Overview of Hypothyroidism in Pregnancy

Abstract

Overt hypothyroidism in pregnancy, defined as an elevated serum thyroid-stimulating hormone (TSH) and reduced serum free thyroxine or a TSH >10 mIU/L, is known to have adverse effects on pregnancy. Subclinical hypothyroidism is typically defined as an elevated TSH and normal FT4 levels. There remains much controversy on the benefit of starting levothyroxine for mothers diagnosed with subclinical hypothyroidism. Recent studies are redefining the normal range for TSH in pregnancy, and the data on whether treatment of subclinical hypothyroidism improves outcomes for the mother and fetus are unclear. One confounding variable is the presence of thyroid peroxidase antibodies, as it may be a surrogate marker for other autoimmune disorders detrimental to pregnancy. If levothyroxine treatment is initiated, the dosing and monitoring strategy is different from nonpregnant individuals. Randomized clinical trials are underway that may better elucidate whether treatment of subclinical hypothyroidism is warranted.

Keywords

hypothyroidism - pregnancy - subclinical hypothyroidism - levothyroxine

• References

• 1 Stagnaro-Green A, Abalovich M, Alexander E , et al; American Thyroid Association Taskforce on Thyroid Disease During Pregnancy and Postpartum. Guidelines of the American Thyroid Association for the diagnosis and management of thyroid disease during pregnancy and postpartum. Thyroid 2011; 21 (10) 1081-1125
• 2 Jonklaas J, Bianco AC, Bauer AJ , et al; American Thyroid Association Task Force on Thyroid Hormone Replacement. Guidelines for the treatment of hypothyroidism: prepared by the American Thyroid Association Task Force on thyroid hormone replacement. Thyroid 2014; 24 (12) 1670-1751
• 3 Teng W, Shan Z, Patil-Sisodia K, Cooper DS. Hypothyroidism in pregnancy. Lancet Diabetes Endocrinol 2013; 1 (3) 228-237
• 4 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 (8) 2543-2565
• 5 Vaidya B, Anthony S, Bilous M , et al. Detection of thyroid dysfunction in early pregnancy: Universal screening or targeted high-risk case finding?. J Clin Endocrinol Metab 2007; 92 (1) 203-207
• 6 Yang H, Shao M, Chen L , et al. Screening strategies for thyroid disorders in the first and second trimester of pregnancy in China. PLoS ONE 2014; 9 (6) e99611
• 7 Wang W, Teng W, Shan Z , et al. The prevalence of thyroid disorders during early pregnancy in China: the benefits of universal screening in the first trimester of pregnancy. Eur J Endocrinol 2011; 164 (2) 263-268
• 8 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) 1699-1707
• 9 Dosiou C, Barnes J, Schwartz A, Negro R, Crapo L, Stagnaro-Green A. Cost-effectiveness of universal and risk-based screening for autoimmune thyroid disease in pregnant women. J Clin Endocrinol Metab 2012; 97 (5) 1536-1546
• 10 Fitzpatrick DL, Russell MA. Diagnosis and management of thyroid disease in pregnancy. Obstet Gynecol Clin North Am 2010; 37 (2) 173-193
• 11 Glinoer D. The regulation of thyroid function in pregnancy: pathways of endocrine adaptation from physiology to pathology. Endocr Rev 1997; 18 (3) 404-433
• 12 Soldin OP, Tractenberg RE, Hollowell JG, Jonklaas J, Janicic N, Soldin SJ. Trimester-specific changes in maternal thyroid hormone, thyrotropin, and thyroglobulin concentrations during gestation: trends and associations across trimesters in iodine sufficiency. Thyroid 2004; 14 (12) 1084-1090
• 13 Medici M, Korevaar TI, Visser WE, Visser TJ, Peeters RP. Thyroid function in pregnancy: what is normal?. Clin Chem 2015; 61 (5) 704-713
• 14 Burrow GN, Fisher DA, Larsen PR. Maternal and fetal thyroid function. N Engl J Med 1994; 331 (16) 1072-1078
• 15 Cignini P, Cafà EV, Giorlandino C, Capriglione S, Spata A, Dugo N. Thyroid physiology and common diseases in pregnancy: review of literature. J Prenat Med 2012; 6 (4) 64-71
• 16 Lazarus JH, Kokandi A. Thyroid disease in relation to pregnancy: a decade of change. Clin Endocrinol (Oxf) 2000; 53 (3) 265-278
