Adrenal crisis

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10.4 Adrenal crisis

1 The prompt recognition of the possibility of adrenal crisis or the risk of adrenal insufficiency is paramount to early and appropriate management.

2 Adrenal crisis should be considered as a possible contributor in any child with acute severe cardiovascular collapse.

3 In children, the majority of cases are due to primary adrenal failure, with congenital adrenal hyperplasia the most common cause.

4 A crisis can be precipitated in a child with known adrenal insufficiency who develops an intercurrent illness or other physiological stress.

5 Signs of glucocorticoid deficiency include hypoglycaemia, hypotension (absolute and postural) and refractory shock.

6 Signs of mineralocorticoid deficiency include dehydration (often out of proportion to estimated fluid losses), hyperkalaemia, hyponatraemia, acidosis, and pre-renal failure.

7 Patients are at risk of hypoglycaemia.

8 The management of adrenal crisis involves immediate fluid resuscitation, replacement of corticosteroid and treating hypoglycaemia.

9 The differential diagnosis of a collapsed neonate (particularly male) in the first 14 days includes adrenal insufficiency.

10 Prevention of adrenal crisis in susceptible children may be possible by following a predetermined action plan during intercurrent illnesses.

Introduction

Adrenal crisis is a life-threatening emergency caused by acute insufficiency of the adrenal hormones cortisol and aldosterone. This can occur in situations of stress where the adrenal gland would normally respond by an increase in glucocorticoid secretion. A crisis can be precipitated in a child with known adrenal insufficiency, who develops an inter-current illness or other physiological stress (e.g. burns, surgery, trauma, and sepsis). In this situation, the increased cortisol requirements of the stress or the altered oral intake of normal replacement therapy results in a relative insufficiency and rapid clinical deterioration. Alternatively, the emergency department (ED) visit may represent a new presentation of adrenal insufficiency in a child previously unrecognised to have the subtle, often non-specific symptoms of lack of adrenal hormones or a child who is at risk due to suppression by prolonged steroid therapy. The prompt recognition of the possibility of adrenal crisis or the risk of adrenal insufficiency is paramount to early and appropriate management. These children are at risk of hypoglycaemia and this needs to be anticipated and managed accordingly.

Adrenal insufficiency can be primary, due to a failure of secretion of the adrenal cortex, or secondary to hypothalamic or pituitary dysfunction. In children, the majority of cases are due to primary adrenal failure, with congenital adrenal hyperplasia the most common cause. The incidence of neonatal congenital adrenal hyperplasia in Australia is estimated at 5.9 cases per 100 000 births.

Primary causes include:

• congenital adrenal hyperplasia;

• Addison’s disease (autoimmune);

• adrenal aplasia/hypoplasia;

• adrenal infarction secondary to haemorrhage/sepsis;

• other – trauma, tumour, post-surgical.

Secondary causes include:

• central nervous system (CNS) tumour or trauma;

• idiopathic;

• exogenous steroid therapy – including inhaled corticosteroids.

Clinical presentation

Clinical features may be subtle; however, the diagnosis should be considered in all children with cardiovascular collapse. Features to look for in history, examination and investigation findings are listed below, with differential diagnosis.

History

• Prior steroid use, including inhaled steroids for asthma or other condition.

• Known congenital adrenal hyperplasia or other adrenal insufficiency on replacement therapy.

• Severe physiological stress (sepsis, trauma, burns, surgery).

• On anticoagulants, haemorrhagic diathesis.

• Neonate with collapse and/or hypoglycaemic event or ambiguous genitalia.

• Symptoms of glucocorticoid deficiency – weakness, fatigue, lethargy, anorexia, vomiting, diarrhoea, weight loss.

Examination

• Signs of glucocorticoid deficiency – hypoglycaemia, hypotension (absolute and postural), refractory shock.

• Signs of mineralocorticoid deficiency – dehydration (often out of proportion to estimated fluid losses), hyperkalaemia, hyponatraemia, acidosis, pre-renal failure.

• Signs of excess adrenocorticotropic hormone secretion – pigmentation of skin, lips, nipples, skin creases.

• Signs of glucocorticoid therapy – Cushing’s syndrome.

• Signs of associated hypothalamic/pituitary abnormality – growth abnormality, midline defects, hypogonadism, diabetes insipidus, hypothermia.

Investigations

• Bedside: finger-prick glucose (hypoglycaemia), electrocardiogram (ECG) (hyperkalaemia).

• Biochemical: glucose, urea and electrolytes, arterial blood gas, save clotted blood for cortisol level and 17-hydroxyprogesterone, if no underlying diagnosis is known.

Differential diagnosis

• Other causes of hyponatraemia – syndrome of inappropriate antidiuretic hormone hypersecretion, nephrogenic or cerebral salt wasting, gastrointestinal or urinary losses.

• Other causes of shock – septicaemia, profound dehydration, duct-dependent cardiac lesion.

Treatment

The management of adrenal crisis involves immediate fluid resuscitation, replacement of corticosteroid and treating hypoglycaemia. The underlying illness causing the stress needs to be treated on its merits. Potential complications, such as hyperkalaemia, may require intervention. In children not previously known to be adrenal deficient, blood (prior to administration of glucocorticoid) should be held for analysis to determine if an underlying condition exists.

Fluid management

Patients known to have adrenal deficiency who are not dehydrated or shocked can have a trial of enteral fluids in the ED. They should be considered to have vomited or potentially not absorbed normal replacement adrenal medication, and should be administered intramuscular (IM) hydrocortisone 2 mg kg^–1 to ensure delivery.

