Empfehlungen der AGG (Arbeitsgemeinschaft Geburtshilfe, Sektion maternale Erkrankungen) zum Umgang mit Schilddrüsenfunktionsstörungen in der Schwangerschaft

Zusammenfassung

Ziel Diese Empfehlungen der AGG (Arbeitsgemeinschaft für Geburtshilfe und Pränatalmedizin, Sektion maternale Erkrankungen) zum Umgang mit Schilddrüsenfunktionsstörungen in der Schwangerschaft haben das Ziel der Verbesserung der Diagnostik und des Managements von Schilddrüsenanomalien während der Schwangerschaft.

Methoden Basierend auf der aktuellen Literatur entwickelten die Mitglieder der Task Force die vorliegenden Empfehlungen und Stellungnahmen. Diese Empfehlungen wurden nach einem Konsens der Mitglieder der Arbeitsgruppe verabschiedet.

Empfehlungen Das folgende Manuskript beschäftigt sich mit einem Einblick in physiologische und pathophysiologische Schilddrüsenveränderungen in der Schwangerschaft, Empfehlungen zur klinischen und subklinischen Hypo-, Hyperthyreose sowie fetale und neonatale Diagnose- und Managementstrategien.

Schlüsselwörter

Schilddrüsenerkrankungen in der Schwangerschaft - Hypothyroidismus - Hyperthyroidismus

• References/Literatur

• 1 Fradkin JE, Eastman RC, Lesniak MA. et al. Specificity spillover at the hormone receptor – exploring its role in human disease. N Engl J Med 1989; 320: 640-645
• 2 Kenimer JG, Hershman JM, Higgins HP. The thyrotropin in hydatidiform moles is human chorionic gonadotropin. J Clin Endocrinol Metab 1975; 40: 482-491
• 3 Azukizawa M, Kurtzman G, Pekary AE. et al. Comparison of the binding characteristics of bovine thyrotropin and human chorionic gonadotropin to thyroid plasma membranes. Endocrinology 1977; 101: 1880-1889
• 4 Carayon P, Lefort G, Nisula B. Interaction of human chorionic gonadotropin and human luteinizing hormone with human thyroid membranes. Endocrinology 1980; 106: 1907-1916
• 5 Hershman JM, Lee HY, Sugawara M. et al. Human chorionic gonadotropin stimulates iodide uptake, adenylate cyclase, and deoxyribonucleic acid synthesis in cultured rat thyroid cells. J Clin Endocrinol Metab 1988; 67: 74-79
• 6 Davies TF, Platzer M. hCG-induced TSH receptor activation and growth acceleration in FRTL-5 thyroid cells. Endocrinology 1986; 118: 2149-2151
• 7 Yoshimura M, Nishikawa M, Horimoto M. et al. Thyroid-stimulating activity of human chorionic gonadotropin in sera of normal pregnant women. Acta Endocrinol (Copenh) 1990; 123: 277-281
• 8 Yoshikawa N, Nishikawa M, Horimoto M. et al. Human chorionic gonadotropin promotes thyroid growth via thyrotropin receptors in FRTL-5 cells. Endocrinol Jpn 1990; 37: 639-648
• 9 Yoshimura M, Nishikawa M, Mori Y. et al. Human chorionic gonadotropin induces c-myc mRNA expression via TSH receptor in FRTL-5 rat thyroid cells. Thyroid 1992; 2: 315-319
• 10 Tomer Y, Huber GK, Davies TF. Human chorionic gonadotropin (hCG) interacts directly with recombinant human TSH receptors. J Clin Endocrinol Metab 1992; 74: 1477-1479
• 11 Weeke J, Dybkjaer L, Granlie K. et al. A longitudinal study of serum TSH, and total and free iodothyronines during normal pregnancy. Acta Endocrinol (Copenh) 1982; 101: 531-537
