problendoПроблемы ЭндокринологииProblems of Endocrinology0375-96602308-1430Endocrinology Research Centre10.14341/probl13665problendo-13665Research ArticleКлиническая эндокринологияClinical endocrinologyОценка абсорбции левотироксина натрия в реальной клинической практике путем проведения перорального теста с одномоментным приемом болюсной дозыEvaluation of sodium levothyroxine absorption in real clinical practice using a single-bolus oral testhttps://orcid.org/0000-0002-8520-8702ТрошинаЕ. А.TroshinaE. A.

Трошина Екатерина Анатольевна, д.м.н., профессор, член-корр. РАН 

Москва

Ekaterina A. Troshina, MD, PhD, Professor

Moscow

troshina@inbox.ruhttps://orcid.org/0000-0001-8077-9381МазуринаН. В.MazurinaN. V.

Мазурина Наталия Валентиновна, д.м.н. 

Москва

Natalya V. Mazurina, MD, PhD

Moscow

natalyamazurina@mail.ruhttps://orcid.org/0009-0007-0651-3615БоташеваМ. Х.BotashevaM. H.

Боташева Медина Харуновна

117292, Москва, ул. Дм. Ульянова, д. 11 

Medina H. Botasheva, MD

11 Dm. Ulyanova street, 117292, Moscow

botasheva.medina@mail.ruhttps://orcid.org/0000-0001-6388-1544ПлатоноваН. М.PlatonovaN. M.

Платонова Надежда Михайловна, д.м.н. 

Москва

Nadezhda M. Platonova, MD, PhD

Moscow

doc-platonova@inbox.ruhttps://orcid.org/0000-0002-9462-8522Першина-МилютинаА. П.Pershina-MilyutinaA. P.

Першина-Милютина Анастасия Павловна

Москва

Anastasiia P. Pershina-Miliutina, MD

Moscow

oa11111998@gmail.comhttps://orcid.org/0009-0001-9129-9620ГасымоваИ. Р.GasymovaI. R.

Гасымова Ирада Расаддин Кызы

Москва

Irada R.K. Gasymova, MD

Moscow

iragasymova@mail.ruНациональный медицинский исследовательский центр эндокринологии им. академика И.И. ДедоваРоссияEndocrinology Research CentreRussian Federation2025180120267161521Copyright © Трошина Е.А., Мазурина Н.В., Боташева М.Х., Платонова Н.М., Першина-Милютина А.П., Гасымова И.Р., 20262026Трошина Е.А., Мазурина Н.В., Боташева М.Х., Платонова Н.М., Першина-Милютина А.П., Гасымова И.Р.Troshina E.A., Mazurina N.V., Botasheva M.H., Platonova N.M., Pershina-Milyutina A.P., Gasymova I.R.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.probl-endojournals.ru/jour/article/view/13665ОБОСНОВАНИЕ

ОБОСНОВАНИЕ. Результаты заместительной терапии гормонами щитовидной железы остаются неудовлетворительными в 30–50% случаев. Для дифференциальной диагностики истинной мальабсорбции левотироксина натрия и псевдомальабсорбции вследствие низкой комплаентности предлагается несколько вариантов теста по оценке всасывания препарата с различными критериями оценки.

ЦЕЛЬ

ЦЕЛЬ. Определить критерии нормальной абсорбции левотироксина натрия при проведении перорального теста с одномоментным приемом болюсной дозы 600 мкг.

МАТЕРИАЛЫ И МЕТОДЫ

МАТЕРИАЛЫ И МЕТОДЫ. В исследовании приняли участие 20 здоровых добровольцев обоих полов в возрасте от 18 до 35 лет с нормальной массой тела. Болюсная доза левотироксина натрия составляла 600 мкг. Образцы крови для определения концентрации свободного тироксина (свТ4) в сыворотке крови были взяты натощак, через 1 час, через 2, 3, 4, 6 часов после приема препарата.

