Addisonian Crises Under the Radar: Misdiagnosis in Modern Medicine

Addisonian crisis, also known as acute adrenal insufficiency or adrenal crisis, is a life-threatening medical emergency caused by an acute drop in cortisol levels in the body.

Though the condition is well-described in endocrine literature, it remains frequently misdiagnosed or underdiagnosed in clinical practice. This is especially true in emergency settings, where its symptoms mimic several other acute illnesses. The lack of specific biomarkers that rapidly confirm the diagnosis and the variability in clinical presentation contribute significantly to the high rate of misdiagnosis.

What Is an Addisonian Crisis?

An Addisonian crisis occurs when the adrenal glands fail to produce adequate amounts of cortisol — a hormone essential for stress response, blood pressure regulation, glucose metabolism, and fluid balance. In primary adrenal insufficiency (Addison’s disease), the adrenal cortex is damaged, usually due to autoimmune destruction. In secondary adrenal insufficiency, the issue lies in the pituitary gland's inability to secrete ACTH, the hormone that stimulates cortisol production.

Crisis can be precipitated by a number of stressors in individuals with known or unknown adrenal insufficiency. These include infections, surgery, trauma, severe emotional stress, or even abrupt discontinuation of corticosteroids.

Why Is Addisonian Crisis Frequently Misdiagnosed?

Addisonian crisis is sometimes referred to as the "great mimicker." The condition shares features with several other acute illnesses such as sepsis, acute gastroenteritis, myocardial infarction, or even psychiatric conditions. Emergency departments often see patients presenting with nonspecific symptoms such as vomiting, diarrhea, abdominal pain, weakness, or confusion — all of which can be easily attributed to more common diagnoses. Unless adrenal insufficiency is already known or suspected, clinicians may not consider adrenal crisis high on the differential diagnosis list.

Another major diagnostic obstacle is the overlap of symptoms with conditions like acute abdomen or hypovolemic shock, leading to misdiagnoses such as appendicitis or gastrointestinal bleeding. Furthermore, patients with chronic adrenal insufficiency may not always communicate their history effectively, particularly during altered mental states or in high-stress situations.

Clinical Presentation

The symptoms of Addisonian crisis typically include a combination of the following:

Severe hypotension (low blood pressure), often unresponsive to fluid resuscitation
Hypovolemic shock
Severe vomiting and diarrhea
hypotension
Muscle weakness or profound fatigue
Confusion, disorientation, or loss of consciousness
Hypoglycemia, particularly in children
Electrolyte imbalances such as hyponatremia (low sodium) and hyperkalemia (high potassium)
Fever or chills
Skin pallor or cyanosis
Tachycardia (rapid heart rate)

These symptoms can develop rapidly, and in many cases, patients deteriorate quickly. Without timely treatment, Addisonian crisis can lead to coma and death.

Essential Blood Tests for Diagnosing an Addisonian Crisis

When an Addisonian crisis is suspected, the following blood tests are critical for diagnosis, assessing severity, and guiding treatment:

Serum Cortisol
- Measures cortisol level; typically low during crisis
- Should ideally be drawn before administering steroids, if possible
Adrenocorticotropic Hormone (ACTH)
- High in primary adrenal insufficiency (Addison’s disease)
- Low or normal in secondary adrenal insufficiency
Electrolytes Panel
- Sodium (Na⁺): often low (hyponatremia)
- Potassium (K⁺): often high (hyperkalemia)
- Chloride (Cl⁻): may be low
- Bicarbonate (HCO₃⁻): may be low (metabolic acidosis)
Blood Glucose
- Often low (hypoglycemia), especially in children
Blood Urea Nitrogen (BUN) and Creatinine
- Often elevated due to dehydration and decreased kidney perfusion
Complete Blood Count (CBC)
- May show:
  - Elevated white blood cells (from stress or infection)
  - Eosinophilia (common in Addison’s disease)
  - Anemia
Plasma Renin Activity and Aldosterone (optional in acute setting)
- High renin and low aldosterone suggest primary adrenal insufficiency
Arterial Blood Gas (ABG) or Venous Blood Gas
- To assess for metabolic acidosis
Thyroid Function Tests (optional)
- To rule out coexisting autoimmune endocrine conditions (e.g., Hashimoto’s)
Infection Markers (if infection suspected)
- C-reactive protein (CRP)
- Blood cultures
- Urinalysis / Chest X-ray / Other cultures as indicated

Note: While many of these tests help confirm the diagnosis, treatment should never be delayed in critically ill patients awaiting results. Cortisol and ACTH should be drawn before hydrocortisone administration if feasible, but treatment should not be withheld for testing.