• 12 Dashe JS, Casey BM, Wells CE. et al. Thyroid-stimulating hormone in singleton and twin pregnancy: importance of gestational age-specific reference ranges. Obstet Gynecol 2005; 106: 753-757
• 13 Männistö T, Surcel HM, Ruokonen A. et al. Early pregnancy reference intervals of thyroid hormone concentrations in a thyroid antibody-negative pregnant population. Thyroid 2011; 21: 291-298
• 14 Li C, Shan Z, Mao J. et al. Assessment of thyroid function during first-trimester pregnancy: what is the rational upper limit of serum TSH during the first trimester in Chinese pregnant women?. J Clin Endocrinol Metab 2014; 99: 73-79
• 15 Alexander EK, Pearce EN, Brent GA. et al. 2017 Guidelines of the American Thyroid Association for the Diagnosis and Management of Thyroid Disease During Pregnancy and the Postpartum. Thyroid 2017; 27: 315-389
• 16 De Groot L, Abalovich M, Alexander EK. et al. Management of thyroid dysfunction during pregnancy and postpartum: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 2012; 97: 2543-2565
• 17 Jiang YX, Sun WJ, Zhang Y. et al. Thyroid function of twin-pregnant women in early pregnancy. Chin Med J (Engl) 2019; 132: 2033-2038
• 18 Ashoor G, Muto O, Poon LC. et al. Maternal thyroid function at gestational weeks 11–13 in twin pregnancies. Thyroid 2013; 23: 1165-1171
• 19 Šálek T, Dhaifalah I, Langova D. et al. Maternal thyroid-stimulating hormone reference ranges for first trimester screening from 11 to 14 weeks of gestation. J Clin Lab Anal 2018; 32: e22405
• 20 Grün JP, Meuris S, De Nayer P. et al. The thyrotrophic role of human chorionic gonadotrophin (hCG) in the early stages of twin (versus single) pregnancies. Clin Endocrinol (Oxf) 1997; 46: 719-725
• 21 Medici M, Korevaar TI, Visser WE. et al. Thyroid function in pregnancy: what is normal?. Clin Chem 2015; 61: 704-713
• 22 McNeil AR, Stanford PE. Reporting Thyroid Function Tests in Pregnancy. Clin Biochem Rev 2015; 36: 109-126
• 23 Lee RH, Spencer CA, Mestman JH. et al. Free T4 immunoassays are flawed during pregnancy. Am J Obstet Gynecol 2009; 200: 260.e1-260.e6
• 24 Anckaert E, Poppe K, Van Uytfanghe K. et al. FT4 immunoassays may display a pattern during pregnancy similar to the equilibrium dialysis ID-LC/tandem MS candidate reference measurement procedure in spite of susceptibility towards binding protein alterations. Clin Chim Acta 2010; 411: 1348-1353
• 25 Sapin R, dʼHerbomez M. Free thyroxine measured by equilibrium dialysis and nine immunoassays in sera with various serum thyroxine-binding capacities. Clin Chem 2003; 49: 1531-1535
• 26 Azizi F, Mehran L, Amouzegar A. et al. Establishment of the trimester-specific reference range for free thyroxine index. Thyroid 2013; 23: 354-359
• 27 Institute of Medicine (US) Panel on Micronutrients. Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc. Washington (DC): National Academies Press (US); 2001
• 28 Berghout A, Wiersinga W. Thyroid size and thyroid function during pregnancy: an analysis. Eur J Endocrinol 1998; 138: 536-542
• 29 Olivares JL, Olivi GI, Verdasco C. et al. Low iodine intake during pregnancy: relationship to placental development and head circumference in newborn. Endocrinol Nutr 2012; 59: 326-330
