Evaluation of sodium levothyroxine absorption in real clinical practice using a single-bolus oral test
https://doi.org/10.14341/probl13665
Abstract
BACKGROUND: Thyroid hormone replacement therapy results remain unsatisfactory in 30-50% of cases. To differentiate between true levothyroxine sodium malabsorption and pseudomalabsorption due to poor compliance, several absorption assessment tests with different evaluation criteria are proposed.
AIM: To determine the criteria for normal absorption of levothyroxine sodium when performing an oral test with a single bolus dose of 600 mсg.
MATERIALS AND METHODS: The study involved 20 healthy volunteers of both sexes, aged 18 to 35 years, with normal body weight. The bolus dose of levothyroxine sodium was 600 mсg. Blood samples for determination of free thyroxine (fT4) concentration in serum were taken on an empty stomach, 1 hour, 2, 3, 4, 6 hours after taking the drug.
RESULTS: After taking levothyroxine sodium at a dose of 600 mcg, the maximum level of free T4 was observed after 2 hours — 21,00 pmol/l [19,20; 23,16]. The minimum increase in the concentration of free T4 2 hours after taking levothyroxine sodium at a dose of 600 mcg was — 18,0%, the maximum — 91,1%.
CONCLUSION: To assess the absorption of levothyroxine sodium, a single oral dose of 600 mcg of levothyroxine sodium is recommended. Absorption of levothyroxine sodium can be considered normal if the increase in free T4 concentration 2, 3, or 4 hours after the bolus dose is at least 18%.
About the Authors
E. A. TroshinaРоссия
Ekaterina A. Troshina, MD, PhD, Professor
Moscow
N. V. Mazurina
Россия
Natalya V. Mazurina, MD, PhD
Moscow
M. H. Botasheva
Россия
Medina H. Botasheva, MD
11 Dm. Ulyanova street, 117292, Moscow
N. M. Platonova
Россия
Nadezhda M. Platonova, MD, PhD
Moscow
A. P. Pershina-Milyutina
Россия
Anastasiia P. Pershina-Miliutina, MD
Moscow
I. R. Gasymova
Россия
Irada R.K. Gasymova, MD
Moscow
References
1. Biruykova EV, Kileinikov DV, Solovieva IV. Hipothyreos: sovremennoye sostoyanie problemy. Meditsinskiy sovet. 2020;7:96-107. doi: https://doi.org/10.21518/2079-701X-2020-7-96-107
2. Manuiylova YA, Morgunova TB, Fadeev VV. Prichiny neeffektivnosty zamestitelnoiy terapii pervichnogo hipothyreosa. Klinicheskaya i experimentalnaya thireoidologiya. 2019;15(1):12-18. doi: https://doi.org/10.14341/ket10163
3. Petunina NA, Martirosyan NS, Telnova ME, i dr. Terapiya hypothyreosa v osobych gruppah patsientov. Effectivnaya pharmakotherapiya. 2021;17(20):38-41. doi: https://doi.org/10.33978/2307-3586-2021-17-20-38-41
4. Eligar V, Taylor PN, Okosieme OE, Leese GP, Dayan CM. Thyroxine replacement: a clinical endocrinologist’s viewpoint. Ann Clin Biochem. 2016;53(Pt4):421-33. doi: https://doi.org/10.1177/0004563216642255
5. Caron P, Grunenwald S, Persani L, Borson-Chazot F, Leroy R, Duntas L. Factors influencing the levothyroxine dose in the hormone replacement therapy of primary hypothyroidism in adults. Rev Endocr Metab Disord. 2022;23(3):463-483. doi: https://doi.org/10.1007/s11154-021-09691-9
6. Colucci P, Yue CS, Ducharme M, Benvenga S. A Review of the Pharmacokinetics of Levothyroxine for the Treatment of Hypothyroidism. Eur Endocrinol. 2013;9(1):40-47. doi: https://doi.org/10.17925/EE.2013.09.01.40
7. Skelin M, et al. Factors Affecting Gastrointestinal Absorption of Levothyroxine: A Review. Clin Ther. 2017;39(2):378-403. doi: https://doi.org/10.1016/j.clinthera.2017.01.005
8. Canaris GJ, Manowitz NR, Mayor G, Ridgway EC. The Colorado thyroid disease prevalence study. Arch Intern Med. 2000;160(4):526-34. doi: https://doi.org/10.1001/archinte.160.4.526
9. Somwaru LL, Arnold AM, Joshi N, Fried LP, Cappola AR. High frequency of and factors associated with thyroid hormone over-replacement and under-replacement in men and women aged 65 and over. J Clin Endocrinol Metab. 2009;94(4):1342-5. doi: https://doi.org/10.1210/jc.2008-1696
10. Caron P, Tudor C, Grunenwald S. Levothyroxine Absorption Test With the Daily Levothyroxine Dose in Patients With «Refractory Hypothyroidism». J Endocr Soc. 2025; 9(4):bvaf017. doi: https://doi.org/10.1210/jendso/bvaf017
