What are the main symptoms of adrenal stress in a patient with a history of chronic diseases, such as diabetes, hypertension, or Chronic Obstructive Pulmonary Disease (COPD), and currently taking medications like steroids, including prednisone (corticosteroid) or dexamethasone (corticosteroid)?

Main Symptoms of Adrenal Insufficiency (Adrenal Stress)

Patients with adrenal insufficiency typically present with profound fatigue (50-95% of cases), nausea and vomiting (20-62%), and unintentional weight loss with anorexia (43-73%), along with postural hypotension and muscle weakness. 1, 2

Cardinal Symptoms

Fatigue and Weakness

• Profound, unrelenting fatigue is the most common symptom, occurring in 50-95% of patients with adrenal insufficiency 1
• Severe weakness and reduced work capacity are hallmark features that distinguish this from ordinary tiredness 2
• Muscle pain or cramps frequently accompany the weakness 3

Gastrointestinal Symptoms

• Nausea occurs in 20-62% of patients, often accompanied by vomiting 3, 1
• Poor appetite and anorexia are particularly common, especially in the morning 3
• Unintentional weight loss occurs in 43-73% of cases 1, 2
• Abdominal pain with peritoneal irritation may be present 3
• Severe vomiting and/or diarrhea are common precipitating events for adrenal crisis 3

Cardiovascular Symptoms

• Postural hypotension (orthostatic hypotension) is a key clinical finding, reflecting insufficient mineralocorticoid therapy in primary adrenal insufficiency 4, 2
• Unexplained hypotension that may progress to shock 3
• Hypotension requiring high-dose vasopressors or multiple vasopressor agents that remains refractory to treatment 3

Neuropsychiatric Symptoms

• Altered mental status, confusion, and difficulty concentrating 3
• Loss of consciousness and coma can occur in acute adrenal crisis 3
• Psychiatric symptoms ranging from depression to frank psychotic manifestations may develop 5

Distinguishing Features by Type

Primary Adrenal Insufficiency (Addison's Disease)

• Skin hyperpigmentation with uneven distribution is characteristic, though normal skin color indicates sufficient replacement therapy 4, 3
• Salt craving is a specific clinical clue for primary adrenal insufficiency 3
• Both glucocorticoid and mineralocorticoid deficiency symptoms are present 3

Secondary Adrenal Insufficiency

• Normal skin color due to low ACTH levels (no hyperpigmentation) 3
• Hyponatremia without hyperkalemia, as mineralocorticoid function remains intact 3
• May have additional pituitary hormone deficiencies 3

Glucocorticoid-Induced Adrenal Insufficiency

• Symptoms develop after tapering or discontinuing supraphysiological doses of glucocorticoids 1
• Patients on ≥20 mg/day prednisone or equivalent for at least 3 weeks who develop unexplained symptoms should be presumed to have adrenal insufficiency 3
• Withdrawal symptoms including myalgia, arthralgia, and malaise may overlap with true adrenal insufficiency 5

Critical Warning Signs of Adrenal Crisis

Unexplained collapse, severe hypotension, and gastrointestinal symptoms (vomiting or diarrhea) should immediately raise suspicion for adrenal crisis, which requires emergency treatment without delay. 3

• Severe weakness with confusion or altered mental status 3
• Hypotension and shock with dehydration 3
• Severe vomiting and/or diarrhea 3
• Unexplained collapse 3

Laboratory Findings Associated with Symptoms

• Hyponatremia is present in 90% of newly diagnosed adrenal insufficiency cases 3
• Hyperkalemia occurs in only ~50% of cases, so its absence cannot rule out the diagnosis 4, 3
• Hypoglycemia may occur, particularly in children 3
• Increased creatinine from prerenal renal failure 3
• Mild hypercalcemia sometimes occurs (10-20% of patients) 3, 6

Important Clinical Pitfalls

• The absence of hyperkalemia cannot rule out adrenal insufficiency, as it is present in only about 50% of cases 4, 3
• Do not rely on electrolyte abnormalities alone to make or exclude the diagnosis 3
• Treatment of suspected acute adrenal insufficiency should NEVER be delayed by diagnostic procedures—if clinically unstable, give 100 mg IV hydrocortisone immediately 4, 3
• Symptoms are often non-specific, leading to delayed diagnosis; physician awareness must be improved to avoid adrenal crisis 2

Special Considerations for Patients on Chronic Steroids

• Patients taking prednisone or dexamethasone for chronic conditions (diabetes, hypertension, COPD) are at high risk for glucocorticoid-induced adrenal insufficiency 1, 7
• Any patient taking ≥5 mg prednisone equivalent for ≥3 months is at risk for HPA axis suppression 5
• Symptoms may develop during tapering or after abrupt discontinuation 5, 1
• Exogenous steroids suppress the HPA axis and can confound diagnostic testing 3