Citation Information :
Gupta NP, Jaiswal A. Levothyroxine Therapy: Its Effect on Subclinical Hypothyroidism. J South Asian Feder Obs Gynae 2024; 16 (3):278-281.
Thyroid hormones are necessary for the desired development and growth of the fetus. There is an essential correlation between thyroid dysfunction in mothers and cognition in children; maternal hypothyroidism also affects reproductive functions, including fertility, abortions, and preterm birth. Due to regular changes in the metabolism of thyroid hormone and thyroid function, trimester-wise thyroid-stimulating hormone (TSH) levels and free thyroxine should be estimated. However, due to variations in age, ethnicity, and iodine intake, it is restricted to one population, which can be misleading to diagnose a euthyroid woman as a patient of hypothyroidism. Therapeutic benefits of levothyroxine remain unclear; however, when an intervention was made during the first trimester, it indicated a reduction of abortions and preterm delivery in women. The harmful effects of treatment with levothyroxine include hypertension, diabetes in pregnancy, and preeclampsia. Intervention with levothyroxine in the second trimester is of no use in reducing cognitive impairment. Thus, routine screening of subclinical hypothyroidism should be performed in all pregnant women to prevent its complications. Intervention with levothyroxine depends on the TSH levels, which vary according to trimester. Hence, the benefits of levothyroxine therapy depend upon the timing of intervention, change in the requirement of thyroxine during pregnancy, and alteration of dose of levothyroxine as required following delivery.
Gietka-Czernel M, Glinicki P. Subclinical hypothyroidism in pregnancy: Controversies on diagnosis and treatment. Pol Arch Intern Med 2021;131(3):266–275. DOI: 10.20452/pamw.15626.
Davis LE, Leveno KJ, Cunningham FG. Hypothyroidism complicating pregnancy. Obstet Gynecol 1988;72(1):108–112. PMID: 3380497.
Wilson KL, Casey BM, McIntire DD, et al. Subclinical thyroid disease and the incidence of hypertension in pregnancy. Obstet Gynecol 2012;119(2, Part 1):315–320. DOI: 10.1097/AOG.0b013e318240de6a.
Gharib H, Tuttle RM, Baskin HJ, et al. Subclinical thyroid dysfunction: A joint statement on management from the American Association of Clinical Endocrinologists, the American Thyroid Association, and the Endocrine Society. Endocr Pract 2004;10(6):497–501. DOI: 10.4158/EP.10.6.497.
Blatt AJ, Nakamoto JM, Kaufman HW. National status of testing for hypothyroidism during pregnancy and postpartum. J Clin Endocrinol Metab 2012;97(3):777–784. DOI: 10.1210/jc.2011-2038.
Treatment of subclinical hypothyroidism or hypothyroxinemia in pregnancy | NEJM [Internet]. [cited 2023 Nov 24].
Antenatal thyroid screening and childhood cognitive function | NEJM [Internet]. [cited 2023 Aug 21].
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. DOI: 10.1089/thy.2014.0029.
Toulis KA, Stagnaro-Green A, Negro R. Maternal subclinical hypothyroidsm and gestational diabetes mellitus: A meta-analysis. Endocrine Practice 2014;20(7):703–714. DOI: 10.4158/EP13440.RA.
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. Li D, editor. PLoS ONE 2017;12(4):e0175708. DOI: 10.1371/journal.pone.0175708.
Ramezani Tehrani F, Nazarpour S, Behboudi-Gandevani S. Isolated maternal hypothyroxinemia and adverse pregnancy outcomes: A systematic review. J Gynecol Obstet Hum Reprod 2021;50(7):102057. DOI: 10.1016/j.jogoh.2020.102057.
Uchida S, Maruyama T, Kagami M, et al. Impact of borderline-subclinical hypothyroidism on subsequent pregnancy outcome in women with unexplained recurrent pregnancy loss. J Obstet Gynaecol Res 2017;43(6):1014–1020. DOI: 10.1111/jog.13319.
Garber JR, Cobin RH, Gharib H, et al. 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. DOI: 10.4158/EP12280.GL.
Pearce EN, Oken E, Gillman MW, et al. Association of first-trimester thyroid function test values with thyroperoxidase antibody status, smoking, and multivitamin use. Endocrine Practice 2008;14(1):33–39. DOI: 10.4158/EP.14.1.33.
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(4):1699–1707. DOI: 10.1210/jc.2009-2009.
Maraka S, Mwangi R, McCoy RG, et al. Thyroid hormone treatment among pregnant women with subclinical hypothyroidism: US national assessment. BMJ 2017;356:i6865. DOI: 10.1136/bmj.i6865.
