Case of the Week: Vomiting and Diarrhea
Author: Sasha Mozelewski, MD
Reviewed by: Christian Gerhart, MD and Jessica Pelletier, DO
You see a 58 year old woman in your waiting room with nausea, vomiting, and diarrhea. She’s visiting from out of town and staying with family who have similar symptoms. She has a history of hypertension and chronic back, hip, and shoulder pain. Her vital signs (VS) show she is afebrile, saturating well on room air, not tachypneic, heart rate (HR) is 84 bpm and blood pressure (BP) is 110/78 mmHg. In triage, the nurses obtain an EKG, which shows normal sinus rhythm and no signs of ischemia, and a viral panel is negative for influenza, RSV, and COVID-19. Basic labs are in process. You think to yourself, “This sounds like gastroenteritis, but she needs a full evaluation” and move on to the next patient while she waits for a bed.
A couple of hours go by, and on re-examination the patient is slumped over and diaphoretic. A family member follows you into the room and tells you, “She’s in town helping me watch the kids the last couple of weeks. One of them came home sick from school. Now we all have this bug, but she’s taken it the hardest. Maybe it’s because she’s been off her medications since she’s been visiting, I don’t know. We’ve been waiting for hours. We were sitting out there, and she was talking to me and then she just slumped over. I don’t think she passed out, but it was close.” Repeat VS are remarkable for HR 122 bpm and hypotension with a BP of 82/64 mmHg. The patient is still afebrile, is not tachypneic, and is saturating well on room air (RA). Point of care test (POCT) glucose is 52 mg/dL. You suspect that this is secondary to poor oral intake given that the patient has no history of diabetes. You start a liter of crystalloid intravenous (IV) fluid and a bolus of D10 while taking a brief history. The patient tells you that she hasn’t felt well the last 2-3 days and has had two episodes of nonbloody, nonbilious emesis per day with a couple of non-bloody loose stools. The family member in the room (daughter) became concerned when the patient didn’t feel she was well enough to watch the kids on her own today. The patient denies chest pain, shortness of breath, abdominal pain, or urinary symptoms. She takes an antihypertensive and a medicine for her chronic pain and denies previous surgeries or substance use.
On physical examination, the patient is diaphoretic and is awake but lethargic and slow to answer questions. She has clear bilateral breath sounds. Her extremities are warm and well perfused. Heart sounds are notable for tachycardia with no murmurs. She is moving all four extremities. Pupils are equal and reactive. There is no abdominal tenderness to palpation, masses, hepatomegaly, or CVA tenderness to palpation. The rest of her exam is completely unrevealing.
Laboratory workup is remarkable for a leukocytosis of 14,000, mild anemia, hyperkalemia, hyponatremia, and otherwise unremarkable complete blood count (CBC), comprehensive metabolic panel (CMP), lipase, and troponin testing. You are suspicious for a bacterial infectious etiology of symptoms and add additional diagnostic studies including a lactate, portable chest x-ray, urinalysis with reflex to microscopy and culture, and a full viral respiratory panel.
On repeat examination her heart rate has improved to 113 bpm but the patient is still hypotensive to 80/60 mmHg despite receiving IV fluids. Her mental status has mildly improved. You don’t feel great about sending her to the CT scanner with her instability and decide to start her on broad-spectrum antibiotics. A repeat POCT glucose is 54 mg/dL. More IV crystalloid and D10 are ordered, but you begin to question what information you are missing. Is there additional medical history that she cannot recall? Are there antihypertensives on her medication list that she is not recalling? The daughter is looking for a way to access the home medication list. Point-of-care cardiac ultrasound reveals normal ejection fraction. Her inferior vena cava (IVC) is mildly collapsible but the patient is still not responding to fluids and you order norepinephrine.
You pause. There has been no trauma. This seems like distributive shock…but why isn’t she responding to IV fluids and pressors? Despite titrating up the norepinephrine, the mean arterial pressure (MAP) is barely 60. You confirm that the patient has been out of her medications. The daughter is finally able to access the medication list from an outside hospital system. Other than hydrochlorothiazide, the patient’s only medication is prednisone 15 mg daily. Apparently, she has been prescribed this for chronic back pain. At last! A diagnosis!
Adrenal Crisis
Discussion
Adrenal crisis is an acute life-threatening condition resulting from lack of cortisol and sometimes aldosterone due to adrenal gland insufficiency. It often occurs in patients with a chronic suppressive process that is exacerbated by an acute event, leading to persistent hypotension and vasodilatory shock. The technical diagnosis includes hypotension with a systolic pressure <100 mmHg that responds within 1-2 hours of intravenous steroid administration.
We will briefly review the physiology of the hypothalamic-pituitary-adrenal (HPA) axis (Figure 1).
Figure 1. HPA Axis (EmDocs)
Primary adrenal insufficiency occurs when there is a direct primary problem with the adrenal glands such as autoimmune disease (Addison’s) or infection (AIDS, tuberculosis). Secondary adrenal insufficiency occurs when there is an issue with the pituitary gland or signaling from the pituitary gland, such as with sudden discontinuation of prolonged steroid use. Tertiary adrenal insufficiency can result from diseases or injury to the hypothalamus.