Children who are dehydrated or shocked require intravenous resuscitation with crystalloid. Initial boluses of 20 mL kg^–1 normal saline should be titrated to restore peripheral circulation in those children with shock. Remaining estimated deficit plus maintenance volumes should then be replaced with 5% dextrose and normal saline over a 24-hour period. The maintenance fluid requirements are 1.5 times normal in this setting and clinical and biochemical (electrolytes and glucose) reassessment is required to tailor fluid therapy to the individual.

Replacement of corticosteroid

Hydrocortisone should be given intravenously, unless access is significantly delayed, where it should be administered IM as an interim alternative. The appropriate dose can be determined by age:

• neonate: 25 mg stat., then 10–25 mg 6-hourly;

• 1 month–1 year: 25 mg stat., then 25 mg 6-hourly;

• 1–3 years: 50 mg stat., then 50 mg 6-hourly;

• 4–10 years: 75 mg stat., then 75 mg 6-hourly;

• >10 years: 100 mg stat., then 100 mg 6-hourly.

Maintenance doses of glucocorticoid and mineralocorticoid are introduced after the child has been stabilised as an inpatient. Generally, glucocorticoid replacement dose is 10–15 mg m^–2 day^–1 orally and mineralocorticoid dose is 0.1–0.2 mg day^–1 for salt-wasting children.

Hypoglycaemia

Hypoglycaemia is treated in the routine fashion using a lower concentration of intravenous dextrose in smaller children. Maintenance fluid will generally require 5–10% dextrose solution added to normal saline.

• neonate/infant: 5 mL kg^–1 of 10% dextrose stat.;

• older child: 2 mL kg^–1 of 25% dextrose stat.;

• maintenance fluid: 5–10% dextrose-containing solution.

Hyperkalaemia

Hyperkalaemia should be treated if K⁺ >7 mmol L^–1 with ECG changes.

• 0.5 mL kg^–1 of 10% calcium gluconate over 3–5 minutes;

• 0.1 U kg^–1 hr^–1 of insulin + 2 mL kg^–1 hr^–1 of 50% dextrose infusion.

Disposition

All children with an established adrenal crisis require inpatient admission.

Discharge may be considered in milder cases, after a period of 6 hours observation, for those susceptible patients who respond well to treatment with oral fluids and increased dose of intramuscular hydrocortisone.

Prognosis

In the absence of bilateral adrenal haemorrhage, the survival rate of patients with adrenal crisis who are diagnosed and treated appropriately approaches that of patients without acute adrenal crisis with similar severity of illness. Because the true incidence of adrenal crisis and bilateral adrenal haemorrhage is unknown, the actual mortality rate is also unknown.

Prevention

At-risk children with an intercurrent illness may prevent an adrenal crisis with an action plan for parents:

• if moderately unwell and/or temperature is 38–39°C give 3× oral dose of oral hydrocortisone;

• if more unwell and/or temperature >39°C give 4× dose of oral hydrocortisone;

• if vomiting give IM 2 mg kg^–1;

• If gastroenteritis or diarrhoea give 4× dose of oral hydrocortisone.

NB. Only the dose of hydrocortisone should be increased, not fludrocortisone. When the stress is over the previous dose should be resumed without tapering.

Controversies and future directions

The role of screening for congenital adrenal hyperplasia (CAH) is controversial. In Australia there is currently no programme in place.

Research indicates that early screening may reduce the morbidity or mortality associated with adrenal crisis.

National newborn screening awaits the development of a more cost-efficient test.

New research suggests that critically ill children with adrenal crisis may be best managed with a single intravenous bolus dose of hydrocortisone followed by a constant rate infusion. This in preference to the 6-hourly boluses used currently.

A further recent research development is that CAH can be diagnosed and treated prenatally if a mother has previously had a child with CAH.

Further reading

Charmandari E., Lichtarowicz-Krynska E.J., Hindmarsh P.C., et al. Congenital adrenal hyperplasia: Management during critical illness. Arch Dis Child. 2001;85(1):26-28.

Fischer J.E., Stalmach T., Fanconi S. Adrenal crisis presenting as hypoglycaemic coma. Intens Care Med. 2000;26:105-108.

Gassner H.L., Toppari J., Quinteiro Gonzalez S., Miller W.L. Near-miss apparent SIDS from adrenal crisis. J Pediatr. 2004;145(2):178-183.

Kirkland L. Adrenal crisis. 2003. eMedicine www.emedicine.com

Macdessi J.S., Randell T.R., Donaghue K.C., et al. Adrenal crisis in children treated with high-dose inhaled corticosteroids for asthma. Med J Aust. 2003;178(5):214-216.

Omori K., Nomura K., Shimizu S., et al. Risk factors for adrenal crisis in patients with adrenal insufficiency. Endocr J. 2003;50(6):745-752.

Royal Children’s Hospital. Clinical Practice Guidelines. 2005. Adrenal Crisis. Available from www.rch.org.au [accessed 19.10.10]

The Children’s Hospital at Westmead. The New Children’s Hospital Handbook. Acute adrenal insufficiency. Available from www.chw.edu.au, 2005. [accessed 19.10.10]

Todd G.R.G., Acerini C.L., Ross-Russell R., et al. Survey of adrenal crisis associated with inhaled corticosteroids in the United Kingdom. Arch Dis Child. 2002;87:457-461.

Van der Kemp H.J., Noordham K., Elvers B., et al. Newborn screening for congenital adrenal hyperplasia in the Netherlands. Paediatrics. 2001;108(6):1320-1324.

Textbook of Paediatric Emergency Medicine