What is the recommended treatment plan for a patient with suspected adrenal insufficiency, presenting with chronic nausea, dizziness, unintentional weight loss, anxiety, and a history of hypotension, who has undergone cosyntropin stimulation testing?

Interpreting Cosyntropin Stimulation Test Results and Treatment Plan

Test Interpretation

A peak cortisol level <500 nmol/L (<18 μg/dL) at 30 or 60 minutes after cosyntropin administration is diagnostic of adrenal insufficiency, while a peak >550 nmol/L (>18-20 μg/dL) is normal and excludes the diagnosis. 1, 2

• The patient's baseline cortisol of 7.8 µg/dL with ACTH of 20 pg/mL suggested either primary adrenal insufficiency (if ACTH should be higher) or secondary adrenal insufficiency (if ACTH is inappropriately low-normal), making the cosyntropin test essential for definitive diagnosis 1, 3
• The standard protocol uses 0.25 mg (250 mcg) cosyntropin IV or IM with cortisol measurements at baseline, 30 minutes, and 60 minutes 1, 2

If Adrenal Insufficiency is Confirmed (Peak Cortisol <18 μg/dL)

Immediate Treatment Initiation

Start hydrocortisone 15-25 mg daily in divided doses immediately—this is lifelong replacement therapy that should never be discontinued. 4, 5, 2, 3

• Preferred regimen: Hydrocortisone 10 mg upon awakening (7:00 AM), 5 mg at noon, and 2.5-5 mg in late afternoon (4:00 PM) 4, 5, 2
• Alternative regimens include 15 mg + 5 mg (morning and noon) or cortisone acetate 25-37.5 mg daily in divided doses 4, 2
• The first dose must be taken immediately upon awakening to mimic physiological cortisol peak 5

Mineralocorticoid Replacement (Primary Adrenal Insufficiency Only)

If the patient has primary adrenal insufficiency (high ACTH with low cortisol), add fludrocortisone 0.05-0.1 mg once daily upon awakening. 4, 2, 3

• Typical dosing range is 50-200 µg daily, adjusted based on blood pressure, salt cravings, orthostatic symptoms, and serum electrolytes 4, 2
• Secondary adrenal insufficiency (low ACTH with low cortisol) does NOT require fludrocortisone since the renin-angiotensin-aldosterone system remains intact 5, 2
• Monitor adequacy by checking for orthostatic hypotension, peripheral edema, serum sodium, and potassium 4, 2

Critical Patient Education (Mandatory)

All patients must receive education on stress dosing, wear a medical alert bracelet, and be prescribed an emergency hydrocortisone 100 mg IM injection kit with self-injection training. 4, 5, 2, 3

• Stress dosing protocol: Double or triple the usual daily dose during fever, illness, or physical stress 4, 2
• Adrenal crisis warning signs requiring immediate ER evaluation: Severe vomiting, confusion, severe weakness, syncope, or severe abdominal pain 4, 1
• Patients must carry a steroid card and medical identification indicating adrenal insufficiency at all times 4, 2

Monitoring and Follow-Up

• Clinical assessment is the primary monitoring tool—plasma ACTH and serum cortisol are NOT useful for dose adjustment 4, 5
• Signs of over-replacement: Weight gain, insomnia, peripheral edema, hypertension 4, 5
• Signs of under-replacement: Lethargy, nausea, poor appetite, weight loss, increased pigmentation 4, 5
• Annual follow-up should include blood pressure, weight, serum electrolytes, and screening for other autoimmune conditions (especially thyroid disease) 4, 2

Drug Interactions Requiring Dose Adjustments

Medications that increase hydrocortisone requirements: Anti-epileptics, rifampin, barbiturates, etomidate, topiramate 4, 5, 2

Medications that decrease hydrocortisone requirements: Grapefruit juice, licorice 4, 5, 2

Medications to avoid with fludrocortisone: NSAIDs, potassium-sparing diuretics 2, 6

If Adrenal Insufficiency is Excluded (Peak Cortisol >18-20 μg/dL)

• The patient's symptoms (chronic nausea, dizziness, weight loss, anxiety, hypotension) require alternative diagnostic workup 3
• Consider other causes: autonomic dysfunction, gastrointestinal disorders, psychiatric conditions, or medication side effects 3
• The patient does NOT require glucocorticoid replacement and should not receive it, as this would cause iatrogenic adrenal suppression 1, 7

Special Considerations for This Patient

Hashimoto's Thyroiditis Interaction

If the patient requires both thyroid hormone replacement and glucocorticoid replacement, start hydrocortisone several days BEFORE initiating thyroid hormone to prevent precipitating adrenal crisis. 1, 5

• Thyroid hormone accelerates cortisol clearance and can unmask or worsen adrenal insufficiency 1, 5

Addressing Current Symptoms

• Morning nausea and lack of appetite are particularly common in adrenal insufficiency and often indicate under-replacement 1
• Taking the first hydrocortisone dose immediately upon awakening (patient can return to sleep afterward) may relieve morning nausea 1
• Weight loss, chronic nausea, and hypotension are classic features of adrenal insufficiency that typically improve with appropriate replacement 1, 3

Critical Pitfall to Avoid

Never attempt to discontinue hydrocortisone in patients with confirmed primary or secondary adrenal insufficiency from non-iatrogenic causes—these conditions are permanent and stopping replacement will precipitate life-threatening adrenal crisis. 2