Skip to main content Accessibility help
×
Hostname: page-component-f554764f5-rvxtl Total loading time: 0 Render date: 2025-04-21T08:57:35.408Z Has data issue: false hasContentIssue false

Chapter 10 - Thyroid Treatment Trials

Published online by Cambridge University Press:  16 April 2025

Roy G. Farquharson
Affiliation:
Liverpool Women’s Hospital
Mary D. Stephenson
Affiliation:
University of Illinois, Chicago
Mariëtte Goddijn
Affiliation:
Amsterdam University Medical Centers
Get access

Summary

Thyroid dysfunction and autoimmunity during pregnancy have been consistently associated with poor maternal and fetal outcomes. Treatment for overt hypo- and hyperthyroidism in pregnant women and women attempting pregnancy is therefore universally recommended. In women with subclinical hypothyroidism, levothyroxine treatment is thought to reduce pregnancy loss, preterm delivery and gestational hypertension although several large trials have failed to demonstrate an effect on child cognition and neurodevelopment. Levothyroxine treatment has also been shown to improve the outcome of fertility treatment in women with subclinical hypothyroidism. However there is currently insufficient evidence to recommend levothyroxine treatment in euthyroid women with thyroid auto-immunity attempting pregnancy as several high-quality randomized trials have failed to demonstrate a beneficial effect of levothyroxine treatment on life birth, miscarriage rate or the outcomes of assisted reproductive therapy.

Type
Chapter
Information
Early Pregnancy , pp. 89 - 95
Publisher: Cambridge University Press
Print publication year: 2025

