A decrease in peripheral thyroid hormone conversion efficiency in patients treated with immune checkpoint inhibitors and L-T3 as a possible alternative therapeutic escape option.

Hypothyroidism is a frequently occurring side effect in patients under treatment with immune checkpoint inhibitors (ICIs). Actually, the origin of hypothyroidism with ICI use is classified as a primary (thyroid) or as secondary/tertiary hypothyroidism (hypothalamus-pituitary). Treatment consists of levothyroxine (L-T4) substitution. Recently, we were rarely confronted with a clinically overt hypothyroidism in three patients under treatment with ICIs who were non-responsive to T4 therapy. As a therapeutical escape, liothyronine (L-T3) was started with a significant clinical and/or biochemical improvement suggesting an underlying functional defect in the peripheral free T4 (fT4) to free T3 (fT3) conversion (as supported by calculation of SPINA-GD). Against this background, we discussed our three patients along an extended review of this clinical topic.