Microcirculation and nadh fluorescence parameters in the skin of patients with overt hypothyroidism and their dynamics after achieving euthyroidism

Cover Page

Cite item

Full Text

Open Access Open Access
Restricted Access Access granted
Restricted Access Subscription or Fee Access

Abstract

Background: Hypothyroidism (HT) is associated with cardiovascular and metabolic disorders, which in some cases do not improve with levothyroxine sodium (LT4) replacement therapy.

Objective: Evaluation of microcirculation and reduced nicotinamide adenine dinucleotide (NADH) fluorescence in the skin of patients with newly diagnosed overt HT before and after achieving euthyroidism with LT4.

Materials and methods: Lipid profiles, complete blood counts, interleukin-6 (IL-6) levels, microcirculation, and NADH fluorescence amplitude (AFNADH) were assessed in forearm skin of 50 healthy volunteers and 14 patients with overt HT at rest, upon cooling to 10°C, and upon heating to 35°C and 42°C. The standard deviation (σ) and blood flow variation coefficient (Kv) were calculated, and wavelet analysis was used to determine the amplitudes of microcirculation fluctuations in the neurogenic (An), myogenic (Am), respiratory (Ar), and cardic (Ac) ranges.

Results: In overt hyperthermia, the microcirculation index upon heating to 42°C, Aм, Aс, and σ were lower than in healthy volunteers. No differences were found in other microcirculation parameters, nor in AFNADH at rest, upon cooling and heating to 35°C. After achieving euthyroidism, no statistically significant changes in microcirculation parameters or AFNADH were observed. During hyperthermia, levels of total cholesterol (TC), low-density lipoproteins (LDL), triglycerides, IL-6, and erythrocyte distribution width (RDW) were higher than in healthy volunteers. Positive changes in these parameters were noted after treatment.

Conclusion: Disturbances in cutaneous microcirculation during hyperthermia are manifested by a decrease in peak hyperemia upon heating to 42°C and a reduction in microcirculation variability due to a decrease in Aм and Aс, which persists after achieving euthyroidism. These changes are associated with dyslipidemia, increased IL-6, and RDW, with subsequent improvement during treatment. AFNADH parameters do not differ between patients with HT and healthy volunteers and do not change during treatment.

About the authors

Ekaterina G. Ryzhkova

I.M. Sechenov First Moscow State Medical University (Sechenov University)

Author for correspondence.
Email: e.g.ryzhkova@bk.ru
ORCID iD: 0000-0003-0069-1692

Postgraduate Student, Department of Endocrinology and Metabolic Health, N.V. Sklifosovsky Institute of Clinical Medicine

Russian Federation, Moscow

T. B. Morgunova

Professorial Clinic of Endocrinology and Diabetes

Email: tanmorgun@mail.ru
ORCID iD: 0000-0003-1500-1586

Cand. Sci. (Med.), Associate Professor, Endocrinologist

Russian Federation, Moscow

V. V. Fadeev

Lomonosov Moscow State University

Email: walfad@mail.ru
ORCID iD: 0000-0002-3026-6315

Dr. Sci. (Med.), Corresponding Member of the Russian Academy of Sciences, Professor, Department of Internal Medicine, Faculty of Fundamental Medicine