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

Book purchase

Temporarily unavailable

References

Krassas, G. E., Poppe, K., Glinoer, D.. Thyroid function and human reproductive health. Endocr Rev. 2010;31(5):702–55.CrossRefGoogle ScholarPubMed
Haddow, J. E., Palomaki, G. E., Allan, W. C., Williams, J. R., Knight, G. J., Gagnon, J., et al. Maternal thyroid deficiency during pregnancy and subsequent neuropsychological development of the child. N Eng J Med. 1999;341(8):549–55.CrossRefGoogle ScholarPubMed
Toloza, F. J. K., Derakhshan, A., Männistö, T., Bliddal, S., Popova, P. V., Carty, D. M., et al. Association between maternal thyroid function and risk of gestational hypertension and pre-eclampsia: a systematic review and individual-participant data meta-analysis. Lancet Diabetes Endocrinol. 2022;10(4):243–52.CrossRefGoogle ScholarPubMed
van den Boogaard, E., Vissenberg, R., Land, J. A., van Wely, M., van der Post, J. A., Goddijn, M., et al. Significance of (sub)clinical thyroid dysfunction and thyroid autoimmunity before conception and in early pregnancy: a systematic review. Hum Reprod Update. 2011;17(5):605–19.CrossRefGoogle ScholarPubMed
Gill, S., Cheed, V., Morton, V. A. H., Gill, D., Boelaert, K., Chan, S., et al. Evaluating the progression to hypothyroidism in preconception euthyroid thyroid peroxidase antibody-positive women. J Clin Endocrinol Metabol. 2022;108(1):124–34.CrossRefGoogle ScholarPubMed
Wang, H., Gao, H., Chi, H., Zeng, L., Xiao, W., Wang, Y., et al. Effect of levothyroxine on miscarriage among women with normal thyroid function and thyroid autoimmunity undergoing in vitro fertilization and embryo transfer: a randomized clinical trial. JAMA. 2017;318(22):2190–8.CrossRefGoogle ScholarPubMed
Negro, R., Mangieri, T., Coppola, L., Presicce, G., Casavola, E. C., Gismondi, R., et al. Levothyroxine treatment in thyroid peroxidase antibody-positive women undergoing assisted reproduction technologies: a prospective study. Hum Reprod. 2005;20(6):1529–33.CrossRefGoogle ScholarPubMed
Dhillon-Smith, R. K., Middleton, L. J., Sunner, K. K., Cheed, V., Baker, K., Farrell-Carver, S., et al. Levothyroxine in women with thyroid peroxidase antibodies before conception. N Eng J Med. 2019;380(14):1316–25.CrossRefGoogle ScholarPubMed
van Dijk, M. M., Vissenberg, R., Fliers, E., van der Post, J. A. M, van der Hoorn, M. P., de Weerd, S., et al. Levothyroxine in euthyroid thyroid peroxidase antibody positive women with recurrent pregnancy loss (T4LIFE trial): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Diabetes Endocrinol. 2022;10(5):322–29.CrossRefGoogle Scholar
Akhtar, M. A., Agrawal, R., Brown, J., Sajjad, Y., Craciunas, L.. Thyroxine replacement for subfertile women with euthyroid autoimmune thyroid disease or subclinical hypothyroidism. Cochrane Database of Syst Rev. 2019;6(6):CD011009.Google ScholarPubMed
Poppe, K., Bisschop, P., Fugazzola, L., Minziori, G., Unuane, D., Weghofer, A.. 2021 European Thyroid Association guideline on thyroid disorders prior to and during assisted reproduction. Eur Thyroid J. 2021;9(6):281–95.Google ScholarPubMed
Kim, C. H., Ahn, J. W., Kang, S., Kim, S. H., Chae, H. D., Kang, B. M.. Effect of levothyroxine treatment on in vitro fertilization and pregnancy outcome in infertile women with subclinical hypothyroidism undergoing in vitro fertilization/intracytoplasmic sperm injection. Fertil Steril. 2011;95(5):1650–54.CrossRefGoogle ScholarPubMed
Velkeniers, B., Van Meerhaeghe, A., Poppe, K., Unuane, D., Tournaye, H., Haentjens, P.. Levothyroxine treatment and pregnancy outcome in women with subclinical hypothyroidism undergoing assisted reproduction technologies: systematic review and meta-analysis of RCTs. Hum Reprod Update. 2013;19(3):251–58.CrossRefGoogle ScholarPubMed
Negro, R., Schwartz, A., Gismondi, R., Tinelli, A., Mangieri, T., Stagnaro-Green, A.. Universal screening versus case finding for detection and treatment of thyroid hormonal dysfunction during pregnancy. J Clin Endocrinol Metab. 2010;95(4):1699–707.CrossRefGoogle ScholarPubMed
Ding, Z., Liu, Y., Maraka, S., Abdelouahab, N., Huang, H.-F., Fraser, W. D., et al. Pregnancy and neonatal outcomes with levothyroxine treatment in women with subclinical hypothyroidism based on new diagnostic criteria: a systematic review and meta-analysis. Front Endocrinol (Lausanne). 2021;12:797423.CrossRefGoogle ScholarPubMed
Alexander, E. K., Pearce, E. N., Brent, G. A., Brown, R. S., Chen, H., Dosiou, C., 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(3):315–89.CrossRefGoogle ScholarPubMed
Thangaratinam, S., Tan, A., Knox, E., Kilby, M. D., Franklyn, J., Coomarasamy, A.. Association between thyroid autoantibodies and miscarriage and preterm birth: meta-analysis of evidence. BMJ. 2011;342:d2616.CrossRefGoogle ScholarPubMed
