Scaffophysiology: Adrenal Crisis
Scaffophysiology is a series of brief disease overviews intended to provide resident physicians guidance on initial management and disposition of patients in the Emergency Department.
Adrenal crisis is a medical emergency that the ED provider must be prepared to handle quickly and efficiently.
What is it?
Adrenal crisis, also known as acute adrenal insufficiency, occurs when there is an acute deprivation of cortisol and aldosterone, two hormones secreted by the adrenal glands. To understand the effects of this, let’s recall that cortisol is known as a “stress hormone.” It’s important to clarify that we are talking about physiologic stress, such as surgery, sickness, or childbirth. In these situations, cortisol performs several vital tasks:
1. Stimulates gluconeogenesis
2. Downregulates the immune system to prevent overreaction
3. Regulates blood pressure
Dysfunction of cortisol secretion, whether the fault of the adrenal gland itself or central signaling from the pituitary gland, leads to a critical medical condition that requires prompt treatment with intravenous steroids.
(Rushworth et al., 2019)
Who is at risk?
Patients at risk for adrenal crisis include those with preexisting hypoadrenalism. Peripheral causes of hypoadrenalism include the following:
Addison’s disease – A primary hypoadrenalism manifesting on physical exam as a thin patient with hyperpigmentation of joints and skin folds (however, keep in mind that these findings may not always be present!)
Side note: People with these diseases will often be well aware of what an adrenal crisis is for them, and they (or family members) can help point you in the right direction. Never discount their suspicion of an adrenal crisis, and choose to treat early! Often they will have an endocrinology plan note in the chart.
Waterhouse-Fredreichsen syndrome – Hemorrhage into the adrenal glands caused by N. meningitidis meningococcemia
Recall that meningococcemia typically presents with a purpuric rash, nuchal rigidity, and central nervous system findings such as AMS.
Rare but disastrous complication on a patient already with a critical illness.
Sudden withdrawal of exogenous corticosteroids – If a patient is on long-term steroid therapy, be on the lookout for adrenal crisis!
If on long term steroids, always discuss with admitting team about stress dose steroids
Pituitary apoplexy – If a blood vessel ruptures into a previously untreated pituitary adenoma, the result is sudden necrosis and central hypoadrenalism.
Sheehan syndrome – Pituitary necrosis occurring in the postpartum period
Bilateral adrenalectomy for adrenal cancer or hyperadrenalism
ETOMIDATE – A rare side effect of this common peri-intubation anesthetic; adrenal crisis results from etomidate’s ability to briefly and distinctly suppress cortisol levels. For this reason, some literature advocates for the use of ketamine in septic patients (see Suggested Reading).
Editors commentary: While ketamine is a completely reasonable choice in many septic patients, don’t be too scared and throw etomidate out the window. Single dose of etomidate is unlikely to cause adrenal suppression of any significant duration or consequence. But if you’ve ever wondered why we use Etomidate for RSI but never have seen an Etomidate drip for long term sedation, now you know.
What are the symptoms?
Symptoms of adrenal crisis are nonspecific. The clinician must have a high index of suspicion; otherwise symptoms can be misinterpreted as simple dehydration, electrolyte derangement, or other common ED pathology. Symptoms include weakness, abdominal pain, nausea, vomiting, diarrhea, confusion, altered mental status, and dehydration. Watch out for meningeal signs (i.e. nuchal rigidity, positive Kernig and Brudzinski signs) and the purpuric rash of meningococcemia.
(Image credit: Mehndiratta, Nayak, Garg, Kumar, & Pandey, 2012)
A. To elicit Kernig’s sign on a supine patient, first flex the hip to 90° and extend the knee. Restriction and pain is noted beyond an angle of 135° drawn between the femur and the tibia.
B. To elicit Brudzinski Contralateral Leg Sign in the supine patient, passively flex one leg. The test is positive if the other leg passively flexes in response.
C. To elicit the Brudzinski Neck Sign, passively flex the neck in the supine position. The test is positive if the hips and knees flex in response.
What labs and imaging should I get?
Laboratory evaluation for suspected adrenal crisis should include:
1. CBC – Evaluate for leukocytosis which may point toward an infectious etiology
2. CMP – Look for LOW sodium and HIGH potassium, as well as prerenal azotemia (BUN/Cr ratio >20)
3. Blood cultures – To evaluate for infectious etiology
4. Serum cortisol – Low cortisol is diagnostic of adrenal crisis. Draw this, but do NOT wait for this to result before treating with steroids!
a. Editor’s commentary: Be careful though, as a single random cortisol level may not be the most useful (unless nonexistent) as it fluctuates through circadian cycles. In the ED, this will almost always be a clinical, not laboratory, decision.
Imaging for suspected adrenal crisis can include:
1. CT of the abdomen/pelvis with IV contrast – Evaluate the adrenal glands for hemorrhage or necrosis. Check with your department to see if an adrenal protocol may be helpful.
2. Chest x-ray – Evaluate for malignancy or infection which may have precipitated an adrenal crisis
What interventions should I perform?
As you are getting your results back, you should already be starting your immediate intervention and preparing this patient for admission to the intensive care unit.
