Detection of misdiagnosed thyroid dysfunction in early pregnancy: using nonpregnant and pregnancy specific reference intervals
Abstract
Objective: The objective was to assess the prevalence of misdiagnosed thyroid dysfunction during the first trimester of pregnancy when nonpregnant reference intervals used.
Materials and Methods: This study, conducted on 233 pregnant women of age between 18 and 35 years during first trimester. Serum thyroid stimulating hormone (TSH), free thyroxine (FT4), thyroperoxidase antibodies (TPO Ab) analyzed and thyroid disorders were grouped, based on the first trimester-specific reference intervals and correlated with nonpregnant reference intervals.
Results: The overall prevalence of autoimmunity was 12.4%. The prevalence of subclinical hypothyroid (SCH) was significantly higher than euthyroid when first trimester-specific reference intervals used rather than nonpregnant reference intervals. If the nonpregnant reference intervals were applied to our study group, 27.9% pregnant women with TSH above the first trimester-specific reference intervals would not have been identified and misclassified as euthyroid. 22.7% would have missed the diagnosis as SCH. 5.2% with low FT4 levels, among this 3% and 2.1% would not have been identified as overt hypothyroid and isolated hypothyroxinemia. The relative risk of autoimmunity was significantly 3.66 times more in SCH than euthyroid, when first trimester-specific reference intervals used.
Conclusion: Misdiagnosis of SCH, overt hypothyroid and autoimmune thyroid disorders occurred during the first trimester of pregnancy if nonpregnant reference intervals used. Undiagnosed hypothyroidism in pregnant women may adversely affect their fetuses; therefore the early and appropriate detection of thyroid dysfunction require reliable pregnancy-specific reference intervals of the thyroid hormones.
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Strecker RT, Echenard M, Eberhart R. Chevailler M-C, Perez V, Quinn F A et al. Evaluation of maternal thyroid function in pregnancy: the importance of using gestational age - specific reference intervals. European Journal of Endocrinology. 2007; 157:509- 514.doi: https://doi.org/10.1530/EJE-07-0249.
Haddow JE, Palomaki GE, Allan WC, Williams JR, Knight GJ, Gagnon J, et al. Maternal thyroid deficiency during pregnancy and subsequent neuropsychological development of the child. N Engl J Med. 1999 Aug; 341(8):549-55.doi: https://doi.org/10.1056/nejm199908193410801.
Pop VJ, Brouwers EP, Vader HL, Vulsma T, van Baar AL, de Vijlder JJ. Maternal hypothyroxinaemia during early pregnancy and subsequent child development: a 3-year follow-up study. Clin Endocrinol (Oxf). 2003 Sep; 59(3): 282-288.doi: https://doi.org/10.1046/j.1365-2265.2003.01822.x.
Stagnaro-Green A, Chen X, Bogden JD, Davies TF, Scholl TO. The thyroid and pregnancy: a novel risk factor for very preterm delivery. Thyroid. 2005 Apr; 15(4): 351-357.doi: https://doi.org/10.1089/thy.2005.15.351.
Bussen S, Steck T, Dietl J. Increased prevalence of thyroid antibodies in euthyroid women with a history of recurrent in-vitro fertilization failure. Hum Reprod. 2000Mar; 15(3): 545-8.doi: https://doi.org/10.1093/humrep/15.3.545.
De Groot L, Abalovich M, Alexander EK, Amino N, Barbour L, Cobin RH, et al. Management of thyroid dysfunction during pregnancy and postpartum:an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2012 Aug; 97(8):2543-65. doi: https://doi.org/10.1210/jc.2011-2803.
Stagnaro-Green A, Abalovich M, Alexander E, Azizi F, Mestman J, Negro R, et al. Guidelines of the American Thyroid Association for the Diagnosis and Management of Thyroid Disease During Pregnancy and Postpartum. Thyroid. 2011 Oct; 21(10):1081-25. doi: https://doi.org/10.1089/thy.2011.0087. Epub. 2011 Jul 25.
Dosiou C, Sanders GD, Araki SS & Crapo LM. Screening pregnant women for autoimmune thyroid disease: a cost-effectiveness analysis. European Journal of Endocrinology. 2008;158:841–851.doi: https://doi.org/10.1530/EJE-07-0882.