Lau, L., Benham, J. L., Lemieux, P., Yamamoto, J., Donovan, L. E.. Impact of levothyroxine in women with positive thyroid antibodies on pregnancy outcomes: a systematic review and meta-analysis of randomised controlled trials. BMJ Open. 2021;11(2):e043751.CrossRefGoogle ScholarPubMed
Wang, X., Zhang, Y., Tan, H., Bai, Y., Zhou, L., Fang, F., et al. Effect of levothyroxine on pregnancy outcomes in women with thyroid autoimmunity: a systematic review with meta-analysis of randomized controlled trials. Fertil Steril. 2020;114(6):1306–14.CrossRefGoogle ScholarPubMed
Wang, Q., Jiang, Y., Lv, H., Lu, Q., Tao, S., Qin, R., et al. Association of maternal mild hypothyroidism with offspring neurodevelopment in TPOAb-negative women: a prospective cohort study. Front Endocrinol (Lausanne). 2022;13:884851.CrossRefGoogle ScholarPubMed
Lain, S. J., Rifas-Shiman, S. L., Pearce, E. N., Nassar, N., Oken, E.. Neonatal thyroxine, maternal thyroid function, and cognition in mid-childhood in a US cohort. Matern Child Health J. 2020;24(4):503–13.CrossRefGoogle Scholar
Smit, B. J., Kok, J. H., Vulsma, T., Briët, J. M., Boer, K., Wiersinga, W. M.. Neurologic development of the newborn and young child in relation to maternal thyroid function. Acta Paediatr. 2000;89(3):291–95.CrossRefGoogle Scholar
Thompson, W., Russell, G., Baragwanath, G., Matthews, J., Vaidya, B., Thompson-Coon, J.. Maternal thyroid hormone insufficiency during pregnancy and risk of neurodevelopmental disorders in offspring: a systematic review and meta-analysis. Clin Endocrinol (Oxf). 2018;88(4):575–84.CrossRefGoogle ScholarPubMed
Lazarus, J. H., Bestwick, J. P., Channon, S., Paradice, R., Maina, A., Rees, R, et al. Antenatal thyroid screening and childhood cognitive function. N Engl J Med. 2012;366(6):493501.CrossRefGoogle ScholarPubMed
Hales, C., Taylor, P. N., Channon, S., McEwan, K., Thapar, A., Langley, K., et al. Controlled antenatal thyroid screening II: effect of treating maternal suboptimal thyroid function on child behavior. J Clin Endocrinol Metab. 2020;105(3):dgz098.CrossRefGoogle ScholarPubMed
Casey, B. M., Thom, E. A., Peaceman, A. M., Varner, M. W., Sorokin, Y., Hirtz, D. G., et al. Treatment of subclinical hypothyroidism or hypothyroxinemia in pregnancy. N Engl J Med. 2017;376(9):815–25.CrossRefGoogle ScholarPubMed
Nazarpour, S., Ramezani Tehrani, F., Simbar, M., Tohidi, M., Alavi Majd, H., Azizi, F.. Effects of levothyroxine treatment on pregnancy outcomes in pregnant women with autoimmune thyroid disease. Eur J Endocrinol. 2017;176(2):253–65.CrossRefGoogle ScholarPubMed
Nazarpour, S., Ramezani Tehrani, F., Simbar, M., Tohidi, M., Minooee, S., Rahmati, M., et al. Effects of levothyroxine on pregnant women with subclinical hypothyroidism, negative for thyroid peroxidase antibodies. J Clin Endocrinol Metab. 2018;103(3):926–35.CrossRefGoogle ScholarPubMed
Nazarpour, S., Ramezani Tehrani, F., Sajedi, F., Rahmati, M., Bidhendi Yarandi, R., Azizi, F.. Lack of beneficiary effect of levothyroxine therapy of pregnant women with subclinical hypothyroidism in terms of neurodevelopment of their offspring. Arch Gynecol Obstet. 2023;309(3):975–85.CrossRefGoogle ScholarPubMed
Lazarus, J., Brown, R. S., Daumerie, C., Hubalewska-Dydejczyk, A., Negro, R., Vaidya, B.. 2014 European Thyroid Association guidelines for the management of subclinical hypothyroidism in pregnancy and in children. Eur Thyroid J. 2014;3(2):7694.CrossRefGoogle ScholarPubMed
Glinoer, D.. The regulation of thyroid function in pregnancy: pathways of endocrine adaptation from physiology to pathology. Endocr Rev. 1997;18(3):404–33.CrossRefGoogle ScholarPubMed
Yassa, L., Marqusee, E., Fawcett, R., Alexander, E. K.. Thyroid hormone early adjustment in pregnancy (the THERAPY) trial. J Clin Endocrinol Metab. 2010;95(7):3234–41.CrossRefGoogle ScholarPubMed
Sullivan, S. D., Downs, E., Popoveniuc, G., Zeymo, A., Jonklaas, J., Burman, K. D.. Randomized trial comparing two algorithms for levothyroxine dose adjustment in pregnant women with primary hypothyroidism. J Clin Endocrinol Metab. 2017;102(9):3499–507.CrossRefGoogle ScholarPubMed
Earl, R., Crowther, C. A., Middleton, P.. Interventions for hyperthyroidism pre-pregnancy and during pregnancy. Cochrane Database Syst Rev. 2013(11):CD008633.CrossRefGoogle Scholar

Save book to Kindle

To save this book to your Kindle, first ensure [email protected] is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about saving to your Kindle.

Note you can select to save to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

Find out more about the Kindle Personal Document Service.

Available formats
×

Save book to Dropbox

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Dropbox.

Available formats
×

Save book to Google Drive

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Google Drive.

Available formats
×