Krisis adrenal atau krisis Addison atau Acute Adrenal Insuffiency

Penyakit Addison adalah penyakit yang disebabkan oleh berkurangnya hormon

yang diproduksi oleh kelenjar adrenal. Penyakit ini tergolong ke dalam kelainan
langka pada kelenjar adrenal.

Penyakit ini dapat terjadi pada pria dan perempuan dari berbagai usia, namun
lebih umum ditemui pada perempuan dan anak-anak. Jika tidak segera diobati,
penyakit Addison bisa membahayakan nyawa penderitanya. Anak dengan
penyakit Addison dapat mengalami keterlambatan masa puber.

Penyebab Penyakit Addison

Penyakit Addison umumnya disebabkan oleh adanya gangguan pada sistem imun
tubuh yang menyerang kelenjar adrenal bagian luar (cortex). Kondisi ini
berdampak pada terganggunya produksi hormon kortisol dan aldosteron yang
dihasilkan oleh kelenjar adrenal. Walaupun demikian, penyebab munculnya
kelainan pada sistem imunitas tubuh penderita penyakit Addison belum diketahui
hingga saat ini.

Kelenjar adrenal terdiri dari dua bagian, yaitu medulla yang terletak di bagian
dalam, dan cortex. Medulla adalah lapisan dalam kelenjar adrenal yang
memproduksi hormon yang serupa dengan adrenalin. Cortex, adalah lapisan luar
kelenjar adrenal yang memproduksi hormon kortikosteroid, yang terdiri dari
glukokortikoid, mineralokortikoid, dan hormon androgens. Beberapa kegunaan
hormon-hormon ini, yaitu:

Mineralokortikoid. Bersama dengan hormon androgen, hormon

mineralokortikoid berfungsi menjaga keseimbangan jumlah natrium dan
kalium di dalam tubuh dan menjaga tekanan darah agar tetap normal.

Androgens. Hormon ini berperan dalam perkembangan seksual pria,

seperti massa otot dan libido. Hormon ini juga diproduksi oleh kelenjar
adrenal perempuan dalam jumlah yang kecil.

Glukokortikoid. Hormon ini bertanggung jawab atas respons sistem

kekebalan tubuh terhadap peradangan, memengaruhi kemampuan tubuh
dalam mengubah makanan menjadi energi, dan mengatasi stress yang
dialami tubuh. Kortisol adalah salah satu hormon Glukokortikoid.

Ada dua jenis penyebab penyakit Addison berdasarkan gangguan yang dialami
oleh kelenjar, yaitu:

Insufiensi atau ketidakcukupan adrenal primer, yaitu penyakit Addison

yang terjadi akibat rusaknya kelenjar adrenal Cortex sehingga tidak
memproduksi hormon dalam jumlah yang cukup. Penyebab paling umum
 kondisi ini adalah akibat penyakit autoimun, di mana sistem imun tubuh
menganggap korteks adrenal sebagai bahan asing dan kemudian
dihancurkan. Adapun penyebab lain insufisiensi adrenal primer, antara lain
terjadinya infeksi, pendarahan, penyakit tuberkulosis, atau menyebarnya
sel kanker ke kelenjar ini.

Insufiensi adrenal sekunder, yaitu ketidakcukupan jumlah hormon

adrenokortikotropik (ACTH) yang dihasilkan tubuh sebagai akibat kondisi
kelenjar pituitari (penghasil ACTH) yang terkena penyakit (misalnya
tumor). Hormon adrenokortikotropik bersifat penting, karena berfungsi
merangsang kelenjar Cortex adrenal untuk memproduksi hormon-hormon
yang telah disebutkan di atas. Insufiensi adrenal sekunder dapat dipicu
oleh permberhentian tiba-tiba terapi kortikosteroid pada penderita penyakit
kronis seperti asma atau arthritis.

Krisis Addisonian, adalah keadaan darurat medis di mana kadar kortisol

sangat rendah. Hal ini dapat diakibatkan karena penyakit Addison yang
tidak diterapi. Stres fisik seperti sakit, infeksi, atau cedera dapat menjadi
pemicu kondisi ini.