• 17 Okosieme OE, Marx H, Lazarus JH. Medical management of thyroid dysfunction in pregnancy and the postpartum. Expert Opin Pharmacother 2008; 9 (13) 2281-2293
• 18 Lazarus J, Brown RS, 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) 76-94
• 19 Negro R, Stagnaro-Green A. Diagnosis and management of subclinical hypothyroidism in pregnancy. BMJ 2014; 349: g4929
• 20 Brabant G, Peeters RP, Chan SY , et al. Management of subclinical hypothyroidism in pregnancy: are we too simplistic?. Eur J Endocrinol 2015; 173 (1) 1-P11
• 21 Rugge JB, Bougatsos C, Chou R. Screening and treatment of thyroid dysfunction: an evidence review for the U.S. Preventive Services Task Force. Ann Intern Med 2015; 162 (1) 35-45
• 22 Surks MI, Ortiz E, Daniels GH , et al. Subclinical thyroid disease: scientific review and guidelines for diagnosis and management. JAMA 2004; 291 (2) 228-238
• 23 Korevaar TI, Medici M, de Rijke YB , et al. Ethnic differences in maternal thyroid parameters during pregnancy: the Generation R study. J Clin Endocrinol Metab 2013; 98 (9) 3678-3686
• 24 Cleary-Goldman J, Malone FD, Lambert-Messerlian G , et al. Maternal thyroid hypofunction and pregnancy outcome. Obstet Gynecol 2008; 112 (1) 85-92
• 25 Casey BM, Dashe JS, Spong CY, McIntire DD, Leveno KJ, Cunningham GF. Perinatal significance of isolated maternal hypothyroxinemia identified in the first half of pregnancy. Obstet Gynecol 2007; 109 (5) 1129-1135
• 26 Lazarus JH, Bestwick JP, Channon S , et al. Antenatal thyroid screening and childhood cognitive function. N Engl J Med 2012; 366 (6) 493-501
• 27 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 (1) 35-43
• 28 Lazarus J. Thyroid regulation and dysfunction in the pregnant patient. In: De Groot LJ, Beck-Peccoz P, Chrousos G, , et al, eds., Endotext. South Dartmouth, MA; 2000
• 29 Stricker R, Echenard M, Eberhart R , et al. Evaluation of maternal thyroid function during pregnancy: the importance of using gestational age-specific reference intervals. Eur J Endocrinol 2007; 157 (4) 509-514
• 30 Leung AS, Millar LK, Koonings PP, Montoro M, Mestman JH. Perinatal outcome in hypothyroid pregnancies. Obstet Gynecol 1993; 81 (3) 349-353
• 31 Allan WC, Haddow JE, Palomaki GE , et al. Maternal thyroid deficiency and pregnancy complications: implications for population screening. J Med Screen 2000; 7 (3) 127-130
• 32 Davis LE, Leveno KJ, Cunningham FG. Hypothyroidism complicating pregnancy. Obstet Gynecol 1988; 72 (1) 108-112
• 33 Su PY, Huang K, Hao JH , et al. Maternal thyroid function in the first twenty weeks of pregnancy and subsequent fetal and infant development: a prospective population-based cohort study in China. J Clin Endocrinol Metab 2011; 96 (10) 3234-3241
• 34 Hallengren B, Lantz M, Andreasson B, Grennert L. Pregnant women on thyroxine substitution are often dysregulated in early pregnancy. Thyroid 2009; 19 (4) 391-394
• 35 Brown R. Disorders of the thyroid gland in infancy, childhood and adolescence. Endotext: http://wwwendotextorg/chapter/disorders-of-the-thyroid-gland-in-infancy-childhood-and-adolescence/ . Accessed August 10, 2016
• 36 Salerno M, Capalbo D, Cerbone M, De Luca F. Subclinical hypothyroidism in childhood - current knowledge and open issues. Nat Rev Endocrinol 2016; : 10.1038/nrendo.2016.100
• 37 Garber JR, Cobin RH, Gharib H , et al; American Association of Clinical Endocrinologists and American Thyroid Association Taskforce on Hypothyroidism in Adults. Clinical practice guidelines for hypothyroidism in adults: cosponsored by the American Association of Clinical Endocrinologists and the American Thyroid Association. Endocr Pract 2012; 18 (6) 988-1028
• 38 American Thyroid Association. Initial Release of New 2016 ATA Guidelines. In: American Thyroid Association (ATA) Satellite Symposium. Boston, MA: ATA; March 31, 2016
• 39 Vissenberg R, van den Boogaard E, van Wely M , et al. Treatment of thyroid disorders before conception and in early pregnancy: a systematic review. Hum Reprod Update 2012; 18 (4) 360-373
• 40 Negro R, Schwartz A, Gismondi R, Tinelli A, Mangieri T, Stagnaro-Green A. 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 (9) E44-E48
