Paediatric Clinical Guideline
9.1 Endocrine: Hypoglycaemia
Short Title: / Adrenal Insufficiency / Adrenal CrisisFull Title: / Guideline for the recognition and management of adrenal insufficiency / adrenal crisis in children and young people
Date of production/Last revision: / March 2008
Explicit definition of patient group to which it applies: / This guideline is intended for children and young people up to the age of 19 years.
Name of contact author / Dr Hisham Arabi, Paediatric SpR
Dr Louise Denvir, Consultant Paediatrician
Ext:
Revision Date / March 2011
This guideline has been registered with the Trust. However, clinical guidelines are 'guidelines' only. The interpretation and application of clinical guidelines will remain the responsibility of the individual clinician. If in doubt contact a senior colleague or expert. Caution is advised when using guidelines after the review date.
Adrenal Insufficiency / Adrenal Crisis: Recognition and management
Background
Adrenal insufficiency is relatively rare in children. For unknown cases the presentation can be very vague and non-specific. If unrecognised acute adrenal insufficiency precipitated by physiological stress may lead to a life-threatening crisis with acute cardiovascular collapse.
Signs and symptoms of adrenal crisis
· Weakness
· Nausea, vomiting
· Abdominal pain
· Dehydration
· Hypoglycaemia
· Seizure
· Hypotension
· Shock
Clues for Diagnosis
History
· Patient known to have adrenal insufficiency
o Primary e.g. congenital adrenal hyperplasia, Addison’s disease
o Secondary e.g. disease of the Hypothalamic-Pituitary axis
· In infants
o Cortisol deficiencies will cause hypoglycaemia and jaundice, while aldosterone deficiencies will result in poor feeding, vomiting and failure to thrive
· Patient on exogenous steroids
o Secondary adrenal insufficiency caused by abrupt discontinuation or stress while on suppressive doses. Those at risk:
§ Prednisolone > 0.3 mg/kg/day or > 10mg / day for > 3 weeks
§ Note: BNF equivalent potencies relate to anti-inflammatory action not growth and adrenal suppressive action. Dexamethasone much more potent that prednisolone.
§ Children on high dose Inhaled steroid: > 800 mcg Beclomethasone or > 400 mcg Fluticasone (or equivalent) for more than 6 month. Note: Flixotide is much more potent than Beclomethasone
§ Repeated courses of exogenous steroids
§ A short course of exogenous steroids within one year of cessation of long-term steroids
§ Morning compared to evening doses and alternate day regimes cause less adrenal suppression
· Undiagnosed primary adrenal insufficiency may cause: chronic fatigue, anorexia, nausea, vomiting, weight loss, recurrent abdominal pain, behavioural changes, developmental delay or a reduction in school performance
· Other autoimmune diseases may be a clue to the presence of Addison’s disease. e.g. recurrent hypoglycaemia in a child with type 1 diabetes mellitus
· Undiagnosed acquired hypothalamic–pituitary disease e.g. craniopharyngioma or pituitary tumours, post-cranial irradiation, hypothalamic or pituitary surgery. Less common causes: vascular insult, trauma and meningitis
Physical Examination
Infants
· Congenital Hypopituitarism features in newborn infant includes:
o jaundice
o micropenis
o cranial midline defect
· Salt-wasting 21-Hydroxylase deficiency (Severe form of congenital adrenal hyperplasia-CAH)
o Female infants
§ virilization at birth
§ ambiguous genitalia
§ enlarged clitoris
§ hyperpigmented
§ fused labia majora
o Males infants
§ scrotal hyperpigmentation
o If unrecognised both sexes will present from day 5 onwards (usually 1st- 4th week of life) with dehydration and salt wasting crisis.