Selain insufisiensi kelenjar adrenal, penyakit Addison dapat juga diturunkan

secara genetik dan penggunaan obat-obatan yang mengandung steroid dalam
jangka panjang.

Beberapa penyakit autoimun lain juga dapat menjadi penyebab berkembangnya

penyakit Addison, antara lain:

Penyakit Celiac

Sindrom Schmidt

Diabetes mellitus tipe 1

Penyakit Graves

Vitiligo

Hipoparatiroid idiopatik

Miestenia gravis.

Gejala Penyakit Addison

Gejala penyakit Addison dapat muncul setelah beberapa bulan. Akan tetapi pada
kasus penyakit Addison yang disebabkan oleh gagal fungsi adrenal yang akut
(krisis Addisonian), gejala bisa timbul tiba-tiba. Beberapa gejala umum yang
mungkin muncul, antara lain:

Tekanan darah rendah, hingga pingsan

Rendahnya level gula darah (Hipoglikemia)

Mual

Diare

Muntah

Kelelahan yang berlebihan

Kehilangan berat badan

Berkurangnya nafsu makan

Mengidam makanan yang asin

Hiperpigmentasi (menggelapnya warna kulit)

Sakit perut

Nyeri otot atau sendi

Kehilangan rambut pada tubuh atau disfungsi seksual pada penderita

perempuan

Menjadi mudah marah

Depresi

Selain gejala umum di atas, krisis Addisonian juga memiliki gejalanya sendiri,
yaitu diare dan muntah-muntah parah yang dapat menyebabkan dehidrasi, serta
rasa sakit di punggung bagian bawah. Kadar potasium naik (hiperkalemia)
sementara kadar sodium rendah (hiponatremia), juga mengalami kehilangan
kesadaran. Seorang perempuan dapat mengalami periode menstruasi yang tidak
teratur sebagai gejala penyakit Addison. Gejala krisis Addison lainnya, yaitu:

Kulit yang pucat, dingin, atau lembap

Pusing
 Berkeringat

Napas yang pendek dan cepat

Otot yang sangat lemah

Segera temui dokter jika Anda mengalami gejala-gejala di atas untuk

mendapatkan diagnosis yang tepat. Krisis Addisonian khususnya, kondisi ini
harus segera ditangani sebelum mengakibatkan koma, bahkan kematian.

Diagnosis Penyakit Addison

Pemeriksaan awal sebelum diagnosis dimulai dengan mengenali gejala penyakit

Addison pada pasien lalu mengecek perubahan warna kulit pada area, seperti siku,
telapak tangan, dan bibir. Dokter juga akan menanyakan sejarah penyakit yang
pernah dialami oleh pasien sebelum melakukan serangkaian tes penunjang,
seperti:

Tes darah. Tes ini dilakukan untuk mengetahui level natrium, kalium,
kortisol, dan ACTH di dalam tubuh yang dapat menjadi pemicu gejala
pada pasien. Tes darah juga dilakukan untuk mengetahui jumlah antibodi
yang bisa menjadi penyebab terjadi kondisi autoimun pada penyakit
Addison.

Tes rangsangan ACTH (hormon adrenokortikotropik). Tes ini dilakukan

untuk mengetahui level kortisol di dalam darah sebelum dan sesudah
ACTH sintetis disuntikkan. Tes ini akan menunjukkan kerusakan pada
kelenjar adrenal jika hasil respons hormon kortisol terhadap ACTH sintetis
berada dalam jumlah yang terbatas atau tidak ada.

Tes fungsi kelenjar tiroid. Kelenjar ini memiliki peranan penting dalam
memproduksi hormon yang mengendalikan perkembangan dan
metabolisme tubuh. Penderita penyakit Addison umumnya memiliki fungsi
kelenjar tiroid yang rendah.

Tes pencitraan, seperti CT dan MRI scan. Tes ini dilakukan untuk
mengetahui ukuran kelenjar adrenal yang tidak normal pada area perut,
atau pada kelenjar pituitari untuk mengetahui penyebab insufisiensi
adrenal primer maupun sekunder.

