INTRODUCTION

Adrenal crisis is a life-threatening medical emergency, associated with a high mortality unless it
is appropriately recognized and early treatment is rendered. Despite it being a treatable condition
for almost 70 years, failure of adequate preventive measures or delayed treatment has often led to
unnecessary deaths. Gastrointestinal illness is the most common precipitant for an adrenal crisis.
Although most patients are educated about “sick day rules,” patients, and physicians too, are
often reluctant to increase their glucocorticoid doses or switch to parenteral injections, and
thereby fail to avert the rapid deterioration of the patients’ condition. Therefore, more can be
done to prevent an adrenal crisis, as well as to ensure that adequate acute medical care is
instituted after a crisis has occurred. There is generally a paucity of studies on adrenal crisis.
Hence, we will review the current literature, while also focusing on the incidence, presentation,
treatment, prevention strategies, and latest recommendations in terms of steroid dosing in stress
situations.

DEFINITION
A disorder in which the adrenal glands don’t produce enough hormones.
Specifically, the adrenal glands produce insufficient amounts of the hormone cortisol and
sometimes aldosterone, too when the body is under stress (e.g., fighting an infection), this
defiency of cortisol can result in a life threatening Addisonian crisis characterized by low blood
pressure.

Addison’s disease is a disorder in which the adrenal glands – which sit on top of the kidneys – do
not produce enough of the hormones cortisol and aldosterone. (Hormones are chemicals that
control the function of tissues or organs.)

Cortisol helps the body respond to stress, including the stress of illness, injury, or surgery. It also
helps maintain blood pressure, heart function, the immune system and blood glucose (sugar)
levels.

Aldosterone affects the balance of sodium and potassium in the blood. This in turn controls the
amount of fluid the kidneys remove as urine, which affects blood volume and blood pressure.

Addison’s disease is also called “primary adrenal insufficiency.” A related disorder, “secondary
adrenal insufficiency,” occurs when the pituitary, a small gland at the base of the brain, does not
secrete enough adrenocorticotropic hormone (ACTH), which activates the adrenal glands to
produce cortisol
INCIDENCE
The risk of adrenal crisis occurring in a patient with adrenal insufficiency has been estimated to
be about 6-10 adrenal crises per 100 patient years (PYs).15-17 These estimates were based on
retrospective studies using questionnaires, and limited by reporting bias. A recent prospective
study found 64 episodes of adrenal crisis in 423 patients with primary and secondary adrenal
insufficiency (8.3 adrenal crises/100 PYs), and, alarmingly, 4 adrenal crisis-related deaths were
noted over a follow-up period of 2 years (0.5 adrenal crisis-related deaths per 100 PYs).
In India the incidence of adrenal crisis is estimated to be 8 per 100 patient years in patients with
adrenal insufficiency. Patients with adrenal crisis present systematically unwell with nonspecific
signs and symptoms often leading to misdiagnosis and delayed treatment.
RISK FACTORS
It is important to be aware of conditions that increase the risk of adrenal crisis in patients with
adrenal insufficiency.
Patients with primary adrenal insufficiency may be at higher risk of adrenal crisis than patients
with secondary adrenal insufficiency, due to the lack of mineralocorticoids and greater risk of
dehydration and hypovolemia.
The true risk of adrenal crisis in patients with glucocorticoid-induced adrenal insufficiency is
difficult to determine, as they form a heterogeneous group and only limited case reports are
available. It is important, nevertheless, to recognize that the most common cause of adrenal
insufficiency is use of exogenous steroids, and these patients are similarly at risk of adrenal
crisis.
Sudden, and often inadvertent, withdrawal of steroids can lead to adrenal crisis. Hence, a detailed
drug history is important, particularly for surreptitious use of steroids. Use of glucocorticoids in
the forms of topical, inhaled, nasal, injectable, intraarticular, intradermal (eg, keloid), paraspinal,
or rectal preparations have all been described to cause suppression of the hypothalamus-
pituitary-adrenal axis. Generally, longer duration, higher dosages, and oral and intraarticular
preparations increase the risk of adrenal suppression. However, there is no dose, duration, or
administration form that can predict adrenal insufficiency, and physicians should exercise a high
level of suspicion..
Diabetes insipidus was also associated with higher risk of adrenal crisis in patients with
secondary adrenal insufficiency, which could be due to the higher risk of dehydration, or the lack
of V1-receptor mediated vasoconstriction during severe stress. Other medical conditions (eg,
type 1 and type 2 diabetes mellitus, hypogonadism) were associated with higher risk of adrenal
crisis in some studies, although the mechanism is not clear..
 Details Mechanism
History Known patient with adrenal insufficiency
(AI) or risk factors for developing AI (Ref
Table 1) History of previous adrenal crisis
Drugs Exogenous steroids (glucocorticoid
Suppress hypothalamus-
therapy, fluticasone, megestrol acetate, pituitary-adrenal axis (sudden
medroxyprogesterone) withdrawal can lead to adrenal
crisis)
Levothyroxine Increases cortisol metabolism
P-450 cytochrome enzyme-inducers: Increases cortisol metabolism
phenytoin, rifampicin, phenobarbitone
P-450 cytochrome enzyme-inhibitors: Reduces endogenous
ketoconazole, fluconazole, etomidate production of cortisol
Anticoagulants Increased risk of adrenal;
hemorrhage.
Medical conditons Thyrotoxicosis Increases cortisol metabolism
Pregnancy Increased requirements in 3rd
trimester of pregnancy
Diabetes insipidus May increase dehydration
Type 1 and type 2 diabetes mellitus Unknown
Type 1 and type 2 diabetes mellitus Unknown
Premature ovarian failure Unknown
Hypogonadism Unknown
ETIOLOGY
Common causes of adrenal insufficiency

