Management of children and young people presenting with an adrenal crisis
(new presentation or with pre-existing adrenal insufficiency)
(new presentation or with pre-existing adrenal insufficiency)
Flowchart
Introduction
Children and young people usually present with an adrenal crisis if they have a pre-existing medical condition that causes adrenal insufficiency (AI) or if there is an abrupt cessation of steroid therapy. However, the initial presentation may be the first presentation of a hitherto undiagnosed adrenal insufficiency.
Presentation with an adrenal crisis is a life-threatening emergency and needs to be managed promptly.
Children and young people usually present with an adrenal crisis if they have a pre-existing medical condition that causes adrenal insufficiency (AI) or if there is an abrupt cessation of steroid therapy. However, the initial presentation may be the first presentation of a hitherto undiagnosed adrenal insufficiency.
Presentation with an adrenal crisis is a life-threatening emergency and needs to be managed promptly.
Scope
All staff working in child health within the Wessex region involved in the care of children up to the age of 18 years.
Children with an adrenal crisis should be discussed with the lead for paediatric endocrinology at each DGH during working hours. See Wessex Paediatric Endocrine Network webpage.
All staff working in child health within the Wessex region involved in the care of children up to the age of 18 years.
Children with an adrenal crisis should be discussed with the lead for paediatric endocrinology at each DGH during working hours. See Wessex Paediatric Endocrine Network webpage.
Purpose
To improve early diagnosis, clinical outcomes and provide an agreed clinical approach to managing children presenting with adrenal insufficiency or an adrenal crisis. There is a separate PIER guideline for management of steroids during illness for those not in an adrenal crisis and not requiring intravenous steroids.
To improve early diagnosis, clinical outcomes and provide an agreed clinical approach to managing children presenting with adrenal insufficiency or an adrenal crisis. There is a separate PIER guideline for management of steroids during illness for those not in an adrenal crisis and not requiring intravenous steroids.
Definitions
Adrenal insufficiency: Inadequate production of glucocorticoid and/or mineralocorticoid by the adrenal gland due to a problem at the level of the adrenal gland (primary), pituitary gland (secondary) or hypothalamus (tertiary).
Adrenal crisis:
Adrenal (“Addisonian”) crisis occurs when the adrenal glands cannot produce sufficient cortisol in response to an increased need. The major clinical features of adrenal crisis are hypotension and volume depletion. Combined glucocorticoid and mineralocorticoid deficiency results in urinary sodium loss, hyponatremia, hyperkalaemia, increased serum urea, and, especially in children, hypoglycaemia.
Adrenal insufficiency: Inadequate production of glucocorticoid and/or mineralocorticoid by the adrenal gland due to a problem at the level of the adrenal gland (primary), pituitary gland (secondary) or hypothalamus (tertiary).
Adrenal crisis:
Adrenal (“Addisonian”) crisis occurs when the adrenal glands cannot produce sufficient cortisol in response to an increased need. The major clinical features of adrenal crisis are hypotension and volume depletion. Combined glucocorticoid and mineralocorticoid deficiency results in urinary sodium loss, hyponatremia, hyperkalaemia, increased serum urea, and, especially in children, hypoglycaemia.
Background
Control of cortisol secretion
Corticotrophin releasing hormone (CRH) secreted by the hypothalamus stimulates the secretion of adrenocorticotrophic hormone (ACTH) from the anterior pituitary, which in turn causes the release of cortisol from the adrenal cortex. Negative feedback occurs at the level of both the pituitary and hypothalamus in response to raised cortisol levels. Exogenous steroids will also cause inhibition of CRH and ACTH release, which if prolonged may lead to adrenal atrophy and suppresses the ability of the adrenal glands to increase the production of cortisol in response to stress, leading to primary and secondary adrenal insufficiency. Cortisol has many important functions including maintenance of blood pressure, blood glucose levels and immunity.
Classification of adrenal insufficiency
As the future management will differ depending on the underlying cause, it is a key management step to identify whether the initial presentation is either primary adrenal insufficiency (associated with an elevated ACTH) or secondary adrenal insufficiency (associated with an inappropriately normal or low ACTH). It is therefore important to take an ACTH sample at presentation (EDTA sample) and other samples (see below) prior to treatment with hydrocortisone.
Primary adrenal insufficiency: These are disorders of the adrenal gland e.g. autoimmune adrenal insufficiency (Addison's disease), congenital adrenal hyperplasia, steroid-induced adrenal suppression. These conditions typically lead to an elevated ACTH at presentation.
Secondary adrenal insufficiency: These conditions lead to disruption of the hypothalami-pituitary axis and deficiency of CRH and/or ACTH e.g. congenital hypopituitarism, brain tumour, acquired (traumatic brain injury, meningitis, abrupt cessation of steroid therapy). At presentation there is an inappropriately normal or low ACTH.
