What are the symptoms of adrenal insufficiency?

Symptoms of Adrenal Insufficiency

Core Clinical Manifestations

Adrenal insufficiency presents with a constellation of nonspecific symptoms that include profound fatigue (50-95% of cases), unintentional weight loss (43-73%), anorexia (43-73%), nausea and vomiting (20-62%), and postural hypotension due to volume depletion. 1, 2

Constitutional Symptoms

• Profound fatigue is the most common symptom, occurring in 50-95% of patients 1, 2
• Unintentional weight loss and anorexia occur in 43-73% of cases 1, 2
• Muscle pain and abdominal pain are frequently reported 1

Cardiovascular Symptoms

• Hypotension and postural hypotension result from volume depletion due to aldosterone loss in primary adrenal insufficiency 3, 4
• Unexplained collapse or syncope should immediately raise suspicion for adrenal crisis 3, 4

Gastrointestinal Symptoms

• Nausea and vomiting occur in 20-62% of patients 3, 2
• Diarrhea is a recognized gastrointestinal manifestation 3, 4
• Severe abdominal pain may indicate impending or established adrenal crisis 3

Distinguishing Features of Primary Adrenal Insufficiency

• Skin hyperpigmentation is a distinguishing feature caused by elevated ACTH levels and occurs specifically in primary adrenal insufficiency 4, 1
• Salt craving is characteristic of primary adrenal insufficiency due to aldosterone deficiency 1

Laboratory Abnormalities

Electrolyte Disturbances

• Hyponatremia is present in 90% of newly presenting cases, though often only marginally reduced 3, 4
• Hyperkalemia occurs in approximately 50% of patients at diagnosis due to aldosterone deficiency 3, 4
• Important caveat: The classic combination of hyponatremia and hyperkalemia is not always present; in the presence of severe vomiting, hypokalemia and alkalosis may paradoxically occur instead 4

Metabolic Abnormalities

• Hypoglycemia is more common in children but can occur in adults, with hypoglycemic seizures possible 4, 5
• Acidosis is a recognized metabolic abnormality 3, 4
• Mild to moderate hypercalcemia occurs in 10-20% of patients at presentation 3, 4

Hematologic and Hepatic Findings

• Anemia, mild eosinophilia, and lymphocytosis may be present 3, 4
• Elevated liver transaminases can occur 3, 4

Severity Grading

The Journal of Clinical Oncology classifies adrenal insufficiency symptoms by severity: 6, 3

Grade 1 (Mild)

• Asymptomatic or mild symptoms where patients can perform activities of daily living 6, 3

Grade 2 (Moderate)

• Symptoms that affect daily activities but patients remain able to perform activities of daily living 6, 3

Grade 3-4 (Severe)

• Medically significant or life-threatening consequences with inability to perform activities of daily living 6, 3
• Orthostasis and volume depletion due to loss of aldosterone 6

Adrenal Crisis Presentation

Adrenal crisis is a life-threatening emergency characterized by severe abdominal pain, nausea, vomiting, unexplained collapse, and vasopressor-resistant hypotension that requires immediate treatment without delay for diagnostic procedures. 3, 4, 7

Critical Features

• Severe abdominal pain, nausea, and vomiting are prominent crisis symptoms 3
• Unexplained collapse may be the presenting manifestation 3, 4
• Vasopressor-resistant hypotension requiring high-dose or multiple vasopressor agents 8

Important Clinical Pitfall

Never delay treatment of suspected adrenal crisis for diagnostic testing—mortality is high if untreated. 8, 7 If unstable, give 100 mg IV hydrocortisone immediately along with 0.9% saline infusion at 1 L/hour 8

Key Diagnostic Considerations

When to Suspect Adrenal Insufficiency

• Any patient presenting with unexplained collapse, hypotension, vomiting or diarrhea should be evaluated for adrenal insufficiency 4
• Hyperpigmentation, hyponatremia, hyperkalemia, acidosis, and hypoglycemia increase clinical suspicion 4
• Any patient taking ≥20 mg/day prednisone or equivalent for at least 3 weeks who develops unexplained hypotension should be presumed to have adrenal insufficiency until proven otherwise 8

Common Pitfall to Avoid

Do not rely on electrolyte abnormalities alone to make or exclude the diagnosis—between 10-20% of patients have mild or moderate hypercalcemia at presentation, and some may have normal electrolytes. 4 The absence of hyperkalemia cannot rule out adrenal insufficiency as it occurs in only ~50% of cases. 3, 4