Basics
Description
- Inadequate hydrocortisone secretion to meet bodys stress requirement
- Adrenal deficiency:
- Inadequate cortisol
- Unresponsive to stimulation with adrenocorticotropic hormone (ACTH)
- Functional hypoadrenalism:
- Inadequate cortisol
- Partial response to stimulation with ACTH
- Addisonian crisis (acute adrenal insufficiency):
- Life-threatening emergency
- Precipitated by intensification of:
- Chronic adrenal insufficiency
- Acute adrenal hemorrhage
- Rapid steroid withdrawal
- Treatment of hypothyroidism with unrecognized adrenal disease
- Steroid-dependent patient under stress owing to pregnancy, surgery, trauma, infection, or dehydration
Etiology
Primary Adrenal Failure
- Adrenal dysgenesis/impaired steroidogenesis:
- Congenital hypoplasia
- Allgrove syndrome:
- ACTH resistance
- Achalasia
- Alacrima
- Glycerol kinase deficiency:
- Psychomotor retardation
- Hypogonadism
- Muscular dystrophy
- Congenital adrenal hyperplasia:
- 21-hydroxylase deficiency accounts for 95% of cases
- Aldosterone synthetase deficiency
- Mitochondrial disease
- Adrenal destruction:
- Autoimmune:
- Autoimmune polyglandular syndrome types 1 and 2 (alopecia universalis, chronic mucocutaneous candidiasis, hypoparathyroid, thyroid autoimmunity, diabetes, celiac disease, pernicious anemia)
- Adrenoleukodystrophy
- Infectious:
- Granulomatous: TB
- Protozoal and fungal: Histoplasmosis, coccidioidomycosis, and candidiasis
- Viral: Cytomegalovirus, herpes simplex virus, and HIV
- Bacterial
- Fungal
- Metastatic tumor
- Infiltration:
- Sarcoid
- Hemochromatosis
- Amyloidosis
- Iron depletion
- Bilateral adrenalectomy
- Hemorrhage:
- Sepsis: Particularly meningococcemia (Waterhouse-Friderichsen syndrome), Pseudomonas infection
- Birth trauma/anoxia
- Pregnancy
- Seizures
- Anticoagulants
- Rhabdomyolysis
- Pharmacologic inhibition:
- Etomidate
- Herbal medications
- Ketoconazole
- Metyrapone
- Suramin
Secondary Adrenal Failure
- Pituitary insufficiency
- Sepsis
- Head trauma
- Hemorrhage
- Infarction (Sheehan syndrome)
- Infiltration: Neoplasm, amyloid, sarcoid, and hemochromatosis
- ACTH deficiency
- Pharmacologic: Glucocorticoid administration, herbal medications
Tertiary Adrenal Failure
- Hypothalamus insufficiency
- Sepsis
- Infiltrative: Neoplasm, amyloid, sarcoid, and hemochromatosis
- Head trauma
Diagnosis
Signs and Symptoms
- Symptoms:
- Depression
- Weakness, tiredness, fatigue
- Anorexia
- Abdominal pain (can mimic acute abdomen)
- Nausea or vomiting
- Salt craving
- Postural dizziness
- Muscle or joint pains
- Dehydration (found in primary adrenal insufficiency only)
- Signs:
- Fever or hypothermia
- Mental status changes
- Hypotension (<110 mm Hg systolic)
- Tachycardia
- Orthostatic BP changes or frank shock
- Weight loss
- Goiter
- Hypogonadism
- Hyperkalemia
- Hypercalcemia
- Sodium depletion
- Azotemia
- Eosinophilia
- Hyperpigmentation (found in primary adrenal insufficiency only)
- Vitiligo
- Addisonian crisis:
- Hypotension and shock
- Hyponatremia
- Hyperkalemia
- Hypoglycemia
Essential Workup
- Lab confirmation of diagnosis not possible in emergency department
- Adrenal crisis: Life-threatening condition:
- High degree of suspicion should prompt initiation of therapy before definitive diagnosis.
- Plasma cortisol level <20 μg/dL accompanied by shock suggests adrenal insufficiency.
- Stat electrolytes:
- BUN, creatinine:
- Elevated owing to dehydration
- Serum glucose levels may be low.