Tes hipoglikemia induksi insulin. Tes ini biasanya dilakukan jika gangguan
pada kelenjar pituitarilah yang menjadi penyebab insufisiensi adrenal
sekunder. Tes ini dilakukan dengan cara memeriksa level glukosa darah
dan kortisol setelah insulin disuntikkan. Orang yang sehat akan memiliki
hasil level glukosa rendah dan meningkatnya kortisol.
Pengobatan Penyakit Addison

Penyakit Addison diterapi menggunakan terapi hormon untuk menggantikan

jumlah hormon yang berkurang, sekaligus mendapatkan manfaat serupa dari
hormon yang hilang tersebut. Beberapa pilihan terapi hormon pengganti yang
mungkin dilakukan, yaitu:

Pemberian kortikosteroid secara oral. Beberapa hormon yang digunakan

untuk menggantikan kortisol, adalah cortisone acetate, prednisone, atau
hydrocortisone. Hormon fludrocortisone mungkin digunakan untuk
menggantikan aldosterone.

Pemberian kortikosteroid melalui suntikan untuk penderita yang

mengalami gejala muntah-muntah.

Dokter dapat menambahkan sodium ke dalam daftar obat pasien untuk pasien
yang mengalami diare atau jika cuaca sedang panas, atau sedang melakukan
latihan fisik yang berat. Dosis obat juga mungkin ditingkatkan bagi pasien yang
berada dalam kondisi stres fisik, seperti sakit akibat infeksi, kecelakaan, atau
harus melalui prosedur operasi terlebih dulu.

Pengobatan Addison juga dilakukan pada krisis Addisonian yang menyebabkan

rendahnya kadar gula darah dan tekanan darah, namun tinggi kadar potasium.
Kondisi yang membahayakan ini membutuhkan penanganan secepatnya dengan
menggunakan metode infus atau suntikan obat melalui pembuluh darah. Obat
yang umumnya digunakan, adalah gula (dextrone), larutan garam (saline), dan
hydrocortisone. Dosis dapat berubah sewaktu-waktu sehingga komunikasi dengan
dokter akan sering terjadi.

Pengobatan terhadap penyakit yang menjadi pemicu berkembangnya penyakit

Addison mungkin dilakukan, seperti pengobatan antibiotik akan dilakukan lebih
dulu untuk mengobati penyakit tuberkulosis.

Beberapa langkah yang bisa dilakukan oleh penderita penyakit Addison agar
terhindar dari situasi darurat, adalah dengan memastikan obat-obatan selalu
tersedia di dekat Anda. Dengan demikian Anda tidak akan melewatkan terapi
pengobatan yang bisa memperburuk penyakit ini dan kesehatan Anda. Siapkan
kartu kesehatan berisi informasi mengenai penyakit, obat, dan nomor-nomor
penting yang dibutuhkan agar orang-orang di sekitar Anda tahu apa yang harus
dilakukan ketika terjadi situasi darurat.

Sumber alo dokter

Medscape
Background
Do not confuse acute adrenal crisis with Addison disease. In 1855, Thomas
Addison described a syndrome of long-term adrenal insufficiency that develops
over months to years, with weakness, fatigue, anorexia, weight loss, and
hyperpigmentation as the primary symptoms. In contrast, an acute adrenal crisis
can manifest with vomiting, abdominal pain, and hypovolemic shock. [1, 2] When
not promptly recognized, adrenal hemorrhage can be a cause of adrenal crisis. See
the images below.

Computed tomographic (CT) scans of the abdomen show normal adrenal glands
several months before the onset of hemorrhage (upper panel) and enlarged
adrenals 2 weeks after an acute episode of bilateral adrenal hemorrhage (lower
panel). The attenuation of the adrenal glands, indicated by arrows, is increased
after the acute event. Reproduced from Rao RH, Vagnucci AH, Amico JA:
Bilateral massive adrenal hemorrhage: early recognition and treatment. Ann Intern
Med. Feb 1 1989;110(3):227-35 with permission from the journal.

Pathophysiology
The adrenal cortex produces 3 steroid hormones: glucocorticoids (cortisol),
mineralocorticoids (aldosterone, 11-deoxycorticosterone), and androgens
(dehydroepiandrosterone). The androgens are relatively unimportant in adults, and
11-deoxycorticosterone is a fairly weak mineralocorticoid in comparison with
aldosterone. 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 mechanism
of action is unclear; an increase in the sodium- and potassium-activated adenosine
triphosphatase (Na+/K+ ATPase) enzyme responsible for sodium transport, as well
as increased carbonic anhydrase activity, has been suggested. 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.

