Acute adrenal insufficiency: an aide-memoire of the critical

importance of its recognition and prevention

A. Gargya,1 E. Chua,2 J. Hetherington,2 K. Sommer3 and M. Cooper4
1
Department of Endocrinology, Royal Prince Alfred Hospital, University of New South Wales, 2Department of Endocrinology, Royal Prince Alfred
Hospital, University of Sydney, 3Department of Endocrinology, Concord Hospital and 4Department of Endocrinology, Concord Hospital, University of
Sydney, Sydney, New South Wales, Australia

Key words Abstract

adrenal crisis, adrenal insufficiency, Addison’s
disease, corticosteroids.
Correspondence
Ash Gargya, Department of Endocrinology,
Royal Prince Alfred Hospital, Missenden Road,
Camperdown, NSW 2050, Australia.
Email: ashgargya@gmail.com
Received 9 July 2015; accepted 16
December 2015.
doi:10.1111/imj.12998
Adrenal crisis is a life-threatening emergency that causes significant excess mortality in
patients with adrenal insufficiency. Delayed recognition by medical staff of an impend-
ing adrenal crisis and failure to give timely hydrocortisone therapy within the emer-
gency department continue to be commonly encountered, even in metropolitan
teaching hospitals. Within the authors’ institutions, several cases of poorly handled
adrenal crises have occurred over the last 2 years. Anecdotal accounts from members
of the Addison’s support group suggest that these issues are common in Australia. This
manuscript is a timely reminder for clinical staff on the critical importance of the recog-
nition, treatment and prevention of adrenal crisis. The manuscript: (i) outlines a case
and the clinical outcome of sub-optimally managed adrenal crisis, (ii) summarises the
clinical features and acute management of adrenal crisis, (iii) provides recommenda-
tions on the prevention of adrenal crisis and (iv) provides guidance on the management
of ‘sick days’ in patients with adrenal insufficiency.

Our index patient was a 51-year-old woman with a 7-
year history of autoimmune primary adrenal insuffi-
ciency. She usually took 20 mg hydrocortisone in the
morning and 10 mg at 3 pm and 100 μg fludrocortisone
twice daily. She had a MedicAlert bracelet (MedicAlert
Foundation, Adelaide, SA, Australia) and an understand-
ing of sick day management. She refused to have a par-
enteral hydrocortisone emergency kit at home, but was
well aware of the need to present to hospital in the event
of an impending crisis. She developed a gastrointestinal
viral infection (of 24-h duration) with vomiting and
diarrhoea. She tripled her oral hydrocortisone dose, but
could not keep the tablets down. The ambulance service
was called. At retrieval, her blood pressure was
80/60 mmHg, and 1 L of Hartmann’s solution was given
en route to hospital. On arrival to the emergency depart-
ment, her blood pressure was 101/62 mmHg, and she
was labelled ‘normotensive’ and triaged to be medically
reviewed within 60 min. Intravenous fluids and hydro-
cortisone were not administered despite repeated
requests by the patient’s family. Three hours elapsed,
and her condition deteriorated, eventuating in
Funding: None.
Conflicts of interest: None.
cardiorespiratory arrest. Her arterial pH was 7.06. She
was resuscitated, intubated and transferred to the inten-
sive care unit (ICU). Her treating endocrinologist was
first notified of her hospital presentation and admission
5 h after the transfer to ICU. Her hospital length of stay
was 16 days, and her admission was complicated by
stress-induced cardiomyopathy and a broken tooth from
intubation. The actual and optimal management of our
index patient is summarised in Table 1.
Discussion
Adrenal crisis is a life-threatening emergency that causes
significant excess mortality in patients with adrenal
insufficiency. Epidemiological studies indicate an inci-
dence of between 5 and 10 adrenal crises per 100 patient
years each year; 1 in 200 patients will die from an adre-
nal crisis.1 A recent Australian study reviewed national
databases over a 13-year period and identified an
increase in adrenal crisis hospital admission rates (fur-
ther highlighting the increasing importance of prompt
medical staff recognition and treatment of adrenal crises)
that was positively correlated with a rise in short-acting
glucocorticoid prescription rates. In lieu of modern-day
lower-dose glucocorticoid replacement regimens, this
study suggests a possible causal relationship between