The adrenal glands secrete critical hormones such as cortisol, aldosterone, and androgens (not depicted above, less important in the acute setting). Cortisol is a catabolic hormone, so it stimulates the production of glucose in the liver and works synergistically with catecholamines to cause vasoconstriction. Loss of cortisol leads to persistent hypoglycemia and increased capillary permeability with resultant hypotension. Cortisol also plays a crucial role in the suppression of our normal immune system and without it one may have an increase in inflammatory cytokines with fever, fatigue, and weakness. Aldosterone, a key player in the renin-angiotensin-angiotensinogen system (RAAS), works to regulate blood pressure by sodium and water retention with wasting of potassium and hydrogen. Blocking this process leads to hyperkalemia, salt wasting with associated fluid loss (further worsening hypotension), and a non-anion gap metabolic acidosis.
Patients may have an underlying process when an acute event disrupts any compensation or baseline hormone production and leads to crisis. Events include trauma, surgery, pregnancy, burns, strenuous exercise, or even emotional stressors. Additionally, medications that are cytochrome P450 inducers can increase the metabolism of hydrocortisone and therefore lead to insufficiency. The most common cause, however, is immediate cessation or lack of appropriate taper of chronic steroid use.
There are two important things to consider when comparing primary versus secondary adrenal insufficiency:
If patients have secondary adrenal insufficiency, or a problem above the adrenal glands, they may have normal potassium levels and less profound hypotension as the production of aldosterone from the RAAS pathway should be unaffected.
Primary adrenal insufficiency may involve skin darkening as the pituitary gland over produces adrenocorticotropic hormone in an attempt to secrete cortisol and inadvertently produces excessive melanocyte-stimulating hormone.
No particular diagnostic study is required prior to treatment; however, it can be helpful to solidify the diagnosis via laboratory testing. Random cortisol levels can be difficult to interpret in the acute setting though a value less than 5 mcg/dL suggests true adrenal insufficiency. Otherwise, be sure to order diagnostic studies to help identify a potential trigger based on the patient’s presenting history.
The treatment for adrenal crisis is intravenous steroids.
- In patients with a known history of adrenal insufficiency or a history that suggests adrenal suppression (such as chronic steroid use) you can give 100 mg hydrocortisone IV initially, followed by 50 mg every 6 hours. If you only have methylprednisolone available, you can give 40 mg IV daily.
- In patients without a known history of adrenal insufficiency, you can start them on dexamethasone 4 mg IV. Dexamethasone does not interfere with cortisol levels and therefore would allow the inpatient team to complete an accurate workup such as with an ACTH stimulation test. In the acute setting, steroid administration should not be delayed if there is true concern for adrenal crisis. One additional thing to consider with dexamethasone is that it has no mineralocorticoid properties, so it is reasonable to give fludrocortisone 0.2 mg orally to supplement this deficiency.
Figure 2. Corticosteroid Conversion Chart (Rebel EM, Meikle AW et al)
Although patients with adrenal crisis are not always septic, they are very likely volume-depleted and should be resuscitated with crystalloid IV fluids as indicated based on your assessment of their volume status. Have a low threshold for empiric antibiotic therapy, as infection is a known trigger of adrenal crisis. You will need to treat hypoglycemia with an initial bolus of D10 or D50 if the patient is too sleepy to tolerate ingesting oral sources of glucose. Be sure to check glucose every 1-2 hours as additional boluses or even a continuous infusion may be required. Electrolyte abnormalities will likely improve with the above treatments; however, if you see EKG changes with the hyperkalemia such as QRS complex widening, loss of P waves, bradycardia, or dysrhythmias, hyperkalemia should be treated accordingly with IV calcium, beta 2 agonists, insulin with dextrose, and potassium binders.
Case Wrap-Up:
This was a completely fictional case of a patient with polymyalgia rheumatica who developed adrenal crisis after contracting viral gastroenteritis and concomitant sudden discontinuation of her daily steroids. These patients often require admission to the intensive care unit and a multi-day taper of high-dose steroids with further inpatient evaluation to ascertain the underlying cause if not already identified.
Pearls and Pitfalls:
● Always look at the medication list
● Adrenal crisis is a classic sepsis mimic
● Hypotension and hypoglycemia indicate adrenal crisis until proven otherwise
● If you are reaching for your second pressor, stop and consider adrenal crisis
References:
https://www.ebmedicine.net/topics/endocrine/adrenal-disorders
https://emergencymedicinecases.com/em-quick-hits-april-2020/
https://rebelem.com/rebel-review/rebel-review-46-steroid-conversion-chart/steroid-conversion-chart/
Meikle AW, Tyler FH. Potency and duration of action of glucocorticoids. Effects of hydrocortisone, prednisone and dexamethasone on human pituitary-adrenal function. Am J Med. 1977 Aug;63(2):200-7. doi: 10.1016/0002-9343(77)90233-9. PMID: 888843.