1. Administer parenteral steroid
a. First-line: IV hydrocortisone
i. Dose: 100mg bolus followed by 25-75mg every 6 hours (or 200mg in 24h continuous IV infusion)
Editor's commentary: Pediatric dosing can be quite complicated: different guidelines exist for weight directed, age directed, but many prefer body surface area dosing. Talk with your neighborhood pediatric intensivists/endocrinologists to get their input.
ii. May gradually taper dose after the first 24 hours
b. Second-line: IV dexamethasone
i. Dose: 4mg every 12 hours
ii. Pediatric: 0.15 mg/kg
iii. Transition to hydrocortisone as soon as possible, as dexamethasone glucocorticoid effects will cause immune suppression and hydrocortisone is far preferred.
2. Administer IV fluids
a. Dose: 1 to 3 liters of 0.9% saline solution over the first 24 hours
i. Pediatric: 10-20 mL/kg bolus and reassess
b. May also use D5 (5% dextrose) in 0.9% saline for hypoglycemia
3. If infection is suspected: Administer empiric antibiotics, as we will be targeting N. meningitidis
a. First-line in adults: IV 2g Ceftriaxone every 12h for 7-21 days
b. Second-line: IV Ampicillin and Gentamicin
i. Dose of ampicillin (adult): 2g every 4 hours for 7-21 days in adults; for kids, 300 to 400 mg/kg/day divided every 4 to 6 hours (maximum daily dose: 12 g/day)
ii. Dose of gentamicin: 5mg/kg/day in 1-3 divided doses for 7-21 days
4. Consider Pressor use after appropriate fluid resuscitation for support of hemodynamics until endogenous stress response can take over.
What is the disposition for this patient?
If your suspicion remains high for adrenal crisis, then at this point you should be calling your intensive care unit for admission. Patients with this condition will require the frequent nursing evaluations and lab draws that only the ICU can offer.
What happens next?
When the patient is admitted, they may undergo an ACTH stimulation test to evaluate for the exact cause of the adrenal crisis. If ACTH administration results in an increase in cortisol, then the cause is central (i.e. pituitary gland dysfunction). However, if ACTH administration does not increase cortisol levels, then the problem lies with the adrenal gland itself. Regardless, this is not a test that you will be performing in the emergency department, and patients with a new diagnosis of adrenal insufficiency would benefit from endocrinologist involvement to start long-term oral steroids such as oral cortisone and oral fludrocortisone if indicated. After the patient is admitted and stabilized on oral medication, they may ultimately be discharged with close outpatient follow-up. These patients may, when sick or undergoing an invasive procedure, be instructed to take a double dose of their steroid while also seeking medical attention.
Post peer-reviewed by: Shyam Murali, MD and Alex Dzurik, MD FACEP FAAEM
Faculty Editor’s Commentary: Adrenal crisis is a challenging diagnosis to make in the emergency department. Our focus will usually be on the hemodynamic ABCs that are always our priority in acute resuscitation. Often primary diagnosis (unless has a congenital malformation that would suggest adrenal dysfunction) of adrenal crisis is delayed until several days in the hospital stay when the patient isn’t responding well to usual therapies. Historically, there was a flippant expression of “no one dies in the ED without steroids,” as hydrocortisone was hoped to be the magical cure-all for all conditions including sepsis, neurogenic trauma, and basically any shock state. Current medical evidence has backed off from this position as routine cases of these do not benefit and may have worse outcomes. However, it is worthwhile to keep in the back of your head when you are reaching for a second pressor to think “could my patient have adrenal crisis?” and discuss this with the admitting service.
But the cases where patients have known history of adrenal suppression, pituitary dysfunction, etc. this should be in the forefront of your mind. Involve your consultants in critical care and endocrinology as these are complex patients that will require longer term management and good continuity of care to ensure good outcomes once they leave your department. It’s a sneaky diagnosis, and best tackled with help.
Bolin, P., MD (Director). Acute Adrenal Insufficiency - CRASH! Medical Review Series [Video file]. 21 Nov, 2015. Retrieved October 1, 2020, from https://www.youtube.com/watch?v=FeH0SgGdCUw
Majesko, Alyssa, and Joseph M Darby. “Etomidate and adrenal insufficiency: the controversy continues.” Critical care (London, England) vol. 14,6 (2010): 338. doi:10.1186/cc9338
Mehndiratta, Manmohan et al. “Appraisal of Kernig's and Brudzinski's sign in meningitis.” Annals of Indian Academy of Neurology vol. 15,4 (2012): 287-8. doi:10.4103/0972-2327.104337
Nieman, L. “Treatment of Adrenal Insufficiency in Adults.” UpToDate, 1 Aug. 2020, www.uptodate.com/contents/treatment-of-adrenal-insufficiency-in-adults.
Rushworth, R. Louise. “Adrenal Crisis: NEJM.” New England Journal of Medicine, 28 Nov. 2019, www.nejm.org/doi/full/10.1056/NEJMra1807486.
Thompson Bastin, Melissa L et al. “Effects of etomidate on adrenal suppression: a review of intubated septic patients.” Hospital pharmacy vol. 49,2 (2014): 177-83. doi:10.1310/hpj4902-177