РЕЗУЛЬТАТЫ

РЕЗУЛЬТАТЫ. После приема левотироксина натрия в дозе 600 мкг максимальный уровень свТ4 отмечался через 2 часа — 21,00 пмоль/л [19,20; 23,16]. Минимальное увеличение концентрации свТ4 через 2 часа после приема левотироксина натрия в дозе 600 мкг составило — 18,0%, максимальное — 91,1%.

ЗАКЛЮЧЕНИЕ

ЗАКЛЮЧЕНИЕ. Для оценки всасывания левотироксина натрия рекомендуется проведение теста — однократный пероральный прием левотироксина натрия в дозе 600 мкг. Всасывание левотироксина натрия может быть расценено как нормальное, если увеличение концентрации свТ4 через 2, 3 или 4 часа после приема болюсной дозы составляет не менее 18%.

BACKGROUND

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

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

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

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

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%.

гипотиреозлевотироксин натриямальабсорбциятест на всасывание левотироксина натрияhypothyroidismlevothyroxine sodiummalabsorptionlevothyroxine sodium absorption testBiryukova E. V. Kileynikov D. V. Solovyeva I. V. Hypothyroidism: current state of the problem Meditsinskiy sovet = Medical Council 2020 05 96 107 7 10.21518/2079-701x-2020-7-96-107Manuylova Yulia A. Morgunova Tatyana B. Fadeyev Valentin V. Causes of treatment failure in primary hypothyroidism Clinical and experimental thyroidology 2019 06 12 18 15 1 10.14341/ket10163Petunina N.A., Martirosyan N.S., Tel'nova M.E. i dr. Terapiya gipotireoza v osobykh gruppakh patsientov // Effektivnaya farmakoterapiya. — 2021. — T. 17. — №20. — S. 38–41. doi: https://doi.org/10.33978/2307-3586-2021-17-20-38-41Eligar V Taylor PN Okosieme OE Leese GP Dayan CM Thyroxine replacement: a clinical endocrinologist’s viewpoint Annals of Clinical Biochemistry: International Journal of Laboratory Medicine 2016 04 421 433 53 4 10.1177/0004563216642255Caron Philippe Grunenwald Solange Persani Luca Borson-Chazot Françoise Leroy Remy Duntas Leonidas Factors influencing the levothyroxine dose in the hormone replacement therapy of primary hypothyroidism in adults Reviews in Endocrine and Metabolic Disorders 2021 10 463 483 23 3 10.1007/s11154-021-09691-9Colucci Philippe Yue Corinne Seng Ducharme Murray Benvenga Salvatore A Review of the Pharmacokinetics of Levothyroxine for the Treatment of Hypothyroidism European Endocrinology 2015 06 40 9 1 10.17925/ee.2013.09.01.40Skelin Marko Lucijanić Tomo Amidžić Klarić Daniela Rešić Arnes Bakula Miro Liberati-Čizmek Ana-Marija Gharib Hossein Rahelić Dario Factors Affecting Gastrointestinal Absorption of Levothyroxine: A Review Clinical Therapeutics 2017 01 378 403 39 2 10.1016/j.clinthera.2017.01.005Canaris Gay J. Manowitz Neil R. Mayor Gilbert Ridgway E. Chester The Colorado Thyroid Disease Prevalence Study Archives of Internal Medicine 2003 03 526 160 4 10.1001/archinte.160.4.526Somwaru Lily L. Arnold Alice M. Joshi Neha Fried Linda P. Cappola Anne R. High Frequency of and Factors Associated with Thyroid Hormone Over-Replacement and Under-Replacement in Men and Women Aged 65 and Over The Journal of Clinical Endocrinology & Metabolism 2009 01 1342 1345 94 4 10.1210/jc.2008-1696Caron Philippe Tudor Charlotte Grunenwald Solange Levothyroxine Absorption Test With the Daily Levothyroxine Dose in Patients With “Refractory Hypothyroidism” Journal of the Endocrine Society 