Гипотиреоз и изолированная гипотироксинемия во время беременности

Неблагоприятное влияние дефицита тиреоидных гормонов у беременной женщины на развитие плода активно обсуждается в литературе на протяжении нескольких десятилетий и практически не вызывает сомнений, особенно когда речь идет о явном гипотиреозе со всеми его атрибутами. Диагностика гипотиреоза во время беременности в клинической практике базируется на определении уровня тиреотропного гормона (ТТГ) и св. Т4. Согласно рекомендациям Эндокринологического общества (США) 2007 г. диагноз гипотиреоз во время беременности, в особенности у женщин, которые являются носительницами антител к тиреоидной пероксидазе (АТ-ТПО) устанавливается при уровне ТТГ, превышающем 2,5 мЕд/л [3]. Однако, если обратиться к оригинальному тексту документа, следует заметить, что эта рекомендация дается не совсем напрямую, а речь идет о целевом диапазоне ТТГ на фоне заместительной терапии при уже существующем гипотиреозе. Тем не менее именно из этого текста постепенно возникло уже широко принятое положение о собственно диагностике гипотиреоза во время беременности уже при обнаружении высоконормального уровня ТТГ. Некоторые противоречия этой рекомендации будут обсуждаться ниже, тем не менее необходимо сразу определиться в терминологии и указать на то, что под гипотиреозом (как во время беременности, так и вне ее) следует понимать ситуацию, когда у больного повышен уровень ТТГ (выше некоей принятой точки разделения), при этом уровень св. Т4 может быть в норме (субклинический гипотиреоз (СГ)) или сниженным (явный или манифестный гипотиреоз). Во время беременности необходимость назначения пациентке заместительной терапии L-T4 независимо от выраженности гипотиреоза сомнений не вызывает.

1. Glinoer D., De Nayer P., Delange F. et al. A randomized trial for the treatment of mild iodine deficiency during pregnancy: maternal and neonatal effects // J. Clin. Endocrinol. Metab. 1995. V. 80. P. 258–269.

2. Negro R., Soldin O.P., Obregon M.-J., Stagnaro-Green A. Hypothyroxinemia and Pregnancy // Endocrin. Pract. 2011. V. 17. P. 1–24.

3. Abalovich M., Amino N., Barbour L.A. et al. Management of thyroid dysfunction during pregnancy and postpartum: an Endocrine Society Clinical Practice Guideline // J. Clin. Endocrinol. Metab. 2007. V. 92. P. S1–47.

4. Pedersen K.M., Laurberg P., Iversen E. et al. Amelioration of some pregnancy-associated variations in thyroid function induced by iodine supplementation // J. Clin. Endocrinol. Metab. 1993. V. 77. P. 1078–1083.

5. Romano R., Jannini E.A., Pepe M. et al. The effects of iodoprophylaxis on thyroid size during pregnancy // Am. J. Obstet. Gynecol. 1991. V. 164. P. 482–485.

6. Liesenkötter K.P., Göpel W., Bogner U. et al. Earliest prevention of endemic goiter by iodine supplementation during pregnancy // Eur. J. Endocrinol. 1996. V. 134. P. 443–448.

7. Caldwell K.L., Miller G.A., Wang R.Y. et al. Iodine status of the U.S. population, National Health and Nutrition Examination Survey 2003–2004 // Thyroid. 2008. V. 18. P. 1207–1214.

8. Andersson M., de Benoist B., Delange F., Zupan J. Prevention and control of iodine deficiency in pregnant and lactating women and in children less than 2-years-old: conclusions and recommendations of the Technical Consultation // Public. Health. Nutr. 2007. V. 10. P. 1606–1611.

9. Caron P., Hoff M., Bazzi S. et al. Urinary iodine excretion during normal pregnancy in healthy women living in the southwest of France: correlation with maternal thyroid parameters // Thyroid. 1997. V. 7. P. 749–754.

10. Pearce E.N., Lazarus J.H., Smyth P.P. et al. Perchlorate and thiocyanate exposure and thyroid function in first-trimester pregnant women // J. Clin. Endocrinol. Metab. 2010. V. 95. P. 3207–3215.

11. Elnagar B., Eltom A., Wide L. et al. Iodine status, thyroid function and pregnancy: study of Swedish and Sudanese women // Eur. J. Clin. Nutr. 1998. V. 52. P. 351–355.

12. Sack J., Goldstein A., Charpak N. et al. Postpartum maternal hyperthyrotropinemia in an area in which iodine supplementation is required // Thyroid. 2003. V. 13. P. 959–964.

13. Moleti M., Lo Presti V.P., Mattina F. et al. Gestational thyroid function abnormalities in conditions of mild iodine deficiency: early screening versus continuous monitoring of maternal thyroid status // Eur. J. Endocrinol. 2009. V. 160. P. 611–617.

