When Your Body Doesn’t Follow the Script: Atypical Adrenal Crisis and its Treatment

By Erica "Jo" Fuller

Case Presentation

60 yo female with PMH of adrenal insufficiency on daily hydrocortisone, Crohn's disease s/p small bowel resection, HFpEF, and OUD on buprenorphine presents to ED with abdominal pain and vision changes that began this morning. Patient reports subjective fever, flushing of the face, dizziness, headaches, dry mouth, nausea, weight loss of 25 pounds over the last 9 months. Denies vomiting, hematuria, or dysuria.

Physical exam

Mouth – dry mucous membranes

Abdominal - Soft, mild right sided tenderness to palpation with right CVA tenderness

Neurological - Intermittently somnolent on examination, although arousable to voice

Skin - Flushed face/malar pattern

Extremities – 3+ pretibial edema BL HEENT, Cardio, Pulmonary, MSK exams unremarkable

ED Course

CBC/CMP WNL except sodium of 132
VBG/ UA unremarkable
EKG: Sinus bradycardia without any signs of ischemia
Imaging
- CT Abdomen/Pelvis: stable biliary and pancreatic ductal dilatation (noted on previous CT scan 1 month prior, with scheduled ERCP follow-up)
- CT Chest: Bronchiolitis
- CT Head/Brain: no acute intracranial abnormality
Assessment: Working diagnosis is adrenal crisis, however an atypical presentation due to lack of fever, no CBC or electrolyte abnormalities other than mild hyponatremia, hypotension which is baseline when comparing BPs taken over the last year.
Management: IV fluids and trial of hydrocortisone 50mg for potential atypical presentation of adrenal crisis, patient showed improvement and was admitted to medicine.

Image source: Johns Hopkins Medicine

Clinical question: When do you initiate hydrocortisone in atypical presentations of adrenal crisis? What sequelae should be addressed during adrenal crisis in the ED?

Summary of Evidence

Adrenal crisis is a life-threatening condition impacting about 5-10% of individuals with adrenal insufficiency each year, marked by the adrenal cortex's failure to produce adequate cortisol. (1) Patients with prolonged steroid use, particularly those with Addison's disease, face a higher risk due to suppression of the hypothalamic-pituitary-adrenal (HPA) axis. Chronic use of exogenous glucocorticoids suppresses natural cortisol production, making it difficult for these patients to generate sufficient cortisol during physiological stress, such as infection, surgery, or trauma. Superimposed gastrointestinal issues like vomiting or diarrhea can hinder the absorption of oral glucocorticoids, further elevating the risk of adrenal crisis. (2,3,4) Moreover, CYP450 inducers like rifampin, phenytoin, and phenobarbital can accelerate the metabolism of corticosteroids, which may result in adrenal insufficiency if the doses of hydrocortisone or fludrocortisone are not properly adjusted. (5)

The current treatment guidelines from the European Society of Endocrinology and the Endocrine Society reference a 2020 study by Prete et al., which evaluated serum cortisol responses under various stress conditions. The study recommends an initial bolus of 50-100 mg of hydrocortisone, followed by a continuous IV infusion of 200 mg over 24 hours, to maintain optimal cortisol levels. This research design involved three models: a cross-sectional study of healthy participants exposed to stressors (like trauma, sepsis, and combat), a longitudinal study on patients undergoing elective surgery, and a pharmacokinetic study with 10 individuals with primary adrenal insufficiency. However, the diversity of stressors across these models makes standardizing the ideal hydrocortisone dose challenging. Furthermore, the small sample size in the pharmacokinetic model limits the generalizability of these findings for adrenal insufficiency patients. (7)