Russian Federation, Moscow

References

  1. Волкова А.Р., Халимов Ю.Ш., Дыгун О.Д. и др. Субклинический гипотиреоз и сердечно-сосудистые заболевания: патогенетические механизмы и клинические последствия. Медицинский совет. 2025;(5):107–12. [Volkova A.R., Khalimov Yu.Sh., Dygun O.D., et al. Subclinical hypothyroidism and cardiovascular diseases: Pathogenetic mechanisms and clinical implications. Meditsinskiy Sovet. 2025;(5):107–12. (In Russ.)]. https://doi.org/10.21518/ms2025-160
  2. Бирюкова Е.В., Абрамова А.Д. Гипотиреоз: от диагностики к успеху терапии. Consilium Medicum. 2025;27(4):210–7. [Biryukova E.V., Abramova A.D. Hypothyroidism: from diagnosis to therapy success. A review. Consilium Medicum. 2025;27(4):210–7. (In Russ.)]. https://doi.org/10.26442/20751753.2025.4.203294
  3. Taylor P.N., Medici M.M., Hubalewska-Dydejczyk A., Boelaert K. Hypothyroidism. Lancet. 2024;404(10460):1347–64. https://doi.org/10.1016/S0140-6736(24)01614-3
  4. Thvilum M., Lind S.M., Ebbehoj E., et al. Quality of life in patients with overt hypothyroidism: a systematic review. Eur J Endocrinol. 2025;193(3):S26–35. https://doi.org/10.1093/ejendo/lvaf179
  5. Sharma S., Tobin V., Vas P.R.J., Rayman G. The LDIFLARE and CCM Methods Demonstrate Early Nerve Fiber Abnormalities in Untreated Hypothyroidism: A Prospective Study. J Clin Endocrinol Metab. 2018;103(8):3094–102. https://doi.org/10.1210/jc.2018-00671
  6. Кулабухова И.С., Елисеева Л.Н., Оранский С.П. и др. Изменения микрососудистого статуса у пациентов с первичным гипотиреозом. Вестник современной клинической медицины. 2018;11(1):29–33. doi: 10.20969/VSKM.2018.11(1).29-33 [Kulabukhova I.S., Eliseyeva L.N., Oranskiy S.P. et al. Microvascular status changes in patients with primary hypothyroidism. Vestnik sovremennoi klinicheskoi meditsiny. 2018;11(1):29–33. (In Russ.)]. https://doi.org/10.20969/VSKM
  7. Kozacz A., Assis G.G.D., Sanocka U., Ziemba A.W. Standard hypothyroid treatment did not restore proper metabolic response to carbohydrate. Endocrine. 2021;71(1):96–103. https://doi.org/10.1007/s12020-020-02334-0
  8. Hou L.Y., Li X., Zhang G.Q., et al. Transiently impaired endothelial function during thyroid hormone withdrawal in differentiated thyroid cancer patients. Front Endocrinol. (Lausanne). 2023;14:1164789. https://doi.org/10.3389/fendo.2023.1164789
  9. Bernardi S., Grillo A., Antonello R.M., et al. Meta-analysis on the Association Between Thyroid Hormone Disorders and Arterial Stiffness. J Endocrine Soc. 2022;6(4):bvac016. https://doi.org/10.1210/jendso/bvac016
  10. Soto-García A.J., Elizondo-Riojas G., Rodriguez-Gutiérrez R., et al. Carotid Intima-Media Thickness in Patients with Subclinical Hypothyroidism: A Prospective Controlled Study. Clin Invest Med. 2021;44(4):E39–45. https://doi.org/10.25011/cim.v44i4.37139
  11. Alexander Y., Osto E., Schmidt-Trucksäss A., et al. Endothelial function in cardiovascular medicine: a consensus paper of the European Society of Cardiology Working Groups on Atherosclerosis and Vascular Biology, Aorta and Peripheral Vascular Diseases, Coronary Pathophysiology and Microcirculation, and Thrombosis. Cardiovasc Res. 2021;117(1):29–42. https://doi.org/10.1093/cvr/cvaa085
  12. Xu C., Sellke F.W., Abid M.R. Assessments of microvascular function in organ systems. Am J Physiol Heart Circ Physiol. 2022;322(6):H891–905. https://doi.org/10.1152/ajpheart.00589.2021
  13. Cracowski J.L., Roustit M. Human Skin Microcirculation. Compr Physiol. 2020;10(3):1105–54. https://doi.org/10.1002/cphy.c190008
  14. Klein I., Ojamaa K. Thyroid hormone: targeting the vascular smooth muscle cell. Circ Res. 2001;88(3):260–1. https://doi.org/10.1161/01.res.88.3.260