14. Moleti M., Lo Presti V.P., Campolo M.C. et al. Iodine prophylaxis using iodized salt and risk of maternal thyroid failure in conditions of mild iodine deficiency // J. Clin. Endocrinol. Metab. 2008. V. 93. P. 2616–2621.

15. Fritz K.S., Wilcox R.B., Nelson J.C. Quantifying spurious free T4 results attributable to thyroxine-binding proteins in serum dialysates and ultrafiltrates // Clin. Chem. 2007. V. 53. P. 985–988.

16. d’Herbomez M., Forzy G., Gasser F. et al. Clinical evaluation of nine free thyroxine assays: persistent problems in particular populations // Clin. Chem. Lab. Med. 2003. V. 41. P. 942–947.

17. Lee R.H., Spencer C.A., Mestman J.H. et al. Free T4 immunoassays are flawed during pregnancy // Am. J. Obstet. Gynecol. 2009. V. 200. P. 260.

18. Sapin R., d’Herbomez M., Schlienger J.L. Free thyroxine measured with equilibrium dialysis and nine immunoassays decreases in late pregnancy // Clin. Lab. 2004. V. 50. P. 581–584.

19. Sapin R., d’Herbomez M. Free thyroxine measured by equilibrium dialysis and nine immunoassays in sera with various serum thyroxine-binding capacities // Clin. Chem. 2003. V. 49. P. 1531–1535.

20. Roti E., Gardini E., Minelli R. et al. Thyroid function evaluation by different commercially available free thyroid hormone measurement kits in term pregnant women and their newborns // J. Endocrinol. Invest. 1991. V. 14. P. 1–9.

21. Klee G.G., Post G. Effect of counting errors on immunoassay precision // Clin. Chem. 1989. V. 35. P. 1362–1366.

22. Levinson S.S. Antibody multi-specificity in immunoassay interference // Clin. Biochem. 1992. V. 25. P. 77–87.

23. Ward G., McKinnon L., Badrick T. et al. Heterophilic antibodies remain a problem for the immunoassay laboratory // Am. J. Clin. Pathol. 1997. V. 108. P. 417–421.

24. Toft A.D., Beckett G.J. Measuring serum thyrotropin and thyroid hormone and assessing thyroid hormone transport / In: Braverman L.E., Utiger R.D. (eds): Werner & Ingbar’s The Thyroid: A Fundamental and Clinical Text. Philadelphia: Lippincott Williams and Wilkins, 2005. P. 329–344.

25. Negro R., Formoso G., Mangieri T. et al. Levothyroxine treatment in euthyroid pregnant women with autoimmune thyroid disease: effects on obstetrical complications // J. Clin. Endocrinol. Metab. 2006. V. 91. P. 2587–2591.

26. Jonklaas J., Kahric-Janicic N., Soldin O.P., Soldin S.J. Correlations of free thyroid hormones measured by tandem mass spectrometry and immunoassay with thyroid-stimulating hormone across 4 patient populations // Clin. Chem. 2009. V. 55. P. 1380–1388.

27. Kahric-Janicic N., Soldin S.J., Soldin O.P. et al. Tandem mass spectrometry improves the accuracy of free thyroxine measurements during pregnancy // Thyroid. 2007. V. 17. P. 303–311.

28. Thienpont L.M., van Uytfanghe K., Beastall G. et al. Report of the IFCC working group for standardization of thyroid function tests, part 2: Free thyroxine and free triiodothyronine // Clin. Chem. 2010. V. 56. P. 902–911.

29. Yue B., Rockwood A.L., Sandrock T, La’ulu S.L. Free thyroid hormones in serum by direct equilibrium dialysis and online solidphase extraction-liquid chromatography/tandem mass spectrometry // Clin. Chem. 2008. V. 54. P. 642–651.

30. Haddow J.E., Palomaki G.E., Allan W.C. et al. Maternal thyroid deficiency during pregnancy and subsequent neuropsycological development of the child // N. Engl. J.Med. 1999. V. 34. P. 549–555.

31. Pop V.J., Kuijpens J.L., van Baar A.L. et al. Low maternal free thyroxine concentrations during early pregnancy are associated with impaired psychomotor development in infancy // Clin. Endocrinol. 1999. V. 50. P. 147–148.

32. Pop V.J., Brouwers E.P, Vader H.L. et al. Maternal hypothyroxinemia during early pregnancy and subsequent child development: a 3-year follow-up study // Clin. Endocrinol. 2003. V. 59. P. 282–288.

