What are the typical symptoms and signs of adrenal insufficiency in an adult patient?

Symptoms of Adrenal Insufficiency

Adrenal insufficiency presents with a constellation of nonspecific symptoms dominated by profound fatigue (50-95% of cases), unintentional weight loss (43-73%), gastrointestinal complaints including nausea and vomiting (20-62%), and postural hypotension, with primary adrenal insufficiency additionally characterized by skin hyperpigmentation and salt craving due to markedly elevated ACTH levels. 1, 2

Core Constitutional Symptoms

• Profound fatigue and weakness are the most common presenting symptoms, occurring in 50-95% of patients, often described as lethargy with loss of "get up and go" and decreased mental concentration 3, 1, 2
• Unintentional weight loss occurs in 43-73% of cases, typically accompanied by poor appetite and anorexia 1, 4, 2
• Muscle pain or cramps are frequently reported, often accompanied by generalized weakness 5, 1

Gastrointestinal Manifestations

• Nausea and vomiting occur in 20-62% of patients, with morning nausea being particularly common and often representing glucocorticoid under-replacement 3, 5, 2
• Poor appetite and anorexia are characteristic features that contribute to weight loss 3, 1
• Abdominal pain may occur, sometimes with peritoneal irritation mimicking an acute abdomen 5

Cardiovascular Signs

• Postural hypotension and orthostatic symptoms reflect insufficient mineralocorticoid activity in primary adrenal insufficiency, manifesting as lightheadedness upon standing 3, 5, 1
• Hypotension can progress to shock and cardiovascular collapse in acute adrenal crisis 5, 6

Distinguishing Features of Primary vs. Secondary Adrenal Insufficiency

Primary Adrenal Insufficiency (Addison's Disease) Specific Features:

• Hyperpigmentation of skin creases, scars, and mucous membranes is pathognomonic for primary adrenal insufficiency, caused by markedly elevated ACTH levels 5, 1, 4
• Salt craving is specific to primary adrenal insufficiency due to aldosterone deficiency 5, 1
• Hyperkalemia occurs in approximately 50% of cases (though its absence does not exclude the diagnosis) 3, 5

Secondary Adrenal Insufficiency Features:

• Normal skin coloration (absence of hyperpigmentation) due to low ACTH production 5
• No salt craving because the renin-angiotensin-aldosterone system remains intact 5
• No hyperkalemia as mineralocorticoid function is preserved 5

Laboratory Abnormalities That May Present as Symptoms

• Hyponatremia is present in 90% of newly diagnosed cases and can cause confusion, altered mental status, or seizures 3, 5, 7
• Hypoglycemia may occur, particularly in children, causing weakness, confusion, or altered consciousness 5

Acute Adrenal Crisis Presentation

Critical pitfall: Never delay treatment of suspected acute adrenal crisis for diagnostic procedures—mortality is high if untreated. 5, 6

• Severe weakness and altered mental status, including confusion, loss of consciousness, or coma 5
• Hypotension and shock with dehydration are hallmark features requiring immediate intervention 5, 6
• Severe vomiting and/or diarrhea often precipitate and accompany acute crisis 5
• Unexplained collapse with cardiovascular instability should immediately raise suspicion 5, 7
• Fever and decreasing mental status in the setting of intercurrent illness 6

Important Clinical Caveats

• The presentation is often nonspecific and diagnosis is frequently delayed, requiring high clinical suspicion in at-risk populations 1, 4, 6
• Hyperkalemia is present in only ~50% of primary adrenal insufficiency cases, so its absence cannot rule out the diagnosis 3, 5
• Mild hypercalcemia may occasionally occur, though the mechanism is unclear 5
• Increased creatinine from prerenal renal failure is a common laboratory finding 5

High-Risk Scenarios Requiring Immediate Consideration

• 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 5
• Vasopressor-resistant hypotension in critically ill patients, particularly those with cirrhosis, warrants screening or empiric hydrocortisone therapy 5
• Patients with autoimmune diseases (hypothyroidism, diabetes) have increased risk and should prompt earlier consideration 6