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Adrenal Crisis (Addisonian Crisis)
Adrenal crisis is a life threatening emergency in patients with primary (classic addisonian crisis), or secondary adrenal failure. It is often precipitated by stress, surgery or intercurrent illness such as infection or MI due to an inadequate glucocorticoid response.
Although patients with secondary adrenal insufficiency may suffer from adrenal crisis, they usually do not have the same degree of volume depletion, because their renin–angiotensin– aldosterone axis is intact.
Diagnosis – This is often difficult as the patient may have vague symptoms and just appear “unwell”, or symptoms are presumed to be part of the presenting illness. It is important to consider this diagnosis and have a low index of suspicion. Patients with adrenal insufficiency often have an alert bracelet or an alert on their patient notes.
Glucocorticoids are produced in the adrenal cortex under the regulation of the hypothalamic–pituitary–adrenal (HPA) axis.
Cortisol has many important metabolic and endocrine functions that are essential for human survival, particularly during stress. Surgery, anaesthesia, trauma, and severe illnesses result in elevated plasma ACTH and cortisol levels. Cortisol is required for the metabolism of carbohydrates, lipids and proteins, and for the maintenance of vascular tone and endothelial integrity. It also potentiates the vasoconstrictor actions of catecholamines and has anti-inflammatory effects on the immune system.
Aldosterone is synthesised in the adrenal cortex under the control of the renin–angiotensin system. It regulates sodium and potassium balance and intravascular volume.
Primary adrenal insufficiency / Addison’s
-is due to intrinsic adrenal gland dysfunction and results in decreased cortisol and aldosterone production. Approximately 90% of the gland must be destroyed for clinical adrenal insufficiency to develop. The commonest cause in developed countries is autoimmune adrenalitis. Other causes include infection (e.g. tuberculosis, HIV), drugs, adrenal haemorrhage, sarcoidosis, metastases, and congenital adrenal hyperplasia.
Secondary adrenal insufficiency
-is due to hypothalamic-pituitary dysfunction causing inadequate ACTH production. This results in cortisol deficiency only. This may be caused by withdrawal of prolonged steroid therapy, pituitary disease or pituitary injury such as trauma, tumour, irradiation or surgery.
Signs and Symptoms
- Severe vomiting and diarrhoea
- Dehydration, hypotension or shock – may be out of proportion to severity of current illness
- Loss of consciousness
- Abdominal pain
- Unexplained hypoglycaemia
- Hyponatremia, hyperkalemia, uraemia, hypercalcemia, or eosinophilia
Adrenal Crisis - Investigations
If suspicion of adrenal crisis:
- Immediate blood glucose using a bedside glucometer.
- Serum glucose, urea, sodium and potassium.
- Venous blood gas to check acid-base status.
If the patient is not known to have adrenal insufficiency the following investigations will help with diagnosis:
- 2mL of clotted blood (serum tube) for cortisol and 17 hydroxyprogesterone levels.
- 2mL of blood in EDTA tube for plasma renin activity and ACTH levels - this should be sent on ice.
- A sample of urine (aim for 5-10mL if possible) for a urinary steroid profile and urinary sodium level.
Where possible, these investigations should be performed prior to administration of steroid, as this helps greatly with interpretation. However, if this is not possible proceed with urgent steroid administration.
Patients will also need appropriate investigation of their current symptoms and possible precipitating cause for the adrenal crisis.
Adrenal Crisis - Treatment
1. IV fluids
Initial treatment with normal saline 10-20mL/kg depending on level of dehydration. Rehydrate as needed.
2. Steroid replacement
Hydrocortisone100mg IV, then 100mg every 6 hours until stable. Hydrocortisone has glucocorticoid and mineralocorticoid effects. This can be provided as a 24 hour infusion of 300-400mg and dose requirements in some patients may vary, consult Endocrinologist.
3. Correct hypoglycaemia
Treat hypoglycaemia (BGL <4 mmol/L)
Hyperkalaemia usually responds to volume replacement and hydrocortisone — IV insulin and glucose should be avoided.
