Developing a machine learning-based predictive model for levothyroxine dosage estimation in hypothyroid patients: a retrospective study
Hypothyroidism, a common endocrine disorder, has a high incidence in women and increases with age. Levothyroxine (LT4) is the standard therapy; however, achieving clinical and biochemical euthyroidism is challenging. Therefore, developing an accurate model for predicting LT4 dosage is crucial. This...
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Frontiers Media S.A.
2025-03-01
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| Series: | Frontiers in Endocrinology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fendo.2025.1415206/full |
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| author | Tran Thi Ngan Tran Thi Ngan Dang Huong Tra Ngo Thi Quynh Mai Hoang Van Dung Nguyen Van Khai Pham Van Linh Nguyen Thi Thu Phuong Nguyen Thi Thu Phuong |
| author_facet | Tran Thi Ngan Tran Thi Ngan Dang Huong Tra Ngo Thi Quynh Mai Hoang Van Dung Nguyen Van Khai Pham Van Linh Nguyen Thi Thu Phuong Nguyen Thi Thu Phuong |
| author_sort | Tran Thi Ngan |
| collection | DOAJ |
| description | Hypothyroidism, a common endocrine disorder, has a high incidence in women and increases with age. Levothyroxine (LT4) is the standard therapy; however, achieving clinical and biochemical euthyroidism is challenging. Therefore, developing an accurate model for predicting LT4 dosage is crucial. This retrospective study aimed to identify factors affecting the daily dose of LT4 and develop a model to estimate the dose of LT4 in hypothyroidism from a cohort of 1,864 patients through a comprehensive analysis of electronic medical records. Univariate analysis was conducted to explore the relationships between clinical and non-clinical variables, including weight, sex, age, body mass index, diastolic blood pressure, comorbidities, food effects, drug-drug interactions, liver function, serum albumin and TSH levels. Among the models tested, the Extra Trees Regressor (ETR) demonstrated the highest predictive accuracy, achieving an R² of 87.37% and the lowest mean absolute error of 9.4 mcg (95% CI: 7.7–11.2) in the test set. Other ensemble models, including Random Forest and Gradient Boosting, also showed strong performance (R² > 80%). Feature importance analysis highlighted BMI (0.516 ± 0.015) as the most influential predictor, followed by comorbidities (0.120 ± 0.010) and age (0.080 ± 0.005). The findings underscore the potential of machine learning in refining LT4 dose estimation by incorporating diverse clinical factors beyond traditional weight-based approaches. The model provides a solid foundation for personalized LT4 dosing, which can enhance treatment precision and reduce the risk of under- or over-medication. Further validation in external cohorts is essential to confirm its clinical applicability. |
| format | Article |
| id | doaj-art-bf232a5ffbcd4603a3ce309f20133d56 |
| institution | DOAJ |
| issn | 1664-2392 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Endocrinology |
| spelling | doaj-art-bf232a5ffbcd4603a3ce309f20133d562025-08-20T02:52:28ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922025-03-011610.3389/fendo.2025.14152061415206Developing a machine learning-based predictive model for levothyroxine dosage estimation in hypothyroid patients: a retrospective studyTran Thi Ngan0Tran Thi Ngan1Dang Huong Tra2Ngo Thi Quynh Mai3Hoang Van Dung4Nguyen Van Khai5Pham Van Linh6Nguyen Thi Thu Phuong7Nguyen Thi Thu Phuong8Faculty of Pharmacy & Biomedical-Pharmaceutical Sciences Research Group, Hai Phong University of Medicine and Pharmacy, Hai Phong, VietnamPharmacy Department, Hai Phong International Hospital, Hai Phong, VietnamFaculty of Pharmacy & Biomedical-Pharmaceutical Sciences Research Group, Hai Phong University of Medicine and Pharmacy, Hai Phong, VietnamFaculty of Pharmacy & Biomedical-Pharmaceutical Sciences Research Group, Hai Phong University of Medicine and Pharmacy, Hai Phong, VietnamDepartment of Rheumatology-Nephrology-Allergy and Immunology, Hai Phong International Hospital, Hai Phong, VietnamFaculty of Public Health, Hai Phong University of Medicine and Pharmacy, Hai Phong, VietnamFaculty of Medicine, Hai Phong University of Medicine and Pharmacy, Hai Phong, VietnamFaculty of Pharmacy & Biomedical-Pharmaceutical Sciences Research Group, Hai Phong University of Medicine and Pharmacy, Hai Phong, VietnamPharmacy Department, Hai Phong International Hospital, Hai Phong, VietnamHypothyroidism, a common endocrine disorder, has a high incidence in women and increases with age. Levothyroxine (LT4) is the standard therapy; however, achieving clinical and biochemical euthyroidism is challenging. Therefore, developing an accurate model for predicting LT4 dosage is crucial. This retrospective study aimed to identify factors affecting the daily dose of LT4 and develop a model to estimate the dose of LT4 in hypothyroidism from a cohort of 1,864 patients through a comprehensive analysis of electronic medical records. Univariate analysis was conducted to explore the relationships between clinical and non-clinical variables, including weight, sex, age, body mass index, diastolic blood pressure, comorbidities, food effects, drug-drug interactions, liver function, serum albumin and TSH levels. Among the models tested, the Extra Trees Regressor (ETR) demonstrated the highest predictive accuracy, achieving an R² of 87.37% and the lowest mean absolute error of 9.4 mcg (95% CI: 7.7–11.2) in the test set. Other ensemble models, including Random Forest and Gradient Boosting, also showed strong performance (R² > 80%). Feature importance analysis highlighted BMI (0.516 ± 0.015) as the most influential predictor, followed by comorbidities (0.120 ± 0.010) and age (0.080 ± 0.005). The findings underscore the potential of machine learning in refining LT4 dose estimation by incorporating diverse clinical factors beyond traditional weight-based approaches. The model provides a solid foundation for personalized LT4 dosing, which can enhance treatment precision and reduce the risk of under- or over-medication. Further validation in external cohorts is essential to confirm its clinical applicability.https://www.frontiersin.org/articles/10.3389/fendo.2025.1415206/fulllevothyroxinehypothyroidismmodel estimationendocrineretrospective study |
| spellingShingle | Tran Thi Ngan Tran Thi Ngan Dang Huong Tra Ngo Thi Quynh Mai Hoang Van Dung Nguyen Van Khai Pham Van Linh Nguyen Thi Thu Phuong Nguyen Thi Thu Phuong Developing a machine learning-based predictive model for levothyroxine dosage estimation in hypothyroid patients: a retrospective study Frontiers in Endocrinology levothyroxine hypothyroidism model estimation endocrine retrospective study |
| title | Developing a machine learning-based predictive model for levothyroxine dosage estimation in hypothyroid patients: a retrospective study |
| title_full | Developing a machine learning-based predictive model for levothyroxine dosage estimation in hypothyroid patients: a retrospective study |
| title_fullStr | Developing a machine learning-based predictive model for levothyroxine dosage estimation in hypothyroid patients: a retrospective study |
| title_full_unstemmed | Developing a machine learning-based predictive model for levothyroxine dosage estimation in hypothyroid patients: a retrospective study |
| title_short | Developing a machine learning-based predictive model for levothyroxine dosage estimation in hypothyroid patients: a retrospective study |
| title_sort | developing a machine learning based predictive model for levothyroxine dosage estimation in hypothyroid patients a retrospective study |
| topic | levothyroxine hypothyroidism model estimation endocrine retrospective study |
| url | https://www.frontiersin.org/articles/10.3389/fendo.2025.1415206/full |
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