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4 "Levothyroxine"
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Original Article
Thyroid
Adequate Dose of Levothyroxine for Thyroid-Stimulating Hormone Suppression after Total Thyroidectomy in Patients with Differentiated Thyroid Cancer
Hyun Jin Ryu, Min Sun Choi, Hyunju Park, Tae Hyuk Kim, Jae Hoon Chung, So Young Park, Sun Wook Kim
Endocrinol Metab. 2024;39(4):615-621.   Published online August 7, 2024
DOI: https://doi.org/10.3803/EnM.2023.1896
  • 14,296 View
  • 190 Download
  • 7 Web of Science
  • 6 Crossref
AbstractAbstract PDFPubReader   ePub   
Background
The adequate dose of levothyroxine (LT4) for patients who have undergone total thyroidectomy (TT) for differentiated thyroid cancer (DTC) is uncertain. We evaluated the LT4 dose required to achieve mild thyroid-stimulating hormone (TSH) suppression in DTC patients after TT.
Methods
The electronic medical records of patients who underwent TT for DTC and received mild TSH suppression therapy were reviewed. Linear regression analysis was performed to evaluate the association between LT4 dose (μg/kg) and an ordinal group divided by body mass index (BMI). We also evaluated the trend in LT4 doses among groups divided by BMI and age.
Results
In total, 123 patients achieved mild TSH suppression (0.1 to 0.5 mIU/L). The BMI variable was divided into three categories: <23 kg/m2 (n=46), ≥23 and <25 kg/m2 (n=30), and ≥25 kg/m2 (n=47). In the linear regression analysis, BMI was negatively associated with the LT4 dose after adjusting for age and sex (P<0.001). The LT4 doses required to achieve mild TSH suppression based on the BMI categories were 1.86, 1.71, and 1.71 μg/kg, respectively (P for trend <0.001). Further analysis with groups divided by age and BMI revealed that a higher BMI was related to a lower LT4 dose, especially in younger patients aged 20 to 39 (P for trend=0.011).
Conclusion
The study results suggest an appropriate LT4 dose for mild TSH suppression after TT based on body weight in patients with DTC. Considering body weight, BMI, and age in estimating LT4 doses might help to achieve the target TSH level promptly.

Citations

Citations to this article as recorded by  
  • A paper-based fluorescent aptasensor utilizing click chemistry strategy for portable detection of thyroid stimulating hormone
    Changxin Huangfu, Yanting Duan, Chenyue Zhan, Ruimin Liang, Jiajie Xu, Minghua Ge
    Microchemical Journal.2026; 225: 118035.     CrossRef
  • Effects of 131I and TSH suppression therapy on METTL3, METTL14 levels and recurrence in thyroid cancer
    Li-Guo Yang
    American Journal of Cancer Research.2025; 15(1): 42.     CrossRef
  • Developing a machine learning-based predictive model for levothyroxine dosage estimation in hypothyroid patients: a retrospective study
    Tran Thi Ngan, Dang Huong Tra, Ngo Thi Quynh Mai, Hoang Van Dung, Nguyen Van Khai, Pham Van Linh, Nguyen Thi Thu Phuong
    Frontiers in Endocrinology.2025;[Epub]     CrossRef
  • Tailoring TSH suppression in differentiated thyroid carcinoma: evidence, controversies, and future directions
    Xinxin Song, Xin Zhi, Linxue Qian
    Endocrine.2025; 89(1): 1.     CrossRef
  • Risk of Osteoporotic Fractures among Patients with Thyroid Cancer: A Nationwide Population-Based Cohort Study
    Eu Jeong Ku, Won Sang Yoo, Yu Been Hwang, Subin Jang, Jooyoung Lee, Shinje Moon, Eun Kyung Lee, Hwa Young Ahn
    Endocrinology and Metabolism.2025; 40(2): 225.     CrossRef
  • Levothyroxine Dosing for Thyroid-Stimulating Hormone Suppression in Patients with Differentiated Thyroid Cancer after Total Thyroidectomy
    Mijin Kim
    Endocrinology and Metabolism.2024; 39(4): 576.     CrossRef
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Review Article
Thyroid
Management of Subclinical Hypothyroidism: A Focus on Proven Health Effects in the 2023 Korean Thyroid Association Guidelines
Eu Jeong Ku, Won Sang Yoo, Hyun Kyung Chung
Endocrinol Metab. 2023;38(4):381-391.   Published online August 8, 2023
DOI: https://doi.org/10.3803/EnM.2023.1778
  • 19,956 View
  • 858 Download
  • 8 Web of Science
  • 13 Crossref
AbstractAbstract PDFPubReader   ePub   
Subclinical hypothyroidism (SCH) is characterized by elevated thyroid-stimulating hormone (TSH) and normal free thyroxine levels. The Korean Thyroid Association recently issued a guideline for managing SCH, which emphasizes Korean-specific TSH diagnostic criteria and highlights the health benefits of levothyroxine (LT4) treatment. A serum TSH level of 6.8 mIU/L is presented as the reference value for diagnosing SCH. SCH can be classified as mild (TSH 6.8 to 10.0 mIU/L) or severe (TSH >10.0 mIU/L), and patients can be categorized as adults (age <70 years) or elderly (age ≥70 years), depending on the health effects of LT4 treatment. An initial increase in serum TSH levels should be reassessed with a subsequent measurement, including a thyroid peroxidase antibody test, preferably 2 to 3 months after the initial assessment. While LT4 treatment is not generally recommended for mild SCH in adults, it is necessary for severe SCH in patients with underlying coronary artery disease or heart failure and it may be considered for those with concurrent dyslipidemia. Conversely, LT4 treatment is generally not recommended for elderly patients, regardless of SCH severity. For those SCH patients who are prescribed LT4 treatment, the dosage should be personalized, and serum TSH levels should be regularly monitored to maintain the optimal LT4 regimen.

