What is the recommended steroid regimen for treating hypophysitis?

Steroid Regimen for Hypophysitis

For hypophysitis with severe symptoms (severe headache, visual disturbances, or hypoadrenalism), initiate intravenous methylprednisolone 1 mg/kg daily; for moderate symptoms without mass effect, use oral prednisolone 0.5-1 mg/kg daily; high-dose steroids are essential for neurological symptoms but do not reverse hormonal deficiencies, which require lifelong hormone replacement therapy. 1

Severity-Based Treatment Algorithm

Severe Presentation (Grade ≥2)

Immediate intervention required for:

• Severe headache with visual disturbances 1
• Hypotension or severe electrolyte disturbances from hypoadrenalism 1
• Any visual field defects 1

Treatment protocol:

• Initiate IV methylprednisolone 1 mg/kg daily after obtaining pituitary axis blood work (9 am cortisol, ACTH, TSH, free T4, LH, FSH, testosterone/estradiol, IGF-1, prolactin) 1
• Provide analgesia for headache (paracetamol and NSAIDs; consult neurology if resistant) 1
• Withhold immune checkpoint inhibitor therapy immediately 1
• Obtain MRI pituitary protocol to assess mass effect 1
• Consider formal visual field assessment 1
• Convert to oral prednisolone and taper over 4 weeks to 5 mg maintenance dose as symptoms improve 1

Moderate Presentation

For headache without visual changes OR fatigue with hemodynamic stability:

• Oral prednisolone 0.5-1 mg/kg once daily after pituitary axis assessment 1
• If no improvement within 48 hours, escalate to IV methylprednisolone as per severe protocol 1
• Withhold checkpoint inhibitor 1
• Monitor thyroid function tests regularly 1

Mild/Asymptomatic Presentation

For vague symptoms (mild fatigue, anorexia) without headache:

• Await pituitary axis confirmation before treatment 1
• Continue checkpoint inhibitor with appropriate hormone replacement 1
• Warn patients to seek urgent review if symptoms worsen 1

Critical Management Principles

Hormone Replacement Takes Priority

Physiologic hormone replacement is the cornerstone of management, not high-dose steroids: 1

• Always start hydrocortisone (20/10/10 mg daily) before thyroid hormone to prevent adrenal crisis 1
• If 9 am cortisol <250 nmol/L or random cortisol <150 nmol/L with symptoms, initiate hydrocortisone immediately 1
• Replace thyroid hormone only after 1 week of cortisol replacement 1
• Lifelong hormone replacement is required in most cases as hormonal deficiencies rarely recover 1

Steroid Tapering Protocol

Taper steroids gradually under close monitoring: 1

• For Grade 2 episodes: wean over 2-4 weeks 1
• For Grade 3/4 episodes: wean over 4 weeks 1
• Do not stop steroids abruptly 1
• Aim for maintenance dose of 5 mg prednisolone 1

Important Caveats

High-dose steroids do NOT reverse hormonal deficiencies from checkpoint inhibitor-induced hypophysitis—they only address mass effect and inflammatory symptoms 1

For steroids >4 weeks, add: 1

• Pneumocystis jiroveci pneumonia (PJP) prophylaxis 1
• Calcium/vitamin D supplementation 1
• Gastric protection 1
• Monitor afternoon glucose for hyperglycemia 1

Patient Safety Measures

All patients with adrenal insufficiency must: 1

• Obtain and carry medical alert bracelet 1
• Receive "sick day rules" education 1
• Have prescription for IM steroid for emergencies 1
• Consider alert card 1

Alternative Immunosuppression

For steroid-refractory cases or when glucocorticoids fail: 2, 3, 4

• Azathioprine (200-300 mg/day) as second-line agent 1, 2, 4, 5
• Methotrexate, cyclosporin A, or rituximab as third/fourth-line options 1, 2, 3
• Medical therapy reduces pituitary mass in 84% of cases and improves anterior pituitary function in 45% 4

Endocrinology consultation is mandatory for all confirmed cases to guide long-term hormone management and steroid tapering 1