What are the signs and symptoms of adrenal insufficiency?

Signs of Adrenal Insufficiency

Adrenal insufficiency should be suspected in any patient presenting with unexplained collapse, hypotension, or gastrointestinal symptoms (vomiting/diarrhea), particularly when accompanied by hyponatremia, as these features represent the most critical diagnostic clues. 1

Cardinal Clinical Manifestations

Cardiovascular Signs

• Hypotension and postural hypotension are hallmark features resulting from volume depletion due to aldosterone loss in primary adrenal insufficiency 1, 2
• Unexplained collapse or syncope should immediately raise suspicion for adrenal crisis 1, 3
• Vasopressor-resistant hypotension requiring multiple agents may indicate underlying adrenal insufficiency 4

Gastrointestinal Symptoms

• Nausea occurs in 20-62% of patients, frequently accompanied by vomiting, poor appetite, and weight loss 4, 5
• Diarrhea is a recognized manifestation 1, 3
• Severe vomiting and abdominal pain are prominent features of adrenal crisis 3
• Anorexia and weight loss occur in 43-73% of patients 5, 2

Constitutional Symptoms

• Fatigue is the most common symptom, occurring in 50-95% of patients 5, 6
• Profound fatigue and reduced work capacity are characteristic 2
• Muscle weakness is frequently reported 6

Dermatologic Signs (Primary Adrenal Insufficiency Only)

• Hyperpigmentation is a distinguishing feature of primary adrenal insufficiency caused by elevated ACTH levels, with uneven distribution 1
• Increased pigmentation may indicate glucocorticoid under-replacement 4
• This sign is absent in secondary adrenal insufficiency where ACTH is low 4

Laboratory Abnormalities

Electrolyte Disturbances

• Hyponatremia is present in 90% of newly diagnosed cases, though often only marginally reduced 4, 1
• Hyperkalemia occurs in approximately 50% of patients at diagnosis due to aldosterone deficiency 1, 3
• The classic combination of hyponatremia and hyperkalemia is not always present—absence of hyperkalemia cannot rule out the diagnosis 4, 1
• In the presence of severe vomiting, hypokalemia and alkalosis may paradoxically occur instead of hyperkalemia 1

Metabolic Abnormalities

• Hypoglycemia is more common in children but can occur in adults, with hypoglycemic seizures possible 1, 7
• Mild to moderate hypercalcemia occurs in 10-20% of patients at presentation 1, 3
• Acidosis is a recognized metabolic abnormality 1, 3

Hematologic and Biochemical Findings

• Anemia, mild eosinophilia, and lymphocytosis may be present 1, 3
• Elevated liver transaminases can occur 1, 3

Severity Grading

Grade 1 (Mild)

• Asymptomatic or mild symptoms where patients can perform daily activities 1, 3

Grade 2 (Moderate)

• Symptoms affect daily activities but patients remain able to perform activities of daily living 1, 3

Grade 3-4 (Severe/Life-Threatening)

• Medically significant or life-threatening consequences with inability to perform activities of daily living 1, 3
• Adrenal crisis is a life-threatening emergency requiring immediate treatment—never delay for diagnostic procedures 1, 8

Critical Pitfalls to Avoid

• Do not rely on electrolyte abnormalities alone to make or exclude the diagnosis—10-20% of patients have mild or moderate hypercalcemia at presentation, and some may have normal electrolytes 4
• Morning nausea and lack of appetite are particularly common in primary adrenal insufficiency and often represent glucocorticoid under-replacement 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 4
• Exogenous steroid use and inhaled steroids (e.g., fluticasone) may confound interpretation of cortisol levels and suppress the HPA axis 4, 1