Hahner et al investigated the frequency and causes of, as well as the risk factors
for, adrenal crisis in patients with chronic adrenal insufficiency. Using a disease-
specific questionnaire, the authors analyzed data from 444 patients, including 254
with primary adrenal insufficiency and 190 with secondary adrenal insufficiency.
At least one adrenal crisis was reported by 42% of patients, including 47% of
those with primary adrenal insufficiency and 35% of patients with the secondary
condition. GI infection and fever were the most common precipitating causes of
crisis. Identified risk factors for adrenal crisis were, for patients with primary
adrenal insufficiency, concomitant nonendocrine disease, and for patients with
secondary adrenal insufficiency, female sex and diabetes insipidus. [3]

A study from the Netherlands, by Smans et al, of patients with adrenal

insufficiency, found the existence of comorbidity to be the most important risk
factor for adrenal crisis, with infections being the most common precipitating
factors. [4]

Epidemiology

Frequency
The incidence of primary adrenocortical insufficiency is variable and depends on
the defining cortisol level and the method of testing (ie, ACTH stimulation versus
single random cortisol level). The underlying disease also is a factor. Studies of
critically ill patients with septic shock demonstrate a de novo (excluding patients
with known adrenal insufficiency or patients on glucocorticoid therapy) incidence
ranging from 19-54%. Secondary adrenal insufficiency has been demonstrated in
31% of patients admitted to a critical care unit.

Annane et al's landmark 2002 study found a very high rate, ie, 76% of all enrolled
patients with septic shock. Of the general perioperative population, in 62,473
anesthetic administrations, only 419 (0.7%) patients required glucocorticoid
supplementation and only 3 hypotensive events were thought to be attributable to
glucocorticoid deficiency. [5] Studies of patients undergoing cardiac or urologic
surgery reveal an incidence of 0.01-0.1%. In a study of 2000 consecutive general
hospital autopsies, only 22 (1.1%) revealed bilateral adrenal hemorrhage;
however, as many as 15% of patients dying in shock have been demonstrated to
have BMAH.
The aforementioned study from the Netherlands, by Smans et al, found the
incidence of adrenal crisis among persons with primary adrenal insufficiency to be
5.2 cases per 100 person-years, while in secondary adrenal insufficiency, the
incidence was reported as 3.6 cases per 100 person-years. [4]

No description regarding racial data, sexual predilection, or age is available in the

literature.

History
History can include the following:

Prior steroid use: Use involves at least 20 mg daily of prednisone or its

equivalent for at least 5 days within the past 12 months. Patients receiving
doses close to normal physiologic levels require only 1 month to recover
normal adrenal function.

Organisms associated with adrenal crisis (eg, Haemophilus influenzae,

Staphylococcus aureus, Streptococcus pneumonia, fungi)

Meningococcemia

Severe physiologic stress [7] (eg, sepsis, trauma, burns, surgery): In a

retrospective review of patients from a level 1 trauma center,
Guillamondegui et al found that trauma patients with acute adrenal
insufficiency who were treated for the condition had shorter hospital stays
and required fewer days in the intensive care unit and on a ventilator than
did untreated patients. [8] In addition, the authors concluded that
recognition and treatment of the condition can reduce trauma patient
mortality by almost 50%.

Azotemia

Anticoagulants, hemorrhagic diathesis

Newborn, complicated pregnancy

Adrenocorticotropin therapy, known primary or secondary adrenocortical

insufficiency

AIDS

Invasive or infiltrative disorders

Tuberculosis
 Topical steroids: Risk of adrenal crisis occurs when used over a large
surface area for a prolonged duration, using occlusive dressings and a
highly potent drug.

Inhaled steroids: Use of a high dose (>0.8mg/d) over a prolonged duration

increases risk; fluticasone may cause suppression at lower dose.

