What is the difference between glucocorticoid and mineralocorticoid in a patient with Addison's disease presenting with hypotension?

Glucocorticoid vs. Mineralocorticoid in Addison's Disease with Hypotension

In Addison's disease presenting with hypotension, both glucocorticoids and mineralocorticoids are deficient and serve distinct physiological roles: glucocorticoids (cortisol) regulate metabolism, immune function, and stress responses, while mineralocorticoids (aldosterone) control sodium retention, potassium excretion, and blood pressure maintenance. 1, 2

Fundamental Differences

Glucocorticoids

• Primary hormone: Cortisol (replaced therapeutically with hydrocortisone or cortisone acetate) 3
• Key functions: Regulate metabolism, modulate immune responses, and enable stress adaptation 3
• Deficiency manifestations: Malaise, fatigue, nausea, weight loss, hypoglycemia (especially in children), and impaired cognitive function including confusion or coma 1, 4
• Replacement dosing: Hydrocortisone 15-25 mg daily or cortisone acetate 20-30 mg daily, divided into 2-3 doses with the largest dose in the morning to mimic circadian rhythm 5, 2

Mineralocorticoids

• Primary hormone: Aldosterone (replaced therapeutically with fludrocortisone) 6
• Key functions: Regulate sodium and potassium homeostasis, maintain extracellular fluid volume, and control blood pressure 1, 7
• Deficiency manifestations: Hyponatremia (present in 90% of newly diagnosed cases), hyperkalaemia (in approximately 50%), dehydration, and hypotension including postural hypotension 1, 2
• Replacement dosing: Fludrocortisone 0.1 mg daily (range 0.1 mg three times weekly to 0.2 mg daily), often requiring sodium chloride supplementation 6, 5

Critical Management in Hypotensive Presentation

Acute Crisis Management

When a patient with Addison's disease presents with hypotension, immediate high-dose hydrocortisone (100 mg IV bolus) serves a dual purpose: it provides glucocorticoid replacement AND saturates the 11β-hydroxysteroid dehydrogenase type 2 enzyme to achieve mineralocorticoid effects. 1, 8

• Administer hydrocortisone 100 mg IV bolus immediately, followed by 100-300 mg/day as continuous infusion or divided boluses every 6 hours 1, 8
• Simultaneously initiate aggressive fluid resuscitation with 0.9% saline: 1 L over the first hour, then 3-4 L over 24-48 hours with frequent hemodynamic monitoring 1, 8
• Do not delay treatment for diagnostic procedures—draw blood for cortisol, ACTH, electrolytes, and glucose, then treat immediately 1

Transition to Maintenance

• Taper parenteral glucocorticoids over 1-3 days to oral maintenance therapy once stabilized 8, 2
• Restart fludrocortisone only when hydrocortisone dose falls below 50 mg/day, as higher doses provide sufficient mineralocorticoid activity 1
• Monitor for postural hypotension, which specifically reflects insufficient mineralocorticoid therapy and/or inadequate salt intake 1

Clinical Pitfalls

Distinguishing Under-Replacement

• Glucocorticoid insufficiency: Lethargy, nausea, poor appetite, weight loss, increased skin pigmentation 5
• Mineralocorticoid insufficiency: Postural hypotension, persistent hyponatremia, hyperkalaemia despite adequate glucocorticoid dosing 1, 2

Avoiding Over-Replacement

• Glucocorticoid excess: Weight gain, insomnia, peripheral edema, increased cardiovascular risk 5
• Mineralocorticoid excess: Transient hypertension (reduce fludrocortisone to 0.05 mg daily if this occurs) 6

Monitoring Strategy

• Clinical assessment is primary—plasma ACTH and serum cortisol are not useful for dose adjustment 5
• Focus on energy levels, mental concentration, pigmentation changes, weight, and blood pressure (including orthostatic measurements) 5, 1
• Check serum sodium and potassium regularly to guide mineralocorticoid dosing 2

Patient Education Essentials

• All patients must wear medical alert identification and carry a steroid emergency card 5, 2
• Train patients in stress dosing: double oral dose for minor illness, use parenteral hydrocortisone 100 mg IM for severe illness with vomiting 8, 5
• Ensure emergency supplies of injectable hydrocortisone are available at home 8