Thyroid Gland and Pregnancy – Clinical Update

Violeta Mladenovic; Ravi Shah; Sanja Medenica; Pinaki Dutta; Nikola Zankovic; Slavica Aksam; Jayaditya Ghosh; MdSadam Hussain; Zoran Gluvic

doi:10.1055/a-2604-4177

Hormone and Metabolic Research, Table of Contents

Horm Metab Res 2025; 57(05): 303-314
DOI: 10.1055/a-2604-4177

Review

Thyroid Gland and Pregnancy – Clinical Update

Violeta Mladenovic

¹Clinic for Endocrinology, Diabetes and Metabolic Diseases, University of Kragujevac, Kragujevac, Serbia (Ringgold ID: RIN127740)

,

Ravi Shah

²Department of Endocrinology, Post Graduate Institute of Medical Education and Research, Chandigarh, India (Ringgold ID: RIN29751)

,

Sanja Medenica

³Department of Endocrinology, Internal Medicine Clinic, Clinical Center of Montenegro, Podgorica, Montenegro

,

Pinaki Dutta

²Department of Endocrinology, Post Graduate Institute of Medical Education and Research, Chandigarh, India (Ringgold ID: RIN29751)

,

Nikola Zankovic

⁴Faculty of Medicine, University of Montenegro, Podgorica, Montenegro (Ringgold ID: RIN187153)

,

Slavica Aksam

⁵Clinic for Gynecology and Obstetrics, University of Belgrade, Belgrade, Serbia

,

Jayaditya Ghosh

²Department of Endocrinology, Post Graduate Institute of Medical Education and Research, Chandigarh, India (Ringgold ID: RIN29751)

,

MdSadam Hussain

²Department of Endocrinology, Post Graduate Institute of Medical Education and Research, Chandigarh, India (Ringgold ID: RIN29751)

,

Zoran Gluvic

⁶Endocrinology, University of Belgrade, Belgrad, Serbia (Ringgold ID: RIN54801)

› Author Affiliations

Abstract

Thyroid function undergoes significant alterations during pregnancy due to changes in hormone levels and higher metabolic demands. The thyroid gland in pregnancy enlarges by 10%; however, in iodine-deficient areas, this growth might reach 40%. Elevated levels of human chorionic gonadotropin (hCG) in early pregnancy leads to increased thyroid hormone production. While triiodothyronine (T3) and thyroid-stimulating hormone (TSH) do not cross the placenta, thyroxine (T4) does. Thyroid hormone demands peaks between weeks 16 and 20 of pregnancy and remains high until delivery. There is a rise in the levels of thyroxine-binding globulin (TBG), during the period of pregnancy, raising total T4 and T3 levels while TSH levels usually decrease. Pregnancy-related thyroid disorders, such as hypothyroidism, hyperthyroidism, and autoimmune thyroid diseases (AITD), carry the potential to impair the well-being of both the child as well as the mother. A range of 5–20% of women belonging to the reproductive age group have AITD, which can be associated with the possibility of infertility, miscarriages, and/or poor pregnancy outcomes. If improperly managed, overt hypothyroidism can cause severe complications such as developmental delay and preeclampsia. Effective management requires regular monitoring and appropriate treatment adjustment. Treatment for hypothyroidism involves levothyroxine, whereas cautious use of antithyroid medications is advised for hyperthyroidism. Postpartum thyroiditis (PPT), an autoimmune condition occurring after childbirth, requires careful management to address both hyperthyroid and hypothyroid phases. A comprehensive understanding and management of these conditions are critical for optimizing maternal and fetal health outcomes. Thyroid disorders are common in women of reproductive age group.

Keywords

thyroid gland - pregnancy - autoimmune thyroid diseases - hypothyroidism - post-partum thyroiditis