  15. Дунаев А.В. Мультимодальная оптическая диагностика микроциркуляторно-тканевых систем организма человека: монография. Старый Оскол, 2022. 440 с.: ил. [Dunaev A.V. Multimodal optical diagnostics of microcirculatory tissue systems of the human body: monograph. Staryi Oskol, 2022. 440 p. (In Russ.)].
  16. Dremin V.V., Kozlov I.O., Zherebtsov E.A., et al. The capabilities of laser Doppler flowmetry in assessment of lymph and blood microcirculation. Regional blood circulation and microcirculation. 2017;16(4):42–9. https://doi.org/10.24884/1682-6655-2017-16-4-42-49
  17. Ryzhkova E., Morgunova T., Potapova E., et al. Fluorescence Spectroscopy With Temperature Functional Tests in the Assessment of Markers of Intracellular Energy Metabolism: Spatial Heterogeneity and Reproducibility of Measurements. J Biophoton. 2024;17(10):e202400294. https://doi.org/10.1002/jbio.202400294
  18. Minson C.T. Thermal provocation to evaluate microvascular reactivity in human skin. J Appl Physiol. 2010;109(4):1239–46. https://doi.org/10.1152/japplphysiol.00414.2010
  19. Pazos-Moura C.C., Moura E.G., Breitenbach M.M.D., Bouskela E. Nailfold Capillaroscopy in Hypothyroidism and Hyperthyroidism: Blood Flow Velocity During Rest and Postocclusive Reactive Hyperemia. Angiology. 1998;49(6):471–6. https://doi.org/10.1177/000331979804900608
  20. Weiss M., Milman B., Rosen B., Zimlichman R. Quantitation of thyroid hormone effect on skin perfusion by laser Doppler flowmetry. J Clin Endocrinol Metab. 1993;76(3):680–2. https://doi.org/10.1210/jcem.76.3.8445026
  21. Клинические рекомендации. Гипотиреоз. Общественная организация «Российская ассоциация эндокринологов». Рубрикатор клинических рекомендаций Минздрава России. 2024. ID: 531_4. 2024. Доступ: https://cr.minzdrav.gov.ru/view-cr/531_4 (дата обращения: 25.01.2026). [Clinical guidelines. Hypothyroidism. Public organization «Russian Association of Endocrinologists» Rubricator of clinical guidelines of the Ministry of Health of the Russian Federation. 2024. ID: 531_4. 2024. Access: https://cr.minzdrav.gov.ru/view-cr/531_4 (date of access: 25.01.2026). (In Russ.)].
  22. Крупаткин А.И., Сидоров В.В. Функциональная диагностика состояния микроциркуляторно-тканевых систем: Колебания, информация, нелинейность (Руководство для врачей). M., 2013. 496 с. [Krupatkin A., Sidorov V. Functional diagnostics of microcirculatory-tissue systems: oscillations, information, nonlinearity: a guide for doctors. M., 2013. 496 p. (In Russ.)].
  23. Mihor A., Gergar M., Gaberšček S., Lenasi H. Skin microvascular reactivity in patients with hypothyroidism. Clin Hemorheol Microcirc. 2016;64(1):105–14. https://doi.org/10.3233/CH-162062
  24. Roberts K.A., van Gent T., Hopkins N.D., et al. Reproducibility of four frequently used local heating protocols to assess cutaneous microvascular function. Microvasc Res. 2017;112:65–71. https://doi.org/10.1016/j.mvr.2017.03.005
  25. Johnson J.M., Minson C.T., Kellogg D.L. Cutaneous vasodilator and vasoconstrictor mechanisms in temperature regulation. Compr Physiol. 2014;4(1):33–89. https://doi.org/10.1002/cphy.c130015
  26. Johnson J.M. Mechanisms of vasoconstriction with direct skin cooling in humans. Am J Physiol Heart Circ Physiol. 2007;292(4):H1690–1. https://doi.org/10.1152/ajpheart.00048.2007
  27. Prakash K., Hamid P. Thyroid Hormone Resistance Syndrome: From Molecular Mechanisms to Its Potential Contribution to Hypertension. Cureus. 2023;15(12):e49913. https://doi.org/10.7759/cureus.49913