Tudela CM, Casey BM, McIntire DD, et al. Relationship of subclinical thyroid disease to the incidence of gestational diabetes. Obstet Gynecol 2012;119(5):983–988. DOI: 10.1097/AOG.0b013e318250aeeb.
Lazarus J, Brown RS, Daumerie C, et al. 2014 European thyroid association guidelines for the management of subclinical hypothyroidism in pregnancy and in children. Eur Thyroid J 2014;3(2):76–94. DOI: 10.1159/000362597.
Guidelines for Diagnosis and Management of Thyroid Disease During Pregnancy [Internet]. American Thyroid Association. 2017 [cited 2023 Nov 24].
Kostecka-Matyja M, Fedorowicz A, Bar-Andziak E, et al. Reference values for TSH and free thyroid hormones in healthy pregnant women in Poland: A prospective, multicenter study. Eur Thyroid J 2017;6(2):82–88. DOI: 10.1159/000453061.
Nazarpour S, Ramezani Tehrani F, Simbar M, et al. Effects of levothyroxine treatment on pregnancy outcomes in pregnant women with autoimmune thyroid disease. Eur J Endocrinol 2017;176(2):253–265. DOI: 10.1530/EJE-16-0548.
Casey BM, Dashe JS, Wells CE, et al. Subclinical hypothyroidism and pregnancy outcomes. Obstet Gynecol 2005;106(1):198–199. DOI: 10.1097/01.AOG.0000152345.99421.22
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(7):2587–2591. DOI: 10.1210/jc.2005-1603.
Shields BM, Knight BA, Hill AV, et al. Five-year follow-up for women with subclinical hypothyroidism in pregnancy. J Clin Endocrinol Metab 2013;98(12):E1941–E1945. DOI: 10.1210/jc.2013-2768.
Negro R. Thoughts about the ‘antenatal thyroid screening and childhood cognitive function’ study. European Thyroid J 2012;1(2): 132–133. DOI: 10.1159/000338349.
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. DOI: 10.1056/NEJM199908193410801.
Pop VJ, Kuijpens JL, Van Baar AL, et al. Low maternal free thyroxine concentrations during early pregnancy are associated with impaired psychomotor development in infancy. Clinical Endocrinology 1999;50(2):149–155. DOI: 10.1046/j.1365-2265.1999.00639.x.
Pop VJ, Brouwers EP, Vader HL, et al. Maternal hypothyroxinaemia during early pregnancy and subsequent child development: A 3-year follow-up study. Clin Endocrinol 2003;59(3):282–288. DOI: 10.1046/j.1365-2265.2003.01822.x.
Fisher DA, Klein AH. Thyroid development and disorders of thyroid function in the newborn. N Engl J Med 1981;304(12):702–712. DOI: 10.1056/NEJM198103193041205.
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. Clinical Endocrinology 2010;72(6):825–829. DOI: 10.1111/j.1365-2265.2009.03743.x.
Korevaar TIM, 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. DOI: 10.1016/S2213-8587(15)00327-7.
Hubalewska-Dydejczyk A, Trofimiuk-Müldner M, Ruchala M, et al. Thyroid diseases in pregnancy: Guidelines of the Polish Society of Endocrinology [Choroby tarczycy w ciąży: Zalecenia postępowania Polskiego Towarzystwa Endokrynologicznego]. Endokrynologia Polska 2021;72(5):425–488. DOI: 10.5603/EP.a2021.0089.
Yassa L, Marqusee E, Fawcett R, et al. Thyroid hormone early adjustment in pregnancy (The THERAPY) trial. J Clin Endocrinol Metab 2010;95(7):3234–3241. DOI: 10.1210/jc.2010-0013.
Sullivan SD, Downs E, Popoveniuc G, et al. Randomized trial comparing two algorithms for levothyroxine dose adjustment in pregnant women with primary hypothyroidism. J Clin Endocrinol Metab 2017;102(9):3499–507. DOI: 10.1210/jc.2017-01086.
Loh JA, Wartofsky L, Jonklaas J, et al. The magnitude of increased levothyroxine requirements in hypothyroid pregnant women depends upon the etiology of the hypothyroidism. Thyroid 2009;19(3):269–275. DOI: 10.1089/thy.2008.0413.
Li P, Lin S, Li L, et al. Effect of mildly elevated thyroid-stimulating hormone during the first trimester on adverse pregnancy outcomes. BMC Endocr Disord 2018;18(1):64. DOI: 10.1186/s12902-018- 0294-7.