Diagnosis Tests & Interpretation
Lab
- CBC with differential:
- Anemia
- Eosinophilia
- Lymphocytosis
- Arterial blood gases:
- Cosyntropin stimulation test:
- Adrenal deficiency:
- Random serum cortisol <20 μg/dL (while stressed)
- ACTH stimulation unresponsive
- Functional hypoadrenalism:
- Random serum cortisol = 20 μg/dL (while stressed)
- 60 min post ACTH stimulation <30 μg/dL or delta cortisol (60 min - baseline) = 9 μg/dL
- Normal anion gap metabolic acidosis due to aldosterone deficiency
- Search for underlying infection
Imaging
CXR: �
- Look for infection or edema
Diagnostic Procedures/Surgery
ECG: �
- Evaluate for electrolyte disturbances
Differential Diagnosis
- Sepsis
- Shock (any cause)
- Acute abdominal emergency
Treatment
Initial Stabilization/Therapy
- Airway, breathing, and circulation management (ABCs)
- Cardiac monitor
- BP support for hypotension:
- Normal saline (0.9%) IV fluids 500 mL-1 L (peds: 20 mL/kg) bolus
- Avoid pressors (if possible):
- May precipitate dysrhythmias
- Supplemental oxygen to meet metabolic needs
- Correct hyperthermia:
- Initiate cooling measures.
Ed Treatment/Procedures
- Glucocorticoid replacement:
- IV hydrocortisone or dexamethasone immediately
- Use IM route if no IV access
- Dexamethasone will not interfere with results of cosyntropin stimulation tests.
- Volume expansion:
- NS (0.9%) or D5NS at rate of 500-1,000 mL/hr for 1st 3-4 hr
- Care should be taken to note patients age, volume, and cardiac and renal function.
- For hypoglycemia:
- Treat life-threatening dysrhythmias secondary to hyperkalemia with calcium, bicarbonate, and insulin/glucose.
- Identification and correction of underlying precipitant
- Should see BP improvement within 4-6 hr of therapy
Medication
- Dexamethasone: 6-10 mg (peds: 0.15 mg/kg per dose) q12h
- Dextrose: 50-100 mL D50 (peds: 2 mL/kg of D10 over 1 min) IV
- Hydrocortisone: 100 mg (peds: 1-2 mg/kg per dose) IV q6h
- Insulin (regular): 10 U by IV push (for hyperkalemia)
- Sodium bicarbonate: 1-2 mEq/kg IV (for hyperkalemia)
Follow-Up
Disposition
Admission Criteria
- All patients with acute adrenal insufficiency
- ICU admission for patients with unstable or potentially unstable cases
Discharge Criteria
- Normal lab evaluation with treated adrenal insufficiency
- Should speak with endocrinologist before discharge with chronic patients
Follow-Up Recommendations
- Should have primary care physician follow-up within a few weeks depending on symptoms.
- May benefit from endocrinology referral.
Pearls and Pitfalls
- Acute adrenal insufficiency is a life-threatening emergency, and treatment should not be delayed in the ED while waiting for definite lab diagnosis.
- Cancer of any type can present with adrenal insufficiency; the most common being lung, melanoma, and breast.
- The benefit from steroids for relative adrenal insufficiency in septic shock is limited to the treatment of shock refractory to vasopressive (mortality benefit and clinical effect is questionable).
- The clinical consequence of a single dose of etomidate for rapid sequence intubation is controversial. Studies do show biochemical adrenal suppression which must be weighed against agents with other undesirable properties while performing a critical, life-saving procedure.
Additional Reading
- Bouillon �R. Acute adrenal insufficiency. Endocrinol Metab Clin N Am. 2006;35:767-775.
- Kwon �KT, Tsai �VW. Metabolic emergencies. Emerg Med Clin N Am. 2007;25:1041-1060.
- Maxime �V, Lesur �O, Annane �D. Adrenal insufficiency in septic shock. Clin Chest Med. 2009;30:17-27.
- Taub �YR, Wolford �RW. Adrenal insufficiency and other adrenal oncologic emergencies. Emerg Med Clin N Am. 2009;27:271-282.
- Tuuri �R, Zimmerman �D. Adrenal insufficiency in the pediatric emergency department. Clin Pediatr Emerg Med. 2009;10:260-271.
- Williams �RH, Melmed, �S, eds. Williams Textbook of Endocrinology 12th ed. Philadelphia, PA: Elsevier/Saunders, 2011.
See Also (Topic, Algorithm, Electronic Media Element)
Cushing Syndrome �
Codes
ICD9
- 255.41 Glucocorticoid deficiency
- 255.5 Other adrenal hypofunction
ICD10
- E27.1 Primary adrenocortical insufficiency
- E27.2 Addisonian crisis
- E27.40 Unspecified adrenocortical insufficiency
SNOMED
- 386584007 adrenal cortical hypofunction (disorder)
- 373662000 Primary adrenocortical insufficiency (disorder)
- 363732003 Addisons disease (disorder)