11. Gonzales KM, Stan MN, Morris JC, et al. The Levothyroxine Absorption Test: A Four-Year Experience (2015-2018) at The Mayo Clinic. Thyroid. 2019;29:1734-1742. doi: https://doi.org/10.1089/thy.2019.0256
12. Sun GE, Pantalone KM, Faiman C, et al. The clinical utility of free thyroxine in oral levothyroxine absorption testing. Endocr Pract. 2014;20:925-929. doi: https://doi.org/10.4158/EP13487.OR
13. Yildirim Simsir I, Soyaltin UE, Ozgen AG. Levothyroxine absorption test results in patients with TSH elevation resistant to treatment. Endocrine. 2019;64:118-121. doi: https://doi.org/10.1007/s12020-019-01889-x
14. Ghosh S, Pramanik S, Biswas K, et al. Levothyroxine Absorption Test to Differentiate Pseudomalabsorption from True Malabsorption. Eur Thyroid J. 2020;9:19-24. doi: https://doi.org/10.1159/000504218
15. Subramaniam K, Babu T, Sreevalsan KC, et al. Levothyroxine Absorption Test – Results and Follow Up of Patients from a Single Center. Indian J Endocrinol Metab. 2023;27:32-36. doi: https://doi.org/10.4103/ijem.ijem_188_21
16. Balla M, Jhingan RM, Rubin DJ. Rapid levothyroxine absorption testing: a case series of nonadherent patients. Int J Endocrinol Metab. 2015;13(4):e31051. doi: https://doi.org/10.5812/ijem.31051
17. Van Wilder N, Bravenboer B, Herremans S, Vanderbruggen N, Velkeniers B. Pseudomalabsorption of levothyroxine: a challenge for the endocrinologist in the treatment of hypothyroidism. Eur Thyroid J. 2017;6(1):52-56. doi: https://doi.org/10.1159/000452489
18. Lewandowski KC, Dąbrowska K, Basińska-Lewandowska M, Bolanowski M, Ruchała M, Lewiński A. Adequate timing and constant supervision are the keys for successful implementation of levothyroxine or levothyroxine/paracetamol absorption test. Thyroid Res. 2020;13:5. doi: https://doi.org/10.1186/s13044-020-00079-6
19. FDA. US Department of Health and Human Services, Food and Drug Administration. December 2000. Guidance for industry levothyroxine sodium tablets—in vivo pharmacokinetic and bioavailability studies and in vitro dissolution testing. Center for Drug Evaluation and Research; 2016. Accessed October 15, 2022
20. Marina M, Ceda GP, Aloe R, Gnocchi C, Ceresini G. Circulating concentrations of free thyroxine after an oral intake of liquid LT4 taken either during fasting conditions or at breakfast. Acta Biomed. 2016;87(3):247-252
21. Walker JN, Shillo P, Ibbotson V, Vincent A, Karavitaki N, Weetman AP, et al. A thyroxine absorption test followed by weekly thyroxine administration: a method to assess nonadherence to treatment. Eur J Endocrinol. 2013;168:913–7. doi: https://doi.org/10.1530/EJE-12-1035
22. Dutta D, Jindal R, Kumar M, Mehta D, Dhall A, Sharma M. Efficacy and Safety of Once Weekly Thyroxine as Compared to Daily Thyroxine in Managing Primary Hypothyroidism: A Systematic Review and Meta-Analysis. Indian J Endocrinol Metab. 2021; 25(2):76-85. doi: https://doi.org/10.4103/ijem.IJEM_789_20
23. Oueslati I, Terzi A, Yazidi M, Kamoun E, Feki M, Chihaoui M. Levothyroxine absorption test in patients with refractory hypothyroidism: how to interpret patient’s response to the test? Endocrine. 2025. doi: https://doi.org/10.1007/s12020-025-04312-w
24. Amiyangoda G, Antonypillai CN, Gunatilake SSC, Weerathunge TT, Ediriweera D, et al. Rapid supervised levothyroxine absorption test in refractory hypothyroidism: suggestion for assessing absorption using two blood samples in low-resource settings. Endocr Connect. 2024;13(10):e240277. doi: https://doi.org/10.1530/EC-24-0277
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For citations:
Troshina E.A., Mazurina N.V., Botasheva M.H., Platonova N.M., Pershina-Milyutina A.P., Gasymova I.R. Evaluation of sodium levothyroxine absorption in real clinical practice using a single-bolus oral test. Problems of Endocrinology. 2025;71(6):15-21. (In Russ.) https://doi.org/10.14341/probl13665
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