Control of cortisol secretion
Corticotrophin releasing hormone (CRH) secreted by the hypothalamus stimulates the secretion of adrenocorticotrophic hormone (ACTH) from the anterior pituitary, which in turn causes the release of cortisol from the adrenal cortex. Negative feedback occurs at the level of both the pituitary and hypothalamus in response to raised cortisol levels. Exogenous steroids will also cause inhibition of CRH and ACTH release, which if prolonged may lead to adrenal atrophy and suppresses the ability of the adrenal glands to increase the production of cortisol in response to stress, leading to primary and secondary adrenal insufficiency. Cortisol has many important functions including maintenance of blood pressure, blood glucose levels and immunity.
Classification of adrenal insufficiency
As the future management will differ depending on the underlying cause, it is a key management step to identify whether the initial presentation is either primary adrenal insufficiency (associated with an elevated ACTH) or secondary adrenal insufficiency (associated with an inappropriately normal or low ACTH). It is therefore important to take an ACTH sample at presentation (EDTA sample) and other samples (see below) prior to treatment with hydrocortisone.
Primary adrenal insufficiency: These are disorders of the adrenal gland e.g. autoimmune adrenal insufficiency (Addison's disease), congenital adrenal hyperplasia, steroid-induced adrenal suppression. These conditions typically lead to an elevated ACTH at presentation.
Secondary adrenal insufficiency: These conditions lead to disruption of the hypothalami-pituitary axis and deficiency of CRH and/or ACTH e.g. congenital hypopituitarism, brain tumour, acquired (traumatic brain injury, meningitis, abrupt cessation of steroid therapy). At presentation there is an inappropriately normal or low ACTH.
Key Points for the assessment of a child with suspected adrenal crisis
Clinical Features of adrenal insufficiency or an adrenal crisis
These may be evident as deficiency of cortisol, aldosterone or both.
- The diagnosis should be considered in a child presenting with: shock, hypotension and volume depletion, hyponatraemia, hyperkalaemia (latter not always present), hypoglycaemia and increased serum urea and creatinine. There may be a more insidious onset with recurrent infections, recurrent episodes of hypoglycaemia or hyponatraemia.
- An adrenal crisis is often triggered by intercurrent illness such as gastro-enteritis or infection, trauma, or non-compliance with steroid replacement therapy.
- Some conditions can mimic the presentation of adrenal insufficiency e.g. sepsis, obstructive uropathy (in neonates), pseudohypoaldosteronism; thus highlighting the importance of taking the correct samples prior to treatment with hydrocortisone.
Clinical Features of adrenal insufficiency or an adrenal crisis
These may be evident as deficiency of cortisol, aldosterone or both.
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Infants:
Hypoglycaemia Jaundice Neonatal hepatitis Poor feeding Weight faltering Hyperpigmentation Collapse, death |
Child:
Nausea, vomiting Weight loss, anorexia Hypotension, Postural hypotension Hypoglycaemia Worsening fatigue Hyperpigmentation Collapse, death History of recurrent infections |
Features of aldosterone deficiency:
Muscle weakness, fatigue, weight loss, nausea and vomiting, salt craving, hypotension/dizziness, hyponatraemia, hyperkalaemia, acidosis.
Muscle weakness, fatigue, weight loss, nausea and vomiting, salt craving, hypotension/dizziness, hyponatraemia, hyperkalaemia, acidosis.
Evidence
- There are no randomised controlled trials that have established the correct dose of hydrocortisone required during an adrenal crisis. Studies in healthy individuals suggest serum cortisol levels rise by a magnitude of 3-5 times during febrile illness and 7 times during anaesthesia. Results, however, are inconsistent and most guidelines suggest a hydrocortisone dose of 50-100 mg/m2 initially followed by a further 50-100 mg/m2/day given as 6 hourly boluses or a continuous infusion (Ref 1).Consensus statements generally agree that doses at the higher end of the range are required during sepsis (Ref 2). The Children's BNF recommends a dose of 2-4mg/kg initially, followed by 2-4mg/kg every 6 hours (Ref 4).
- As under-dosing is potentially hazardous, most treatment regimes are based on prevention of under-dosage initially rather than on reducing potential short-term effects of potential over-dosage. It is recommended that after initial treatment, doses are reduced gradually depending on clinical response and the severity of the illness.
- Children and Young People at risk of adrenal crisis will have access to a dose of Intramuscular Hydrocortisone - they may have received this from the parents or ambulance crew before arriving in hospital. This method of administration can also be used if intravenous access is delayed in hospital.
Guideline for the Management of an adrenal crisis
1. Obtain IV access. If obtaining IV access is delayed, give IM hydrocortisone.
2. The investigations required depend on whether this is:
1. Obtain IV access. If obtaining IV access is delayed, give IM hydrocortisone.
2. The investigations required depend on whether this is:
- A: a new presentation
- B: a child known to have adrenal insufficiency/at risk of adrenal insufficiency.