Full Text

References

References
1 Alexander EK, Pearce EN, Brent GA. et al. 2017 Guidelines of the AmericantThyroid association for the diagnosis and management of thyroid disease during pregnancy and the postpartum. Thyroid 2017; 27: 315-389 Corrigendum: Thyroid 2017; 27: 1212
2 Brent GA. The debate over thyroid-function screening in pregnancy. N Engl J Med 2012; 366: 562-563
3 Mladenovic V. Thyroid and pregnancy. Exp Appl Biomed Res (Sciendo) 2023; 24: 249-254
4 Henrichs J, Bongers-Schokking JJ, Schenk JJ. et al. Maternal thyroid function during early pregnancy and cognitive functioning in early childhood: the generation R study. J Clin Endocrinol Metab 2010; 95: 4227-4234
5 Lazarus JH, Bestwick JP, Channon S. et al. Antenatal thyroid screening and childhood cognitive function. N Engl J Med 2012; 366: 493-501 Corrigendum: N Engl J Med. 2012; 366: 1650
6 Negro R, Mestman JH. Thyroid disease in pregnancy. Best Pract Res Clin Endocrinol Metab 2011; 25: 927-943
7 Glinoer D, Spencer CA. Serum TSH determinations in pregnancy: how, when and why?. Nat Rev Endocrinol 2010; 6: 526-529
8 Horacek J, Spitalnikova S, Dlabalova B. et al. Universal screening detects two-times more thyroid disorders in early pregnancy than targeted high-risk case finding. Eur J Endocrinol 2010; 163: 645-650
9 Galofré JC, Haber RS, Mitchell AA. et al. Increased postpartum thyroxine replacement in Hashimoto's thyroiditis. Thyroid 2010; 20: 901-908
10 Fantz CR, Dagogo-Jack S, Ladenson JH. et al. Thyroid function during pregnancy. Clin Chem 1999; 45: 2250-2258
11 Männistö T, Hartikainen AL, Vääräsmäki M. et al. Smoking and early pregnancy thyroid hormone and anti-thyroid antibody levels in euthyroid mothers of the Northern Finland Birth Cohort 1986. Thyroid 2012; 22: 944-950
12 López-Muñoz E, Mateos-Sánchez L, Mejía-Terrazas GE. et al. Hypothyroidism and isolated hypothyroxinemia in pregnancy, from physiology to the clinic. Taiwan J Obstet Gynecol 2019; 58: 757-763
13 Rajput R, Singh B, Goel V. et al. Trimester-specific reference interval for thyroid hormones during pregnancy at a tertiary care hospital in Haryana, India. Indian J Endocrinol Metab 2016; 20: 810-815
14 Singh P, Boelaert K. Controversies in thyroid disease management in pregnancy. Clin Med (Lond) 2025; 25: 100287
15 Marwaha RK, Chopra S, Gopalakrishnan S. et al. Establishment of reference range for thyroid hormones in normal pregnant Indian women. BJOG 2008; 115: 602-606
16 Springer D, Zima T, Limanova Z. Reference intervals in evaluation of maternal thyroid function during the first trimester of pregnancy. Eur J Endocrinol 2009; 160: 791-797
17 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
18 Khan I, Okosieme OE, Lazarus JH. Current challenges in the pharmacological management of thyroid dysfunction in pregnancy. Expert Rev Clin Pharmacol 2017; 10: 97-109
19 Casey BM, Thom EA, Peaceman AM. et al. Treatment of subclinical hypothyroidism or hypothyroxinemia in pregnancy. N Engl J Med 2017; 376: 815-825
20 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
21 Lazarus J. Thyroid regulation and dysfunction in the pregnant patient. In: Feingold KR, Anawalt B, Blackman MR et al. (eds); Endotext. South Dartmouth (MA): MDText.com, Inc.; 2000
22 Teng W, Shan Z, Patil-Sisodia K. et al. Hypothyroidism in pregnancy. Lancet Diabetes Endocrinol 2013; 1: 228-237
23 Teti C, Panciroli M, Nazzari E. et al. Iodoprophylaxis and thyroid autoimmunity: an update. Immunol Res 2021; 69: 129-138
24 Fumarola A, Grani G, Romanzi D. et al. Thyroid function in infertile patients undergoing assisted reproduction. Am J Reprod Immunol 2013; 70: 336-341
25 Orouji Jokar T, Fourman LT, Lee H. et al. Higher TSH levels within the normal range are associated with unexplained infertility. J Clin Endocrinol Metab 2018; 103: 632-639