Wang W1, Teng W, Shan Z, Wang S, Li J, Zhu L et al. The prevalence of thyroid disorders during early pregnancy in China: the benefits ofuniversal screening in the first trimester of pregnancy. Eur J Endocrinol. 2011 Feb; 164(2):263-8. doi: https://doi.org/10.1530/EJE-10-0660. Epub 2010 Nov 8.
Leslie D, Lipsky P, Notkins AL. Autoantibodies as predictors of disease. J Clin Invest. 2001 Nov; 108(10):1417-22.doi: https://dx.doi.org/10.1172%2FJCI14452.
Ratan Chandra Mandal, Debasish Bhar, Anjan Das, Sandip Roy Basunia, Sudeshna Bhar Kundu, Chinmay Mahapatra. Subclinical hypothyroidism in pregnancy: An emerging problem in Southern West Bengal: A cross-sectional study. J Nat Sc Biol Med. 2016; 7(1):80-84.doi: https://dx.doi.org/10.4103%2F0976-9668.175080.
Sieiro Netto L, Medina Coeli C, Micmacher E, Mamede Da Costa S, Nazar L, Galvão D et al. Influence of thyroid autoimmunity and maternal age on the risk of miscarriage. Am J Reprod Immunol. 2004 Nov; 52(5):312-652: 312-316.doi: https://doi.org/10.1111/j.1600-0897.2004.00227.x.
Kontiainen S, Melamies L, Miettinen A, Weber T. Thyroid autoantibodies in serum samples with abnormal TSH levels. APMIS. 1994 Sep; 102(9):716-20.doi: https://doi.org/10.1111/j.1699-0463.1994.tb05225.x.
Baloch Z, Carayon P, Conte-Devolx B, Demers LM, Feldt-Rasmussen U, Henry JF, et al. Laboratory medicine practice guidelines. Laboratory support for the diagnosis and monitoring of thyroid disease. Thyroid 2003; 13:3-126.doi: https://doi.org/10.1089/105072503321086962.
Surks MI, Ortiz E, Daniels GH, Sawin CT, Col NF, Cobin RH, et al. Subclinical thyroid disease: Scientific review and guidelines for diagnosis and management. JAMA. 2004; 291:228-38.doi: https://doi.org/10.1001/jama.291.2.228.
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:E44-8.
Gayathri R, Lavanya S, Raghavan K. Subclinical hypothyroidism and autoimmune thyroiditis in pregnancy - A study in south Indian subjects. J Assoc Physicians India. 2009; 57:691-3. http://www.japi.org/october_2009/article_03.pdf.
Aggarwal N, Suri V, Joshi B, Dutta P, Bhanshali A, Mukhopadhyay K. Prevalence and impact of subclinical hypothyroidism on pregnancy - Prospective study from apex institute of North India. Indian J Appl Res. 2014; 4:404-6.
Dhanwal DK, Prasad S, Agarwal AK, Dixit V, Banerjee AK. High prevalence of subclinical hypothyroidism during first trimester of pregnancy in North India. Indian J Endocrinol Metab. 2013; 17:281-4.doi: https://doi.org/10.4103/2230-8210.109712.
Klein RZ, Haddow JE, Faix JD, Brown RS, Hermos RJ, Pulkkinen A et al. Prevalence of thyroid deficiency in pregnant women. Clin Endocrinol (Oxf). 1991 Jul; 35(1):41-6.doi: https://doi.org/10.1111/j.1365-2265.1991.tb03494.x.
Vaidya B, Anthony S,Bilous M,Shields B,Drury J,Hutchinson S &Bilous R.Detection of thyroid dysfunction in early pregnancy: Universal screening or targeted high risk case finding. Journal of Clinical Endocrinology and Metabolism. 2007; 92: 203-207.doi: https://doi.org/10.1210/jc.2006-1748.
Brent GA. Diagnosing thyroid dysfunction in pregnant women:is case finding enough?Journal of Clinical Endocrinology and Metabolism. 2007; 92:39-41.doi: https://doi.org/10.1210/jc.2006-2461.
Jinfang Xing, Enwu Yuan, Jing Li, Yuchao Zhang, Xiangying Meng, Xia Zhang et al. Trimester- and Assay-Specific Thyroid Reference Intervals for Pregnant Women in China. International Journal of Endocrinology. 2016, Article ID 3754213, 5pp.doi: http://dx.doi.org/10.1155/2016/3754213.