Primary adrenal insufficiency Autoimmune adrenalitis

Infections (tuberculosis, systemic fungal infections,
AIDS)
Metastasis (from lung, breast, kidney) (rare), lymphoma
Congenital adrenal hyperplasia
Adrenomyeloneuropathy/ adrenoleukodystrophy
Bilateral adrenal hemorrhage
Bilateral adrenalectomy
Secondary adrenal insufficiency Pituitary or metastatic tumor
Other tumors (craniopharyngioma, meningioma)
Pituitary surgery or radiation
Lymphocytic hypophysitis
Head trauma
Pituitary apoplexy/Sheehan’s syndrome Pituitary
infiltration (sarcoidosis, histiocytosis) Empty-sella
syndrome
Glucocorticoid-induced adrenal Long-term exogenous glucocorticoid use
insufficiency
Table 1 Common Causes of Adrenal Insufficiency
PATHOPHYSIOLOGY

The adrenal cortex produces 3 steroid hormones: glucocorticoids (cortisol), mineralocorticoids

(aldosterone, 11-deoxycorticosterone), and androgens (dehydroepiandrosterone). The primary
hormone of importance in acute adrenal crisis is cortisol; adrenal aldosterone production is
relatively minor.
 Cortisol enhances gluconeogenesis and provides substrate through proteolysis, protein
synthesis inhibition, fatty acid mobilization, and enhanced hepatic amino acid uptake.
 Cortisol indirectly induces insulin secretion to counterbalance hyperglycemia but also
decreases insulin sensitivity.
 Cortisol exercises a significant anti-inflammatory effect by stabilizing lysosomes,
reducing leukocytic responses, and blocking cytokine production.
 Phagocytic activity is preserved, but cell-mediated immunity is diminished, in situations
of cortisol deficiency.
 Finally, cortisol facilitates free-water clearance, enhances appetite, and suppresses
adrenocorticotropic hormone (ACTH) synthesis.
Aldosterone is released in response to angiotensin II stimulation via the renin-angiotensin-
aldosterone system, hyperkalemia, hyponatremia, and dopamine antagonists. Its effect on its
primary target organ, the kidney, is to promote reabsorption of sodium and secretion of
potassium and hydrogen. The net effect is to increase intravascular volume. The renin-
angiotensin-aldosterone system is unaffected by exogenous glucocorticoids, and ACTH
deficiency has a relatively minor effect on aldosterone levels.
Adrenocortical hormone deficiency results in the reverse of these hormonal effects, producing
the clinical findings of adrenal crisis.
 Primary adrenocortical insufficiency occurs when the adrenal glands fail to release
adequate amounts of these hormones to meet physiologic needs, despite release of ACTH
from the pituitary. Infiltrative or autoimmune disorders are the most common cause, but
adrenal exhaustion from severe chronic illness also may occur.
 Secondary adrenocortical insufficiency occurs when exogenous steroids have suppressed
the hypothalamic-pituitary-adrenal (HPA) axis. Too rapid withdrawal of exogenous
steroid may precipitate adrenal crisis, or sudden stress may induce cortisol requirements
in excess of the adrenal glands' ability to respond immediately. In acute illness, a normal
cortisol level may actually reflect adrenal insufficiency because the cortisol level should
be quite elevated.
Bilateral massive adrenal hemorrhage (BMAH) occurs under severe physiologic stress
(eg, myocardial infarction, septic shock, complicated pregnancy) or with concomitant
coagulopathy or thromboembolic disorders.