• 30 Lean MI, Lean ME, Yajnik CS. et al. Iodine status during pregnancy in India and related neonatal and infant outcomes. Public Health Nutr 2014; 17: 1353-1362
• 31 Vermiglio F, Lo Presti VP, Moleti M. et al. Attention deficit and hyperactivity disorders in the offspring of mothers exposed to mild-moderate iodine deficiency: a possible novel iodine deficiency disorder in developed countries. J Clin Endocrinol Metab 2004; 89: 6054-6060
• 32 Bath SC, Steer CD, Golding J. et al. Effect of inadequate iodine status in UK pregnant women on cognitive outcomes in their children: results from the Avon Longitudinal Study of Parents and Children (ALSPAC). Lancet 2013; 382: 331-337
• 33 Hynes KL, Otahal P, Hay I. et al. Mild iodine deficiency during pregnancy is associated with reduced educational outcomes in the offspring: 9-year follow-up of the gestational iodine cohort. J Clin Endocrinol Metab 2013; 98: 1954-1962
• 34 Bundesinstitut für Risikobewertung. Jod, Folat/Folsäure und Schwangerschaft. Accessed November 08, 2022 at: https://www.bfr.bund.de/cm/350/jod-folat-folsaeure-und-schwangerschaft.pdf
• 35 Verhagen NJE, Gowachirapant S, Winichagoon P. et al. Iodine Supplementation in Mildly Iodine-Deficient Pregnant Women Does Not Improve Maternal Thyroid Function or Child Development: A Secondary Analysis of a Randomized Controlled Trial. Front Endocrinol (Lausanne) 2020; 11: 572984
• 36 Harding KB, Peña-Rosas JP, Webster AC. et al. Iodine supplementation for women during the preconception, pregnancy and postpartum period. Cochrane Database Syst Rev 2017; (03) CD011761
• 37 Leung AM, Avram AM, Brenner AV. et al. Potential risks of excess iodine ingestion and exposure: statement by the american thyroid association public health committee. Thyroid 2015; 25: 145-146
• 38 Korevaar TIM, Medici M, Visser TJ. et al. Thyroid disease in pregnancy: new insights in diagnosis and clinical management. Nat Rev Endocrinol 2017; 13: 610-622
• 39 Cooper DS, Laurberg P. Hyperthyroidism in pregnancy. Lancet Diabetes Endocrinol 2013; 1: 238-249
• 40 Taylor PN, Albrecht D, Scholz A. et al. Global epidemiology of hyperthyroidism and hypothyroidism. Nat Rev Endocrinol 2018; 14: 301-316
• 41 Spencer L, Bubner T, Bain E. et al. Screening and subsequent management for thyroid dysfunction pre-pregnancy and during pregnancy for improving maternal and infant health. Cochrane Database Syst Rev 2015; (09) CD011263
• 42 Casey BM, Thom EA, Peaceman AM. et al. Treatment of Subclinical Hypothyroidism or Hypothyroxinemia in Pregnancy. N Engl J Med 2017; 376: 815-825
• 43 Deutsche Gesellschaft für Endokrinologie. Deutsche Gesellschaft für Endokrinologie rät zu Aufklärung – Jodmangel gefährdet Mutter und Kind. 2012. Accessed November 08, 2022 at: https://www.endokrinologie.net/pressemitteilungen-archiv/120606.php
• 44 Fuhrer D. [Thyroid illness during pregnancy]. Internist (Berl) 2011; 52: 1158-1166
• 45 Taylor PN, Muller I, Nana M. et al. Indications for treatment of subclinical hypothyroidism and isolated hypothyroxinaemia in pregnancy. Best Pract Res Clin Endocrinol Metab 2020; 34: 101436
• 46 Dong AC, Morgan J, Kane M. et al. Subclinical hypothyroidism and thyroid autoimmunity in recurrent pregnancy loss: a systematic review and meta-analysis. Fertil Steril 2020; 113: 587-600.e1