Citations

Citations to this article as recorded by  
  • Sex differences in prevalence of subclinical hypothyroidism and its clinical correlates in overweight or obese, first-episode drug-naïve Chinese patients with major depressive disorder
    Qiyue Qiu, Wan Yin Tew, Chenxi Liu, Jie Zhang, Bo Liu, Mun Fei Yam, Shichang Yang, Xiang-Yang Zhang
    Journal of Affective Disorders.2026; 398: 121068.     CrossRef
  • Assessment of Serum Adropin Levels in Patients with Subclinical Hypothyroidism
    Tuba Yılmaz Yıldırım, Mehmet Zorlu, Eray Metin Güler, Muharrem Kıskaç, Hakan Beyaztaş
    Bezmialem Science.2026;[Epub]     CrossRef
  • Evaluation of the add on effect of Majoone Sarkhas with levothyroxine in primary hypothyroidism: a randomized standard control adjuvant clinical study
    Md Anzar Alam, Mohd Aleemuddin Quamri, Ghulamuddin Sofi, Nafis Haider
    Drug Metabolism and Personalized Therapy.2025; 40(2): 121.     CrossRef
  • Macro-Thyrotropin Syndrome: Prevalence and Clinical Profile of an Under-Recognised Rare Entity in Thyroidology
    Maitri M. Patel, Dhara K. Patel, Lalitkumar B. Patel, Chetan B. Dharaiya, Dhruvkumar M. Patel, Ravi M. Vasani, Mukundkumar V. Patel
    Indian Journal of Endocrinology and Metabolism.2025; 29(1): 95.     CrossRef
  • Long-term forecasting and evaluation of medicine consumption for the ATC class H with a focus on thyroid hormones in OECD countries using ARIMA models
    Lilly Josephine Bindel, Roland Seifert
    Naunyn-Schmiedeberg's Archives of Pharmacology.2025; 398(8): 10691.     CrossRef
  • Incidence and risk factors for early thyroxin supplementation therapy after hemithyroidectomy for benign conditions in Europe. A Eurocrine® registry-based study
    Jesús M. Villar-del-Moral, Juan I. Arcelus-Martínez, Antonio Becerra-Massare, Nuria Muñoz-Pérez, María C. Olvera-Porcel, Cristina Martínez-Santos
    Updates in Surgery.2025; 77(5): 1593.     CrossRef
  • DIAGNÓSTICO E MANEJO DO HIPOTIREOIDISMO SUBCLÍNICO: UMA REVISÃO DE LITERATURA
    Dayane Beserra Costa Felício, Mariana Barbosa Silva, Mileide Beatriz de Lima Santos, Yasmin Cabral Menezes de Oliveira, Vinícius de Lima Paes, Ana Paula Simadon, Cleyciane Camila de Souza Belo Nogueira, Giulia Costa Moura
    REVISTA FOCO.2025; 18(4): e8209.     CrossRef
  • Subclinical Hypothyroidism after a Three-Month Course of Low-Dose Amiodarone.
    Rano Kirkimbayeva, Telman Seisembekov, Bakyt Iskakova, Nauryzbay Bekishuly, Assel Chinybayeva, Galiya Smailova, Diana Aibulova, Aya Aitpayeva, Aidana Butabayeva, Zhansaya Yerkhanova, Olzhas Yesseneyev, Ayan Abdrakhmanov
    Journal of Clinical Medicine of Kazakhstan.2025; 22(2): 54.     CrossRef
  • Impact of subclinical hypothyroidism on glycemic markers and insulin resistance in nondiabetic Iraqi patients: a cross-sectional study
    Maysam Riyadh Mohammed Hussein Alaasam, Raffat Hilal Abboodi, Hayder Nadhim Mohsin Al-Khayyat
    INTERNATIONAL JOURNAL OF ENDOCRINOLOGY (Ukraine).2025; 21(6): 583.     CrossRef
  • Clinical Implications of Different Thyroid-Stimulating Hormone (TSH) Reference Intervals between TSH Kits for the Management of Subclinical Hypothyroidism
    Won Sang Yoo
    Endocrinology and Metabolism.2024; 39(1): 188.     CrossRef
  • Serum Vitamin B12 and Holotranscobalamin Levels in Subclinical Hypothyroid Patients in Relation to Thyroid-Stimulating Hormone (TSH) Levels and the Positivity of Anti-thyroid Peroxidase Antibodies: A Case-Control Study
    Muqdad Al-Mousawi, Sherwan Salih, Ameer Ahmed, Barhav Abdullah
    Cureus.2024;[Epub]     CrossRef
  • Severe Symptomatic Anemia as a Rare Initial Manifestation of Type 3 Polyglandular Autoimmune Syndrome: A Case Report
    Hugo Goncalves, Francisco De Oliveira Simões, Rosa Sá, Bárbara Fraga Campos, Rui M Domingues, Narciso Oliveira, Teresa Pimentel
    Cureus.2024;[Epub]     CrossRef
  • Evaluation of the effects of thyroid functions on frailty in geriatric patients using the Edmonton, SOF and FRAIL Scales
    Galip Can Uyar, Mustafa Kemal Kılıç
    BMC Geriatrics.2024;[Epub]     CrossRef
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Original Articles
Clinical Study
Detection of Polyethylene Glycol Thyrotropin (TSH) Precipitable Percentage (Macro-TSH) in Patients with a History of Thyroid Cancer
Massimo Giusti, Lucia Conte, Anna Maria Repetto, Stefano Gay, Paola Marroni, Miranda Mittica, Michele Mussap
Endocrinol Metab. 2017;32(4):460-465.   Published online December 14, 2017
DOI: https://doi.org/10.3803/EnM.2017.32.4.460
  • 9,392 View
  • 132 Download
  • 9 Web of Science
  • 8 Crossref
AbstractAbstract PDFPubReader   
Background