If K >6.0 place patient on cardiac monitor if not already monitored.
5. Treat underlying disease
Consider precipitants, e.g. sepsis, myocardial infarction, pancreatitis, and treat as appropriate.
Adrenal Crisis - Further References and Resources
Clinical Excellence Commission: Patient Safety Watch 1/15 - Adrenal Insufficiency: Diagnostic and Management Dilemmas
Relative Adrenal Insufficiency
The term ‘Relative Adrenal Insufficiency’ (RAI) describes a state of inadequate physiological response to cortisol in the context of critical illness or stress. This condition may also be referred to as ‘Critical Illness Related Corticosteroid Insufficiency’. The term is reserved for the subnormal corticosteroid production in critical illness, in the absence of structural defects in the hypothalamic-pituitary-adrenal axis. There is currently no consensus on diagnostic criteria for this condition.
The term RAI is separate from other causes of true adrenal insufficiency – primary, secondary and tertiary dependent upon the ‘level’ of the disease process (adrenal, pituitary or hypothalamic), the most common being administration of exogenous glucocorticoid causing suppression of the hypothalamic-pituitary-adrenal axis.
There is general agreement that septic patients have too little cortisol relative to their ‘stressed state’, however there is disagreement about how much is too little, or even how to identify these patients, given the unreliability of cortisol levels or short synacthen tests levels in the septic patients. Despite many years of debate and multiple trials, there is still a lack of complete agreement on the mortality benefit of steroid use in refractory septic shock, but we have drawn out the main features of the current expert consensus:
- The current consensus is described in the Surviving Sepsis Campaign
- Use hydrocortisone (50 mg, 6 hourly) in severe sepsis where shock is refractory to fluids and vasopressors.
- Don't use steroids if there is no shock or it is managed with fluids and vasopressors.
- ACTH (synacthen) test does not appear to be able to predict patients who will benefit from steroids.
- Most papers suggest fludrocortisone is not required.
- Thyroid Storm is a medical emergency.
- It mimics many other conditions – sepsis / stimulant ingestion / heat stroke.
- Mortality rate is high, but early diagnosis and specific interventions improve outcomes.
- Managed in High Dependency / Intensive Care Unit.
A hyperthyroid state with evidence of end organ dysfunction.
- Tachycardia out of proportion with other findings.
- 90% have CNS disturbance.
- Usually sudden onset.
- Precipitated by infection / trauma / surgery / DKA / withdrawal of thyroid drug, iodine administration
- Mortality usually from cardiovascular collapse / high output cardiac failure
Thyroid specific - "The 5 Bs"
|1. Block synthesis|
|200–250mg every 4 hours|
Also blocks peripheral conversion
|2. Block release|
Inorganic iodine. Any of:
**Administer AT LEAST 1 hour after PTU (iodine load can exacerbate thyroid storm)***
Choose one agent and stick to it – not interchangeable
If true iodine allergy, use lithium carbonate
|3. Block conversion||Steroids – hydrocortisone 300mg IV||100mg IV 8 hourly|
|4. Beta-blockers||Propanolol 60-80mg PO 4 hourly (or 0.5mg–1mg slow IV push over 10 minutes)||Also inhibits peripheral conversion|
|5. Block entero-hepatic circulation||Cholestyramine 4g PO 6 hourly|
- Treat underlying cause – look specifically for infection / AMI.
- Strongly consider broad spectrum, empirical antibiotics after appropriate cultures taken, in consultation with local guidelines.
- Aggressive fluid rehydration, correct electrolyte imbalances.
- Cooling – aggressive [avoid aspirin – displaces T4].
- Benzodiazepines for control of agitation/ minimize sympathetic outflow.
- Haemodynamic support – ionotropes/ DCCV [often arrhythmias fail to respond to standard treatment, often need DCCV].
- Will need high level medical unit disposition – likely HDU / ICU care…remember DISPOSITION early: where is your patient going after ED?