Introduction
Acute adrenal insufficiency, also termed adrenal crisis, is a
life-threatening endocrine emergency brought about by a lack of production of the
adrenal hormone cortisol, the major glucocorticoid. Identifying patients at risk and
prompt management can save lives. This guideline aims to take the non-specialist through
the initial phase of assessment and management.
Underlying conditions
Primary adrenal insufficiency is caused by loss of function of the adrenal
gland itself, for example due to autoimmune-mediated destruction of adrenocortical
tissue or surgical removal of the adrenal glands or due to inborn disruption of adrenal
cortisol production in congenital adrenal hyperplasia.
Secondary adrenal insufficiency is caused if the regulation of adrenal
cortisol production by the pituitary is compromised, this can be the consequence of
tumours in the hypothalamic–pituitary area. However, pituitary regulation of
cortisol production is also switched off in patients who receive chronic exogenous
glucocorticoid treatment with doses ≥5 mg prednisolone
equivalent for more than 4 weeks. This may also be caused by long-lasting
glucocorticoid injections into joints or chronic application of glucocorticoid cream
or
inhalers.
In primary adrenal insufficiency cortisol deficiency is aggravated by a lack of adrenal
aldosterone production, a hormone important for blood pressure and electrolyte
regulation. This puts primary adrenal insufficiency patients at a somewhat higher
risk
of adrenal crisis.
Clinical presentation
Clinical signs and symptoms:
Fatigue, lack of energy, weight loss
Low blood pressure, postural dizziness and hypotension (≥20 mmHg
drop in BP from supine to standing position), dizziness, collapse, in severe cases
hypovolaemic shock
Abdominal pain, tenderness and guarding, nausea, vomiting (in particular in
primary adrenal insufficiency), history of weight loss
Fever
Confusion, somnolence, in severe cases delirium or coma
Back and leg cramps/spasms are commonly reported and can be distracting if not
recognised for what they are (electrolyte derangement in large muscles?)
In primary adrenal insufficiency: generalised skin hyperpigmentation,
in particular in areas exposed to mechanical shear stress (palmar creases,
nipples, scars, inside of oral mucosa)
In secondary adrenal insufficiency: alabaster-like, pale skin;
dependent on underlying conditions also signs and symptoms of other pituitary axis
deficiencies
Lab findings:
Hyponatraemia (in primary and secondary adrenal insufficiency)
Hyperkalaemia (in primary adrenal insufficiency)
Pre-renal failure (increased serum creatinine due to hypovolaemia)
Normochromic anaemia, sometimes also lymphocytosis and eosinophilia
Hypoglycaemia (primarily in affected children; can cause long-term neurological
deficits, if not promptly treated)
Investigations for suspected adrenal crisis in patients not already known to have
adrenal failure
Adrenal insufficiency should be ruled out in any acutely ill patient with
signs or symptoms potentially suggestive of acute adrenal
insufficiency
Assess blood pressure and fluid balance status; if clinically
feasible, measure blood pressure from supine to standing to check for postural
drop
Take drug history (glucocorticoids?)
Bloods:
Sodium, potassium, urea, creatinine
Full blood counts
TSH, fT4 (hyperthyroidism can trigger adrenal crisis; acute
adrenal insufficiency can increase TSH due to loss of inhibitory control of
TRH release, do not replace with thyroxine if
TSH ≤ 10 mU/L)
Paired serum cortisol and plasma ACTH
Diagnostic measures should never delay prompt treatment of a suspected
adrenal crisis! There are no adverse consequences of initiating
life-saving hydrocortisone treatment and diagnosis can be safely and formally
established once the patient has clinically recovered
If the patient is haemodynamically stable, consider performing a short
Synacthen test (serum cortisol at baseline and 30 min after i.v.
injection of 250 micrograms ACTH1–24); however, if the patient
is severely ill, confirmation of diagnosis can be safely left until after clinical
recovery following implementation of emergency dose hydrocortisone treatment
Serum/plasma aldosterone and plasma renin (aldosterone will be low and
renin high in primary adrenal insufficiency; observe special sample collection and
transport conditions; can be left to confirmation of diagnosis after clinical
recovery)
Management of adrenal crisis
Hydrocortisone (immediate bolus injection of 100 mg hydrocortisone
i.v. or i.m. followed by continuous intravenous infusion of 200 mg
hydrocortisone per 24 h (alternatively 50 mg
hydrocortisone per i.v. or i.m. Injection every 6 h)
Rehydration with rapid intravenous infusion of 1000 mL of isotonic
saline infusion within the first hour, followed by further intravenous
rehydration as required (usually 4–6 L in 24 h; monitor for
fluid overload in case of renal impairment and in elderly patients)
Contact an endocrinologist for urgent review of the patient, advice
on further tapering of hydrocortisone, investigation of the underlying cause of
disease including diagnosis of primary vs secondary adrenal insufficiency
Tapering of hydrocortisone can be started after clinical recovery guided by an
endocrinologist. In patients with primary adrenal insufficiency, mineralocorticoid
replacement needs to be initiated (starting dose 100 micrograms fludrocortisone
once daily) as soon as the daily glucocorticoid dose is below 50 mg
hydrocortisone/24 h
Precipitating factors
In more than half of patients with adrenal insufficiency the diagnosis of adrenal
failure is only established after presentation with an acute adrenal crisis
However, patients with established adrenal insufficiency and those receiving
chronic exogenous supraphysiological glucocorticoid treatment (e.g. for asthma or
autoimmune disease) are at permanent risk of adrenal crisis. Most frequent causes
are:
Chronic glucocorticoid intake is suddenly stopped
Failure to observe Sick Day Rule 1: the need to double daily
oral glucocorticoid dose during intercurrent illness with fever that
requires bed rest and/or antibiotics
Failure to observe Sick Day Rule 2: the need to administer
glucocorticoids per i.v. or i.m. injection or iv infusion during prolonged
vomiting or diarrhoea, during preparation for colonoscopy or in case of
acute trauma or surgery requiring general anaesthesia
After emergency care: how to prevent an adrenal crisis
Regular review of the patient by an endocrinologist, initially
monthly, in the long-term every 6–12 months
Education of patients and partner/parents regarding symptom awareness
and the correct adjustment of glucocorticoid replacement dose:
Sick Day Rule 1: the need to double daily oral glucocorticoid
dose during illness with fever that requires bed rest and/or antibiotics
Ensure they have an additional supply of hydrocortisone tablets so that they
can double their dose for at least 7 days
Sick Day Rule 2: the need to administer glucocorticoids per
i.v. or i.m. injection during prolonged vomiting or diarrhoea, during
preparation for colonoscopy or in case of acute trauma or surgery
Teach the patient and partner/parents how to self-administer and inject
hydrocortisone and provide them with a Hydrocortisone Emergency
Injection kit (100 mg hydrocortisone sodium succinate for
injection; hyperlink to ADSHG and Pit foundation where there are picture
tutorials on using this); check regularly that their kit is up to date
Provide the patient with a Steroid Emergency Card
www.endocrinology.org/adrenal-crisis and encourage them to wear
medical alert bracelets, in addition to keeping the steroid emergency card with
them at all times and showing it to any health care professional they are dealing
with
Provide them with emergency phone numbers and contact details for the patient
self-help groups
Further information
For further information and to request a steroid card, please go to the Society for
Endocrinology’s website www.endocrinology.org/adrenal-crisis.