Owing to its large molecular size, polyethylene glycol (PEG)-precipitable thyrotropin (TSH) can accumulate in the circulation, elevating TSH levels. PEG-precipitable TSH can be used to detect macro-TSH (mTSH) in serum. Our aim was to evaluate the prevalence of mTSH in patients who had undergone thyroidectomy for thyroid cancer.

Methods

Seventy-three thyroid cancer patients and 24 control subjects on levothyroxine (LT4) TSH-suppressive or replacement therapy were evaluated. Screening for mTSH was performed by adding PEG to serum in order to precipitate γ-globulin. A percentage of PEG-precipitable TSH ≥80% was considered suggestive of mTSH.

Results

No correlation between free-T4 (fT4) and TSH levels was found. PEG-precipitable TSH was 39.3%±1.9% in thyroid cancer patients and 44.1%±3.9% in controls. Macro-TSH was deemed to be present in one thyroid cancer patient and in two control subjects. Only in the thyroid cancer group was PEG-precipitable TSH found to be negatively correlated with fT4 concentration. No correlation was found between PEG-precipitable TSH and other clinical conditions in any patients.

Conclusion

The presence of mTSH seems to be a rare phenomenon in thyroid cancer. In some patients with low PEG-precipitable TSH, a reduction in LT4 dosage could be suggested. LT4 dosage adjusted to body weight is the main factor in maintaining TSH in a semi-suppressed or normal range. Evaluation of mTSH could be necessary in patients in whom a balance is required between adequate TSH suppression and the avoidance of unnecessary exogenous hyperthyroxinemia.

