Prediction-based prompt levothyroxine replacement to prevent a hypothyroid state after immune-related adverse events involving the thyroid gland
Immune checkpoint inhibitors (ICIs) are used for various malignancies, although they frequently cause immune-related adverse events involving the thyroid gland (thyroid irAEs). We conducted a retrospective cohort study to elucidate thyroid function outcomes. Fifty of 639 patients who received PD-1 b...
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| Language: | English |
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The Japan Endocrine Society
2023-10-01
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| Series: | Endocrine Journal |
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| Online Access: | https://www.jstage.jst.go.jp/article/endocrj/70/10/70_EJ23-0262/_html/-char/en |
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| author | Ichiro Yamauchi Takuro Hakata Taku Sugawa Daisuke Kosugi Haruka Fujita Kentaro Okamoto Yohei Ueda Toshihito Fujii Daisuke Taura Norio Harada Nobuya Inagaki |
| author_facet | Ichiro Yamauchi Takuro Hakata Taku Sugawa Daisuke Kosugi Haruka Fujita Kentaro Okamoto Yohei Ueda Toshihito Fujii Daisuke Taura Norio Harada Nobuya Inagaki |
| author_sort | Ichiro Yamauchi |
| collection | DOAJ |
| description | Immune checkpoint inhibitors (ICIs) are used for various malignancies, although they frequently cause immune-related adverse events involving the thyroid gland (thyroid irAEs). We conducted a retrospective cohort study to elucidate thyroid function outcomes. Fifty of 639 patients who received PD-1 blockade therapy met criteria and were divided into the following groups: thyrotoxicosis with subsequent hypothyroidism (Toxic-Hypo, n = 21); thyrotoxicosis without subsequent hypothyroidism (Toxic, n = 9); and hypothyroidism without prior thyrotoxicosis (Hypo, n = 20). The Toxic-Hypo group developed thyroid irAEs earlier than the Toxic group (26 vs. 91 days; p < 0.001), and had higher serum free T4 levels (3.210 vs. 1.880 ng/dL; p = 0.011). In addition, positive anti-thyroglobulin antibodies (TgAbs) at thyroid irAE onset were more common in the Toxic-Hypo group (93.3%) than in the Toxic group (0.0%; p = 0.005) and Hypo group (44.4%; p = 0.007). The Toxic-Hypo group developed severe hypothyroidism and required larger levothyroxine (LT4) doses than the Hypo group (75 vs. 25 μg/day; p = 0.007). We predicted that patients with positive TgAbs who developed severe thyrotoxicosis within 4 weeks after the first ICI administration would develop subsequent hypothyroidism. We treated 4 such patients with prompt LT4 replacement, characterized by LT4 initiation after thyrotoxicosis improvement and quick dose titration. Their euthyroid state was successfully maintained, in contrast with patients receiving conventional replacement. In conclusion, rapid-onset severe thyrotoxicosis in patients with TgAbs correlated with a high likelihood of subsequent hypothyroidism. Accordingly, prompt LT4 replacement is suggested to prevent a severely hypothyroid state. |
| format | Article |
| id | doaj-art-5377cab0fa8d4a11b42f449e3fa68f31 |
| institution | Kabale University |
| issn | 1348-4540 |
| language | English |
| publishDate | 2023-10-01 |
| publisher | The Japan Endocrine Society |
| record_format | Article |
| series | Endocrine Journal |
| spelling | doaj-art-5377cab0fa8d4a11b42f449e3fa68f312025-01-22T06:19:20ZengThe Japan Endocrine SocietyEndocrine Journal1348-45402023-10-01701098799810.1507/endocrj.EJ23-0262endocrjPrediction-based prompt levothyroxine replacement to prevent a hypothyroid state after immune-related adverse events involving the thyroid glandIchiro Yamauchi0Takuro Hakata1Taku Sugawa2Daisuke Kosugi3Haruka Fujita4Kentaro Okamoto5Yohei Ueda6Toshihito Fujii7Daisuke Taura8Norio Harada9Nobuya Inagaki10Department of Diabetes, Endocrinology and Nutrition, Kyoto University Graduate School of Medicine, Kyoto 606-8507, JapanDepartment of Diabetes, Endocrinology and Nutrition, Kyoto University Graduate School of Medicine, Kyoto 606-8507, JapanDepartment of Diabetes, Endocrinology and Nutrition, Kyoto University Graduate School of Medicine, Kyoto 606-8507, JapanDepartment of Diabetes, Endocrinology and Nutrition, Kyoto University Graduate School of Medicine, Kyoto 606-8507, JapanDepartment of Diabetes, Endocrinology and Nutrition, Kyoto University