Older children
· Milder form of Congenital Adrenal Hyperplasia (CAH):
o Precocious virilization in both males and females
§ pubic hair
§ phallic/clitoric enlargement
§ accelerated growth and skeletal development
· Chronic Primary Adrenal Insufficiency
o Increase skin pigmentation
§ areolae, genitalia, scars, palmer crease, axillae, pigmented lines in gum)
o some patient may have loss of pubic and axillary hair
· Orthostatic hypotension or postural tachycardia if not frankly hypotensive
· Signs of high dose steroid side effects
o replacement steroids should not cause these side effects
Side effects of long term steroids
Short-Term Therapy (< 3 weeks)· Gastritis
· Growth arrest
· Increased Appetite
· Hypercalciuria
· High blood sugars and glycosuria
· Immune suppression
· Masked symptoms of infection, esp. fever and inflammation
· Toxic psychosis
Long-Term Therapy (> 3 weeks)
· Gastric ulcers
· Short stature
· Weight gain
· Osteoporosis, fractures
· Slipped epiphyses
· Ischemic bone necrosis
· Benign intracranial pressure
· Poor wound healing
· Catabolism
· Cataracts
· Bruising (capillary fragility)
· Adrenal/pituitary suppression
· Muscle wasting
· Toxic psychosis
Laboratory Findings
· Hypoglycaemia is common in both primary and secondary adrenal insufficiency
· Hyponatraemia and hyperkalaemia are common in primary adrenal insufficiency ( deficient aldosterone secretion)
· Hyponatraemia may also be seen in secondary adrenal insufficiency (water retention from lack of cortisol to antagonize vasopressin effect)
Investigations to Establish Diagnosis
If adrenal crisis is suspected do not wait for results before starting treatment
In all patients
· Blood glucose using BM stix
· Serum glucose and U&E
· Arterial or capillary blood gases
In suspected new cases of adrenal insufficiency
· Acute samples
· before administering exogenous steroid if possible
· liaise with biochemistry to let them know Renin, Aldosterone and ACTH are being sent and send immediately
· 1 x Lithium Heparin (Green) tube to be sent for:
o Cortisol level
o Aldosterone
· 1 x EDTA (PURPLE) tube to be sent for:
o Renin
o Serum ACTH
All infants and in children with precocious virilization
· Serum 17 OHP (17 Hydroxyprogesterone)
· Urine for steroid profile
Condition / Cortisol / ACTH / 17-OHP / Aldosterone / ReninPrimary adrenal failure / ↓ / ↑ / ↔ / ↓ / ↑
ACTH deficiency
(Pituitary/hypothalamus) / ↓ / ↓ / ↔ / ↔ / ↔
21-Hydroxylase Deficiency / ↓ / ↑ / ↑ / ↔
or
↓( salt wasting form) / ↔
or
↑( salt wasting form)
· 08:00- 09:00 am Cortisol and ACTH:
o A good screening test for chronic suspected cases, (if the child on steroid treatment discuss with endocrine team)
o cortisol levels >180 nmol/l is indicative of a normal adrenal function
· Discuss with Endocrinology team specific diagnostic tests in new cases
Contact numbers
· Dr Randell, Consultant in Paediatric Endocrinology and Diabetes: bleep 80-8924
· Dr Denvir, Consultant Paediatrician with special interest in Endo: bleep 80-8934
· Endocrinology secretary ext 63393/63328
· Endocrinology registrar bleep 84-1411
· Sister Jean Green, Paediatric Growth Nurse ext 65123
Management of children presenting acutely with adrenal crisis
· Assess A B C
· Obtain IV access and take samples (see above)
· If signs of circulatory failure give IV bolus of 20mls/kg of 0.9% sodium chloride followed by maintenance fluids (0.45% saline with 5% dextrose)
· Give IV hydrocortisone
o 25mg (<10 kg), 50 mg (10-25 kg), 100mg (> 25kg) and continue 6 hourly until well with no diarrhoea/vomiting and stable blood sugar and electrolytes.
o If unable to gain IV access give IM hydrocortisone
· If BM < 2.6mmol/L
o In unknown cases send hypoglycaemia screen bloods, see hypoglycaemia guideline)
o Give 5ml/kg 10% dextrose bolus followed by maintenance fluids
§ If unable to gain IV access and not drowsy or unresponsive give sugar orally (eg.100ml coke, lemonade, orange juice, 2-3 dextrose tablets, milk feed, Glucogel)
§ If drowsy or unresponsive give IM Glucagon 0.5 mg < 25 kg, 1 mg > 25 kg
· Identify and treat potential precipitating causes such as sepsis
· Close observation on the ward including BP and Glasgow coma score
· Strict fluid input and output
· Regular blood sugar and electrolyte monitoring
· Fluid and electrolyte imbalance should be corrected appropriately
· Weigh child on admission and where possible compare this weight to previous recorded measures
In known cases of adrenal insufficiency
· Consider doubling dose of replacement hydrocortisone for 24 hours once back on regular oral medication
· Omit fludrocortisone until on oral hydrocortisone replacement
· Omit DDAVP until electrolytes stable and on oral fluids or following discussion with endocrinologist
Patient should be tolerating oral fluids/medication with no diarrhoea or vomiting and have stable blood sugars and electrolytes before discharge
As soon as possible let the endocrine team know about all cases of suspected or known adrenal insufficiency for advice on ongoing management
Long-term management
· Safety and Identification
o All patients should carry a steroid treatment card (available from pharmacy) and be advised to obtain a medic-alert bracelet (application forms www.medicalert.org.uk).
· What to do if patient is unwell at home or presents to hospital
o An individualized plan using the template in appendix 1 or 2 should be given to all patients before they leave hospital.
o Record that this information has been given in the notes.
· Monitoring of patients on replacement steroids
o This will be undertaken by endocrine team. Ensure follow up in place.
· Monitoring of patients on long term high dose steroids
o Monitor growth, fasting blood glucose, electrolytes and blood pressure at least 3 monthly.
o Check bone profile and vitamin D status 3 monthly. Maintain corrected calcium, phosphate, magnesium in the normal range. Keep vitamin D levels > 50 nmol/L.
o A regular assessment of bone mineral density is advised, only after discussion with endocrine team, and all symptoms of back pain investigated for vertebral collapse. Bisphosphonates are the only agents of proven benefit in the management of symptomatic steroid-induced osteoporosis. Please discuss each case with endocrinology team.