2025 03 9 4 10.1210/jendso/bvaf017Gonzales Kristen M. Stan Marius N. Morris John C. Bernet Victor Castro M. Regina The Levothyroxine Absorption Test: A Four-Year Experience (2015–2018) at The Mayo Clinic Thyroid 2019 11 1734 1742 29 12 10.1089/thy.2019.0256Ching Sun Grace E. Pantalone Kevin M. Faiman Charles Gupta Manjula Olansky Leann Hatipoglu Betul The Clinical Utility of Free Thyroxine in Oral Levothyroxine Absorption Testing Endocrine Practice 2014 08 925 929 20 9 10.4158/ep13487.orYildirim Simsir Ilgin Soyaltin Utku Erdem Ozgen Ahmet Gokhan Levothyroxine absorption test results in patients with TSH elevation resistant to treatment Endocrine 2019 03 118 121 64 1 10.1007/s12020-019-01889-xGhosh Sujoy Pramanik Subhodip Biswas Kaushik Bhattacharjee Kingshuk Sarkar Rajib Chowdhury Subhankar Mukhopadhyay Pradip Levothyroxine Absorption Test to Differentiate Pseudomalabsorption from True Malabsorption European Thyroid Journal 2019 11 19 24 9 1 10.1159/000504218Subramaniam Karthik Babu Tom Sreevalsan K. C. Mathew Shemy Levothyroxine Absorption Test – Results and Follow Up of Patients from a Single Center Indian Journal of Endocrinology and Metabolism 2023 03 32 36 27 1 10.4103/ijem.ijem_188_21Balla Mamtha Jhingan Ram M. Rubin Daniel J. Rapid Levothyroxine Absorption Testing: A Case Series of Nonadherent Patients International Journal of Endocrinology and Metabolism 2015 10 13 4 10.5812/ijem.31051Van Wilder Nancy Bravenboer Bert Herremans Sarah Vanderbruggen Nathalie Velkeniers Brigitte Pseudomalabsorption of Levothyroxine: A Challenge for the Endocrinologist in the Treatment of Hypothyroidism European Thyroid Journal 2016 11 52 56 6 1 10.1159/000452489Lewandowski Krzysztof C. Dąbrowska Katarzyna Basińska-Lewandowska Magdalena Bolanowski Marek Ruchała Marek Lewiński Andrzej Adequate timing and constant supervision are the keys for successful implementation of levothyroxine or levothyroxine/paracetamol absorption test Thyroid Research 2020 05 13 1 10.1186/s13044-020-00079-6FDA. 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, 2022Marina 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):247-252Walker J N Shillo P Ibbotson V Vincent A Karavitaki N Weetman A P Wass J A H Allahabadia A A thyroxine absorption test followed by weekly thyroxine administration: a method to assess non-adherence to treatment European Journal of Endocrinology 2013 04 913 917 168 6 10.1530/eje-12-1035Dutta Deep Jindal Radhika Kumar Manoj Mehta Divij Dhall Anil Sharma Meha Efficacy and Safety of Once Weekly Thyroxine as Compared to Daily Thyroxine in Managing Primary Hypothyroidism Indian Journal of Endocrinology and Metabolism 2021 09 76 85 25 2 10.4103/ijem.ijem_789_20Oueslati Ibtissem Terzi Ameni Yazidi Meriem Kamoun Elyes Feki Moncef Chihaoui Melika Levothyroxine absorption test in patients with refractory hypothyroidism: how to interpret patient’s response to the test? Endocrine 2025 06 166 171 90 1 10.1007/s12020-025-04312-wAmiyangoda G Antonypillai C N Gunatilake S S C Weerathunge T T Ediriweera D Kosgallana S G P D Jayawardana R D P Thissera H A N D Emalka W J Daraniyagala H U Rapid supervised levothyroxine absorption test in refractory hypothyroidism: suggestion for assessing absorption using two blood samples in low-resource settings Endocrine Connections 2024 08 13 10 10.1530/ec-24-0277

The authors declare that there are no conflicts of interest present.