Thyroid autoimmunity impairs the thyroidal response to hCG: Two population-based prospective cohort studies

T.I. Korevaar, E.A. Steegers, V.J.M. Pop, M.A. Broeren, L. Chaker, Y.B. de Rijke, V.W. Jaddoe, M. Medici, T.J. Visser, H. Tiemeier, R.P. Peeters

Research output: Contribution to journalArticleScientificpeer-review

Abstract

Context:
Thyroperoxidase antibody (TPOAb) positivity is the main risk factor for thyroid dysfunction during pregnancy and is consistently associated with premature delivery. However, the underlying mechanism is currently unknown. We hypothesized that TPOAb positivity may interfere with gestational thyroid stimulation induced by the pregnancy hormone human chorionic gonadotropin (hCG).
Design, Setting, and Participants:
Thyrotropin (TSH), free thyroxine (FT4), TPOAbs, and/or hCG concentrations were measured in early and late pregnancy of 7587 pregnant women from 2 Dutch population-based prospective cohorts (n = 5924, Generation R study; n = 1663, Holistic Approach to Pregnancy and the First Postpartum Year study).
Interventions:
None.
Main Outcome Measure(s):
Thyroidal response to hCG stimulation, premature delivery.Results:In TPOAb-negative women, hCG was positively associated with FT4 and negatively with TSH in both cohorts (P < 0.0001). In contrast, in TPOAb-positive women, hCG was not associated with FT4 or TSH in either cohort (all P > 0.40; P for interaction TPOAb positive vs negative ≤ 0.05). Overall, TPOAb positivity was associated with a 1.7-fold higher risk of premature delivery. TPOAb-positive women with an adequate response of FT4 to hCG (high FT4 concentration with high hCG concentration) did not have a higher risk of premature delivery. In contrast, TPOAb-positive women with an inadequate FT4 response to hCG (low FT4 concentration with high hCG concentration) had a 2.2- to 2.8-fold higher risk of premature delivery.
Conclusion:
TPOAb-positive women display an impaired thyroidal response to hCG and this may explain the higher risk of premature delivery in these women. This abnormal response in TPOAb-positive women might suggest that these women require a different treatment approach than TPOAb-negative women.
Original languageEnglish
Pages (from-to)69-77
JournalJournal of Clinical Endocrinology and Metabolism
Volume102
Issue number1
DOIs
Publication statusPublished - 2017

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Chorionic Gonadotropin
Autoimmunity
Antibodies
Thyrotropin
Thyroxine
Hormones

Cite this

Korevaar, T.I. ; Steegers, E.A. ; Pop, V.J.M. ; Broeren, M.A. ; Chaker, L. ; de Rijke, Y.B. ; Jaddoe, V.W. ; Medici, M. ; Visser, T.J. ; Tiemeier, H. ; Peeters, R.P. / Thyroid autoimmunity impairs the thyroidal response to hCG : Two population-based prospective cohort studies. In: Journal of Clinical Endocrinology and Metabolism. 2017 ; Vol. 102, No. 1. pp. 69-77.
@article{6645599ad9d74b0985e6937237c3a5ff,
title = "Thyroid autoimmunity impairs the thyroidal response to hCG: Two population-based prospective cohort studies",
abstract = "Context:Thyroperoxidase antibody (TPOAb) positivity is the main risk factor for thyroid dysfunction during pregnancy and is consistently associated with premature delivery. However, the underlying mechanism is currently unknown. We hypothesized that TPOAb positivity may interfere with gestational thyroid stimulation induced by the pregnancy hormone human chorionic gonadotropin (hCG).Design, Setting, and Participants:Thyrotropin (TSH), free thyroxine (FT4), TPOAbs, and/or hCG concentrations were measured in early and late pregnancy of 7587 pregnant women from 2 Dutch population-based prospective cohorts (n = 5924, Generation R study; n = 1663, Holistic Approach to Pregnancy and the First Postpartum Year study).Interventions:None.Main Outcome Measure(s):Thyroidal response to hCG stimulation, premature delivery.Results:In TPOAb-negative women, hCG was positively associated with FT4 and negatively with TSH in both cohorts (P < 0.0001). In contrast, in TPOAb-positive women, hCG was not associated with FT4 or TSH in either cohort (all P > 0.40; P for interaction TPOAb positive vs negative ≤ 0.05). Overall, TPOAb positivity was associated with a 1.7-fold higher risk of premature delivery. TPOAb-positive women with an adequate response of FT4 to hCG (high FT4 concentration with high hCG concentration) did not have a higher risk of premature delivery. In contrast, TPOAb-positive women with an inadequate FT4 response to hCG (low FT4 concentration with high hCG concentration) had a 2.2- to 2.8-fold higher risk of premature delivery.Conclusion:TPOAb-positive women display an impaired thyroidal response to hCG and this may explain the higher risk of premature delivery in these women. This abnormal response in TPOAb-positive women might suggest that these women require a different treatment approach than TPOAb-negative women.",
author = "T.I. Korevaar and E.A. Steegers and V.J.M. Pop and M.A. Broeren and L. Chaker and {de Rijke}, Y.B. and V.W. Jaddoe and M. Medici and T.J. Visser and H. Tiemeier and R.P. Peeters",
year = "2017",
doi = "10.1210/jc.2016-2942",
language = "English",
volume = "102",
pages = "69--77",
journal = "Journal of Clinical Endocrinology and Metabolism",
issn = "0021-972X",
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Korevaar, TI, Steegers, EA, Pop, VJM, Broeren, MA, Chaker, L, de Rijke, YB, Jaddoe, VW, Medici, M, Visser, TJ, Tiemeier, H & Peeters, RP 2017, 'Thyroid autoimmunity impairs the thyroidal response to hCG: Two population-based prospective cohort studies', Journal of Clinical Endocrinology and Metabolism, vol. 102, no. 1, pp. 69-77. https://doi.org/10.1210/jc.2016-2942