  28. Gluvic Z.M., Obradovic M.M., Sudar-Milovanovic E.M., et al. Regulation of nitric oxide production in hypothyroidism. Biomed Pharmacother. 2020;124:109881. https://doi.org/10.1016/j.biopha.2020.109881
  29. Heymsfield S.B., Smith B., Dahle J., et al. Resting Energy Expenditure: From Cellular to Whole‐Body Level, a Mechanistic Historical Perspective. Obesity. 2021;29(3):500–11. https://doi.org/10.1002/oby.23090
  30. Izkhakov E., Vaisman N., Barnes S., et al. Body Composition, Resting Energy Expenditure, and Metabolic Changes in Women Diagnosed with Differentiated Thyroid Carcinoma. Thyroid. 2019;29(8):1044–51. https://doi.org/10.1089/thy.2018.0483
  31. Cioffi F., Giacco A., Goglia F., Silvestri E. Bioenergetic Aspects of Mitochondrial Actions of Thyroid Hormones. Cells. 2022;11(6):997. doi: 10.3390/cells11060997
  32. Eom Y.S., Wilson J.R., Bernet V.J. Links between Thyroid Disorders and Glucose Homeostasis. Diabetes Metab J. 2022;46(2):239–56. https://doi.org/10.4093/dmj.2022.0013
  33. Rossi M., Carpi A., Di Maria C., et al. Skin blood flowmotion and microvascular reactivity investigation in hypercholesterolemic patients without clinically manifest arterial diseases. Physiol Res. 2009;58(1):39–47. https://doi.org/10.33549/physiolres.931351
  34. Ference B.A., Ginsberg H.N., Graham I., et al. Low-density lipoproteins cause atherosclerotic cardiovascular disease. 1. Evidence from genetic, epidemiologic, and clinical studies. A consensus statement from the European Atherosclerosis Society Consensus Panel. Eur Heart J. 2017;38(32):2459–72. https://doi.org/10.1093/eurheartj/ehx144
  35. Ketelhuth D.F.J., Bäck M. Myeloid-specific interleukin-6 response: from vascular effects to the potential for novel personalized medicines. Eur Heart J Open. 2024;4(4):oeae047. https://doi.org/10.1093/ehjopen/oeae047
  36. Li R., He T., Xing Z., et al. The immune system in Hashimoto’s thyroiditis: Updating the current state of knowledge on potential therapies and animal model construction. Autoimmun Rev. 2025;24(6):103783. https://doi.org/10.1016/j.autrev.2025.103783
  37. Berta D.M., Gelaw Y., Shiferaw E., et al. Hematological Abnormalities and Associated Factors Among Patients with Hypothyroidism at the University of Gondar Comprehensive Specialized Hospital. J Blood Med. 2024;15:157–69. https://doi.org/10.2147/JBM.S453015
  38. Uydu H.A., Bostan M., Atak M., et al. Cholesterol forms and traditional lipid profile for projection of atherogenic dyslipidemia: lipoprotein subfractions and erythrocyte membrane cholesterol. J Membr Biol. 2014;247(2):127–34. https://doi.org/10.1007/s00232-013-9611-2
  39. Lichtman M.A. Red cell distribution width as a bellwether of prognosis. Blood Cells Mol Dis. 2024 Nov;109:102884. https://doi.org/10.1016/j.bcmd.2024.102884
  40. Shivaprasad C., Rakesh B., Anish K., et al. Impairment of health-related quality of life among Indian patients with hypothyroidism. Indian J Endocr Metab. 2018;22(3):335. https://doi.org/10.4103/ijem.IJEM_702_17
  41. Изосимова А.В., Можеров А.М., Ширманова М.В. и др. FLIM-имиджинг автофлуоресценции НАД(Ф)Н Т-клеток в лимфатических узлах для оценки эффективности анти-CTLA-4-иммунотерапии. Современные технологии в медицине. 2023;15(3):5. [Izosimova A.V., Mozherov A.M., Shirmanova M.V., et al. Fluorescence lifetime imaging of NAD(P)H T cells autofluorescence in the lymphatic nodes to assess the effectiveness of anti-CTLA-4 immunotherapy. Sovremennye Tekhnologii v Meditsine. 2023;15(3):5. (In Russ.)]. https://doi.org/10.17691/stm2023.15.3.01

Supplementary files

Supplementary Files
Action
1. JATS XML
Download

Copyright (c) 2026 Bionika Media

License URL: https://journals.eco-vector.com/2073-4034/about/editorialPolicies