What is the best course of treatment for a patient with adrenal insufficiency presenting with low cortisol levels and weight gain?

Treatment of Adrenal Insufficiency with Low Cortisol and Weight Gain

Initiate glucocorticoid replacement therapy immediately with hydrocortisone 15-25 mg daily in divided doses (typically 10 mg at 7 AM, 5 mg at noon, and 2.5-5 mg at 4 PM), and add fludrocortisone 0.05-0.1 mg daily if primary adrenal insufficiency is confirmed. 1, 2

Diagnostic Confirmation First

Before initiating treatment in stable patients, confirm the diagnosis:

• Measure morning (8 AM) serum cortisol and ACTH levels to distinguish primary from secondary adrenal insufficiency 1, 3
• Primary adrenal insufficiency: Low cortisol (<250 nmol/L or <9 μg/dL) with elevated ACTH 1, 2
• Secondary adrenal insufficiency: Low cortisol with low or inappropriately normal ACTH 1, 3
• Perform cosyntropin stimulation test if morning cortisol is 5-18 μg/dL (140-500 nmol/L): administer 0.25 mg cosyntropin IV/IM, measure cortisol at 30 and 60 minutes—peak <500 nmol/L (<18 μg/dL) confirms adrenal insufficiency 1, 2, 3

Critical caveat: If the patient is clinically unstable with hypotension, severe weakness, or vomiting, never delay treatment for diagnostic testing—give hydrocortisone 100 mg IV immediately and draw blood for cortisol/ACTH beforehand if possible 1, 2

Treatment Algorithm by Clinical Severity

Severe Symptoms (Adrenal Crisis)

• Immediate IV hydrocortisone 100 mg bolus, followed by 100 mg IV every 6-8 hours or continuous infusion of 200 mg/24 hours 1, 2
• IV 0.9% saline infusion at 1 L/hour (at least 2L total) for volume resuscitation 1, 2
• Identify and treat precipitating factors (infection, trauma, surgery) 2

Moderate Symptoms

• Outpatient treatment at 2-3 times maintenance dose: hydrocortisone 30-50 mg daily or prednisone 20 mg daily 1, 2
• Taper to maintenance dose over 5-10 days as symptoms improve 1, 2

Mild Symptoms or Maintenance Therapy

• Hydrocortisone 15-25 mg daily in divided doses (10 mg at 7 AM, 5 mg at noon, 2.5-5 mg at 4 PM) to mimic physiological cortisol rhythm 1, 2, 3
• Alternative: Prednisone 3-5 mg daily (20 mg hydrocortisone = 5 mg prednisone) 2, 3
• For primary adrenal insufficiency only: Add fludrocortisone 0.05-0.1 mg daily for mineralocorticoid replacement 1, 2, 3
• For secondary adrenal insufficiency: Glucocorticoid replacement alone—no fludrocortisone needed 1, 2

Addressing Weight Gain Specifically

Weight gain in adrenal insufficiency is paradoxical but occurs in 43-73% of patients and reflects:

• Anorexia and poor appetite leading to metabolic changes 3
• Potential under-replacement if already on treatment—assess for morning nausea, fatigue, salt cravings, and orthostatic hypotension 1
• Adjust hydrocortisone timing: Have patient wake earlier to take first dose, then return to sleep to relieve morning symptoms 1
• Optimize mineralocorticoid dosing if primary AI: titrate fludrocortisone 50-200 μg daily based on blood pressure, salt cravings, and plasma renin (target upper half of reference range) 1, 2

Common pitfall: Do not over-replace glucocorticoids attempting to treat weight gain—this causes iatrogenic Cushing's syndrome and worsens weight gain 4

Mandatory Patient Education

• Stress dosing protocol: Double usual dose for minor illness, triple for moderate illness (fever, vomiting), immediate ER visit for severe illness 2
• Emergency injectable hydrocortisone 100 mg IM kit with self-injection training 1, 2
• Medical alert bracelet or necklace indicating adrenal insufficiency 1, 2, 3
• Warning signs of adrenal crisis: severe weakness, confusion, abdominal pain, vomiting, hypotension 1

Critical Pitfalls to Avoid

• Never use dexamethasone for chronic replacement in primary adrenal insufficiency—it lacks mineralocorticoid activity 1
• Never initiate thyroid hormone before glucocorticoid replacement in patients with concurrent hypothyroidism—this precipitates adrenal crisis 1
• Check for drug interactions: Anti-epileptics, antifungals, rifampin, and NSAIDs alter hydrocortisone requirements; psyllium/bulking agents impair absorption 1, 5
• Avoid grapefruit juice and licorice—they decrease hydrocortisone requirements 1

Follow-Up Monitoring

• Reassess in 2-4 weeks to evaluate symptom response and adjust dosing 4
• Annual screening for associated autoimmune conditions (thyroid disease, diabetes, celiac disease, pernicious anemia) 1
• Monitor for over-replacement: weight gain, hypertension, hyperglycemia, osteoporosis 4
• Assess mineralocorticoid adequacy: check orthostatic blood pressure, serum sodium/potassium, plasma renin activity 1, 2