Immune-Related Adverse Events for Endocrine Toxicities - Hypothyroidism

• Monitor patients with TSH and free thyroxine every 4 to 6 weeks routinely during ICPi therapy.

• Test for TSH and free thyroxine in symptomatic patients.

For all patients where an IRAE diagnosis is being considered, it is always recommended to involve the specialist or team prescribing the immune checkpoint therapy. 

Grade 1:

1. Continue ICPi with close follow-up and monitoring of TSH, free thyroxine.

Grade 2:

1. May hold ICPi until symptoms resolve to baseline.

2. Consider endocrinology consult.

3. Consider thyroid hormone supplementation in symptomatic patients with any degree of TSH elevation or in asymptomatic patients with TSH levels that persist > 10 mIU/L (measured 4 weeks apart).

4. Monitor TSH every 6 to 8 weeks while titrating hormone replacement to normal TSH.

5. Free thyroxine can be used in the short term (2 weeks) to ensure adequacy of therapy in those with frank hypothyroidism where the free thyroxine was initially low.

6. Once adequately treated, monitor thyroid function (at least TSH) every 6 weeks while on active therapy or as needed for symptoms to ensure appropriate replacement. 

Grade 3-4:

1. Should hold ICPi until symptoms resolve to baseline with appropriate supplementation.

2. Consider endocrinology consult.

3. Consider admission for IV therapy if signs of myxedema (bradycardia, hypothermia).

4. Consider thyroid supplementation and offer reassessment as in grade 2.

See Brahmer 2018 for full ASCO guidelines.

Distinguishing primary hormonal problems from secondary hormonal problems is necessary. 

Monitoring both TSH and free thyroxine levels helps distinguish primary hypothyroidism from central hypothyroidism which may be due to ICPi hypophysitis.