Endocrine Atlas

Checkpoint Inhibitor Endocrinology

What Are Immune Checkpoint Inhibitors (ICIs)?

ICIs are cancer immunotherapy drugs (e.g., pembrolizumab, nivolumab, ipilimumab) that enhance the immune system to fight cancer. They cause immune-related adverse events (irAEs), including endocrine toxicities.

Common Endocrine IrAEs:

1. Thyroid Disorders (Most Common - 10-20%):

  • Hyperthyroidism (Thyroiditis): Transient; often progresses to hypothyroidism
  • Hypothyroidism: Permanent; requires lifelong levothyroxine
  • Symptoms: Fatigue, palpitations (hyper), weight changes
  • Timing: 6-12 weeks after starting ICI

2. Hypophysitis (Pituitary Inflammation) (1-10%, Higher with Ipilimumab):

  • Symptoms: Headache, fatigue, nausea, vision changes
  • Labs: Low ACTH, cortisol, TSH, LH/FSH, testosterone/estrogen
  • MRI: Enlarged pituitary (early); often normal or atrophic later
  • Treatment: Steroids (acutely); lifelong hormone replacement (hydrocortisone, levothyroxine, sex hormones)
  • Timing: 6-12 weeks

3. Primary Adrenal Insufficiency (Rare - <1%):< /strong>

  • Symptoms: Fatigue, hypotension, hyponatremia, hyperkalemia
  • Life-Threatening: Adrenal crisis possible
  • Treatment: Lifelong hydrocortisone, fludrocortisone

4. Type 1 Diabetes (Rare - <1%):< /strong>

  • Rapid Onset: DKA may be presenting feature
  • Treatment: Insulin (lifelong)

5. Hypoparathyroidism (Very Rare)

Screening & Monitoring:

  • Baseline (Before Starting ICI): TSH, cortisol (AM), glucose
  • During Treatment:
    • TSH, free T4 every 4-6 weeks initially, then every 6-12 weeks
    • AM cortisol if symptoms (fatigue, hypotension)
    • Glucose monitoring
  • If Symptoms: Full pituitary panel (ACTH, cortisol, TSH, LH, FSH, testosterone/estrogen, prolactin, GH/IGF-1)

Management:

  • Thyrotoxicosis (Hyperthyroid Phase): Beta-blockers for symptoms; usually self-limited
  • Hypothyroidism: Levothyroxine (lifelong)
  • Hypophysitis: High-dose steroids (pulse methylprednisolone) + hormone replacement
  • Adrenal Insufficiency: Hydrocortisone (stress dosing education)
  • Diabetes: Insulin
  • Continue ICI: Most endocrine irAEs do NOT require stopping immunotherapy (except severe/life-threatening)

Prognosis:

  • Most endocrine irAEs are permanent and require lifelong hormone replacement
  • Early recognition and treatment prevent serious complications

Key Points:

  • Checkpoint inhibitors cause endocrine irAEs (thyroid, pituitary, adrenal, diabetes)
  • Most common: Thyroid disorders (hypo/hyperthyroidism)
  • Hypophysitis: Headache + multiple hormone deficiencies → requires lifelong replacement
  • Monitor TSH, cortisol regularly during ICI treatment
  • Most endocrine irAEs are permanent
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