ESPE Yearbook of Paediatric Endocrinology

Thyroid. 2022 May;32(5):496-504. doi: 10.1089/thy.2021.0685. Epub 2022 Mar 31. PMID: 35199588

Brief Summary: This retrospective monocenter case-control study assessed levothyroxine requirements to achieve euthyroidism defined as two consecutive normal TSH measurements (0.3-4.7 mIU/L) separated by ≥ 6 weeks in adult patients with immune checkpoint inhibitor (ICI) associated permanent hypothyroidism (cases) compared to patients with Hashimoto thyroiditis or athyreosis (controls). Patients with ICI-associated hypothyroidism required higher LT4 doses than patients with Hashimoto thyroiditis to achieve normal biochemical thyroid parameters.

ICI-associated hypothyroidism is the consequence of drug-induced destructive thyroiditis by ICI, such as anti-programmed cell death 1 (anti-PD-1), anti-programmed cell death ligand 1 (anti-PD-L1), or anti-cytotoxic T lymphocyte-associated protein 4 (anti-CTLA-4) molecules [1]. In the Yearbook 2021, we highlighted possible genetic factors modulating the risk for ICI-associated hypothyroidism [2].

This study focuses on treatment. Cases and controls were identified in the electronic medical records of the center. Patients with ICI-associated hypothyroidism (n=103) were identified, of whom n=66 achieved a stable euthyroid state under LT4 substitution therapy over more than 6 consecutive weeks and were classified as cases (71% post anti-PD1 treatment). Controls were n= 118 patients with antibody proven Hashimoto thyroiditis associated hypothyroidism, and n=74 patients with athyreosis post-surgery, or post-radioactive iodine ablation. Patients with ICI-associated hypothyroidism required higher LT4 doses than patients with Hashimoto thyroiditis, but comparable doses to athyreotic patients.

This study adds important new understanding of ICI-associated hypothyroidism by direct comparison to the two further major groups of adult patients with hypothyroidism. These data suggest a rapid destruction of the thyroid tissue compared to Hashimoto thyroiditis, rendering the patients functionally athyreotic as after thyroidectomy. The results may lead to a disease stratified replacement dose at diagnosis and during follow-up in this patient group.

References: 1. Endocrine Toxicity of Cancer Immunotherapy Targeting Immune Checkpoints. Chang LS, Barroso-Sousa R, Tolaney SM, Hodi FS, Kaiser UB, Min L. Endocr Rev. 2019 Feb 1;40(1):17-65. doi: 10.1210/er.2018-00006. PMID: 30184160. 2. Genetic variation associated with thyroid autoimmunity shapes the systemic immune response to PD-1 checkpoint blockade. Khan Z, Hammer C, Carroll J, Di Nucci F, Acosta SL, Maiya V, Bhangale T, Hunkapiller J, Mellman I, Albert ML, McCarthy MI, Chandler GS. Nat Commun. 2021 Jun 7;12(1):3355. doi: 10.1038/s41467-021-23661-4. PMID: 34099659.