Citations

Citations to this article as recorded by  
  • PEG Precipitation to Detect Macro‐TSH in Clinical Practice: A Systematic Review
    Tommaso Piticchio, Isabella Chiardi, Andrea Tumminia, Francesco Frasca, Mario Rotondi, Pierpaolo Trimboli
    Clinical Endocrinology.2025; 102(3): 235.     CrossRef
  • Exploration of post-PEG precipitation TSH recovery in hypothyroid patients
    Jing Yin, Zhanjun Mei, Bo Zhang, Fang Tang
    Frontiers in Endocrinology.2025;[Epub]     CrossRef
  • Prevalence and Pathogenesis of Macro-Thyrotropin in Neonates: Analysis of Umbilical Cord Blood from 939 Neonates and Their Mothers
    Naoki Hattori, Kohzo Aisaka, Ayato Yamada, Takeshi Matsuda, Akira Shimatsu
    Thyroid.2023; 33(1): 45.     CrossRef
  • Pars Distalis and Pars Tuberalis Thyroid-Stimulating Hormones and Their Roles in Macro-Thyroid-Stimulating Hormone Formation
    Eleonore Fröhlich, Richard Wahl
    International Journal of Molecular Sciences.2023; 24(14): 11699.     CrossRef
  • Falsely Elevated Thyroid Stimulating Hormone in Two Cases Requiring Special Follow-up
    Serpil YANIK ÇOLAK, Eray ÖZGÜN, Burak ANDAÇ, Mine OKUR, Buket YILMAZ BÜLBÜL, Mehmet ÇELİK
    Namık Kemal Tıp Dergisi.2023; 11(4): 395.     CrossRef
  • A comparative cross-sectional study on sleep quality in patients with a history of differentiated thyroid carcinoma and its correlation with quality of life
    Marsida Teliti, Eleonora Monti, Martina Comina, Lucia Conte, Lara Vera, Stefano Gay, Giorgia Saccomani, Diego Ferone, Massimo Giusti
    Endocrine.2021; 73(2): 347.     CrossRef
  • A rare cause of subclinical hypothyroidism: macro-thyroid-stimulating hormone
    Cem Onur Kirac, Sedat Abusoglu, Esra Paydas Hataysal, Aysegul Kebapcilar, Suleyman Hilmi Ipekci, Ali Ünlü, Levent Kebapcilar
    Diagnosis.2020; 7(1): 75.     CrossRef
  • Neuroendocrine neoplasms – think about it and choose the most appropriate diagnostic and therapeutic steps
    Christian A. Koch, S. Petersenn
    Reviews in Endocrine and Metabolic Disorders.2018; 19(2): 107.     CrossRef
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Factors Influencing Peripheral Conversion of Thyroxine to Tri-Iodothyronine in Athyreotic Individuals during Levothyroxine Replacement.
Eui Young Kim, Won Gu Kim, Tae Yong Kim, Jong Ho Yoon, Suck Joon Hong, Young Kee Shong, Won Bae Kim
Endocrinol Metab. 2010;25(2):119-124.   Published online June 1, 2010
DOI: https://doi.org/10.3803/EnM.2010.25.2.119
  • 5,684 View
  • 67 Download
AbstractAbstract PDF
BACKGROUND
Tri-iodothyronine (T3) is the main active hormone, and 20% of this is derived from the thyroid gland and 80% is from the peripheral tissue according to 5'-monodeiodination of thyroxine (T4). In the previous studies, normal T3 levels were achieved with traditional levothyroxine (LT4) therapy alone in athyreotic patients, but there has been no data about the factors influencing peripheral conversion of LT4. The aim of this study was to determine the factor(s) influencing peripheral conversion of LT4 to T3 in athyreotic patients during LT4 replacement. METHODS: The patients who underwent total-thyroidectomy for any cause, and mostly for thyroid cancers, at Asan Medical Center between 2000 and 2008 were enrolled. The free T4, T3 and thyroid stimulating hormone (TSH) levels and age, gender, weight, height, body mass index (BMI) and the T4 dose were measured. Only patients with normal ranges of free T4 and TSH were included in the analysis. RESULTS: A total of 143 patients were enrolled. The mean T3, free T4 and TSH levels were 143.7 ng/dL, 1.4 ng/dL and 1.6 microU/mL, respectively. The mean weight and BMI were 62.9 kg and 24.6 kg/m2, respectively. We divided them into two groups according to the serum T3 level and we compared the characteristics of the groups. There were no differences in age, the gender distribution, the T4 dose/weight and the BMI between the low T3 group (T3 < or = 122 ng/dL, n = 14) and the normal T3 group (T3 > 122 ng/dL, n = 129). In the low T3 group, the mean body weight was significantly lower than that of the normal T3 group (59.0 +/- 6.0 vs. 63.4 +/- 9.9, respectively, P = 0.025). CONCLUSION: Lean body mass seems to be an important factor for determining the peripheral conversion of T4 to T3 in human. This suggest that a combination of T3/T4 is better than T4 only when we treat the patients with hypothyroidism and who have a negligible amount of functioning thyroid tissue, if they have a low lean body mass.
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