What are the diagnosis and treatment options for a man experiencing symptoms of adrenal fatigue, such as persistent fatigue, insomnia, and decreased stamina?

"Adrenal Fatigue" Is Not a Real Medical Diagnosis

"Adrenal fatigue" is not recognized by any endocrinology society and has no scientific evidence supporting its existence as a medical condition. 1 However, the symptoms you describe—persistent fatigue, insomnia, and decreased stamina—warrant evaluation for actual adrenal insufficiency, a legitimate and potentially life-threatening condition that requires specific diagnostic testing. 2

Why "Adrenal Fatigue" Is a Myth

• A systematic review of 58 studies examining cortisol profiles in fatigued individuals found no substantiation that "adrenal fatigue" exists as an actual medical condition. 1
• The term has been used by some practitioners to describe alleged chronic stress-related adrenal dysfunction, but this concept is not endorsed by the Endocrine Society, American Association of Clinical Endocrinologists, or any major endocrinology organization. 1
• Studies attempting to link fatigue with cortisol abnormalities show systematically conflicting results, regardless of test methodology used. 1

What You Actually Need to Rule Out: True Adrenal Insufficiency

The symptoms you describe overlap significantly with genuine adrenal insufficiency, which affects up to 279 per 1 million individuals and can be fatal if untreated. 3 True adrenal insufficiency presents with:

• Fatigue (present in 50-95% of patients) 3
• Nausea and vomiting (20-62% of patients) 3
• Weight loss and poor appetite (43-73% of patients) 3
• Insomnia or sleep disturbances 4
• Decreased stamina and generalized weakness 4

Critical Distinction: These Are Real Symptoms Requiring Real Diagnosis

While "adrenal fatigue" doesn't exist, adrenal insufficiency absolutely does and requires specific biochemical confirmation. 2, 5

Diagnostic Algorithm for Your Symptoms

Step 1: Obtain Morning (8 AM) Blood Tests

Draw these labs first thing in the morning (around 8 AM): 2, 3

• Serum cortisol
• Plasma ACTH
• Serum sodium and potassium (hyponatremia present in 90% of cases; hyperkalemia in ~50%) 2
• Serum glucose (hypoglycemia can occur) 2
• DHEAS (dehydroepiandrosterone sulfate) 3

Step 2: Interpret Initial Results

Primary adrenal insufficiency (Addison's disease): 2, 3

• Morning cortisol <250 nmol/L (<9 μg/dL) with elevated ACTH
• Low DHEAS
• Often accompanied by hyponatremia and/or hyperkalemia

Secondary adrenal insufficiency: 3

• Morning cortisol 140-275 nmol/L (5-10 μg/dL) with low or inappropriately normal ACTH
• Low or low-normal DHEAS

Glucocorticoid-induced adrenal insufficiency: 3

• Similar pattern to secondary insufficiency
• History of recent glucocorticoid use (prednisone ≥20 mg daily for ≥3 weeks) 6

Step 3: Confirmatory Testing When Results Are Indeterminate

If morning cortisol is between 250-550 nmol/L (9-20 μg/dL), perform cosyntropin stimulation test: 2, 6

• Administer 0.25 mg cosyntropin (tetracosactide) intramuscularly or intravenously
• Measure serum cortisol at baseline, 30 minutes, and 60 minutes
• Peak cortisol <500 nmol/L (<18 μg/dL) is diagnostic of adrenal insufficiency 2
• Peak cortisol >550 nmol/L (>20 μg/dL) rules out adrenal insufficiency 2, 6

Step 4: Determine Underlying Cause (If Adrenal Insufficiency Confirmed)

For primary adrenal insufficiency: 2

• Measure 21-hydroxylase (anti-adrenal) autoantibodies (positive in ~85% of autoimmune cases)
• If antibodies negative, obtain CT scan of adrenals to evaluate for hemorrhage, tumor, tuberculosis, or infiltrative disease
• In males, check very long-chain fatty acids (VLCFA) to rule out adrenoleukodystrophy

For secondary adrenal insufficiency: 3

• MRI of pituitary to evaluate for tumors, hemorrhage, or infiltrative disease
• Assess other pituitary hormone axes

Treatment If Adrenal Insufficiency Is Confirmed

Maintenance Glucocorticoid Replacement

Hydrocortisone 15-25 mg daily in divided doses: 2, 3

• Typical regimen: 10 mg at 7:00 AM, 5 mg at 12:00 PM, 2.5-5 mg at 4:00 PM
• Alternative regimens: 15+5 mg, 10+10 mg, or 10+5+5 mg
• First dose immediately upon waking; last dose at least 6 hours before bedtime

Alternative: Prednisone 3-5 mg daily (if hydrocortisone not tolerated) 2, 3

Mineralocorticoid Replacement (Primary Adrenal Insufficiency Only)

Fludrocortisone 0.05-0.2 mg daily 2, 3

• Adjust based on blood pressure (orthostatic hypotension indicates under-replacement)
• Monitor for peripheral edema (indicates over-replacement)
• Encourage unrestricted salt intake 2

Critical Patient Education

All patients with confirmed adrenal insufficiency must: 2, 3

• Wear medical alert identification jewelry
• Carry emergency injectable hydrocortisone 100 mg IM kit with self-injection training
• Double or triple oral glucocorticoid dose during minor illness, fever, or physical stress
• Seek immediate medical attention for vomiting, severe illness, or inability to take oral medications

What If Testing Is Normal?

If adrenal function testing is completely normal, consider these alternative diagnoses for your symptoms: 4

Chronic Insomnia Disorder

• Requires dissatisfaction with sleep quality, difficulty initiating/maintaining sleep ≥3 nights per week for ≥3 months
• First-line treatment: Cognitive Behavioral Therapy for Insomnia (CBT-I) 4
• Pharmacological therapy only if CBT-I insufficient after 2-4 weeks 4

Other Medical Conditions to Evaluate

• Thyroid dysfunction (hypothyroidism)
• Anemia
• Sleep apnea (if sleepiness rather than fatigue predominates) 4
• Depression or anxiety disorders
• Chronic fatigue syndrome (diagnosis of exclusion)

Common Pitfalls to Avoid

Never delay treatment if adrenal crisis is suspected. 2, 7 If you present with severe symptoms (hypotension, vomiting, confusion, severe weakness), treatment with IV hydrocortisone 100 mg and IV saline must be given immediately—before diagnostic testing is completed.

Don't rely solely on electrolyte abnormalities. 2 Hyponatremia may be only marginally reduced, and hyperkalemia is absent in ~50% of cases. Normal electrolytes do not rule out adrenal insufficiency.

Avoid testing while on glucocorticoids. 6 Prednisone, dexamethasone, and even inhaled fluticasone suppress the HPA axis and invalidate cortisol testing. If you're currently taking steroids, testing must wait until after appropriate washout period (typically 3 months after discontinuation for secondary insufficiency evaluation).

Recognize that fatigue alone has low specificity. 8 Up to 20% of primary care patients report fatigue, but only a small percentage have underlying medical disease. However, when fatigue is accompanied by weight loss, nausea, hyperpigmentation (in primary insufficiency), or orthostatic hypotension, adrenal insufficiency becomes much more likely. 2, 8