Obtaining biochemical investigations before hydrocortisone administration is a key management step to identify the underlying diagnosis. If investigations are taken after hydrocortisone is given, the hydrocortisone will interfere with the results of the investigations.
Treatment with hydrocortisone should not be delayed.
Treatment with hydrocortisone should not be delayed.
A: IF A NEW PRESENTATION OF SUSPECTED ADRENAL CRISIS, take all of the following:
To evaluate whether primary or secondary adrenal insufficiency:
- ACTH (EDTA sample)
- Cortisol
- Glucose
- Renal profile
- Renin
- Aldosterone
- Urine electrolytes
- Blood and urine cultures; FBC
- Specific investigations
- 17-OHP
- Testosterone
- Urine steroid profile (consider urgent catheter specimen in neonate)
B: If presenting with adrenal crisis IN A CHILD KNOWN TO HAVE ADRENAL INSUFFICIENCY OR IS AT RISK OF ADRENAL INSUFFICIENCY (e.g. on long-term steroids)
- renal profile
- cortisol
- glucose
- blood and urine cultures; FBC
3. Give 2mg/kg IV hydrocortisone promptly (Ref 4). If shocked or suspected sepsis, give 4mg/kg hydrocortisone.
4. If signs of shock, give 20ml/kg 0.9% saline as a push and repeat as required.
5. If blood glucose <3mmol/L, give 2ml/kg 10% dextrose over 10 minutes. Recheck glucose after 10 minutes and give further dextrose until blood glucose > 4mmol/L.
6. If hyperkalaemia, treat, and institute cardiac monitoring.
7. If signs of sepsis, start antibiotics
8. Give further IV hydrocortisone as:
- 12.5mg/m2 to be given IV 6 hourly (i.e. 50mg/m2/24 hours), or as a continuous infusion (50mg hydrocortisone in 50ml 0.9% saline over 24 h).
- Or if there are signs of shock or suspected sepsis: give 25mg/m2 to be given IV 6 hourly (i.e. 100mg/m2/day)
9. Start maintenance IV fluids as 0.9% saline with 5% dextrose, but 10% dextrose may be required to maintain normoglycaemia.
10. Consider transfer to paediatric HDU, inform on call consultant.
11. Monitor vital signs, and renal profile, glucose and blood gas 2-6 hourly depending on the severity of the illness. Regular senior review.
12. After the first 24 hours:
- if clinically improving, the dose of hydrocortisone per 24 hours can be halved.
- if back to normal and tolerating oral feeds and fluids, give 30mg/m2/day hydrocortisone IV or oral for 48 hours or until well, then maintenance dose.
- Arrange open access
- Check patient and/or carers are familiar with sick-day rules for managing steroids during intercurrent illness (see PIER guideline for Sick Day Rules)
- Prescribe IM hydrocortisone to be given at times of emergency and train family in administration at times of emergency.
- Inform lead for paediatric endocrinology at the DGH about admission during working hours. See website: https://www.piernetwork.org/endocrine-network.html
Implementation
- `This guideline will be disseminated through the Wessex Paediatric Endocrine Network. The network centre lead at each DGH will inform their department the guideline is available.
Process for Monitoring Effectiveness
- Effectiveness of the guideline will be monitored by feedback to the lead author.
Appendix A
For quick reference use BSA tables in the appendix section on BNFc.
https://bnfc.nice.org.uk/guidance/body-surface-area-in-children-image.html
- BSA (m2) = Square root of (weight in kg x height in cm/3600)
For quick reference use BSA tables in the appendix section on BNFc.
https://bnfc.nice.org.uk/guidance/body-surface-area-in-children-image.html
References
- Bornstein (chair) et al. Diagnosis and Treatment of Primary Adrenal Insufficiency: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab 2016
- Park J, Didi M, Blair J. The diagnosis and treatment of adrenal insufficiency during childhood and adolescence. Arch Dis Child 2016; 101:860-865
- UK standards for Paediatric Endocrinology, BSPED & RCPCH, 2019. Available at: https://www.bsped.org.uk/media/1580/uk-standards-for-paediatric-endocrinology-2019.pdf (last accessed Feb 2020)
- BNF for Children (2018) British National Formulary for Children 2018-19. London: British Medical Association and the Royal Pharmaceutical Society for Great Britain.
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Document Version:
1.0 Lead Author: Dr Ed Hind, Consultant Paediatrician Co-Author: Dr Justin Davies, Consultant Paediatric Endocrinologist |
Approving Network:
Wessex Paediatric Endocrine Network Date of Approval: 02/2020 Review Date: 02/2023 |
PIER ContactGary Connett
PIER Clinical Lead, Southampton Children's Hospital Tremona Road, Southampton Hampshire, SO16 6YD |
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