Congenital adrenal hyperplasia (CAH): A retrospective study by

Rushworth et al indicated that in pediatric patients with CAH, adrenal
crises occur mostly in the younger ones. The study, which evaluated 573
admissions for medical problems in children with CAH, found that 21 of
37 adrenal crises occurred in patients aged 1-5 years, with another six in
children aged up to 1 year. [9]

Physical
See the list below:

Unexplained shock, usually refractory to fluid and pressor resuscitation

Nausea, vomiting, abdominal or flank pain

Hyperthermia or hypothermia

Causes
See the list below:

Rapid withdrawal of long-term steroid therapy

Ketoconazole

Phenytoin

Rifampin

Mitotane

Septic shock

Differential Diagnoses
Septic Shock

Sepsis is defined as life-threatening organ dysfunction due to dysregulated

host response to infection, and organ dysfunction is defined as an acute change in
total Sequential Organ Failure Assessment (SOFA) score greater than 2 points
secondary to the infection cause. [1] Septic shock occurs in a subset of patients with
sepsis and comprises of an underlying circulatory and cellular/metabolic
abnormality that is associated with increased mortality. Septic shock is defined by
persisting hypotension requiring vasopressors to maintain a mean arterial pressure
of 65 mm Hg or higher and a serum lactate level greater than 2 mmol/L (18
mg/dL) despite adequate volume resuscitation. [1] This new 2016 definition, also
called Sepsis-3, eliminates the requirement for the presence of systemic
inflammatory response syndrome (SIRS) to define sepsis, and it removed the
severe sepsis definition. What was previously called severe sepsis is now the new
definition of sepsis.

Signs and symptoms

Detrimental host responses to infection occupy a continuum that ranges from
sepsis to severe sepsis to septic shock and multiple organ dysfunction syndrome
(MODS). The specific clinical features depend on where the patient falls on that
continuum.

Signs and symptoms of sepsis are often nonspecific and include the following:

Fever, chills, or rigors

Confusion

Anxiety

Difficulty breathing

Fatigue, malaise

Nausea and vomiting

Alternatively, typical symptoms of systemic inflammation may be absent in severe

sepsis, especially in elderly individuals.

It is important to identify any potential source of infection. Localizing signs and

symptoms referable to organ systems may provide useful clues to the etiology of
sepsis and are as follows:

Head and neck infections Severe headache, neck stiffness, altered mental
status, earache, sore throat, sinus pain/tenderness, cervical/submandibular
lymphadenopathy
 Chest and pulmonary infections Cough (especially if productive),
pleuritic chest pain, dyspnea, dullness on percussion, bronchial breath
sounds, localized rales, any evidence of consolidation

Cardiac infections Any new murmur, especially in patients with a history

of injection or IV drug use

Abdominal and gastrointestinal (GI) infections Diarrhea, abdominal

pain, abdominal distention, guarding or rebound tenderness, rectal
tenderness or swelling

Pelvic and genitourinary (GU) infections Pelvic or flank pain, adnexal

tenderness or masses, vaginal or urethral discharge, dysuria, frequency,
urgency

Bone and soft-tissue infections Localized limb pain or tenderness, focal

erythema, edema, swollen joint, crepitus in necrotizing infections, joint
effusions

Skin infections Petechiae, purpura, erythema, ulceration, bullous

formation, fluctuance

Diagnosis septic shock

Patients with sepsis may present in a myriad of ways, and a high index of clinical
suspicion is necessary to identify subtle presentations. The hallmarks of severe
sepsis and septic shock are changes that occur at the microvascular and cellular
level and may not be clearly manifested in the vital signs or clinical examination.
This process includes diffuse activation of inflammatory and coagulation
cascades, vasodilation and vascular maldistribution, capillary endothelial leakage,
and dysfunctional utilization of oxygen and nutrients at the cellular level.

Cardiac monitoring, noninvasive blood pressure monitoring, and pulse oximetry

are indicated in patients with septic shock.

Laboratory tests septic shock

The following are investigative studies to detect a clinically suspected focal

infection, the presence of a clinically occult focal infection, and complications of
sepsis and septic shock:

Complete blood count with differential

Coagulation studies (eg, prothrombin time [PT], activated partial

thromboplastin time [aPTT], fibrinogen levels)
 Blood chemistry (eg, sodium, chloride, magnesium, calcium, phosphate,
glucose, lactate)

Renal and hepatic function tests (eg, creatinine, blood urea nitrogen,
bilirubin, alkaline phosphatase, alanine aminotransferase, aspartate
aminotransferase, albumin, lipase)

Blood cultures

Urinalysis and urine cultures

Gram stain and culture of secretions and tissue

Laboratory Studies
See the list below:

Serum chemistry: Abnormalities are present in as many as 56% of patients.

