A decrease in peripheral thyroid hormone conversion efficiency in patients treated with immune checkpoint inhibitors...

Area of Science:

• Endocrinology
• Oncology
• Immunology

Background:

• Immune checkpoint inhibitors (ICIs) frequently cause hypothyroidism.
• Hypothyroidism in ICI patients can be primary (thyroid) or central (hypothalamus-pituitary).
• Standard treatment involves levothyroxine (L-T4) substitution.

Purpose of the Study:

• To investigate cases of ICI-induced hypothyroidism unresponsive to L-T4.
• To explore the potential role of impaired peripheral T4 to T3 conversion.
• To evaluate liothyronine (L-T3) as a therapeutic alternative.

Main Methods:

• Case series of three patients with ICI-induced hypothyroidism.
• Analysis of treatment response to L-T4 and subsequent L-T3 therapy.
• Assessment of peripheral free T4 (fT4) to free T3 (fT3) conversion, including SPINA-GD calculation.

Main Results:

• Three patients on ICIs developed hypothyroidism resistant to L-T4.
• Initiation of L-T3 resulted in significant clinical and biochemical improvement in these patients.
• Findings suggest a functional defect in peripheral T4 to T3 conversion.

Conclusions:

• Impaired peripheral T4 to T3 conversion may underlie some cases of ICI-induced hypothyroidism.
• Liothyronine (L-T3) may be an effective treatment option for non-responsive cases.
• Further research is needed to elucidate the mechanisms and optimize management.