Endocrine-related adverse conditions in patients receiving immune checkpoint inhibition: an ESE clinical practice guideline

Thyroid

• Thyroid dysfunction represents the most common ICI-related endocrine adverse event. Anti-PD-1/PD-L1 treatment carries a higher risk than anti-CTLA4 treatment, with the highest risk for combined treatment (55). Most cases are asymptomatic or mild (grade I or II). Hypothyroidism is most frequent with an estimated incidence of 2.5–3.8% (anti-CTLA4), 3.9–8.5% (anti-PD1/PDL1), and 10.2–16.4% (combination treatment), typically occurring at a median time of 8–12 weeks post ICI initiation (56). In a minority of cases, especially in patients treated with anti-CTLA4, central hypothyroidism can develop (TSH deficiency), mostly along with ACTH deficiency which should not be missed and always be treated prior to the initiation of thyroid hormone replacement (see above). Thyrotoxicosis, typically preceding hypothyroidism, has a lower incidence estimated at 0.2–5.2% (anti-CTLA4), 0.6–3.7% (anti-PD1/PDL1), and 8.0–11.1% (combination treatment) (56). The incidence is believed to be underreported, as thyrotoxicosis is typically mild and transient and therefore at risk to remain undetected. Thyrotoxicosis has a rapid onset, typically 4–6 weeks post ICI initiation, and lasts approximately 6 weeks (57). The time to onset of thyrotoxicosis is shorter in case of ICI combination treatment. Rare cases of Graves’ hyperthyroidism and thyroid eye disease have been described (58, 59).