Bexarotene-induced hypothyroidism and dyslipidemia; a nation-wide study
Central hypothyroidism and dyslipidemia are well-known adverse events (AEs) of bexarotene therapy. Although hypothyroidism is known to cause dyslipidemia, no study has examined the association between hypothyroidism and dyslipidemia in patients undergoing bexarotene therapy. The aim of this study is...
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The Japan Endocrine Society
2024-08-01
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| Series: | Endocrine Journal |
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| Online Access: | https://www.jstage.jst.go.jp/article/endocrj/71/8/71_EJ23-0699/_html/-char/en |
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| author | Katsunori Manaka Junichiro Sato Yusuke Hikima Hirofumi Horikoshi Maho Taguchi Akimichi Morita Hiraku Suga Hikari Boki Taku Fujimura Yoji Hirai Takatoshi Shimauchi Chiharu Tateishi Eiji Kiyohara Ikko Muto Hideki Nakajima Riichiro Abe Kazuyasu Fujii Chikako Nishigori Eiji Nakano Kentaro Yonekura Takeru Funakoshi Masahiro Amano Tomomitsu Miyagaki Reiko Yamashita Makoto Sugaya Toshihisa Hamada Masaomi Nangaku Taroh Iiri Noriko Makita |
| author_facet | Katsunori Manaka Junichiro Sato Yusuke Hikima Hirofumi Horikoshi Maho Taguchi Akimichi Morita Hiraku Suga Hikari Boki Taku Fujimura Yoji Hirai Takatoshi Shimauchi Chiharu Tateishi Eiji Kiyohara Ikko Muto Hideki Nakajima Riichiro Abe Kazuyasu Fujii Chikako Nishigori Eiji Nakano Kentaro Yonekura Takeru Funakoshi Masahiro Amano Tomomitsu Miyagaki Reiko Yamashita Makoto Sugaya Toshihisa Hamada Masaomi Nangaku Taroh Iiri Noriko Makita |
| author_sort | Katsunori Manaka |
| collection | DOAJ |
| description | Central hypothyroidism and dyslipidemia are well-known adverse events (AEs) of bexarotene therapy. Although hypothyroidism is known to cause dyslipidemia, no study has examined the association between hypothyroidism and dyslipidemia in patients undergoing bexarotene therapy. The aim of this study is to examine this association. A retrospective observational study was performed among 294 patients who initiated bexarotene therapy in Japan (nation-wide postmarketing complete surveillance). Jonckheere-Terpstra (one sided) test was performed to evaluate the effect of the bexarotene dose on lipid metabolisms, and regression analyses were performed to evaluate associations of bexarotene dose, free thyroxine (FT4), body mass index (BMI), and lipid metabolisms. Most patients developed hypothyroidism. Two-third of patients showed FT4 values below the lower limit at 1 week. Triglycerides (TG) increased in a bexarotene dose–dependent manner, and grade ≥3 AEs on hypertriglyceridemia was observed in 39% of the patients. Additionally, one-third of grade ≥3 AEs on hypertriglyceridemia occurred within 1 week. The delta_FT4 (difference in FT4 from baseline) negatively correlated with TG increase at 1 week (p = 0.012) but not with low density lipoprotein cholesterol (LDL-C) increase at any week. Bexarotene-induced hypothyroidism is almost inevitable and occurred quickly. Bexarotene-induced hypertriglyceridemia showed positive bexarotene dose dependency and negative delta_FT4 dependency. Prophylactic and appropriate thyroid hormone compensation therapy and starting bexarotene at low doses with subsequent titration while managing dyslipidemia may have a beneficial effect for the successful continuation of bexarotene therapy without severe endocrine and metabolic AEs. |
| format | Article |
| id | doaj-art-db10afb4e2ca4574be48c145484d1872 |
| institution | Kabale University |
| issn | 1348-4540 |
| language | English |
| publishDate | 2024-08-01 |
| publisher | The Japan Endocrine Society |
| record_format | Article |
| series | Endocrine Journal |
| spelling | doaj-art-db10afb4e2ca4574be48c145484d18722025-01-22T05:14:15ZengThe Japan Endocrine SocietyEndocrine Journal1348-45402024-08-0171877778710.1507/endocrj.EJ23-0699endocrjBexarotene-induced hypothyroidism and dyslipidemia; a nation-wide studyKatsunori Manaka0Junichiro Sato1Yusuke Hikima2Hirofumi Horikoshi3Maho Taguchi4Akimichi Morita5Hiraku Suga6Hikari Boki7Taku Fujimura8Yoji Hirai9Takatoshi Shimauchi10Chiharu Tateishi11Eiji Kiyohara12Ikko Muto13Hideki Nakajima14Riichiro Abe15Kazuyasu Fujii16Chikako Nishigori17Eiji Nakano18Kentaro Yonekura19Takeru Funakoshi20Masahiro Amano21Tomomitsu Miyagaki22Reiko Yamashita23Makoto Sugaya24Toshihisa Hamada25Masaomi Nangaku26Taroh Iiri27Noriko Makita28Division of Nephrology and Endocrinology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, JapanDivision of Nephrology and Endocrinology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, JapanDivision of Nephrology and Endocrinology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, JapanDivision of Nephrology and Endocrinology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, JapanDivision of Nephrology and Endocrinology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, JapanDepartment of Geriatric and Environmental Dermatology, Nagoya City University Graduate School of Medical Sciences, Nagoya 467-8601, JapanDepartment of Dermatology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, JapanDepartment of