33. Vermiglio F., Lo Presti V.P., Moleti M. et al. Attention deficit and hyperactivity disorders in the offspring of mothers exposed to mild- moderate iodine deficiency disorder in developed countries // J. Clin. Endocrinol. Metab. 2004. V. 89. P. 6054–6060.

34. Kooistra L., Crawford S., van Baar A.L. et al. Neonatal effects of maternal hypothyroxinemia during early pregnancy // Pediatrics. 2006. V. 117. P. 161–167.

35. Li Y., Shan Z., Teng W. et al. Abnormalities of maternal thyroid function during pregnancy affect neuropsychological development of their children at 25-30 months // Clin. Endocrinol. 2010. V. 72. P. 825–829.

36. Henrichs J., Bongers-Schokking J.J., Schenk J.J. et al. Maternal thyroid function during early pregnancy and cognitive functioning in early childhood: the Generation R study // J. Clin. Endocrinol. Metab. 2010. V. 95. P. 4227–4234.

37. Casey B.M., Dashe J.S., Spong C.Y. et al. Perinatal significance of isolated maternal hypothyroxinemia identified in the first half of pregnancy // Obstet. Gynecol. 2007. V. 109(5). P. 1129–35.

38. Contempré B., Jauniaux E., Calvo R. et al. Detection of thyroid hormone in human embryonic cavities during the first trimester of pregnancy // J. Clin. Endocrinol. Metab. 1993. V. 77. P. 1719–1722.

39. Calvo R.M., Jauniax E., Gulbis B. et al. Fetal tissues are exposed to biologically relevant free thyroxine concentrations during early phases of development // J. Clin. Endocrinol. Metab. 2002. V. 87. P. 1768–1777.

40. Calvo R.M., Obregón M.J., Ruiz de Oña C., Escobar del Rey F., Morreale de Escobar G. Congenital hypothyroidism, as studied in rats: Crucial role of maternal thyroxine but not of 3,5,3’-triiodothyronine in the protection of the fetal brain // J. Clin. Invest. 1990. V. 86. P. 889–899.

41. Obregon M.J., Escobar del Rey F., Morreale de Escobar G. The effects of iodine deficiency on thyroid hormone deiodination // Thyroid. 2005. V. 15. P. 917–929.

42. Morreale de Escobar G., Obregon M.J., Escobar del Rey F. Maternal thyroid hormones early in pregnancy and fetal brain development // Best. Pract. Res. Clin. Endocrinol. Metab. 2004. V. 18. P. 225–248.

43. Kester M.H.A., Martínez de Mena R., Obregón M.J. et al. Iodothyronine levels in the human developing brain: Major regulatory roles of iodothyronine deiodinases in different areas // J. Clin. Endocrinol. Metab. 2004. V. 89. P. 3117–3128.

44. Lavado-Autric R., Ausó E., Garcia-Velasco J.V. et al. Early maternal hypothyroxinemia alters histogenesis and cerebral cortex cytoarchitecture of the progeny // J. Clin. Invest. 2003. V. 111. P. 1073–1082.

45. Ausó E., Lavado-Autric R., Cuevas E. et al. A moderate and transient deficiency of maternal thyroid function at the beginning of fetal neocorticogenesis alters neuronal migration // Endocrinol. 2004. V. 145. P. 4037–4047.

46. Morrreale de Escobar G., Obregуn M.J., Escobar del Rey F. Iodine deficiency and brain development in the first half of pregnancy Public // Health. Nutrit. 2007. V. 10. P. 1554–1570.

47. Morreale de Escobar G., Obregon M.J., Escobar del Rey F. Is neuropsychological development related to maternal hypothyroidism or to maternal hypothyroxinemia? // J. Clin. Endocrinol. Metab. 2000. V. 85. P. 3975–3987.

48. Berbel P., Obregón M.J., Bernal J. et al. Iodine supplementation during pregnancy: a public health challenge // Trends Endocrinol. Metab. 2007. V. 18. P. 338–343.

49. Berbel P., Mestre J.L., Santamaría A. et al. Delayed neurobehavioral development in children born to pregnant women with mild hypothyroxinemia during the first month of gestation: the importance of early iodine supplementation // Thyroid. 2009. V. 19. P. 511–519.

50. Velasco I., Carreira M., Santiago P. et al. Effect of iodine prophylaxis during pregnancy on neurocognitive development of children during the first two years of life // J. Clin. Endocrinol. Metab. 2009. V. 94. P. 3234–3241.

51. Bibbins-Domingo K., Chertow G.M., Coxson P.G. et al. Projected effect of dietary salt reductions on future cardiovascular disease // N. Eng. J. Med. 2010. V. 362. P. 590–599.

52. Soldin O.P., Pearce E.N., Stagnaro-Green A. Dietary salt reductions and cardiovascular disease // N. England. J. Med. 2010. V. 362. P. 2224.