26 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
27 Dutta P, Singhal S, Sachdeva NK. et al. Diagnostic utility of serum GH, IGF-1 and IGFBP3 in patients of acromegaly with uncontrolled diabetes: a pilot study. J Assoc Physicians India 2014; 62: 686-690
28 Mazzilli R, Medenica S, Di Tommaso AM. et al. The role of thyroid function in female and male infertility: a narrative review. J Endocrinol Invest 2023; 46: 15-26
29 van den Boogaard E, Vissenberg R, Land JA. et al. Significance of (sub)clinical thyroid dysfunction and thyroid autoimmunity before conception and in early pregnancy: a systematic review. Hum Reprod Update 2016; 22: 532-533
30 Thangaratinam S, Tan A, Knox E, Kilby MD. et al. Association between thyroid autoantibodies and miscarriage and preterm birth: meta-analysis of evidence. BMJ 2011; 342: d2616
31 Consortium on Thyroid and Pregnancy – Study Group on Preterm Birth. Korevaar TIM, Derakhshan A. 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
32 Gietka-Czernel M, Glinicki P. Subclinical hypothyroidism in pregnancy: controversies on diagnosis and treatment. Pol Arch Intern Med 2021; 131: 266-275
33 Wang H, Gao H, Chi H. 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; 31: 2190-2198
34 van Dijk MM, Vissenberg R, Fliers E. 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: 322-329
35 Dhillon-Smith RK, Middleton LJ, Sunner KK. et al. Levothyroxine in women with thyroid peroxidase antibodies before conception. N Engl J Med 2019; 380: 1316-1325
36 Sullivan SA. Hypothyroidism in pregnancy. Clin Obstet Gynecol 2019; 62: 308-319
37 Maraka S, Singh Ospina NM, Mastorakos G. et al. Subclinical hypothyroidism in women planning conception and during pregnancy: who should be treated and how?. J Endocr Soc 2018; 2: 533-546
38 Maraka S, Ospina NM, O'Keeffe DT. et al. Subclinical hypothyroidism in pregnancy: a systematic review and meta-analysis. Thyroid 2016; 26: 580-590
39 Korevaar TI, Muetzel R, Medici M. et al. Association of maternal thyroid function during early pregnancy with offspring IQ and brain morphology in childhood: a population-based prospective cohort study. Lancet Diabetes Endocrinol 2016; 4: 35-43
40 Derakhshan A, Männistö T, Chen L. et al. Association of gestational free and total triiodothyronine with gestational hypertension, preeclampsia, preterm birth, and birth weight: an individual participant data meta-analysis. J Clin Endocrinol Metab 2024; 109: e1290-e1298
41 Toloza FJ, Maraka S. Isolated maternal hypothyroxinemia is associated with preterm delivery. Clin Thyroidol 2021; 33: 80-82
42 Levie D, Korevaar TIM, Bath SC. et al. Thyroid function in early pregnancy, child IQ, and autistictTraits: a meta-analysis of individual pparticipant data. J Clin Endocrinol Metab 2018; 103: 2967-2979
43 Thompson W, Russell G, Baragwanath G. et al. Maternal thyroid hormone insufficiency during pregnancy and risk of neurodevelopmental disorders in offspring: a systematic review and meta-analysis. Clin Endocrinol (Oxf) 2018; 88: 575-584
44 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
45 Lee SY, Pearce EN. Testing, monitoring, and treatment of thyroid dysfunction in pregnancy. J Clin Endocrinol Metab 2021; 106: 883-892
46 Hales C, Taylor PN, Channon S. et al. Controlled antenatal thyroid screening II: effect of treating maternal suboptimal thyroid function onchild Ccgnition. J Clin Endocrinol Metab 2018; 103: 1583-1591
47 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 2011; 97: 2543-2565 Corrigendum: J Clin Endocrinol Metab 2021; 106: e2461
48 Negro R, Schwartz A, Gismondi R. et al. Universal screening versus case finding for detection and treatment of thyroid hormonal dysfunction during pregnancy. J Clin Endocrinol Metab 2010; 95: 1699-1707
