Evaluating the Progression to Hypothyroidism in Preconception Euthyroid Thyroid Peroxidase Antibody-Positive Women

Sofia Gill; Versha Cheed; Victoria A H Morton; Dayna Gill; Kristien Boelaert; Shiao Chan; Arri Coomarasamy; Rima K Dhillon-Smith

doi:10.1210/clinem/dgac525

Evaluating the Progression to Hypothyroidism in Preconception Euthyroid Thyroid Peroxidase Antibody-Positive Women

Sofia Gill, Versha Cheed, Victoria A H Morton, Dayna Gill, Kristien Boelaert, Shiao Chan, Arri Coomarasamy, Rima K Dhillon-Smith^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

Abstract

CONTEXT: Thyroid peroxidase antibody (TPOAb) positivity is prevalent in women of reproductive age and predisposes to thyroid dysfunction, particularly hypothyroidism, which has adverse effects on pregnancy.

OBJECTIVE: This study aimed to report the rate of development of abnormal thyroid function among initially euthyroid TPOAb-positive women recruited into the TABLET trial, to identify factors associated with the development of hypothyroidism, and to compare outcomes between euthyroid and treated hypothyroid individuals.

METHODS: This observational cohort study, conducted at 49 UK hospitals between 2011 and 2016, included euthyroid TPOAb-positive women 16 to 40 years of age with a history of miscarriage or subfertility, planning pregnancy, randomized to levothyroxine 50 mcg daily or placebo. Abnormal thyroid function, conception rate, and live birth rate (LBR) ≥34 weeks were analyzed.

RESULTS: Among the women, 70/940 (7.4%) developed subclinical (SCH) or overt (OH) hypothyroidism: 27/470 taking levothyroxine and 43/470 placebo (relative risk [RR] 0.63; 95% CI, 0.39-1.00; P = 0.05); 83% of cases emerged prepregnancy. Baseline median serum TSH concentrations and TPOAb titers were significantly higher in those who developed hypothyroidism vs those who did not (P < 0.001). Treated SCH/OH demonstrated a higher failure-to-conceive rate compared with euthyroid women (adjusted RR 2.02 [1.56-2.62]; P < 0.001). The LBR ≥ 34 weeks was similar in the treated SCH/OH and euthyroid groups (adjusted RR 1.09 [0.77-1.55]; P = 0.6).

CONCLUSION: Approximately 7% of euthyroid TPOAb-positive women will develop hypothyroidism within 1 year preconception or in pregnancy. Conception rates are lower in women with treated SCH/OH compared with euthyroid women, but LBR are comparable. Thyroid function in TPOAb-positive women should be monitored regularly, when trying to conceive, to ensure prompt diagnosis and appropriate treatment initiation.

Original language	English
Pages (from-to)	124-134
Number of pages	11
Journal	The Journal of clinical endocrinology and metabolism
Volume	108
Issue number	1
Early online date	14 Sept 2022
DOIs	https://doi.org/10.1210/clinem/dgac525
Publication status	Published - Jan 2023

Bibliographical note

Funding:
This study was directly linked to the TABLET Trial, funded by the NIHR Efficacy and Mechanism Evaluation (EME) programme (grant number 09/100/10).

© The Author(s) 2022. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: [email protected].

Keywords

Female
Humans
Pregnancy
Abortion, Spontaneous
Autoantibodies
Hypothyroidism/drug therapy
Iodide Peroxidase
Thyroid Diseases/complications
Thyrotropin
Thyroxine/therapeutic use
Adolescent
Young Adult
Adult

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Cite this

@article{ec7b97027d094a78bca0f8987595d86c,

title = "Evaluating the Progression to Hypothyroidism in Preconception Euthyroid Thyroid Peroxidase Antibody-Positive Women",

abstract = "CONTEXT: Thyroid peroxidase antibody (TPOAb) positivity is prevalent in women of reproductive age and predisposes to thyroid dysfunction, particularly hypothyroidism, which has adverse effects on pregnancy.OBJECTIVE: This study aimed to report the rate of development of abnormal thyroid function among initially euthyroid TPOAb-positive women recruited into the TABLET trial, to identify factors associated with the development of hypothyroidism, and to compare outcomes between euthyroid and treated hypothyroid individuals.METHODS: This observational cohort study, conducted at 49 UK hospitals between 2011 and 2016, included euthyroid TPOAb-positive women 16 to 40 years of age with a history of miscarriage or subfertility, planning pregnancy, randomized to levothyroxine 50 mcg daily or placebo. Abnormal thyroid function, conception rate, and live birth rate (LBR) ≥34 weeks were analyzed.RESULTS: Among the women, 70/940 (7.4%) developed subclinical (SCH) or overt (OH) hypothyroidism: 27/470 taking levothyroxine and 43/470 placebo (relative risk [RR] 0.63; 95% CI, 0.39-1.00; P = 0.05); 83% of cases emerged prepregnancy. Baseline median serum TSH concentrations and TPOAb titers were significantly higher in those who developed hypothyroidism vs those who did not (P < 0.001). Treated SCH/OH demonstrated a higher failure-to-conceive rate compared with euthyroid women (adjusted RR 2.02 [1.56-2.62]; P < 0.001). The LBR ≥ 34 weeks was similar in the treated SCH/OH and euthyroid groups (adjusted RR 1.09 [0.77-1.55]; P = 0.6).CONCLUSION: Approximately 7% of euthyroid TPOAb-positive women will develop hypothyroidism within 1 year preconception or in pregnancy. Conception rates are lower in women with treated SCH/OH compared with euthyroid women, but LBR are comparable. Thyroid function in TPOAb-positive women should be monitored regularly, when trying to conceive, to ensure prompt diagnosis and appropriate treatment initiation.",