Graduate School of Medicine, Kyoto 606-8507, JapanDepartment of Diabetes, Endocrinology and Nutrition, Kyoto University Graduate School of Medicine, Kyoto 606-8507, JapanDepartment of Diabetes, Endocrinology and Nutrition, Kyoto University Graduate School of Medicine, Kyoto 606-8507, JapanDepartment of Diabetes, Endocrinology and Nutrition, Kyoto University Graduate School of Medicine, Kyoto 606-8507, JapanDepartment of Diabetes, Endocrinology and Nutrition, Kyoto University Graduate School of Medicine, Kyoto 606-8507, JapanDepartment of Diabetes, Endocrinology and Nutrition, Kyoto University Graduate School of Medicine, Kyoto 606-8507, JapanMedical Research Institute Kitano Hospital, PIIF Tazuke-kofukai, Osaka 530-8480, JapanImmune checkpoint inhibitors (ICIs) are used for various malignancies, although they frequently cause immune-related adverse events involving the thyroid gland (thyroid irAEs). We conducted a retrospective cohort study to elucidate thyroid function outcomes. Fifty of 639 patients who received PD-1 blockade therapy met criteria and were divided into the following groups: thyrotoxicosis with subsequent hypothyroidism (Toxic-Hypo, n = 21); thyrotoxicosis without subsequent hypothyroidism (Toxic, n = 9); and hypothyroidism without prior thyrotoxicosis (Hypo, n = 20). The Toxic-Hypo group developed thyroid irAEs earlier than the Toxic group (26 vs. 91 days; p < 0.001), and had higher serum free T4 levels (3.210 vs. 1.880 ng/dL; p = 0.011). In addition, positive anti-thyroglobulin antibodies (TgAbs) at thyroid irAE onset were more common in the Toxic-Hypo group (93.3%) than in the Toxic group (0.0%; p = 0.005) and Hypo group (44.4%; p = 0.007). The Toxic-Hypo group developed severe hypothyroidism and required larger levothyroxine (LT4) doses than the Hypo group (75 vs. 25 μg/day; p = 0.007). We predicted that patients with positive TgAbs who developed severe thyrotoxicosis within 4 weeks after the first ICI administration would develop subsequent hypothyroidism. We treated 4 such patients with prompt LT4 replacement, characterized by LT4 initiation after thyrotoxicosis improvement and quick dose titration. Their euthyroid state was successfully maintained, in contrast with patients receiving conventional replacement. In conclusion, rapid-onset severe thyrotoxicosis in patients with TgAbs correlated with a high likelihood of subsequent hypothyroidism. Accordingly, prompt LT4 replacement is suggested to prevent a severely hypothyroid state.https://www.jstage.jst.go.jp/article/endocrj/70/10/70_EJ23-0262/_html/-char/enimmune-related adverse events (iraes)thyrotoxicosishypothyroidismimmune checkpoint inhibitor (ici)levothyroxine |
| spellingShingle | Ichiro Yamauchi Takuro Hakata Taku Sugawa Daisuke Kosugi Haruka Fujita Kentaro Okamoto Yohei Ueda Toshihito Fujii Daisuke Taura Norio Harada Nobuya Inagaki Prediction-based prompt levothyroxine replacement to prevent a hypothyroid state after immune-related adverse events involving the thyroid gland Endocrine Journal immune-related adverse events (iraes) thyrotoxicosis hypothyroidism immune checkpoint inhibitor (ici) levothyroxine |
| title | Prediction-based prompt levothyroxine replacement to prevent a hypothyroid state after immune-related adverse events involving the thyroid gland |
| title_full | Prediction-based prompt levothyroxine replacement to prevent a hypothyroid state after immune-related adverse events involving the thyroid gland |
| title_fullStr | Prediction-based prompt levothyroxine replacement to prevent a hypothyroid state after immune-related adverse events involving the thyroid gland |
| title_full_unstemmed | Prediction-based prompt levothyroxine replacement to prevent a hypothyroid state after immune-related adverse events involving the thyroid gland |
| title_short | Prediction-based prompt levothyroxine replacement to prevent a hypothyroid state after immune-related adverse events involving the thyroid gland |
| title_sort | prediction based prompt levothyroxine replacement to prevent a hypothyroid state after immune related adverse events involving the thyroid gland |
| topic | immune-related adverse events (iraes) thyrotoxicosis hypothyroidism immune checkpoint inhibitor (ici) levothyroxine |
| url | https://www.jstage.jst.go.jp/article/endocrj/70/10/70_EJ23-0262/_html/-char/en |
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