• 47 Zhang Y, Wang H, Pan X. et al. Patients with subclinical hypothyroidism before 20 weeks of pregnancy have a higher risk of miscarriage: A systematic review and meta-analysis. PLoS One 2017; 12: e0175708
• 48 Benhadi N, Wiersinga WM, Reitsma JB. et al. Higher maternal TSH levels in pregnancy are associated with increased risk for miscarriage, fetal or neonatal death. Eur J Endocrinol 2009; 160: 985-991
• 49 Negro R, Schwartz A, Gismondi R. et al. Increased pregnancy loss rate in thyroid antibody negative women with TSH levels between 2.5 and 5.0 in the first trimester of pregnancy. J Clin Endocrinol Metab 2010; 95: E44-E48
• 50 Schneuer FJ, Nassar N, Tasevski V. et al. Association and predictive accuracy of high TSH serum levels in first trimester and adverse pregnancy outcomes. J Clin Endocrinol Metab 2012; 97: 3115-3122
• 51 Liu H, Shan Z, Li C. et al. Maternal subclinical hypothyroidism, thyroid autoimmunity, and the risk of miscarriage: a prospective cohort study. Thyroid 2014; 24: 1642-1649
• 52 Consortium on Thyroid and Pregnancy – Study Group on Preterm Birth. Korevaar TIM, Derakhshan A, Taylor PN. et al. Association of Thyroid Function Test Abnormalities and Thyroid Autoimmunity With Preterm Birth: A Systematic Review and Meta-analysis. JAMA 2019; 322: 632-641
• 53 Yang J, Liu Y, Liu H. et al. Associations of maternal iodine status and thyroid function with adverse pregnancy outcomes in Henan Province of China. J Trace Elem Med Biol 2018; 47: 104-110
• 54 Nassie DI, Ashwal E, Raban O. et al. Is there an association between subclinical hypothyroidism and preterm uterine contractions? A prospective observational study. J Matern Fetal Neonatal Med 2017; 30: 881-885
• 55 Dong AC, Stephenson MD, Stagnaro-Green AS. The Need for Dynamic Clinical Guidelines: A Systematic Review of New Research Published After Release of the 2017 ATA Guidelines on Thyroid Disease During Pregnancy and the Postpartum. Front Endocrinol (Lausanne) 2020; 11: 193
• 56 Korevaar TI, Schalekamp-Timmermans S, de Rijke YB. et al. Hypothyroxinemia and TPO-antibody positivity are risk factors for premature delivery: the generation R study. J Clin Endocrinol Metab 2013; 98: 4382-4390
• 57 Andersen SL, Andersen S, Vestergaard P. et al. Maternal Thyroid Function in Early Pregnancy and Child Neurodevelopmental Disorders: A Danish Nationwide Case-Cohort Study. Thyroid 2018; 28: 537-546
• 58 Hales C, Taylor PN, Channon S. et al. Controlled Antenatal Thyroid Screening II: Effect of Treating Maternal Suboptimal Thyroid Function on Child Cognition. J Clin Endocrinol Metab 2018; 103: 1583-1591
• 59 Zhao L, Jiang G, Tian X. et al. Initiation timing effect of levothyroxine treatment on subclinical hypothyroidism in pregnancy. Gynecol Endocrinol 2018; 34: 845-848
• 60 Nazarpour S, Ramezani Tehrani F, Simbar M. et al. Effects of Levothyroxine on Pregnant Women With Subclinical Hypothyroidism, Negative for Thyroid Peroxidase Antibodies. J Clin Endocrinol Metab 2018; 103: 926-935
• 61 Allan WC, Haddow JE, Palomaki GE. et al. Maternal thyroid deficiency and pregnancy complications: implications for population screening. J Med Screen 2000; 7: 127-130