• 41 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 (11) 1642-1649
• 42 Taylor PN, Minassian C, Rehman A , et al. TSH levels and risk of miscarriage in women on long-term levothyroxine: a community-based study. J Clin Endocrinol Metab 2014; 99 (10) 3895-3902
• 43 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 (8) 549-555
• 44 Brent GA. The debate over thyroid-function screening in pregnancy. N Engl J Med 2012; 366 (6) 562-563
• 45 Reid SM, Middleton P, Cossich MC, Crowther CA, Bain E. Interventions for clinical and subclinical hypothyroidism pre-pregnancy and during pregnancy. Cochrane Database Syst Rev 2013; 5 (5) CD007752
• 46 Sheehan PM, Nankervis A, Araujo Júnior E, Da Silva Costa F. Maternal thyroid disease and preterm birth: systematic review and meta-analysis. J Clin Endocrinol Metab 2015; 100 (11) 4325-4331
• 47 Maraka S, Ospina NM, O'Keeffe DT , et al. Subclinical hypothyroidism in pregnancy: a systematic review and meta-analysis. Thyroid 2016; 26 (4) 580-590
• 48 Tudela CM, Casey BM, McIntire DD, Cunningham FG. Relationship of subclinical thyroid disease to the incidence of gestational diabetes. Obstet Gynecol 2012; 119 (5) 983-988
• 49 Casey B. Effect of treatment of maternal subclinical hypothyroidism or hypethyroxinemia on IQ in offspring. Am J Obstet Gynecol 2016; 214: S2
• 50 Thangaratinam S, Tan A, Knox E, Kilby MD, Franklyn J, Coomarasamy A. Association between thyroid autoantibodies and miscarriage and preterm birth: meta-analysis of evidence. BMJ 2011; 342: d2616
• 51 Karakosta P, Alegakis D, Georgiou V , et al. Thyroid dysfunction and autoantibodies in early pregnancy are associated with increased risk of gestational diabetes and adverse birth outcomes. J Clin Endocrinol Metab 2012; 97 (12) 4464-4472
• 52 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 (11) 4382-4390
• 53 He X, Wang P, Wang Z, He X, Xu D, Wang B. Thyroid antibodies and risk of preterm delivery: a meta-analysis of prospective cohort studies. Eur J Endocrinol 2012; 167 (4) 455-464
• 54 Negro R, Formoso G, Mangieri T, Pezzarossa A, Dazzi D, Hassan H. Levothyroxine treatment in euthyroid pregnant women with autoimmune thyroid disease: effects on obstetrical complications. J Clin Endocrinol Metab 2006; 91 (7) 2587-2591
• 55 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 2011; 17 (5) 605-619
• 56 Vissenberg R, van Dijk MM, Fliers E , et al. Effect of levothyroxine on live birth rate in euthyroid women with recurrent miscarriage and TPO antibodies (T4-LIFE study). Contemp Clin Trials 2015; S1551-7144(15)30061-6
• 57 Ghassabian A, Bongers-Schokking JJ, de Rijke YB , et al. Maternal thyroid autoimmunity during pregnancy and the risk of attention deficit/hyperactivity problems in children: the Generation R Study. Thyroid 2012; 22 (2) 178-186
• 58 Mandel SJ, Larsen PR, Seely EW, Brent GA. Increased need for thyroxine during pregnancy in women with primary hypothyroidism. N Engl J Med 1990; 323 (2) 91-96
• 59 Alexander EK, Marqusee E, Lawrence J, Jarolim P, Fischer GA, Larsen PR. Timing and magnitude of increases in levothyroxine requirements during pregnancy in women with hypothyroidism. N Engl J Med 2004; 351 (3) 241-249
• 60 Yassa L, Marqusee E, Fawcett R, Alexander EK. Thyroid hormone early adjustment in pregnancy (the THERAPY) trial. J Clin Endocrinol Metab 2010; 95 (7) 3234-3241
• 61 Loh JA, Wartofsky L, Jonklaas J, Burman KD. The magnitude of increased levothyroxine requirements in hypothyroid pregnant women depends upon the etiology of the hypothyroidism. Thyroid 2009; 19 (3) 269-275
• 62 Anselmo J, Cao D, Karrison T, Weiss RE, Refetoff S. Fetal loss associated with excess thyroid hormone exposure. JAMA 2004; 292 (6) 691-695
• 63 Abalovich M, Vázquez A, Alcaraz G , et al. Adequate levothyroxine doses for the treatment of hypothyroidism newly discovered during pregnancy. Thyroid 2013; 23 (11) 1479-1483
• 64 Yu X, Chen Y, Shan Z , et al. The pattern of thyroid function of subclinical hypothyroid women with levothyroxine treatment during pregnancy. Endocrine 2013; 44 (3) 710-715