What is the treatment for adrenal fatigue and brain fog?

"Adrenal Fatigue" Is Not a Recognized Medical Diagnosis—Rule Out True Adrenal Insufficiency First

The term "adrenal fatigue" is not recognized by major endocrine societies and lacks validated diagnostic criteria or evidence-based treatment. However, the symptoms you describe—fatigue and brain fog—can indicate genuine adrenal insufficiency, a life-threatening condition that requires immediate evaluation and treatment. 1, 2

Critical First Step: Exclude True Adrenal Insufficiency

Before attributing symptoms to non-specific "adrenal fatigue," you must definitively rule out adrenal insufficiency, which presents with nearly identical symptoms but requires lifelong hormone replacement. 2, 3

Diagnostic Workup

• Obtain early morning (8 AM) serum cortisol and plasma ACTH as the first-line diagnostic tests—this is the standard recommended by the Endocrine Society. 4, 2

• Morning cortisol <250 nmol/L (<9 μg/dL) with elevated ACTH is diagnostic of primary adrenal insufficiency. 4, 5

• Morning cortisol 140-275 nmol/L (5-10 μg/dL) with low or inappropriately normal ACTH suggests secondary adrenal insufficiency. 4, 2

• If morning cortisol is intermediate (5-10 μg/dL), perform a cosyntropin stimulation test: administer 0.25 mg cosyntropin intramuscularly or intravenously, then measure serum cortisol at 30 and 60 minutes—a peak cortisol <500-550 nmol/L (<18-20 μg/dL) is diagnostic of adrenal insufficiency. 4, 2

• Check basic metabolic panel for hyponatremia (present in 90% of cases) and hyperkalemia (present in 50% of primary adrenal insufficiency cases), though normal electrolytes do not exclude the diagnosis. 4, 5

Key Clinical Pitfalls

• Do not rely on electrolyte abnormalities alone—10-20% of patients with adrenal insufficiency have normal electrolytes at presentation. 4

• Exogenous steroids (including prednisone, dexamethasone, and inhaled fluticasone) suppress the HPA axis and confound diagnostic testing—if the patient is on any corticosteroids, testing may be unreliable. 4

• If the patient is clinically unstable with suspected adrenal crisis (hypotension, severe nausea/vomiting, altered mental status), give IV hydrocortisone 100 mg immediately and start 0.9% saline at 1 L/hour—never delay treatment for diagnostic testing. 5, 2

If Adrenal Insufficiency Is Confirmed: Treatment Protocol

Glucocorticoid Replacement

• Hydrocortisone 15-25 mg daily in divided doses (typically 10 mg upon waking, 5 mg at noon, and 5 mg in early afternoon) is the preferred glucocorticoid replacement, as it mimics the natural diurnal cortisol rhythm. 1, 2, 6

• Alternative: Prednisone 3-5 mg daily if hydrocortisone is unavailable, though hydrocortisone is preferred. 4, 2

Mineralocorticoid Replacement (Primary Adrenal Insufficiency Only)

• Fludrocortisone 50-200 μg once daily in the morning is required for primary adrenal insufficiency to replace aldosterone deficiency. 1, 7, 2, 6

• Encourage liberal salt intake and avoid potassium-containing salt substitutes. 7

• Monitor blood pressure (supine and standing), serum sodium, and potassium to assess adequacy of mineralocorticoid replacement—target normal blood pressure without orthostatic hypotension and normal electrolytes. 1, 7

Patient Education to Prevent Adrenal Crisis

• Instruct patients to double or triple their glucocorticoid dose during minor illness (fever, infection, gastrointestinal upset) and to use parenteral hydrocortisone 100 mg IM during severe illness or inability to take oral medications. 5, 2, 6

• Prescribe an emergency hydrocortisone 100 mg IM injection kit and train the patient and family members on self-injection. 4

• All patients must wear a medical alert bracelet or necklace indicating adrenal insufficiency to trigger stress-dose corticosteroids by emergency medical personnel. 4, 2

• Gastrointestinal illness with vomiting/diarrhea is the most common trigger for adrenal crisis—even mild upset stomach can precipitate crisis if oral medications cannot be absorbed. 5

Annual Screening for Associated Autoimmune Conditions

• Monitor thyroid function (TSH, FT4, TPO antibodies) every 12 months, as subclinical thyroid disease can contribute to fatigue. 1

• Screen annually for diabetes (plasma glucose, HbA1c), anemia (complete blood count), and vitamin B12 deficiency due to autoimmune gastritis. 1

• In patients with frequent diarrhea, test for celiac disease (tissue transglutaminase antibodies and total IgA). 1

If Adrenal Insufficiency Is Ruled Out: Address "Brain Fog" and Fatigue

Once true adrenal insufficiency is definitively excluded, the symptoms of fatigue and brain fog require a different approach, as "adrenal fatigue" has no validated treatment. 8

Evidence-Based Management of Fatigue and Cognitive Symptoms

• Psychoeducational interventions and cognitive behavioral therapy (CBT) have demonstrated measurable reduction in fatigue with small to moderate effects—CBT addresses dysfunctional thoughts, sleep dysregulation, and activity dysregulation. 1

• Mindfulness-based stress reduction (MBSR) combines meditation, psychoeducational elements, and movement exercises to improve well-being and reduce fatigue. 1

• Energy preservation strategies: counsel patients on task prioritization, activity pacing, and delegation of less important activities—information and counseling should include partners or family members. 1

• Self-management support through patient organizations, online support groups, and symptom diaries can help patients monitor patterns and identify fatigue-promoting activities. 1

• Multidisciplinary rehabilitation teams should address physical, psychological, and psychiatric aspects, with management of fatigue as a key component—this approach is supported by evidence from post-COVID-19 syndrome management. 1

Important Caveats

• Do not prescribe glucocorticoids for "adrenal fatigue" in the absence of confirmed adrenal insufficiency—supraphysiological glucocorticoid use causes iatrogenic secondary adrenal insufficiency and significant morbidity. 4, 2

• Screen for other treatable causes of fatigue: thyroid dysfunction, anemia, vitamin B12 deficiency, celiac disease, diabetes, and depression. 1

• If symptoms persist despite negative workup, consider referral to an integrated multidisciplinary assessment service for comprehensive evaluation. 1