49 Cooper DS, Biondi B. Subclinical thyroid disease. Lancet 2012; 379: 1142-1154
50 Lata K, Dutta P, Sridhar S. et al. Thyroid autoimmunity and obstetric outcomes in women with recurrent miscarriage: a case-control study. Endocr Connect 2013; 2: 118-124
51 Tańska K, Gietka-Czernel M, Glinicki P. et al. Thyroid autoimmunity and its negative impact on female fertility and maternal pregnancy outcomes. Front Endocrinol (Lausanne) 2023; 13: 1049665
52 Huang N, Chen L, Lian Y. et al. Impact of thyroid autoimmunity on in vitro fertilization/intracytoplasmic sperm injection outcomes and fetal weight. Front Endocrinol (Lausanne) 2021; 12: 698579
53 Medenica S, Garalejić E, Abazović D. et al. Pregnancy outcomes and newborn characteristics in women with follicular fluid thyroid autoantibodies undergoing assisted reproduction. J Med Biochem 2023; 42: 27-33
54 Busnelli A, Paffoni A, Fedele L. et al. The impact of thyroid autoimmunity on IVF/ICSI outcome: a systematic review and meta-analysis. Hum Reprod Update 2016; 22: 793-794
55 Medenica S, Abazovic D, Ljubić A. et al. The role of cell and gene therapies in the treatment of infertility in patients with thyroid autoimmunity. Int J Endocrino 2022; 4842316
56 Godines-Enriquez MS, Miranda-Velásquez S, Enríquez-Pérez MM. et al. Prevalence of thyroid autoimmunity in women with recurrent pregnancy loss. Medicina (Kaunas) 2021; 57: 96
57 Gameil MA, Marzouk RE, Elsebaie AH. et al. Influence of thyroid autoimmunity at various clinical stages of hypothyroidism on the risk of miscarriage before 20 weeks of gestation. Hormones (Athens) 2023; 22: 587-593
58 De Leo S, Pearce EN. Autoimmune thyroid disease during pregnancy. Lancet Diabetes Endocrinol 2018; 6: 575-586
59 Abbassi-Ghanavati M, Casey BM, Spong CY. et al. Pregnancy outcomes in women with thyroid peroxidase antibodies. Obstet Gynecol 2010; 116: 381-386
60 FIGO Working Group on Good Clinical Practice in Maternal-Fetal Medicine. Good clinical practice advice: thyroid and pregnancy. Int J Gynaecol Obstet 2019; 144: 347-351
61 Negro R, Schwartz A, Gismondi R. et al. Universal screening versus case finding for detection and treatment of thyroid hormonal dysfunction during pregnancy. J Clin Endocrinol Metab 2010; 95: 1699-1707
62 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; 91: 2587-2591
63 Poppe K, Glinoer D. Thyroid autoimmunity and hypothyroidism before and during pregnancy. Hum Reprod Update 2003; 9: 149-161
64 Haddow JE, Palomaki GE, Allan WC. et al. Maternal thyroid deficiency during pregnancy and subsequent neuropsychological development of the child. N Engl J Med 1999; 341: 549-555
65 Amouzegar A, Mehran L, Takyar M. et al. Tehran thyroid study (TTS). Int J Endocrinol Metab 2018; 16: e84727
66 Wang H, Gao H, Chi H. 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: 2190-2198
67 Arafah BM. Increased need for thyroxine in women with hypothyroidism during estrogen therapy. N Engl J Med 2001; 344: 1743-1749
68 Moleti M, Di Mauro M, Sturniolo G. et al. Hyperthyroidism in the pregnant woman: maternal and fetal aspects. J Clin Transl Endocrinol 2019; 16: 100190
69 Iijima S. Pitfalls in the assessment of gestational transient thyrotoxicosis. Gynecol Endocrinol 2020; 36: 662-667
70 Sorah K, Alderson TL. Hyperthyroidism in pregnancy. In. StatPearls [Internet]; 2025. https://www.ncbi.nlm.nih.gov/books/NBK559203/
71 Jagtap SV, Aher V, Gadhiya S. et al. Gestational trophoblastic disease - clinicopathological study at tertiary care hospital. J Clin Diagn Res 2017; 11: EC27-EC30
72 Pearce EN. Management of thyrotoxicosis: preconception, pregnancy, and the postpartum period. Endocr Pract 2019; 25: 62-68
73 Budenhofer BK, Ditsch N, Jeschke U. et al. Thyroid (dys-)function in normal and disturbed pregnancy. Arch Gynecol Obstet 2013; 287: 1-7