Withdrawal of steroids
· Long-term pharmacological glucocorticoid therapy inhibits transcription of the gene(s) for glucocorticoid receptors, thus reducing the number of receptors per cell. Physiologic concentrations of glucocorticoids will elicit subphysiologic cellular responses.
· Therapy for a couple of months will completely suppress the hypothalamo-pituitary-adrenal axis but will not cause adrenal atrophy. Therapy of years’ duration may result in almost total atrophy of the adrenal fasciculate / reticularis,
· Never stop long-term steroids abruptly.
o Dose should be weaned over 3 weeks (e.g. by 25% weekly) if < 1 year’s treatment
o Over months if > 1 year’s treatment.
o When withdrawal is done with steroids other than hydrocortisone, measurement of morning cortisol values can be a useful adjunct. Morning cortisol values of 180 nmol/l or more indicate that the dose can be reduced safely. (NB. cortisol concentrations may normalise during the day before the response to synacthen and illness returns).
· Remember that adrenals may remain suppressed for months to a year following withdrawal. Consider performing a standard short synacthen test pre discontinuation and then 6 months later if suboptimal. Steroid cover (hydrocortisone) may be required in the interim as replacement or for illness or surgery, depending on result. Discuss with endocrinology team pre synacthen testing and with results.
· Symptoms of possible adrenal insufficiency to look for after glucocorticoid withdrawal are malaise, anorexia, headache, lethargy, nausea and fever. This symptom complex does not include salt loss, as adrenal glomerulosa function is regulated principally by the renin-angiotensin system and remains normal. However, blood pressure can fall abruptly, as glucocorticoids are required for the action of catecholamines in maintaining vascular tone.
Surgery (long term high dose and replacement steroids)
· Do not omit regular glucocorticoid prior to surgery
· Regular fludrocortisone is omitted until tolerating enteral intake
· Inform the anaesthetist and give 2mg/kg hydrocortisone at induction
· Further doses of IV hydrocortisone will be required 6 hourly
o Stress dose equal to 30 mg/m2/day until enteral intake tolerated
o Regular oral steroid treatment should then be restarted
· Following major surgery double dose of regular replacement hydrocortisone for 24 hours
· Dexamethasone may be used instead in neurosurgical patients as it has less mineralocorticoid effect discuss with endocrinology team as doses may not need to be increased
Management of patients with combined anterior and posterior pituitary deficiencies (see also diabetes insipidus guideline)
· In situations of cortisol insufficiency, the patient is unable to excrete a water load and where combined anterior and posterior pituitary hormone deficiencies exist and Desmopressin (DDAVP) therapy is used there is always the danger of dilutional hyponatraemia.
· In patients who are unwell and suffer with a combination of anterior and posterior pituitary defects no further Desmopressin (DDAVP) should be given until the plasma electrolytes have been checked. Water intoxication is difficult to treat and can be dangerous. It is usually safer to under-treat the diabetes insipidus at this stage and simply replace the fluid losses.
· Patients with absent thirst and diabetes insipidus are amongst the highest risk group. These patients need to attend hospital, even if they are slightly ill, as their fluid balance is usually precarious.
References
1. Dorothy I. Shulman, Mark R. Palmert et al, Adrenal insufficiency: still a cause of morbidity and death in childhood. Pediatrics 2007 Vol. 119 No. 2 , pp. e484-e494.
2. Todd GRG, Acerini CL, Ross-Russell R, Zahra S, Warner JT, McCance D. Survey of adrenal crisis associated with inhaled corticosteroids in the United Kingdom. Arch Dis Child. 2002;87 :457 –461.
3. Agwu JC, Spoudeas H, Hindmarsh PC, et al. Test of adrenal insufficiency. Arch Dis Child 1999;80:330–3.
4. C Russo, E J Davis, P R Betts, J H Davies. The importance of re-evaluation, re-investigation and follow-up of adrenal insufficiency, Arch Dis Child Educ Prac 2007;92:ep109-ep113.
5. Perry R, Kecha O, Paquette J, Huot C, Van Vliet G, Deal C. Primary adrenal insufficiency in children: twenty years experience at the Sainte-Justine Hospital, Montreal. J Clin Endocrinol Metab.2005;90 :3243 –3250.
6. Wilson TA, Speiser P. Adrenal insufficiency. Available at: www.emedicine.com/PED/topic47.htm. Accessed April 30, 2006
7. White PC, Speiser PW. Congenital adrenal hyperplasia due to 21-hydroxylase deficiency. Endocr Rev. 2000;21 :245 –291.
8. Dunlop KA, Carson DJ, Steen HJ, McGovern V, McNaboe J, Sheilds MD. Monitoring growth in asthmatic children treated with high dose inhaled glucocorticoids does not predict adrenal suppression. Arch Dis Child. 2004;89 :713 –715.
9. Brook, C., Clayton, P., and Williams, J., Clinical Pediatric Endocrinology. 2005. 5th ed. Blacwell Pub Ltd.