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Immune-Related Adverse Events for Endocrine Toxicities - Hypothyroidism

CTCAE-based severity grade for hypothyroidism from checkpoint inhibitor therapy.

Immune-Related Adverse Events for Endocrine Toxicities - Hypothyroidism
Clinical picture
ResultNo hypothyroidism

No evidence of hypothyroidism.

When to use

  • Grading hypothyroidism (primary or secondary to hypophysitis) that develops during or after immune checkpoint inhibitor therapy.

Formula

CTCAE v5.0 general endocrine-toxicity grading applied to ICPi-related hypothyroidism: Grade 1, asymptomatic; Grade 2, symptomatic and thyroid hormone replacement indicated; Grade 3, severe symptoms limiting self-care, hospitalization indicated; Grade 4, life-threatening (e.g., myxedema coma).

Pearls and pitfalls

  • Check TSH and free T4 at baseline and periodically during ICPi therapy; a low TSH with low free T4 suggests hypophysitis rather than primary thyroiditis and warrants pituitary-axis work-up and imaging.
  • ICPi therapy can usually continue through grade 1-2 hypothyroidism once levothyroxine replacement is started.

References

  1. Schneider BJ, Naidoo J, Santomasso BD, et al. J Clin Oncol. 2021;39(36):4073-4126.
  2. National Cancer Institute. Common Terminology Criteria for Adverse Events (CTCAE) v5.0.