Thyroid autoimmunity impairs the thyroidal response to hCG : Two population-based prospective cohort studies. / Korevaar, T.I.; Steegers, E.A.; Pop, V.J.M.; Broeren, M.A.; Chaker, L.; de Rijke, Y.B.; Jaddoe, V.W.; Medici, M.; Visser, T.J.; Tiemeier, H.; Peeters, R.P.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 102, No. 1, 2017, p. 69-77.

Research output: Contribution to journalArticleScientificpeer-review

TY - JOUR

T1 - Thyroid autoimmunity impairs the thyroidal response to hCG

T2 - Two population-based prospective cohort studies

AU - Korevaar, T.I.

AU - Steegers, E.A.

AU - Pop, V.J.M.

AU - Broeren, M.A.

AU - Chaker, L.

AU - de Rijke, Y.B.

AU - Jaddoe, V.W.

AU - Medici, M.

AU - Visser, T.J.

AU - Tiemeier, H.

AU - Peeters, R.P.

PY - 2017

Y1 - 2017

N2 - Context:Thyroperoxidase antibody (TPOAb) positivity is the main risk factor for thyroid dysfunction during pregnancy and is consistently associated with premature delivery. However, the underlying mechanism is currently unknown. We hypothesized that TPOAb positivity may interfere with gestational thyroid stimulation induced by the pregnancy hormone human chorionic gonadotropin (hCG).Design, Setting, and Participants:Thyrotropin (TSH), free thyroxine (FT4), TPOAbs, and/or hCG concentrations were measured in early and late pregnancy of 7587 pregnant women from 2 Dutch population-based prospective cohorts (n = 5924, Generation R study; n = 1663, Holistic Approach to Pregnancy and the First Postpartum Year study).Interventions:None.Main Outcome Measure(s):Thyroidal response to hCG stimulation, premature delivery.Results:In TPOAb-negative women, hCG was positively associated with FT4 and negatively with TSH in both cohorts (P < 0.0001). In contrast, in TPOAb-positive women, hCG was not associated with FT4 or TSH in either cohort (all P > 0.40; P for interaction TPOAb positive vs negative ≤ 0.05). Overall, TPOAb positivity was associated with a 1.7-fold higher risk of premature delivery. TPOAb-positive women with an adequate response of FT4 to hCG (high FT4 concentration with high hCG concentration) did not have a higher risk of premature delivery. In contrast, TPOAb-positive women with an inadequate FT4 response to hCG (low FT4 concentration with high hCG concentration) had a 2.2- to 2.8-fold higher risk of premature delivery.Conclusion:TPOAb-positive women display an impaired thyroidal response to hCG and this may explain the higher risk of premature delivery in these women. This abnormal response in TPOAb-positive women might suggest that these women require a different treatment approach than TPOAb-negative women.

AB - Context:Thyroperoxidase antibody (TPOAb) positivity is the main risk factor for thyroid dysfunction during pregnancy and is consistently associated with premature delivery. However, the underlying mechanism is currently unknown. We hypothesized that TPOAb positivity may interfere with gestational thyroid stimulation induced by the pregnancy hormone human chorionic gonadotropin (hCG).Design, Setting, and Participants:Thyrotropin (TSH), free thyroxine (FT4), TPOAbs, and/or hCG concentrations were measured in early and late pregnancy of 7587 pregnant women from 2 Dutch population-based prospective cohorts (n = 5924, Generation R study; n = 1663, Holistic Approach to Pregnancy and the First Postpartum Year study).Interventions:None.Main Outcome Measure(s):Thyroidal response to hCG stimulation, premature delivery.Results:In TPOAb-negative women, hCG was positively associated with FT4 and negatively with TSH in both cohorts (P < 0.0001). In contrast, in TPOAb-positive women, hCG was not associated with FT4 or TSH in either cohort (all P > 0.40; P for interaction TPOAb positive vs negative ≤ 0.05). Overall, TPOAb positivity was associated with a 1.7-fold higher risk of premature delivery. TPOAb-positive women with an adequate response of FT4 to hCG (high FT4 concentration with high hCG concentration) did not have a higher risk of premature delivery. In contrast, TPOAb-positive women with an inadequate FT4 response to hCG (low FT4 concentration with high hCG concentration) had a 2.2- to 2.8-fold higher risk of premature delivery.Conclusion:TPOAb-positive women display an impaired thyroidal response to hCG and this may explain the higher risk of premature delivery in these women. This abnormal response in TPOAb-positive women might suggest that these women require a different treatment approach than TPOAb-negative women.

U2 - 10.1210/jc.2016-2942

DO - 10.1210/jc.2016-2942

M3 - Article

VL - 102

SP - 69

EP - 77

JO - Journal of Clinical Endocrinology and Metabolism

JF - Journal of Clinical Endocrinology and Metabolism

SN - 0021-972X

IS - 1

ER -