Adrenal crisis presents with hypotension or hypovolemic shock and nonspecific symptoms such as nausea, vomiting, abdominal pain, fatigue, fever, and altered consciousness. Laboratory abnormalities often include hyponatremia, hyperkalemia, hypoglycemia, lymphocytosis, and eosinophilia. (2) However, several atypical cases have been documented with varying symptoms and laboratory results. For instance, a case report described a young man with severe hyponatremia, hypotension, and somnolence initially misdiagnosed as atypical anorexia nervosa. Another case involved an adolescent male presenting with shock and hyperpigmentation, initially suggestive of septic shock. (8, 9) Because of potentially life-threatening complications, a low threshold for treatment in adrenal crisis should be considered. Adrenal crisis can be suspected in any patient with shock plus at least one of the nonspecific symptoms above, especially in those with a history of adrenal insufficiency or recent glucocorticoid use. (1,2) Screening for adrenal insufficiency is crucial, as delayed diagnosis contributes to up to 50% of cases. (6)

Adrenal crisis symptoms, such as hypotension, electrolyte imbalances, and hypoglycemia, can progress to more severe complications. Hypotension from severe fluid loss and vasodilation can lead to shock, which is often unresponsive to standard treatments like inotropes or fluids unless parenteral glucocorticoids are given promptly. Electrolyte imbalances, including hyponatremia and hyperkalemia, arise from combined glucocorticoid and mineralocorticoid deficiencies, causing significant metabolic disturbances that may lead to cardiovascular instability. Additionally, cortisol deficiency causes hypoglycemia, which can lead to seizures, coma, or death. Immediate administration of hydrocortisone, aggressive fluid resuscitation, and correction of electrolyte abnormalities and hypoglycemia are important for effective management in the emergency setting before they progress to life-threatening conditions. (10)

In addition to early recognition of adrenal insufficiency symptoms, patient education on adjusting hydrocortisone doses during stress can help prevent adrenal crisis. For minor stressors (e.g., fever, mild illness), they should double their home glucocorticoid dose. In cases of major stress, such as severe illness or surgery, patients are advised to use an intramuscular or intravenous injection of 100 mg hydrocortisone, followed by 50 mg every 6 hours if needed. (1) However, a 2020 study by Arafah questioned current high-dose glucocorticoid protocols, suggesting lower perioperative doses may still maintain adequate cortisol levels. This study administered 20 mg orally before surgery, followed by smaller IV doses over 48 hours. (11) The drawbacks of the study stem from its focus on pharmacokinetics rather than morbidity outcomes limits its applicability to clinical practice. Regardless, an action plan for stress hydrocortisone dosing can save lives. Figure 1 below shows a stress glucocorticoid dose chart for adrenal insufficiency from Miller et al.(12) Patients can have this chart filled out by their doctor and reference it in times of emergency to prevent adrenal crisis progression. Figure 1: Hydrocortisone Stress Dosing Plan for Adrenal Insufficiency (12)

Recommendations

In conclusion, the following recommendations have been found from the exploration stated above for the diagnosis, management, and prevention of adrenal crisis.

Maintain a low threshold for initiating treatment in adrenal crisis. Screen for glucocorticoid or adrenal insufficiency history with hypotension or shock plus at least one nonspecific symptom such as hyponatremia, fever, abdominal pain, and altered mental status.
Symptoms of adrenal crisis to address in the emergency setting: hypotension and shock, volume depletion, electrolyte imbalances, and hypoglycemia. Administer a bolus of 50-100 mg hydrocortisone immediately followed by IV infusion of 200 mg hydrocortisone over 24 hours. Address volume depletion with 1L isotonic saline within the first hour. Monitor and correct electrolyte disturbances (hyponatremia and hyperkalemia) as needed. Give IV dextrose for hypoglycemia.
Provide patient education for stress hydrocortisone dosing.
- For minor stressors such as fever, illness requiring bed rest, or minor outpatient procedures, double routine hydrocortisone.
- For major stressors, such as trauma, or surgery, administer IM/IV injection of 100 mg hydrocortisone, followed by continuous infusion or repeated boluses of 50 mg every 6 hours

References

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