356 © 2016 Royal Australasian College of Physicians

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Table 1 Initial in-hospital management of the index patient presenting with adrenal crisis

Triage Medical Parenteral Hydrocortisone Endocrine Outcome

assessment hydrocortisone dose consult

Index patient Addison’s disease After 3 h Administered 100 mg IV 5 h after ICU ICU admission 7 days
noted but after cardiac admission 16 days hospital
triaged as non- arrest admission
urgent Complicated by stress-
induced
cardiomyopathy and
broken tooth from
intubation
Dissatisfied family
Optimal Identify at risk of Rapid, ideally Administer 100 mg IM or Yes Expect clinical
management adrenal crisis within 10 min immediately IV recovery in
24–48 h, depending
on precipitant

ICU, intensive care unit.

adrenal crisis events and the increasing use of short-
acting glucocorticoids +/− reduced effective doses.2
Although the treatment of an adrenal crisis should be
straightforward, delayed recognition by medical staff of
an impending or established adrenal crisis and failure to
give timely hydrocortisone therapy within the emer-
gency department continue to be commonly encoun-
tered even in metropolitan teaching hospitals. Within
the authors’ institutions, several cases of poorly handled
adrenal crises, such as the case above, have occurred
over the last 2 years. Anecdotal accounts from members
of the Addison’s support group suggest that these issues
are common throughout Australia. Several clinical and
sociological factors appear to account for these delays
and potentially life-threatening omissions. Clinical staff
commonly fail to recognise the severity of an impending
adrenal crisis as hypotension develops rapidly. Emer-
gency department staff are often concerned about preci-
pitating harmful effects with the administration of
hydrocortisone. However, such effects are unlikely, and
the risks are considerably outweighed by the likely bene-
fits. Perhaps of most concern is that there are many
instances where glucocorticoid treatment is delayed even
when patients (and/or their carers) clearly outline the
need for treatment, and the need is emphasised in writ-
ten materials or MedicAlert bracelets.
Suspected adrenal crisis requires immediate therapeu-
tic intervention (in undiagnosed adrenal insufficiency,
treatment usually precedes biochemical proof of diagno-
sis). Treatment is simple and entails parenteral hydrocor-
tisone (an initial bolus dose of 100 mg hydrocortisone)
and isotonic saline to correct volume depletion. Prompt
recognition and treatment of an impending crisis gener-
ally results in clinical recovery within 24 h.1 It has been
observed that clinical recovery from untreated adrenal
insufficiency presenting with confusion and somnolence
can take several days or even up to 1 week. Parenteral
hydrocortisone followed by a timely change to an
increased dose of oral glucocorticoids with subsequent
tapering and overlap (generally 24–48 h following clini-
cal improvement) is recommended, depending on the
precipitant. Treatment of the inter-current illness and/or
precipitant (e.g. with antibiotics etcetera) is required.
Infections, particularly gastroenteritis, are the most fre-
quent causes of an adrenal crisis.1,3 Patients on long-term
exogenous glucocorticoids (for a non-endocrine condi-
tion) are at risk of an adrenal crisis.
Patient education is considered critical to prevent
crises.4 Preventative strategies to ensure early recogni-
tion and timely intervention of an impending adrenal
crisis are essential to reduce morbidity (including hospi-
tal length of stay and time to clinical recovery) and mor-
tality from a crisis. Patients and carers of those with
adrenal insufficiency commonly understand their condi-
tion very well, sometimes even better than the health
professionals, and feel distressed and frustrated while
encountering barriers to emergency care. Listening to a
well-informed patient and/or carer in adrenal crisis who
says that he or she needs steroids and taking urgent
action will avoid unnecessary deaths from this treatable
medical problem.5 Proper information on ‘sick day’ man-
agement with written instructions on glucocorticoid dose
adjustment during stressful situations is usually provided
(Table 2). Recommendations regarding glucocorticoid
coverage during non-surgical illnesses are largely based
on expert opinion; the guidelines provided herein are in
general agreement with other published
recommendations.1,6–8 Individuals with adrenal

