Clinical Practice Guidelines

Adrenal crisis and acute adrenal insufficiency

  • Background

    An adrenal crisis is a physiological event caused by an acute relative insufficiency of adrenal hormones. It may be precipitated by physiological stress in a susceptible patient. It should be considered in patients who have a history of:

    • known primary adrenal insufficiency (see below)
    • hypopituitarism (any known pituitary hormone deficit or clinical features indicating increased risk), or
    • previously or currently being on prolonged steroid therapy. 

    Adrenal crisis may also be first presentation of underlying disease or there may be history suggestive of chronic hypoadrenalism. 

    Adrenal hypofunction may be:

     i)   primary:

     e.g. Addison's disease, congenital adrenal hyperplasia, congenital adrenal hypoplasia, adrenoleukodystrophy,  adrenal haemorrhage in newborns or in fulminating infections (Waterhouse-Friedrichsen syndrome) 

    or

    ii)  secondary to deficient ACTH secretion:
        hypopituitarism, cessation of glucocorticoid therapy, pituitary-hypothalamic pathology including cranial irradiation

    Assessment

    Acute adrenal insufficiency occurs in both primary and secondary adrenal failure. 

    Cortisol deficiency presents with weakness, fatigue, anorexia, nausea, vomiting, hypotension and hypoglycaemia. 
    In primary adrenal hypofunction, cortisol deficiency is combined with mineralocorticoid deficiency to cause hyperkalaemia and hyponatraemia, acidosis and dehydration. 

    Pigmentation may be present in primary adrenal failure and there may be CNS signs in ALD

    Investigations

    Investigations to be done in all cases of possible adrenal insufficiency / crisis:

    • Immediate blood glucose using a bedside glucometer. 
    • Serum glucose, urea, sodium and potassium.
    • Arterial or capilliary acid base.

    In many cases the underlying diagnosis will be known.  However, if this is the initial presentation, the following investigations will help with diagnosis

    • 2 ml of clotted blood (serum tube) for analysis of cortisol and 17 hydroxyprogesterone.  
    • 2ml of blood in EDTA tube for plasma renin activity and ACTH levels - this should be sent on ice to the core lab
    • 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 (e.g. patient is too shut-down to allow for blood-letting), proceed with urgent steroid administration and management as below.

    Prevention of adrenal crisis in a susceptible child

    1. During illness (eg. flu, fever) the usual oral dose of steroid should be tripled.  If the child sustains trauma (e.g fracture / laceration requiring sutures, steroid may need to be given parenterally (see  'stress' hydrocortisone  in 'steroid replacement' section below).
    2. Surgery or anaesthesia : Increased parenteral hydrocortisone should be given before surgery and general anaesthesia and 'stress' cover continued post-op also. Please see separate CPG 'Adrenal insufficiency - steroid replacement before and after surgery or procedure requiring GA'. 
    3. Patients on corticosteroids should wear an identification disc or bracelet carrying the words "Adrenal insufficiency:  In emergency give hydrocortisone at 2mg/kg IM/ IV".

    NB.  Vomiting in a child who is susceptible to adrenal crisis

    • A child who is susceptible to adrenal crisis (i.e. known to have primary or secondary adrenal insufficiency), who presents with vomiting or diarrhoea, should be considered to have incipient adrenal crisis, even if they are otherwise well.  This is because oral meds are not reliably absorbed in this scenario.
    • Where there is an obvious cause eg. in a setting of other family members with gastro etc, the child should be given an initial 'stress' dose of IV / IM Solu-Cortef as outlined in 'treatment' below and watched for ~4-6 hours in the Emergency Dept. 
    • If there is any doubt as to their clinical status or ability to tolerate oral hydrocortisone thereafter, admission and ongoing parenteral hydrocortisone is advised. 
      Please discuss such cases with the endocrinology fellow / consultant on call.

    Treatment of adrenal crisis

    VERY IMPORTANT: Fluids, Solu-Cortef and Florinef must be tailored to the individual needs of the patient.  Careful monitoring of vital signs, fluid balance, glucose and electrolytes is essential to prevent over or under treatment.


    1. INTRAVENOUS FLUIDS

    Fluid requirements:

    Maintenance = 100ml/kg/day for first 10kg body weight, 50ml/kg/day for next 10kg, 25ml/kg/day for each successive 10kg
    Deficit = 100ml/kg for 10% dehydration, 60 ml/kg for 6% dehydration and 30ml/kg for 3% dehydration. 

    Shock or severe dehydration:

    1. Give isotonic saline (0.9% saline) bolus at 10-20ml/kg during the first hour of treatment. This may be repeated until circulation is restored.
    2. Replace remaining deficit + maintenance fluid requirements evenly over 24 hours.  Commence this rehydration with Plasma-Lyte 148 and 5% Glucose.  If potassium is high, use 0.9% saline and 5% glucose
    3. Check pH, electrolytes and glucose frequently
      • Blood gas and BGL hourly x 2 hours; then 2-4 hourly once normoglycaemic and acidosis correcting.
      • U&E: 2 hourly initially (more frequently if significant hyperkalemia - see below) 
      • interval can then be extended once glucose stable and electrolytes normalising.
    4. Avoid rapid rise in serum sodium.