Laboratory Findings

Laboratory investigations in suspected Addisonian crisis usually reveal the following abnormalities:

Low serum cortisol levels
Elevated ACTH levels (in primary adrenal insufficiency)
Low serum sodium (hyponatremia)
High serum potassium (hyperkalemia)
Hypoglycemia (low blood glucose)
Elevated blood urea nitrogen (BUN) and creatinine due to dehydration
Metabolic acidosis

Importantly, cortisol levels must be interpreted in context, especially during acute illness, when normal stress response should raise cortisol significantly. A low or even inappropriately normal cortisol level during severe illness may indicate adrenal insufficiency.

Treatment for an Addisonian Crisis (Acute Adrenal Crisis)

Immediate hospitalization is required. Standard emergency treatment includes:

Intravenous hydrocortisone – to rapidly replace missing cortisol
Intravenous fluids (saline and dextrose) – to correct dehydration and maintain blood pressure
Glucose supplementation – to treat or prevent hypoglycemia
Fludrocortisone – to replace aldosterone if needed (especially in primary adrenal insufficiency)
Treatment of the underlying cause – such as antibiotics for infection or surgery for trauma

Early recognition and fast intervention are critical to prevent shock, organ failure, or death.

Triggers and Risk Factors

Known triggers for Addisonian crisis include:

Infections (especially gastrointestinal or systemic infections)
Physical trauma or surgery
Emotional stress
Sudden withdrawal of long-term corticosteroid therapy
Inadequate steroid coverage during stress in patients with known adrenal insufficiency
Poor medication adherence
Gastrointestinal illnesses that impair oral steroid absorption

Many crises occur in patients with previously undiagnosed adrenal insufficiency, making initial presentation even more dangerous.

The Consequences of Misdiagnosis

Failure to promptly recognize and treat Addisonian crisis can be fatal. The mortality rate associated with untreated crisis is high, primarily due to shock, severe electrolyte imbalance, and hypoglycemia. Delayed treatment leads to prolonged hospital stays, ICU admissions, and long-term complications. In some reported cases, patients undergo unnecessary surgeries or treatments due to incorrect diagnoses (e.g., appendectomy for abdominal pain during adrenal crisis).

The consequences are not only medical but also psychological. Many patients who experience multiple misdiagnoses lose trust in healthcare providers and may avoid seeking medical help in the future. Misdiagnosis also burdens emergency healthcare systems by leading to repeat visits, diagnostic imaging, and unnecessary interventions.

Emergency Treatment Protocol

The treatment of Addisonian crisis is urgent and should begin as soon as the condition is suspected, even before confirmatory test results are available. Standard treatment includes:

Immediate intravenous (IV) administration of hydrocortisone, typically 100 mg as a bolus followed by continuous infusion or repeated boluses
Rapid IV infusion of isotonic saline (0.9% sodium chloride) to correct hypotension and dehydration
IV dextrose-containing fluids to manage hypoglycemia
Correction of electrolyte imbalances
Identification and treatment of underlying precipitating causes (e.g., antibiotics for infections)

Time is critical. Delaying treatment until diagnostic confirmation can cost lives.

Prevention and Awareness

Given that adrenal crisis can be prevented with appropriate management, prevention strategies are critical. Patients with known adrenal insufficiency should be:

Educated about stress-dose steroid protocols
Advised to carry a medical alert bracelet or card
Equipped with emergency injectable hydrocortisone (e.g., Solu-Cortef) for use in crisis situations
Monitored closely during illness or surgery with temporary increase in steroid dosing as per medical guidance

Healthcare providers across specialties — not just endocrinologists — should be trained to recognize the signs and symptoms of adrenal crisis, particularly in emergency medicine, critical care, and general practice settings.

Scientific Evidence

Several peer-reviewed sources underscore the challenges of diagnosing Addisonian crisis and its life-threatening nature:

NIH/NIDDK: Highlights common symptoms and emergency management protocols
https://www.niddk.nih.gov/health-information/endocrine-diseases/addisons-disease

Endocrine Society Clinical Guidelines (2016): Provide evidence-based recommendations on adrenal insufficiency and crisis management
https://academic.oup.com/jcem/article/100/11/E1484/283605

Disclaimer: By accessing and reading this blog, you acknowledge that the information provided is for general informational purposes only and does not constitute medical advice, diagnosis, or treatment. The content is intended to address commonly asked questions and is derived from reputable scientific literature. Always consult a qualified healthcare professional for medical concerns or conditions.

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