CLINICAL MANIFESTATIONS

The damage to the adrenal glands happens slowly over time, and symptoms occur gradually. The
most common symptoms include:

 Abdominal pain
 Abnormal menstrual periods
  Craving for salty food
 Dehydration
 Depression
 Diarrhea
 Irritability
 Lightheadedness or dizziness when standing up
 Loss of appetite
 Low blood glucose
 Low blood pressure
 Muscle weakness
 Nausea
 Patches of dark skin, especially around scars, skin folds, and joints
 Sensitivity to cold
 Unexplained weight loss
 Vomiting
 Worsening fatigue (extreme tiredness)

In some cases – such as an injury, illness, or time of intense stress – symptoms can come on
quickly and cause a serious event called an Addisonian crisis, or acute adrenal insufficiency. An
Addisonian crisis is a medical emergency. If it is not treated, it can lead to shock and death.
Symptoms of an Addisonian crisis include:

 Feeling restless, confused, or afraid, or other mental changes

 Dehydration
 Extreme weakness
 Having trouble staying awake, or a total loss of consciousness
 High fever
 Lightheadedness or feeling faint
 Paleness
 Severe vomiting and diarrhea
 Sudden, deep pain in the lower back, belly or legs

DIAGNOSTIC STUDIES

 History and physical: Your doctor will review your symptoms and perform a physical
exam. Dark patches on your skin might be a clue for your doctor to consider testing for
Addison’s disease.
 Blood tests: These will be done to measure the levels of sodium, potassium, cortisol and
ACTH in your blood.
 ACTH stimulation test: This tests the adrenal glands’ response after you are given a
shot of artificial ACTH. If the adrenal glands produce low levels of cortisol after the shot,
they may not be functioning properly.
 X-rays: These may be done to look for calcium deposits on the adrenal glands.
  Computed tomography (CT scan): Computed tomography uses computers to combine
many X-ray images into cross-sectional views. A CT scan might be done to evaluate the
adrenals and/or pituitary gland. For example, it can show if the immune system has
damaged the adrenal glands or if the glands are infected.

MANAGEMENT
Medical Management

 Administration of glucocorticoids in supraphysiologic or stress doses is the only

definitive therapy. 
o Dexamethasone does not interfere with serum cortisol assay and, thus, may be the
initial drug of choice. However, because dexamethasone has little mineralocorticoid
activity, fluid and electrolyte replacement are essential.
o A short ACTH stimulation test may be performed during resuscitation. Once
complete, hydrocortisone 100 mg IV every 6 hours is the preferred treatment to provide
mineralocorticoid support.
o Delaying glucocorticoid replacement therapy while awaiting the results of the
ACTH stimulation test is inappropriate and dangerous
EMERGENCY MEASURES
1) Establish intravenous access with a large-gauge needle
2) Draw blood for stat serum electrolytes and glucose and routine measurement of plasma
cortisol and ACTH. Do not wait for laboratory results.
3) Infuse 2 to 3 L of 0.9% saline solution or 5% dextrose in 0.9% saline solution as
quickly as possible. Monitor for signs of fluid overload by measuring central or
peripheral venous pressure and listening for pulmonary rales. Reduce infusion rate if
indicated.
4) Inject intravenous hydrocortisone (100 mg immediately and every 6 hr)
5) Use supportive measures as needed.
 Continue i.v 0.9% saline at a slower rate for the next 24 to 48 hr.
 Search for and treat possible infectious precipitating causes of the adrena; crisis
 Perform a short ACTH stimulation test to confirm the diagnosis of adrenal
insufficiency, if he is not a known case.
 Determine the type of adrenal insufficiency and its cause if nt already known
 Taper glucocorticoids to maintainance dosage over 1 to 3 days, (0.1mg by mouth
daily) when saline infusion is stopped.
 Begin mineralocorticoid replacement with fludrocortisones (0.1mg by miuth
daily) when salin infusion is stopped.
 Glucorcorticoid replacement
 Dexamethasone or prenisone (longer-acting or once daily acting) acting
 Alternative therapy with hydrocortisone BID-TID
 Meneralocorticoid replacement
 Fludrocortisones
 Liberal salt intake
 Patient education
Nursing Management

Assessment

 Level of stress; note any illness or stressors that may precipitate problems
 Fluid and electrolyte status
 VS and postural blood pressures
 Note signs and symptoms related to adrenocortical insufficiency such as weight changes,
muscle weakness, and fatigue
 Medications
 Monitor for signs and symptoms of Addisonian crisis

Nursing Process: The Care of the Patient with Adrenocortical Insufficiency

Diagnoses

Activity intolerance and fatigue

Risk for fluid volume deficit
Knowledge deficit

Interventions

Risk for fluid deficit; monitor for signs and symptoms of fluid volume deficit, encourage fluids
and foods, select foods high in sodium, administer hormone replacement as prescribed

Activity intolerance; avoid stress and activity until stable, perform all activities for patient when
in crisis, maintain a quiet nonstressful environment, measures to reduce anxiety

Further Outpatient Care

 Treat any underlying or precipitating disorder as clinically indicated.

