfere with serum cortisol assay and may therefore be the initial drug of choice.
• However, because dexamethasone has little mineralocorticoid activity, fluid and electrolyte replacement is essential.

Resuscitation

• ABCDs which may include:
  • Oxygen
  • IV Normal Saline fluid boluses (500-1000 ml for adult, 10-20 ml/kg for a child)
  • IV Dextrose (25-50 ml 50% Dextrose for adult, 2-5 ml/kg 10% Dextrose for child) as required
• Continued intravenous replacement of estimated dehydration:
  • Usually 5%+ over 8+ hours
  • Using 5% dextrose in normal saline
  • Take into account age, volume, cardiac & renal function
  • Unlikely to require added potassium initially
• 200 mg hydrocortisone - 100 mg/m² or approximately 4 mg/kg for child - IV stat:
  • Then 100 mg hydrocortisone (2 mg/kg for child) IV every 6 hours during first 24 hours.
  • Thereafter hydrocortisone dose can usually be halved again.
  • With such high doses of glucocorticoid, mineralocorticoids are not required.
  • When dosage is reduced further, add fludrocortisone 0.05-0.2 mg/day, aiming at normotension, normokalaemia and a plasma renin activity in the upper normal range.⁵
• If hypotension persists give additional corticosteroids and consider vasopressors e.g. dopamine.
  • Investigate adrenal haemorrhage especially if patient receiving anticoagulants.
  • Reversal of coagulopathy should be attempted with fresh frozen plasma.
• Treat underlying precipitating disorder e.g. infection with antibiotics.
• When testing for adrenal insufficiency and treating at same time, replace hydrocortisone with dexamethasone added to the infusion together with corticotropin.
• Collect blood and urine for analysis of cortisol and urinary-OHCS levels.

• Early dose adjustments (e.g. doubling usual maintenance dose) are required to cover the increased glucocorticoid demand in stress.
• Careful and repeated education of patients and their partners is the best strategy to avoid this life-threatening emergency.
• Avoid exposure to chickenpox or measles. If exposed seek medical advice without delay.
• Patients do not require cover for routine dentistry. Patients undergoing general anaesthesia for procedures may require supplementary steroids depending on the dose and duration of steroid treatment.⁶

Other underlying associated endocrinopathies, which should be excluded:

• Hypothyroidism may mask the Addisons disease and the thyroxine replacement may precipitate an acute adrenal crisis.
• On steroid replacement therapy the "hypothyroidism" will resolve.⁷

Death may be caused by circulatory collapse and arrhythmias with hypoglycaemia contributing.
Prognosis is the same as for patients without adrenal insufficiency if precipitating condition is diagnosed and treated appropriately.