Symptoms of Adrenal Insufficiency
Adrenal insufficiency presents with a constellation of nonspecific symptoms dominated by profound fatigue (50-95% of patients), gastrointestinal complaints including nausea and vomiting (20-62%), and unintentional weight loss with anorexia (43-73%), while primary adrenal insufficiency is distinguished by skin hyperpigmentation and salt craving due to elevated ACTH levels. 1, 2, 3
Constitutional Symptoms
- Profound fatigue and weakness are the most common presenting symptoms, occurring in 50-95% of patients, often described as debilitating and progressive 2, 3, 4
- Unintentional weight loss occurs in 43-73% of patients, typically accompanied by poor appetite and anorexia 2, 3
- Easy fatigability that interferes with daily activities is characteristic 4
Gastrointestinal Manifestations
- Nausea and vomiting affect 20-62% of patients and may be particularly prominent in the morning 1, 2
- Diarrhea is a recognized gastrointestinal symptom 1
- Abdominal pain can be severe and is a prominent feature, especially during adrenal crisis 3
- Severe vomiting may indicate impending or established adrenal crisis 1
Cardiovascular Signs
- Hypotension and postural hypotension result from volume depletion due to aldosterone loss in primary adrenal insufficiency 1, 3, 4
- Unexplained collapse or syncope should immediately raise suspicion for adrenal crisis 1
- Orthostasis with volume depletion is characteristic 5
Features Specific to Primary Adrenal Insufficiency
- Hyperpigmentation is a distinguishing feature caused by elevated ACTH levels, affecting skin and mucous membranes 1, 3
- Salt craving occurs due to aldosterone deficiency 3
- The combination of hyperpigmentation with other symptoms strongly suggests primary rather than secondary adrenal insufficiency 1, 3
Laboratory Abnormalities (Often Present Before Diagnosis)
- Hyponatremia is present in 90% of newly presenting cases, though often only marginally reduced 1, 6
- Hyperkalemia occurs in approximately 50% of patients at diagnosis due to aldosterone deficiency 1, 6
- 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
- Anemia, mild eosinophilia, and lymphocytosis may be present 1
Critical Pitfall to Avoid
The absence of hyperkalemia cannot rule out adrenal insufficiency, as it is present in only about 50% of cases—do not rely on electrolyte abnormalities alone to make or exclude the diagnosis. 1, 6 The classic combination of hyponatremia and hyperkalemia is not always present, making diagnosis challenging 1
Adrenal Crisis Presentation (Life-Threatening Emergency)
- Severe abdominal pain, nausea, and vomiting are prominent crisis symptoms 1
- Unexplained collapse may be the presenting manifestation 1
- Hypotension requiring vasopressors that remains refractory to treatment 6
- Altered mental status and decreasing consciousness 4
- Treatment should NEVER be delayed by diagnostic procedures if adrenal crisis is suspected 1, 6
Distinguishing Primary vs. Secondary Adrenal Insufficiency
- Primary adrenal insufficiency: Hyperpigmentation, salt craving, hyponatremia PLUS hyperkalemia (when present) 1, 3
- Secondary adrenal insufficiency: Hyponatremia WITHOUT hyperkalemia, no hyperpigmentation, no salt craving 6
- History of exogenous steroid use or pituitary disorders suggests secondary adrenal insufficiency 2, 3