Dermatology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, JapanDepartment of Dermatology, Tohoku University Graduate School of Medicine, Sendai 980-8575, JapanDepartment of Dermatology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Okayama 700-8558, JapanDepartment of Dermatology, Hamamatsu University School of Medicine, Hamamatsu 431-3192, JapanDepartment of Dermatology, Osaka Metropolitan University Graduate School of Medicine, Osaka 545-8586, JapanDepartment of Dermatology, Course of Integrated Medicine, Graduate School of Medicine, Osaka University, Suita 560-8531, JapanDepartment of Dermatology, Kurume University School of Medicine, Kurume 830-0011, JapanDepartment of Dermatology, Kochi Medical School, Kochi University, Nankoku 783-8505, JapanDivision of Dermatology, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8510, JapanDepartment of Dermatology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima 890-8544, JapanDivision of Dermatology, Kobe University Graduate School of Medicine, Kobe 657-8501, JapanDivision of Dermatology, Kobe University Graduate School of Medicine, Kobe 657-8501, JapanDepartment of Dermatology, Imamura General Hospital, Kagoshima 890-0064, JapanDepartment of Dermatology, Keio University School of Medicine, Tokyo 160-8582, JapanDepartment of Dermatology, Faculty of Medicine, University of Miyazaki, Miyazaki 889-2192, JapanDepartment of Dermatology, St. Marianna University School of Medicine, Kawasaki 216-8511, JapanMinophagen Pharmaceutical Co., Ltd., Tokyo 160-0023, JapanDepartment of Dermatology, International University of Health and Welfare, Narita 286-8686, JapanDepartment of Dermatology, Takamatsu Red Cross Hospital, Takamatsu 760-0017, JapanDivision of Nephrology and Endocrinology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, JapanDepartment of Pharmacology, St. Marianna University School of Medicine, Kawasaki 216-8511, JapanDivision of Nephrology and Endocrinology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, JapanCentral hypothyroidism and dyslipidemia are well-known adverse events (AEs) of bexarotene therapy. Although hypothyroidism is known to cause dyslipidemia, no study has examined the association between hypothyroidism and dyslipidemia in patients undergoing bexarotene therapy. The aim of this study is to examine this association. A retrospective observational study was performed among 294 patients who initiated bexarotene therapy in Japan (nation-wide postmarketing complete surveillance). Jonckheere-Terpstra (one sided) test was performed to evaluate the effect of the bexarotene dose on lipid metabolisms, and regression analyses were performed to evaluate associations of bexarotene dose, free thyroxine (FT4), body mass index (BMI), and lipid metabolisms. Most patients developed hypothyroidism. Two-third of patients showed FT4 values below the lower limit at 1 week. Triglycerides (TG) increased in a bexarotene dose–dependent manner, and grade ≥3 AEs on hypertriglyceridemia was observed in 39% of the patients. Additionally, one-third of grade ≥3 AEs on hypertriglyceridemia occurred within 1 week. The delta_FT4 (difference in FT4 from baseline) negatively correlated with TG increase at 1 week (p = 0.012) but not with low density lipoprotein cholesterol (LDL-C) increase at any week. Bexarotene-induced hypothyroidism is almost inevitable and occurred quickly. Bexarotene-induced hypertriglyceridemia showed positive bexarotene dose dependency and negative delta_FT4 dependency. Prophylactic and appropriate thyroid hormone compensation therapy and starting bexarotene at low doses with subsequent titration while managing dyslipidemia may have a beneficial effect for the successful continuation of bexarotene therapy without severe endocrine and metabolic AEs.https://www.jstage.jst.go.jp/article/endocrj/71/8/71_EJ23-0699/_html/-char/enbexarotenehypothyroidismdyslipidemiahypertriglyceridemia |
| spellingShingle | Katsunori Manaka Junichiro Sato Yusuke Hikima Hirofumi Horikoshi Maho Taguchi Akimichi Morita Hiraku Suga Hikari Boki Taku Fujimura Yoji Hirai Takatoshi Shimauchi Chiharu Tateishi Eiji Kiyohara Ikko Muto Hideki Nakajima Riichiro Abe Kazuyasu Fujii Chikako Nishigori Eiji Nakano Kentaro Yonekura Takeru Funakoshi Masahiro Amano Tomomitsu Miyagaki Reiko Yamashita Makoto Sugaya Toshihisa Hamada Masaomi Nangaku Taroh Iiri Noriko Makita Bexarotene-induced hypothyroidism and dyslipidemia; a nation-wide study Endocrine Journal bexarotene hypothyroidism dyslipidemia hypertriglyceridemia |
| title | Bexarotene-induced hypothyroidism and dyslipidemia; a nation-wide study |
| title_full | Bexarotene-induced hypothyroidism and dyslipidemia; a nation-wide study |
| title_fullStr | Bexarotene-induced hypothyroidism and dyslipidemia; a nation-wide study |
| title_full_unstemmed | Bexarotene-induced hypothyroidism and dyslipidemia; a nation-wide study |
| title_short | Bexarotene-induced hypothyroidism and dyslipidemia; a nation-wide study |
| title_sort | bexarotene induced hypothyroidism and dyslipidemia a nation wide study |
| topic | bexarotene hypothyroidism dyslipidemia hypertriglyceridemia |
| url | https://www.jstage.jst.go.jp/article/endocrj/71/8/71_EJ23-0699/_html/-char/en |
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