• 62 Smith A, Eccles-Smith J, DʼEmden M. et al. Thyroid disorders in pregnancy and postpartum. Aust Prescr 2017; 40: 214-219
• 63 Liu X, Andersen SL, Olsen J. et al. Maternal hypothyroidism in the perinatal period and childhood asthma in the offspring. Allergy 2018; 73: 932-939
• 64 Jolving LR, Nielsen J, Kesmodel US. et al. Chronic diseases in the children of women with maternal thyroid dysfunction: a nationwide cohort study. Clin Epidemiol 2018; 10: 1381-1390
• 65 Yassa L, Marqusee E, Fawcett R. et al. Thyroid hormone early adjustment in pregnancy (the THERAPY) trial. J Clin Endocrinol Metab 2010; 95: 3234-3241
• 66 Galofre JC, Haber RS, Mitchell AA. et al. Increased postpartum thyroxine replacement in Hashimotoʼs thyroiditis. Thyroid 2010; 20: 901-908
• 67 Promintzer-Schifferl M, Krebs M. [Thyroid disease in pregnancy: Review of current literature and guidelines]. Wien Med Wochenschr 2020; 170: 35-40
• 68 Rivkees SA, Mattison DR. Ending propylthiouracil-induced liver failure in children. N Engl J Med 2009; 360: 1574-1575
• 69 Hasosah M, Alsaleem K, Qurashi M. et al. Neonatal Hyperthyroidism with Fulminant Liver Failure: A Case Report. J Clin Diagn Res 2017; 11: SD01-SD02
• 70 Tan JY, Loh KC, Yeo GS. et al. Transient hyperthyroidism of hyperemesis gravidarum. BJOG 2002; 109: 683-688
• 71 Chan GW, Mandel SJ. Therapy insight: management of Gravesʼ disease during pregnancy. Nat Clin Pract Endocrinol Metab 2007; 3: 470-478
• 72 Smith C, Thomsett M, Choong C. et al. Congenital thyrotoxicosis in premature infants. Clin Endocrinol (Oxf) 2001; 54: 371-376
• 73 Abeillon-du Payrat J, Chikh K, Bossard N. et al. Predictive value of maternal second-generation thyroid-binding inhibitory immunoglobulin assay for neonatal autoimmune hyperthyroidism. Eur J Endocrinol 2014; 171: 451-460
• 74 Peleg D, Cada S, Peleg A. et al. The relationship between maternal serum thyroid-stimulating immunoglobulin and fetal and neonatal thyrotoxicosis. Obstet Gynecol 2002; 99: 1040-1043
• 75 Barbosa RM, Andrade KC, Silveira C. et al. Ultrasound Measurements of Fetal Thyroid: Reference Ranges from a Cohort of Low-Risk Pregnant Women. Biomed Res Int 2019; 2019: 9524378
• 76 Gietka-Czernel M, Dębska M, Kretowicz P. et al. Fetal thyroid in two-dimensional ultrasonography: nomograms according to gestational age and biparietal diameter. Eur J Obstet Gynecol Reprod Biol 2012; 162: 131-138
• 77 Ho SS, Metreweli C. Normal fetal thyroid volume. Ultrasound Obstet Gynecol 1998; 11: 118-122
• 78 Radaelli T, Cetin I, Zamperini P. et al. Intrauterine growth of normal thyroid. Gynecol Endocrinol 2002; 16: 427-430
• 79 Ranzini AC, Ananth CV, Smulian JC. et al. Ultrasonography of the fetal thyroid: nomograms based on biparietal diameter and gestational age. J Ultrasound Med 2001; 20: 613-617
• 80 Zamperini P, Gibelli B, Gilardi D. et al. Pregnancy and thyroid cancer: ultrasound study of foetal thyroid. Acta Otorhinolaryngol Ital 2009; 29: 339-344
• 81 Huel C, Guibourdenche J, Vuillard E. et al. Use of ultrasound to distinguish between fetal hyperthyroidism and hypothyroidism on discovery of a goiter. Ultrasound Obstet Gynecol 2009; 33: 412-420