Hyponatremia is common (although not diagnostic); hyperkalemia,
metabolic acidosis, and hypoglycemia also may be present. However, the
absence of laboratory abnormalities does not exclude the diagnosis of
adrenal crisis.

Serum cortisol: Less than 20 mcg/dL in severe stress or after ACTH

stimulation is indicative of adrenal insufficiency.

ACTH test (diagnostic): Determine baseline serum cortisol, then

administer ACTH 250 mcg intravenous push (IVP), and then draw serum
cortisol 30 and 60 minutes after ACTH administration. An increase of less
than 9 mcg/dL is considered diagnostic of adrenal insufficiency.

CBC: Anemia (mild and nonspecific), lymphocytosis, and eosinophilia

(highly suggestive) may be present.

Serum thyroid levels: Assess for autoimmune, infiltrative, or multiple

endocrine disorders.

Cultures: Perform blood and other cultures as clinically indicated.

Infection is a common cause of acute adrenal crisis.

Imaging Studies
See the list below:

Chest radiography: Assess for tuberculosis, histoplasmosis, malignant

disease, sarcoid, and lymphoma.
 Abdominal CT scanning: Visualize adrenal glands for hemorrhage (as in
the image below), atrophy, infiltrative disorders, and metastatic disease.
Adrenal hemorrhage appears as hyperdense, bilaterally enlarged adrenal
glands.

Computed tomographic (CT) scans of the abdomen show normal adrenal glands
several months before the onset of hemorrhage (upper panel) and enlarged
adrenals 2 weeks after an acute episode of bilateral adrenal hemorrhage (lower
panel). The attenuation of the adrenal glands, indicated by arrows, is increased
after the acute event. Reproduced from Rao RH, Vagnucci AH, Amico JA:
Bilateral massive adrenal hemorrhage: early recognition and treatment. Ann Intern
Med. Feb 1 1989;110(3):227-35 with permission from the journal.
Other Tests
See the list below:

Electrocardiography

o Prolongation of the QT interval can induce ventricular arrhythmias.

o Deep negative T waves have been described in acute adrenal crisis.

Histologic Findings
Histology depends on the cause of the adrenal failure. In primary adrenocortical
failure, histologic evidence of infection, infiltrative disease, or other condition
may be demonstrated. Secondary adrenocortical insufficiency may cause atrophy
of the adrenals or no histologic evidence at all, especially if due to exogenous
steroid ingestion. Appearance of bilateral adrenal hemorrhage may be striking, as
if bags of blood are replacing the glands.

Medical Care
See the list below:

Administration of glucocorticoids in supraphysiologic or stress doses is

the only definitive therapy. [10, 11]

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.

In addition to corticosteroid replacement, aggressive fluid replacement

with 5% or 10% intravenous dextrose and saline solutions and treatment of
hyperkalemia is mandatory. Fludrocortisone, a mineralocorticoid, may also
be given.
 A thorough search for a precipitating cause and administration of empiric
antibiotics is indicated. Reversal of coagulopathy should be attempted with
fresh frozen plasma.

Pressors (eg, dopamine, norepinephrine) may be necessary to combat

hypotension.

Consultations
See the list below:

Endocrinologist

Infectious disease specialist

Critical care physician

Cardiologist

Surgeon

Other consultations as clinically indicated

Guidelines Summary
Guidelines from Britains Society for Endocrinology on the emergency
management of adrenal crisis, published in 2016, include the following diagnostic
recommendations [12] :

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

Assess patient drug history; determine whether there has been

glucocorticoid use

Perform appropriate blood tests: Sodium, potassium, urea, and creatinine;

full blood counts; thyroid-stimulating hormone and free thyroxine; paired
serum cortisol and plasma ACTH

