Signs and Symptoms of Adrenal Insufficiency
The diagnosis of primary adrenal insufficiency should be considered in all patients presenting with unexplained collapse, hypotension, vomiting or diarrhea, with hyperpigmentation, hyponatremia, hyperkalemia, acidosis and hypoglycemia increasing clinical suspicion. 1
Cardinal Clinical Manifestations
Most Common Presenting Symptoms
- Fatigue occurs in 50-95% of patients and is often the most prominent complaint 2
- Nausea and vomiting affect 20-62% of patients at presentation 2
- Anorexia and weight loss are present in 43-73% of cases, representing unintentional weight loss 2, 3
- Profound fatigue and muscle weakness are hallmark features that distinguish this from common fatigue 3
Cardiovascular Signs
- Hypotension and postural hypotension result from volume depletion due to aldosterone loss in primary adrenal insufficiency 4, 3
- Unexplained collapse or syncope should immediately raise suspicion for adrenal crisis 1, 5
Dermatologic Findings (Primary Adrenal Insufficiency)
- Hyperpigmentation is a distinguishing feature of primary adrenal insufficiency caused by elevated ACTH levels 1, 3
- Salt craving occurs specifically in primary adrenal insufficiency due to mineralocorticoid deficiency 6, 3
Gastrointestinal Symptoms
- Abdominal pain can be prominent, particularly in adrenal crisis 6, 3
- Diarrhea is a recognized gastrointestinal manifestation 4
- Severe vomiting may indicate impending or established adrenal crisis 1
Laboratory Abnormalities
Electrolyte Disturbances
- Hyponatremia is present in 90% of newly presenting cases, though often only marginally reduced 1
- Hyperkalemia occurs in approximately 50% of patients at diagnosis due to aldosterone deficiency 1
- The classic combination of hyponatremia and hyperkalemia is not always present, making diagnosis challenging 1
Important caveat: In the presence of severe vomiting, hypokalaemia and alkalosis may paradoxically be present instead of the expected hyperkalemia 1
Other Laboratory Findings
- Hypoglycemia is more common in children but can occur in adults, with hypoglycemic seizures possible 1
- Mild to moderate hypercalcemia occurs in 10-20% of patients at presentation 1
- Acidosis is a recognized metabolic abnormality 1
- Anemia, mild eosinophilia, and lymphocytosis may be present 1
- Elevated liver transaminases can occur 1
Severity Grading
Mild Symptoms (Grade 1)
- Asymptomatic or mild symptoms where patients can perform daily activities 4
Moderate Symptoms (Grade 2)
- Symptoms affect daily activities but patients remain able to perform activities of daily living 4
Severe Symptoms (Grade 3-4)
- Medically significant or life-threatening consequences with inability to perform activities of daily living 4
Adrenal Crisis Presentation
Adrenal crisis is a life-threatening emergency that requires immediate treatment and should never be delayed by diagnostic procedures. 1
Crisis Features
- Severe abdominal pain, nausea, and vomiting are prominent crisis symptoms 4
- Unexplained collapse may be the presenting manifestation 4
- Hypotension and shock can develop rapidly 2
- Altered mental status may occur 2
- Death if untreated makes this a true medical emergency 2
Clinical Pitfalls
Non-Specific Presentation
The symptoms of adrenal insufficiency often mimic more prevalent diseases, leading to delayed diagnosis 5. Primary adrenal insufficiency has been called a "master of disguise" because unexplained syncope, vomiting, weight loss, or hypoglycemia may be attributed to other conditions 5.
Diagnostic Delays
Initial signs and symptoms are frequently nonspecific, contributing to late diagnosis and potentially fatal outcomes if unrecognized 6. Physician awareness must be improved to avoid adrenal crisis 3.
Confounding Factors
Exogenous steroid use (oral prednisolone, dexamethasone) and inhaled steroids (fluticasone) may confound interpretation of cortisol levels 1.