    Moderate dehydration:

    • Normal saline 10 ml/kg i.v. bolus. Repeat until circulation is restored.
    • Administer remaining deficit plus maintenance fluid volume as Plasma-Lyte 148 and 5% Glucose (unless hyperkalaemic) evenly over 24 hours.
    • Check blood gas, electrolytes and glucose frequently as above

    Mild or no dehydration:

    • No bolus.
    • 1-1.5 times maintenance fluid volume as Plasma-Lyte 148 and 5% Glucose (unless hyperkalaemic) administered evenly over 24 hours.
    • Check electrolytes and glucose frequently as above / clinically indicated

    * Note: 10% dextrose may be required to maintain normoglycaemia - see below


    2. STEROID REPLACEMENT

    1. Give IV bolus of hydrocortisone hemisuccinate (Solu-Cortef) immediately (dose for age as shown below).  If IV access is not immediately available, give IM while establishing intravenous access
    2. Follow with hydrocortisone 6hourly IV.

      Recommended doses of 'Stress' Hydrocortisone (given i.m or i.v. ) at different ages*:

      • Neonate - 6 weeks: 25 mg stat initial dose, and then 5-10mg, 6 hourly
      • 6 weeks up to 3 years: 25 mg stat initial dose, then 10mg, 6 hourly
      • Children aged 3-12 years: 50 mg stat initial dose, then 12.5 -25mg, 6 hourly (use 12.5mg as 6 hourly ongoing dose if aged 3-6 yrs and 25mg 6 hourly if aged >7yrs)
      • Adolescents and adults: 100 mg stat initial dose, then 25mg, 6 hourly

      *These dose should also be used prior to and in the initial day(s) post surgery / GA in a child with known adrenal insufficiency. For elective procedures, the initial dose can given at induction, with 6 hourly dosing continuing thereafter.   Once child is stable and tolerating oral intake post-op, hydrocortisone cover can then be changed to oral route (see 'c' below)

       *The doses outlined equate to approximately 50-75mg/m2 as a stat dose initially, followed by 50-75mg per m2/day divided in 4 doses (6 hourly).  Some centres give a continuous infusion of hydrocortisone at 100mg/m2/24 hours after the initial bolus as above.  The endocrinologist on call can advise on this, if an infusion is thought to be necessary.

    3. When child is stable, reduce the IV dose, or if tolerating oral meds switch to triple dose oral hydrocortisone replacement (~30-50mg/m2/day).  This can then be gradually reduced to maintenance levels (10-15 mg/m2/day in primary adrenal insufficiency, or 6-8 mg/m2/day in secondary adrenal insufficiency) over about 5 days.  Endocrinology team will advise on dosing schedule. 
    4. Mineralocorticoid replacement:  in patients with mineralocorticoid deficiency start fludrocortisone (Florinef) at maintenance doses (usually 0.05 - 0.1 mg daily) as soon as patient can tolerate oral fluids. 
      Initial correction is achieved with saline, fluids and the mineralocorticoid activity of stress dose hydrocortisone (20mg = ~ 0.1 mg Florinef). 
      NB. Prednisolone has little / no mineralocorticoid activity.

    3. TREAT HYPOGLYCAEMIA

    Hypoglycaemia is common in infants and small children with adrenal insufficiency.

    • Treat with i.v. bolus of 2-5 ml/kg 10% dextrose.and recheck BGL after 30 minutes to ensure recovery to >4.0mmol/l.
    • Maintenance fluids may require up to 10% dextrose and Plasma-Lyte 148 to maintain normoglycaemia.
    • Monitor BGLs hourly initially, then 2-4 hourly; less frequently once stable.

    4. HYPERKALAEMIA

    This usually normalises with fluid and electrolyte and steroid replacement.

    • Patients with a K+ above 6.0mmol/l should have ECG and be on cardiac monitor.
    • If potassium is above 7.0 mmol/L and hyperkalaemic ECG changes are present (eg. peaked T waves ± wide QRS complex ± flattened P waves), treat with either of the following:
    1. give 10% calcium gluconate 0.5 ml/kg i.v. slowly over 10 mins.  Ideally this should be given through central venous access; at a minimum, ensure good peripheral access as extravasation can cause nasty burns.  This will stabilise the myocardium until fluids and steroid replacement act to lower serum K+
    2. Alternatively, commence infusion of insulin 0.1 units/kg/hr i.v. together with an infusion of 10% dextrose at 5-10 ml/kg/hr.  K+ will usually decrease within 30-60minutes. Monitor U&E hourly and discontinue therapy once K+ <6.0mmol/l or ECG changes revert. Monitor BGLs hourly for at least 4 hours as there is a risk of delayed hypoglycaemia after insulin is stopped (ensure dextrose containing fluids are used for ongoing fluid replacement as above).

    Precipitating Causes

    Look for and treat precipitating cause of illness.

    Consider consultation with local paediatric team when:

    - In all cases of adrenal insufficiency

    Consider transfer when:

    - Severe electrolyte or glucose abnormalities - such as hyperkalaemia
    - Children not responding to stress dose steroids.
    - Haemodynamic instability
    - Children requiring care above the level of comfort of the local hospital.

    For emergency advice and paediatric or neonatal ICU transfers, call the Paediatric Infant Perinatal Emergency Retrieval (PIPER) Service: 1300 137 650.

     

     

    Information Specific to RCH

    Admit all patients.

    Discuss ongoing investigations, management and steroid replacement with the endocrinologist / fellow on call.

    Last updated March 2016