What is the difference between hydrocortisone and prednisolone for a patient with central hypothyroidism or suspected hypophysitis?

Hydrocortisone vs Prednisolone in Central Hypothyroidism and Hypophysitis

For physiologic glucocorticoid replacement in central adrenal insufficiency from hypophysitis, hydrocortisone 15-20 mg daily in divided doses is strongly preferred over prednisolone, while high-dose prednisolone 1-2 mg/kg/day is reserved exclusively for acute inflammatory treatment of severe hypophysitis with mass effect or visual symptoms. 1

Key Pharmacologic Differences

Hydrocortisone is the preferred agent for physiologic replacement because:

• It has a short half-life (2-4 hours) allowing recreation of normal diurnal cortisol rhythm 1, 2
• It provides both glucocorticoid AND mineralocorticoid activity 2
• Standard replacement dosing is 15-20 mg daily in divided doses (typically 10 mg morning, 5 mg afternoon, or 15 mg morning/5 mg at 3 pm) 1
• Equivalency: 20 mg hydrocortisone = 5 mg prednisolone 1, 3

Prednisolone has distinct characteristics:

• Longer half-life with predominantly glucocorticoid effects 2
• Lacks significant mineralocorticoid activity 2
• Carries risk of over-replacement when used for chronic maintenance 1
• Can be used in special circumstances when patients cannot adhere to multi-dose hydrocortisone regimens 1

Clinical Application Algorithm

For Mild Hypophysitis (Grade 1-2) with Central Adrenal Insufficiency:

Use hydrocortisone for physiologic replacement:

• Start hydrocortisone 15-20 mg daily in divided doses (e.g., 10 mg at 7 AM, 5 mg at 3 PM) 1
• This is MAINTENANCE therapy, not anti-inflammatory treatment 1
• Continue indefinitely as recovery of central adrenal insufficiency is rare 1

For Severe Hypophysitis (Grade 3-4) with Mass Effect or Visual Symptoms:

Use HIGH-DOSE prednisolone for acute inflammatory suppression:

• Prednisolone 1-2 mg/kg/day (or equivalent methylprednisolone) for acute phase 1
• Taper over 1-2 weeks down to physiologic maintenance 1
• Once tapered to ≤5 mg prednisolone equivalent, transition to hydrocortisone maintenance dosing 1
• Very high-dose IV glucocorticoids show better visual field recovery (91.7% vs 54.5% oral) and corticotroph axis recovery (54.8% vs 28.1%) 4

Critical Sequencing for Central Hypothyroidism:

ALWAYS start corticosteroids BEFORE thyroid hormone replacement:

• Initiate hydrocortisone first, wait several days 1
• Then start levothyroxine 1 mcg/kg 1
• Starting thyroid hormone before steroids accelerates cortisol clearance and can precipitate adrenal crisis 1
• Goal free T4 in upper half of reference range (TSH unreliable in central hypothyroidism) 1

Common Pitfalls to Avoid

Do not use prednisolone for routine maintenance replacement:

• Long-acting steroids like prednisolone carry over-replacement risk 1
• Cannot recreate physiologic diurnal rhythm 1
• Reserve for specific situations: inability to adhere to multi-dose regimen or acute inflammatory treatment 1

Do not confuse anti-inflammatory dosing with replacement dosing:

• Replacement: hydrocortisone 15-20 mg/day 1
• Anti-inflammatory: prednisolone 1-2 mg/kg/day (equivalent to 80-160 mg hydrocortisone for 70 kg patient) 1
• High-dose steroids do NOT improve recovery of hormone deficiencies—they only treat inflammatory mass effect 5

Recognize that high-dose steroids may not improve endocrine outcomes:

• One retrospective study of 25 patients showed systemic high-dose corticosteroids did not improve resolution of secondary adrenal insufficiency (0% recovery regardless of treatment) or secondary hypothyroidism 5
• However, very high-dose IV glucocorticoids (>1 mg/kg prednisolone equivalent) for >6.5 weeks showed better corticotroph recovery (57.1%) in primary autoimmune hypophysitis 4
• The discrepancy likely reflects different pathophysiology: checkpoint inhibitor hypophysitis vs primary autoimmune hypophysitis 4, 5

Stress Dosing Education

All patients require education on increasing hydrocortisone during illness:

• Double or triple usual dose during fever, infection, or physical stress 1
• Emergency injectable hydrocortisone 100 mg IM kit with self-injection training 1
• Medical alert bracelet indicating adrenal insufficiency 1
• Endocrine consultation for surgical planning or high-stress treatments 1