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Table 2 Sick day management for patients on glucocorticoid therapy

Issue Symptoms Temperature Dose adjustment Duration of oral dose

adjustment

Trivial e.g. mild cold No temperature (less than No change N/A

Brief Communications

illness 37.4 C)
Mildly e.g. mild infection (such as cystitis) with low grade 37.5–38.5 C 2× normal oral dose Until recovery plus 1–2 days
unwell temperature
More e.g. high fevers >38.5 C 3× normal oral dose† Until recovery plus 2 days
unwell e.g. gastroenteritis with vomiting +/− diarrhoea or Could be normal or raised Early parenteral hydrocortisone (50–100 mg IV bolus Until recovery plus 2 days
pneumonia etc followed by 25–50 mg IV every 8 h till the condition
stabilises) then 2–3× normal oral dose
Minor dental procedure (>1 h under local anaesthetic), significant injury 2× normal oral dose 24 h
or major emotional stress
Major surgery or procedure with general anaesthetic Parenteral hydrocortisone (50–100 mg IV bolus at Continue for 48 h post
induction followed by 25–50 mg IV every 8 h till procedure
stable) then 2× normal oral dose

†The ‘3 × 3 rule’ means tripling the patient’s usual oral dose for 3 days or for the duration of the illness after which the patient resumes their usual dose.6,7

Table 3 Ambulance service role in managing acute adrenal insufficiency

NSW VIC ACT QLD SA NT WA TAS

Are there clinical practice guidelines and/or drug therapy Yes No Yes Yes No Yes No No
protocols for acute adrenal insufficiency?
Does the ambulance carry parenteral hydrocortisone? No No† Yes Yes Yes Yes No† No†
Can paramedics administer patient’s own emergency parenteral Yes Yes‡ Yes Yes Yes Yes No Yes‡
hydrocortisone?

†Only dexamethasone (adrenal insufficiency is not stated as an indication for its use).
‡If patient is carrying a letter stating it is required in the appropriate clinical setting.

© 2016 Royal Australasian College of Physicians

 Brief Communications

insufficiency are encouraged to carry an emergency card
and/or a MedicAlert bracelet that succinctly reflects glu-
cocorticoid dependency. Every patient should be pro-
vided with an emergency kit for parenteral
hydrocortisone self-administration (this injection can be
administered by a trained relative and/or a healthcare
professional, e.g. paramedic, prior to transfer to the hos-
pital emergency department). Table 3 summarises
whether each Australian state’s ambulance service has
clinical practice guidelines and/or drug therapy protocols
for managing acute adrenal insufficiency, whether par-
enteral hydrocortisone is available in the ambulance
and, if unavailable, whether paramedics are able to
administer the patient’s emergency parenteral hydrocor-
tisone. Patient education group meetings may be an
effective intervention.9 Hospital computer systems may
be able to ‘flag’ patients with adrenal insufficiency.
In conclusion, prompt recognition and treatment of an
impending adrenal crisis is critical to reduce its associated
morbidity and mortality. Healthcare workers must be
acutely aware of its presentation (including the initial
false appearance of clinical stability with potential rapid
deterioration) and appreciate the urgency of its treat-
ment. Patients, carers and families must be well educated
and updated on ‘sick day’ management using a struc-
tured and quality-controlled approach. A MedicAlert or
emergency card and an emergency hydrocortisone kit
ready for use by self or others are an essential part of
patient management.

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