 Carefully monitor growth and development in pediatric patients.
 Recommend medical tag or bracelet that alerts emergency personnel to adrenal gland
insufficiency.
 If exposed to chickenpox, prophylaxis with varicella-zoster immune globulin is indicated.
 If exposed to measles, prophylaxis with immune globulin is indicated.
 Closely observe for reactivation of tuberculosis in patients with latent disease.

Further Inpatient Care

o Admit to ICU as clinically indicated.

 o Perform fluid resuscitation and hemodynamic monitoring as clinically indicated.
o Monitor serum electrolytes, magnesium, and glucose every 4-6 hours until stable.
o Search for precipitating cause of crisis (eg, infection, myocardial infarction, unreported
exogenous steroid use within 12 mo, autoimmune disorder)

COMPLICATIONS

 Immunosuppression: primary adrenal insufficiency is most often caused when the body’s
immune system attacks the healthy adrenal glands by mistake.
 Hypoglycemia: depleted cortisol increases insulin sensitivity in patients with adrenal
insufficiency and is thought to involve hypoglycemia.
 Weight gain: when the adrenal’s aren’t balanced, the boddy;s fight-or-flight response
kicks in and the body prepare for the worst case scenario by storing calories to see
through the crisis. The stored calories show up as that extra fat.
 Electrolyte imbalance: The electrolyte disturbances in primary adrenal insufficiency are
due to the diminished secretion of cortisol and aldosterone. A major function of
aldosterone is to increase urinary potassium secretion. This leads to hyperkalemia,
hyponatremia, and hypotension.
 Delayed wound healing: cortisol, one of the hprmones that is very responsive to stress is
a factor. Stress- induced elevation in cortiso; interferes with activities important for
wound healing, including the production of pro- inflammatory cytokines at the wound
site that are important for the early parts of the healing process.
 Shock: A deficiency of aldosterone in particular causes the body to excrete large
amounts of sodium and retain potassium, leading to low levels of sodium and high
levels of potassium in the blood. The kidneys are not able to retain sodium easily, so
when a person with Addison disease loses too much sodium, the level of sodium in the
blood falls, and the person becomes dehydrated. Severe dehydration and a low sodium
level reduce blood volume and can lead to shock

PATIENT EDUCATION

 Instruct the patient regarding the importance of careful attention to health and fluid intake
and to double maintenance doses when ill until medical attention is obtained
 Avoid exposure to chickenpox, or measles; if exposed, seek medical advice without delay
 Notify physician or seek medical attention for persistent nausea and vommiting, fatigue
and abdominal pain
Follow up
JOURNAL REFERENCE

The American journal of medicine; Adrenal crisis: still a deadly event in the 21 st century; Troy
H.K. Puar, MBBS, MRCP (UK), Nike M.M.L. Stikkelbroeck, MD, PhD, Lisanne C.C.J. Smans,
MD, PhD, Pierre M.J. Zelissen, MD, PhD, Ad. R.M.M. Hermus, MD, PhD; Elsevier Inc. 2016

Abstract

Adrenal crisis is a life-threatening medical emergency, associated with a high mortality unless it
is appropriately recognized and early treatment is rendered. Despite it being a treatable condition
for almost 70 years, failure of adequate preventive measures or delayed treatment has often led to
unnecessary deaths. Gastrointestinal illness is the most common precipitant for an adrenal crisis.
Although most patients are educated about “sick day rules,” patients, and physicians too, are
often reluctant to increase their glucocorticoid doses or switch to parenteral injections, and
thereby fail to avert the rapid deterioration of the patients’ condition. Therefore, more can be
done to prevent an adrenal crisis, as well as to ensure that adequate acute medical care is
instituted after a crisis has occurred. There is generally a paucity of studies on adrenal crisis.
Hence, we will review the current literature, while also focusing on the incidence, presentation,
treatment, prevention strategies, and latest recommendations in terms of steroid dosing in stress
situations.

BIBLIOGRAPHY
1. Chintamani; Lewis’s Medical Surgical Nursing, Assessment and Management of Clinical
Problems; Elsevier, 2011, Reprint 2013
2. Mariann M. Harding; Lewis;s Medical Surgical Nursing; Assessment And Management
of Clinical Problems; Eleventh edition; Elsevier
3. Janice L. Henkle, Keery H. Cheever; Brunner and Suddarth’s A Textbook of Medical and
Surgical Nursing; 14th Edition; Wolter Kluwer: 2018
4. Net reference:
www.nurseslabs.com
www.winchesterhospital.org
https://www.slideshare.net/premmjha/adrenal-crisis
https://emedicine.medscape.com/article/116716-overview