What is the indication for using Hydrocortisone (cortisol) and Fludrocortisone (fludrocortisone) in a patient with Chronic Thromboembolic Pulmonary Hypertension (CTEPH) and a history of parapneumonic effusion, suspected of having adrenal insufficiency?

Hydrocortisone + Fludrocortisone Indications

Primary Indication: Adrenal Insufficiency

The combination of hydrocortisone and fludrocortisone is indicated for primary adrenal insufficiency (Addison's disease), where both glucocorticoid and mineralocorticoid replacement are required. 1, 2

Primary Adrenal Insufficiency (Addison's Disease)

• Hydrocortisone 15-25 mg daily in divided doses (typically 10 mg at 7:00 AM, 5 mg at 12:00 PM, and 2.5-5 mg at 4:00 PM) provides glucocorticoid replacement 3, 4
• Fludrocortisone 0.05-0.2 mg daily (usual dose 0.1 mg) provides mineralocorticoid replacement 1, 4
• This combination approximates normal adrenal activity with minimal risk of unwanted effects 1
• Primary adrenal insufficiency is characterized by high ACTH with low cortisol, often accompanied by hyponatremia and hyperkalemia (though hyperkalemia occurs in only ~50% of cases) 3

Diagnostic Confirmation Required

Before initiating this combination therapy, adrenal insufficiency must be confirmed:

• Morning cortisol <250 nmol/L (<9 μg/dL) with elevated ACTH in acute illness is diagnostic of primary adrenal insufficiency 3
• ACTH stimulation test with peak cortisol <500 nmol/L (<18 μg/dL) confirms the diagnosis 3
• Measure 21-hydroxylase autoantibodies to identify autoimmune etiology (accounts for ~85% of cases in Western populations) 3

Secondary Indication: Salt-Losing Adrenogenital Syndrome

• Fludrocortisone 0.1-0.2 mg daily is indicated for treating salt-losing adrenogenital syndrome 1
• This condition requires mineralocorticoid replacement in addition to glucocorticoid therapy 1

Critical Illness-Related Corticosteroid Insufficiency (CIRCI)

In septic shock not responsive to fluid and moderate-to-high-dose vasopressor therapy, hydrocortisone <400 mg/day for ≥3 days is recommended, with fludrocortisone 50 mcg daily added in some protocols. 5

• The combination of hydrocortisone 200 mg/day plus fludrocortisone 50 mcg daily was used in some septic shock trials 5, 4
• However, current guidelines primarily recommend hydrocortisone alone for septic shock, as the added benefit of fludrocortisone remains controversial 5
• This indication applies only to septic shock with vasopressor-resistant hypotension, not sepsis without shock 5

Context-Specific Consideration: CTEPH Patient with Suspected Adrenal Insufficiency

In your patient with CTEPH and parapneumonic effusion history:

Diagnostic Workup Priority

• Perform ACTH stimulation test immediately if adrenal insufficiency is suspected based on clinical features (unexplained hypotension, hyponatremia, fatigue, nausea) 3
• Do not delay treatment if the patient is hemodynamically unstable—give hydrocortisone 100 mg IV immediately plus 0.9% saline infusion 3, 5
• Adrenal insufficiency can present with hypo-osmolar hyponatremia nearly identical to SIADH and must be excluded before diagnosing SIADH 3

Treatment Algorithm if Confirmed

1. If primary adrenal insufficiency confirmed: Start hydrocortisone 15-25 mg daily in divided doses PLUS fludrocortisone 0.05-0.1 mg daily 3, 1
2. If secondary adrenal insufficiency confirmed: Start hydrocortisone alone (no fludrocortisone needed, as the renin-angiotensin-aldosterone system remains intact) 3
3. Monitor adequacy by assessing salt cravings, orthostatic blood pressure, peripheral edema, serum sodium, potassium, and plasma renin activity 3, 1

CTEPH Management Considerations

• CTEPH treatment is independent of adrenal insufficiency management: Anticoagulation, pulmonary endarterectomy evaluation, or balloon pulmonary angioplasty proceed based on CTEPH severity and operability 6, 7, 8
• Perioperative stress dosing required if the patient undergoes pulmonary endarterectomy: Hydrocortisone 100 mg IV at induction, followed by 200 mg/24h continuous infusion 5
• The parapneumonic effusion history does not contraindicate corticosteroid therapy once infection is adequately treated 2

Critical Pitfalls to Avoid

• Never use fludrocortisone alone without glucocorticoid replacement in primary adrenal insufficiency—both are required 1, 4
• Do not add fludrocortisone in secondary adrenal insufficiency unless specific mineralocorticoid deficiency is documented 3
• Never delay emergency treatment for diagnostic testing in suspected adrenal crisis—mortality is high if untreated 3, 5
• Educate all patients on stress dosing, provide emergency injectable hydrocortisone kit, and ensure they wear medical alert identification 3