• 82 Ceccaldi PF, Cohen S, Vuillard E. et al. Correlation between Colored Doppler Echography of Fetal Thyroid Goiters and Histologic Study. Fetal Diagn Ther 2010; 27: 233-235
• 83 Laurberg P, Bournaud C, Karmisholt J. et al. Management of Gravesʼ hyperthyroidism in pregnancy: focus on both maternal and foetal thyroid function, and caution against surgical thyroidectomy in pregnancy. Eur J Endocrinol 2009; 160: 1-8
• 84 Luton D, Le Gac I, Vuillard E. et al. Management of Gravesʼ Disease during Pregnancy: The Key Role of Fetal Thyroid Gland Monitoring. J Clin Endocrinol Metab 2005; 90: 6093-6098
• 85 Iijima S. Current knowledge about the in utero and peripartum management of fetal goiter associated with maternal Gravesʼ disease. Eur J Obstet Gynecol Reprod Biol X 2019; 3: 100027
• 86 Clementi M, Di Gianantonio E, Pelo E. et al. Methimazole embryopathy: delineation of the phenotype. Am J Med Genet 1999; 83: 43-46
• 87 Andersen SL, Knøsgaard L, Olsen J. et al. Maternal Thyroid Function, Use of Antithyroid Drugs in Early Pregnancy, and Birth Defects. J Clin Endocrinol Metab 2019; 104: 6040-6048
• 88 Andersen SL, Andersen S. Antithyroid drugs and birth defects. Thyroid Res 2020; 13: 11
• 89 Kahaly GJ, Bartalena L, Hegedüs L. et al. 2018 European Thyroid Association Guideline for the Management of Gravesʼ Hyperthyroidism. Eur Thyroid J 2018; 7: 167-186
• 90 Bliddal S, Rasmussen ÅK, Sundberg K. et al. Antithyroid drug-induced fetal goitrous hypothyroidism. Nat Rev Endocrinol 2011; 7: 396-406
• 91 Matsumoto T, Miyakoshi K, Saisho Y. et al. Antenatal management of recurrent fetal goitrous hyperthyroidism associated with fetal cardiac failure in a pregnant woman with persistent high levels of thyroid-stimulating hormone receptor antibody after ablative therapy. Endocr J 2013; 60: 1281-1287
• 92 Mendez A, Bigras JL, Deladoëy J. et al. Tricuspid regurgitation and abnormal aortic isthmic flow: prenatal manifestations of hyperthyroidism: fetal heart and hyperthyroidism. Ultrasound Obstet Gynecol 2017; 50: 132-134
• 93 Nachum Z, Rakover Y, Weiner E. et al. Gravesʼ disease in pregnancy: prospective evaluation of a selective invasive treatment protocol. Am J Obstet Gynecol 2003; 189: 159-165
• 94 Juusela AL, Nazir M, Patel Batra Z. et al. Fetal Heart Rate as an Indirect Indicator of Treatment Response in Fetal Hyperthyroidism Secondary to Transplacental Passage of Maternal Thyrotropin Receptor Antibodies. J Clin Gynecol Obstet 2019; 8: 91-96
• 95 Doucette S, Tierney A, Roggensack A. et al. Neonatal Thyrotoxicosis with Tricuspid Valve Regurgitation and Hydrops in a Preterm Infant Born to a Mother with Gravesʼ Disease. AJP Rep 2018; 8: e85-e88
• 96 Sato Y, Murata M, Sasahara J. et al. A case of fetal hyperthyroidism treated with maternal administration of methimazole. J Perinatol 2014; 34: 945-947
• 97 Deutsche Gesellschaft für Kinderendokrinologie und -diabetologie (DGKED) e.V.. Diagnostik bei Neugeborenen von Müttern mit Schilddrüsenfunktionsstörungen. AWMF-Register-Nummer Nr. 174-024. 2018. Accessed November 08, 2022 at: https://www.awmf.org/uploads/tx_szleitlinien/174-024l_S2k_Diagnostik-bei-Neugeborenen-von-Muettern-mit-Schilddruesenfunktionsstoerungen_2019-02.pdf