What is the treatment for a patient with a positive cosyntropin (adrenocorticotropic hormone stimulation) test result indicating adrenal insufficiency?

Treatment for Positive Cosyntropin Test (Confirmed Adrenal Insufficiency)

Patients with a positive cosyntropin test (peak cortisol <500-550 nmol/L or <18-20 μg/dL) require lifelong glucocorticoid replacement therapy, with hydrocortisone 15-25 mg daily in divided doses as the preferred treatment. 1, 2

Immediate Management Based on Clinical Severity

Stable Outpatients (Chronic Replacement)

• Initiate hydrocortisone 15-25 mg daily in divided doses (typically 10 mg upon waking, 5 mg at noon, and 2.5-5 mg at 4 PM) to mimic physiological cortisol secretion 1, 2
• Alternative regimens include 15+5 mg, 10+10 mg, or 10+5+5 mg depending on individual response 3
• Cortisone acetate 18.75-31.25 mg daily (equivalent to hydrocortisone 15-25 mg) can be used as an alternative 1
• Prednisone 3-5 mg daily may be considered in select patients who experience marked fluctuations with hydrocortisone 3, 2

Primary vs. Secondary Adrenal Insufficiency: Critical Treatment Distinction

• Primary adrenal insufficiency requires BOTH glucocorticoid AND mineralocorticoid replacement 1, 2
  • Add fludrocortisone 50-200 μg daily (children and younger adults may require higher doses up to 500 μg) 1, 3
  • Advise unrestricted salt intake and salty foods 1
  • Monitor for adequacy by assessing orthostatic blood pressure, salt cravings, and peripheral edema 3
• Secondary adrenal insufficiency requires ONLY glucocorticoid replacement (mineralocorticoid function remains intact) 3

Moderately Symptomatic Patients

• Initiate outpatient treatment at 2-3 times maintenance dose (hydrocortisone 30-50 mg total daily or prednisone 20 mg daily) 3
• Taper to maintenance dosing once symptoms stabilize 3

Critically Ill or Adrenal Crisis

• Administer IV hydrocortisone 100 mg immediately, followed by 100 mg every 6-8 hours until clinical recovery 1, 2
• Infuse 0.9% saline at 1 L/hour (at least 2L total) until hemodynamic improvement 1, 3
• Never delay treatment for diagnostic procedures if adrenal crisis is suspected 1, 3
• Obtain blood samples for cortisol and ACTH before treatment if possible, but do not delay therapy 1
• Identify and treat the underlying precipitant (infection, trauma, surgery) 1

Etiologic Workup After Diagnosis Confirmation

Once adrenal insufficiency is confirmed, determine the underlying cause as this affects treatment decisions and follow-up. 1

Primary Adrenal Insufficiency Workup

• Measure 21-hydroxylase autoantibodies (21OH-Ab) first—autoimmunity accounts for ~85% of primary adrenal insufficiency in Western populations 1, 3
• If 21OH-Ab positive: diagnosis of autoimmune Addison's disease is established; no further etiologic testing generally needed 1
• If 21OH-Ab negative, obtain CT imaging of adrenals to evaluate for tuberculosis (calcifications), hemorrhage, tumors, metastases, or infiltrative disease 1, 3
• In males with negative antibodies, measure very long-chain fatty acids (VLCFA) to screen for adrenoleukodystrophy 1, 3
• Consider APS-1 in young patients with hypoparathyroidism, candidiasis, or other autoimmune features—measure interferon omega antibodies or AIRE gene mutation analysis 1

Secondary Adrenal Insufficiency Workup

• Evaluate for pituitary pathology with MRI of pituitary if secondary adrenal insufficiency suspected (low cortisol with low/inappropriately normal ACTH) 3
• Assess for other pituitary hormone deficiencies 3
• Review medication history for opioids, glucocorticoids, or other agents that suppress ACTH 2

Mandatory Patient Education and Safety Measures

All patients with confirmed adrenal insufficiency must receive comprehensive education and safety equipment to prevent life-threatening adrenal crisis. 1, 3, 2

Essential Patient Instructions

• Wear medical alert identification jewelry or carry a steroid alert card at all times 1, 3, 2
• Double or triple glucocorticoid dose during fever, illness, or physical stress 3
• Prescribe injectable hydrocortisone 100 mg IM kit with self-injection training for emergency use 3, 2
• Educate on warning signs of impending adrenal crisis: severe weakness, confusion, vomiting, diarrhea, abdominal pain, hypotension 3

Stress Dosing Guidelines

• Minor stress (mild illness, dental procedures): Double usual daily dose for 1-2 days 3
• Moderate stress (moderate illness, minor surgery): Hydrocortisone 50-75 mg daily 3
• Major stress (major surgery, severe illness): Hydrocortisone 100-150 mg daily 3
• During delivery: Parenteral hydrocortisone required 1

Critical Pitfalls to Avoid

• Never use dexamethasone alone for chronic replacement in primary adrenal insufficiency—it lacks mineralocorticoid activity and is inadequate 3, 4
• When treating concurrent hypothyroidism and adrenal insufficiency, start corticosteroids several days BEFORE initiating thyroid hormone to prevent precipitating adrenal crisis 3
• Avoid liquorice and grapefruit juice—they decrease hydrocortisone requirements and interfere with fludrocortisone 1, 3
• Do not stop fludrocortisone if hypertension develops—reduce the dose instead 1
• Hyperkalemia is present in only ~50% of primary adrenal insufficiency cases—its absence does not rule out the diagnosis 1, 3

Monitoring and Follow-Up

• Review patients at least annually with assessment of weight, blood pressure, serum electrolytes, and overall well-being 1
• Monitor bone mineral density every 3-5 years to assess for glucocorticoid-related complications 1
• Screen periodically for new autoimmune disorders (particularly hypothyroidism, diabetes, celiac disease, pernicious anemia) in autoimmune Addison's disease 3
• Adjust fludrocortisone based on orthostatic blood pressure, salt cravings, and plasma renin activity 3
• Mandatory endocrine consultation for newly diagnosed patients, pre-operative planning, and recurrent adrenal crises 3