If the patient is hemodynamically stable, consider performing a short

Synacthen test (serum cortisol at baseline and 30min after intravenous
injection of 250 g ACTH 124)
 Serum/plasma aldosterone and plasma renin

Diagnostic measures should never delay prompt treatment of a suspected

adrenal crisis

The guidelines include the following recommendations for emergency treatment

[12]
:

Administer hydrocortisone: Immediate bolus injection of 100mg

hydrocortisone intravenously or intramuscularly followed by continuous
intravenous infusion of 200mg hydrocortisone per 24hours (alternatively,
50mg hydrocortisone per intravenous or intramuscular injection every 6h)

Rehydrate with rapid intravenous infusion of 1000mL of isotonic saline

infusion within the first hour, followed by further intravenous rehydration
as required (usually 4-6L in 24h; 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, and investigation of the underlying
cause of the disease, including the diagnosis of primary versus secondary
adrenal insufficiency

Tapering of hydrocortisone can be started after clinical recovery guided by

an endocrinologist; in patients with primary adrenal insufficiency,
mineralocorticoid replacement must be initiated (starting dose 100 g
fludrocortisone once daily) as soon as the daily glucocorticoid dose is
below 50mg of hydrocortisone every 24hours

Medication Summary
Corticosteroids are the mainstays of treatment. Other medications, such as
pressors (eg, dopamine, norepinephrine) or antibiotics, are administered as
clinically indicated.

Corticosteroids

Class Summary
These agents have anti-inflammatory properties and cause profound and varied
metabolic effects. They modify the body's immune response to diverse stimuli.

Dexamethasone (Decadron, Baldex, Dexone)

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Used as empiric treatment of shock in suspected adrenal crisis or insufficiency
until serum cortisol levels are drawn.

Hydrocortisone (Hydrocortone, Hydrocort)

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DOC because of mineralocorticoid activity and glucocorticoid effects.

Cortisone (Cortone)

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Oral DOC for patients with adrenocortical insufficiency.

Use in patients undergoing moderate stress surgery (eg, vascular bypass, total
joint replacement) who can take PO postoperatively.

Fludrocortisone (Florinef)

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Acts on renal distal tubules to enhance reabsorption of sodium. Increases urinary

excretion of both potassium and hydrogen ions. The consequence of these 3
primary effects, together with similar actions on cation transport in other tissues,
appears to account for the spectrum of physiological activities characteristic of
mineralocorticoids. Used in adrenal insufficiency. Produces marked sodium
retention and increased urinary potassium excretion.

Methylprednisolone (Medrol, Solu-Medrol, Depo-Medrol)

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Usually third-line DOC for adrenal crisis because of lack of mineralocorticoid

activity.

Consider use in patients with fluid overload, edema, or hypokalemia.

Vasopressors

Class Summary
These agents are potent vasoconstrictors, inotropes and chronotropes. They should
be used with caution in conjunction with corticosteroids and intravenous fluid
support.

Norepinephrine (Levophed)

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For protracted hypotension following adequate fluid-volume replacement.

Stimulates beta1- and alpha-adrenergic receptors, which in turn, increases cardiac
muscle contractility and heart rate, as well as vasoconstriction. As a result,
systemic blood pressure and coronary blood flow increase. After obtaining a
response, the rate of flow should be adjusted and maintained at a low-normal
blood pressure, such as 80-100 mm Hg systolic, sufficient to perfuse vital organs.

Dopamine (Intropin)

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Stimulates both adrenergic and dopaminergic receptors. Hemodynamic effect is

dependent on the dose.

Further Outpatient Care

See the list below:

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
See the list below:

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).

Inpatient & Outpatient Medications

See the list below:

Taper steroid dose as outlined previously (see Medication).

Complications
See the list below:

Immunosuppression

Hypertension

Salt retention

Hypokalemia

Weight gain

Delayed wound healing

Hyperglycemia

Metabolic alkalosis

Prognosis
See the list below:

Prognosis is the same as for patients without adrenal insufficiency if the

condition is diagnosed and treated appropriately.
Patient Education
See the list below:

Instruct patients 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

vomiting, fatigue, and abdominal pain.

For excellent patient education materials, see eMedicineHealth's Thyroid

& Metabolism Center and patient education article Anatomy of the
Endocrine System.