A longitudinal study of TSH-receptor antibody in normal pregnancies — ASN Events
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A longitudinal study of TSH-receptor antibody in normal pregnancies (#319)

Elif I Ekinci 1 2 3 , Wei-Ling Chiu* 4 , Ken Sikaris 5 , Zhong X Lu 6 7 , Intissar Bittar 8 , Que Lam 9 , Nick Crinis 10 , Christine A Houlihan 11 12
  1. MBBS, FRACP, PhD; Department of Endocrinology, Austin Health, Melbourne
  2. Department of Medicine, University of Melbourne, Melbourne
  3. Menzies School of Health Research, Darwin
  4. MBChB, BSci; Department of Medicine, Eastern Health, Melbourne
  5. MBBS, FRCPA; Department of Chemical Pathology, Melbourne Pathology, Melbourne
  6. MBBS, FRCPA, PhD; Department of Chemical Pathology, Melbourne Pathology, Melbourne
  7. Department of Medicine, Monash University, Melbourne
  8. BSci; Department of Biochemistry, Austin Health, Melbourne
  9. MBBS, FRCPA; Department of Biochemistry, Austin Health, Melbourne
  10. BSci; Department of Biochemistry, Austin Health, Melbourne
  11. MBBS, FRACP, MD; Department of Endocrinology, Austin Health, Melbourne
  12. Mercy Hospital for Women, Melbourne

*Equal first author contribution, presenting author

Background: Graves’ Disease has a high prevalence in young women, with frequent onset after pregnancy 1, and fetal microchimerism is a proposed trigger 2.  In addition, the physiologic lowered immune responsiveness of pregnancy is thought responsible for the amelioration of Graves’ disease that is commonly experienced in pregnancy.  The potential multiple influences on thyroid auto-immunity in pregnancy led us to study the longitudinal changes in TSH-receptor antibody (TSHRAb) in a cohort of healthy women throughout gestation and post-partum.

Methods: Healthy women were recruited as part of a longitudinal study of thyroid function in pregnancy.  Serum TSHRAb, TSH and free T4 (fT4) were measured at trimester-1 (T1), trimester-2 (T2), trimester-3 (T3) and post-partum (PP) using Roche assays.  The cutoff value used was TSHRAb <1.75 IU/L. 

Results: Data were available for T1: 135 women at 12±0.2 (mean±SE, weeks); T2: 96 at 24.4±0.3; T3: 79 at 35.8±0.2; PP: 84 at 13±0.4.  At T1, 8% (11/135) individuals had positive TSHRAb (3.2±0.3 IU/L).  Of these women, 22% (2/9) and 13% (1/8) remained positive at T2 and T3, respectively, and 50% (3/6) were positive again at post-partum (χ2, p<0.001).  Of the women who had negative TSHRAb at T1 (1.0±0.02 IU/L), 30% (21/71) had a transient positive result at T3 (3.1±0.1 IU/L).  At baseline, there was a significant difference in fT4 (17±0.9 versus 15.1±0.3 mmol/L, p=0.03) between TSHRAb positive and negative groups, without differences in TSH.  There were no differences in thyroid function at any other time-points.

Conclusions: An unexpectedly high rate of positive TSHRAb was observed at baseline and throughout normal pregnancy.  The finding of a transient trimester-3 rise in TSHRAb is a novel finding of this study and was not associated with altered thyroid function.  This finding requires further investigation, and if confirmed may represent an important variation of normal immunologic expression of TSHRAb in the third trimester of pregnancy.   

  1. Tada H, Hidaka Y, Tsuruta E, Kashiwai T, Tamaki H, Iwatani Y, et al. Prevalence of postpartum onset of disease within patients with Graves' disease of child-bearing age. Endocr J. 1994 Jun;41(3):325-7.
  2. Waldorf K NJ. Autoimmune Disease During Pregnancy And The Microchimerism Legacy Of Pregnancy. Immunol Invest. 2008;37(5):631-44.
  3. 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):1081-125.
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