74 Harn-A-Morn P, Dejkhamron P, Tongsong T. et al. Pregnancy outcomes among women with Graves' hyperthyroidism: a retrospective cohort study. J Clin Med 2021; 10: 4495
75 Krassas GE. Thyroid disease and female reproduction. Fertil Steril 2000; 74: 1063-1070
76 Poppe K, Glinoer D, Van Steirteghem A. et al. Thyroid dysfunction and autoimmunity in infertile women. Thyroid 2002; 12: 997-1001
77 Männistö T, Mendola P, Grewal J. et al. Thyroid diseases and adverse pregnancy outcomes in a contemporary US cohort. J Clin Endocrinol Metab 2013; 98: 2725-2733
78 Andersen SL, Andersen S, Vestergaard P. et al. Maternal thyroid function in early pregnancy and childneurodevelopmental disorders: a Danish nationwide case-cohort study. Thyroid 2018; 28: 537-546
79 Casey BM, Dashe JS, Wells CE. et al. Subclinical hyperthyroidism and pregnancy outcomes. Obstet Gynecol 2006; 107: 337-341
80 Nguyen CT, Sasso EB, Barton L. et al. Graves' hyperthyroidism in pregnancy: a clinical review. Clin Diabetes Endocrinol 2018; 4: 4
81 Iijima S. Effects of fetal involvement of inadvertent radioactive iodine therapy for the treatment of thyroid diseases during an unsuspected pregnancy. Eur J Obstet Gynecol Reprod Biol 2021; 259: 53-59
82 Mandel SJ, Cooper DS. The use of antithyroid drugs in pregnancy and lactation. J Clin Endocrinol Metab 2001; 86: 2354-2359
83 Kahaly GJ, Bartalena L, Hegedüs L. et al. 2018 European thyroid association guideline for the management of Graves' hyperthyroidism. Eur Thyroid J 2018; 7: 167-186
84 Laurberg P, Bournaud C, Karmisholt J. et al. Management of Graves' 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
85 Bhatia N, Mitharwal SM. Hydatidiform mole with uncontrolled hyperthyroidism: an anesthetic challenge. J Anaesthesiol Clin Pharmacol 2016; 32: 537-538
86 Kang JR, Cox R, Kluesner J. Postpartum thyroiditis mimicking central hypothyroidism: the perfect thyming. Cureus 2023; 15: e42630
87 Paschou SA, Bletsa E, Papazisi M. et al. Screening and management of major endocrinopathies during pregnancy: an update. Endocrine 2023; 80: 10-19
88 Stagnaro-Green A, Schwartz A, Gismondi R. et al. High rate of persistent hypothyroidism in a large-scale prospective study of postpartum thyroiditis in southern Italy. J Clin Endocrinol Metab 2011; 96: 652-657
89 Lucas A, Pizarro E, Granada ML. et al. Postpartum thyroiditis: long-term follow-up. Thyroid 2005; 15: 1177-1181
90 Stuckey BG, Kent GN, Ward LC. et al. Postpartum thyroid dysfunction and the long-term risk of hypothyroidism: results from a 12-year follow-up study of women with and without postpartum thyroid dysfunction. Clin Endocrinol (Oxf) 2010; 73: 389-395
91 Lee SY, Pearce EN. Assessment and treatment of thyroid disorders in pregnancy and the postpartum period. Nat Rev Endocrinol 2022; 18: 158-171
92 Nicholson WK, Robinson KA, Smallridge RC. et al. Prevalence of postpartum thyroid dysfunction: a quantitative review. Thyroid 2006; 16: 573-582
93 Moleti M, Mauro MD, Alibrandi A. et al. Postpartum thyroiditis in women with euthyroid and hypothyroid Hashimoto's thyroiditis antedating pregnancy. J Clin Endocrinol Metab 2020; 105: dgaa197
94 Marqusee E, Hill JA, Mandel SJ. Thyroiditis after pregnancy loss. J Clin Endocrinol Metab 1997; 82: 2455-2457
95 Kuijpens JL, Vader HL, Drexhage HA. et al. Thyroid peroxidase antibodies during gestation are a marker for subsequent depression postpartum. Eur J Endocrinol 2001; 145: 579-584
96 Shahbazian HB, Sarvghadi F, Azizi F. Ultrasonographic characteristics and follow-up in post-partum thyroiditis. J Endocrinol Invest 2005; 28: 410-412
97 Oyibo SO, Green OS, Laliwala NM. et al. Biochemical transition during triphasic postpartum thyroiditis: confusion with central hypothyroidism. Endocrinol Diabetes Metab Case Rep. 2021: 21-0069