Hypophysitis (inflammation of the pituitary gland)

Grading Toxicity (Overall)

  • Asymptomatic or mild symptoms; clinical or diagnostic observation only (headache, fatigue)
  • Moderate symptoms; limiting age-appropriate instrumental ADLs (headache, fatigue)
  • Severe or medically significant symptoms; limiting self-care ADL (sepsis, severe ataxia)
  • Urgent intervention required (sepsis, severe ataxia)


Overall Strategy:

  • Ipilimumab to be withheld for any symptomatic hypophysitis and discontinued for symptomatic reactions persisting ≥6 weeks or for inability to reduce steroid dose to ≤7.5 mg prednisone or equivalent per day
  • Nivolumab to be withheld for Grade 2/3 hypophysitis and discontinued for Grade 4 hypophysitis. Pembrolizumab to be withheld for Grade 2 hypophysitis and withheld or discontinued for Grade 3/4 hypophysitis
  • 1 mg/kg methylprednisolone (or equivalent) IV to be given daily
    • If given during acute phase, may reverse inflammatory process
    • To be followed with prednisone 1-2 mg/kg daily with gradual tapering over at least 4 weeks
  • Long-term supplementation of affected hormones is often required
    • Secondary hypothyroidism requiring levothyroxine replacement
    • Secondary hypoadrenalism requiring replacement hydrocortisone
      • Typical dose: 20 mg qAM and 10 mg qPM
  • Assess risk of opportunistic infection based on duration of steroid taper (and consider prophylaxis if needed)
  • Collaborative management approach with endocrinology (particularly if permanent loss of organ function)

Nursing Implementation:

  • ACTH and thyroid panel should be checked at baseline and prior to each dose of ipilimumab
  • Ensure that MRI is ordered with pituitary cuts or via pituitary protocol
  • Anticipate treatment with corticosteroid and immunotherapy hold
  • Review proper administration of steroid
    • Take with food
    • Take in AM
  • Educate patient regarding possibility of permanent loss of organ function (pituitary; possibly others if involved [thyroid, adrenal glands])
  • Sick-day instructions, vaccinations, etc

*Steroid taper instructions/calendar as a guide but not an absolute

  • Taper should consider patient’s current symptom profile
  • Close follow-up in person or by phone, based on individual need & symptomatology
  • Anti-acid therapy daily as gastric ulcer prevention while on steroids
  • Review steroid medication side effects: mood changes (anger, reactive, hyperaware, euphoric, mania), increased appetite, interrupted sleep, oral thrush, fluid retention
  • Be alert to recurring symptoms as steroids taper down & report them (taper may need to be adjusted)

Long-term high-dose steroids:

  • Consider antimicrobial prophylaxis (sulfamethoxazole/trimethoprim double dose M/W/F; single dose if used daily) or alternative if sulfa-allergic (e.g., atovaquone [Mepron®] 1500 mg po daily)
  • Consider additional antiviral and antifungal coverage
  • Avoid alcohol/acetaminophen or other hepatoxins


  • Symptoms of adrenal insufficiency