keywords = "Female, Humans, Pregnancy, Abortion, Spontaneous, Autoantibodies, Hypothyroidism/drug therapy, Iodide Peroxidase, Thyroid Diseases/complications, Thyrotropin, Thyroxine/therapeutic use, Adolescent, Young Adult, Adult",

author = "Sofia Gill and Versha Cheed and Morton, {Victoria A H} and Dayna Gill and Kristien Boelaert and Shiao Chan and Arri Coomarasamy and Dhillon-Smith, {Rima K}",

note = "Funding: This study was directly linked to the TABLET Trial, funded by the NIHR Efficacy and Mechanism Evaluation (EME) programme (grant number 09/100/10). {\textcopyright} The Author(s) 2022. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: [email protected].",

year = "2023",

month = jan,

doi = "10.1210/clinem/dgac525",

language = "English",

volume = "108",

pages = "124--134",

journal = "The Journal of clinical endocrinology and metabolism",

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TY - JOUR

T1 - Evaluating the Progression to Hypothyroidism in Preconception Euthyroid Thyroid Peroxidase Antibody-Positive Women

AU - Gill, Sofia

AU - Cheed, Versha

AU - Morton, Victoria A H

AU - Gill, Dayna

AU - Boelaert, Kristien

AU - Chan, Shiao

AU - Coomarasamy, Arri

AU - Dhillon-Smith, Rima K

N1 - Funding: This study was directly linked to the TABLET Trial, funded by the NIHR Efficacy and Mechanism Evaluation (EME) programme (grant number 09/100/10). © The Author(s) 2022. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: [email protected].

PY - 2023/1

Y1 - 2023/1

N2 - CONTEXT: Thyroid peroxidase antibody (TPOAb) positivity is prevalent in women of reproductive age and predisposes to thyroid dysfunction, particularly hypothyroidism, which has adverse effects on pregnancy.OBJECTIVE: This study aimed to report the rate of development of abnormal thyroid function among initially euthyroid TPOAb-positive women recruited into the TABLET trial, to identify factors associated with the development of hypothyroidism, and to compare outcomes between euthyroid and treated hypothyroid individuals.METHODS: This observational cohort study, conducted at 49 UK hospitals between 2011 and 2016, included euthyroid TPOAb-positive women 16 to 40 years of age with a history of miscarriage or subfertility, planning pregnancy, randomized to levothyroxine 50 mcg daily or placebo. Abnormal thyroid function, conception rate, and live birth rate (LBR) ≥34 weeks were analyzed.RESULTS: Among the women, 70/940 (7.4%) developed subclinical (SCH) or overt (OH) hypothyroidism: 27/470 taking levothyroxine and 43/470 placebo (relative risk [RR] 0.63; 95% CI, 0.39-1.00; P = 0.05); 83% of cases emerged prepregnancy. Baseline median serum TSH concentrations and TPOAb titers were significantly higher in those who developed hypothyroidism vs those who did not (P < 0.001). Treated SCH/OH demonstrated a higher failure-to-conceive rate compared with euthyroid women (adjusted RR 2.02 [1.56-2.62]; P < 0.001). The LBR ≥ 34 weeks was similar in the treated SCH/OH and euthyroid groups (adjusted RR 1.09 [0.77-1.55]; P = 0.6).CONCLUSION: Approximately 7% of euthyroid TPOAb-positive women will develop hypothyroidism within 1 year preconception or in pregnancy. Conception rates are lower in women with treated SCH/OH compared with euthyroid women, but LBR are comparable. Thyroid function in TPOAb-positive women should be monitored regularly, when trying to conceive, to ensure prompt diagnosis and appropriate treatment initiation.

AB - CONTEXT: Thyroid peroxidase antibody (TPOAb) positivity is prevalent in women of reproductive age and predisposes to thyroid dysfunction, particularly hypothyroidism, which has adverse effects on pregnancy.OBJECTIVE: This study aimed to report the rate of development of abnormal thyroid function among initially euthyroid TPOAb-positive women recruited into the TABLET trial, to identify factors associated with the development of hypothyroidism, and to compare outcomes between euthyroid and treated hypothyroid individuals.METHODS: This observational cohort study, conducted at 49 UK hospitals between 2011 and 2016, included euthyroid TPOAb-positive women 16 to 40 years of age with a history of miscarriage or subfertility, planning pregnancy, randomized to levothyroxine 50 mcg daily or placebo. Abnormal thyroid function, conception rate, and live birth rate (LBR) ≥34 weeks were analyzed.RESULTS: Among the women, 70/940 (7.4%) developed subclinical (SCH) or overt (OH) hypothyroidism: 27/470 taking levothyroxine and 43/470 placebo (relative risk [RR] 0.63; 95% CI, 0.39-1.00; P = 0.05); 83% of cases emerged prepregnancy. Baseline median serum TSH concentrations and TPOAb titers were significantly higher in those who developed hypothyroidism vs those who did not (P < 0.001). Treated SCH/OH demonstrated a higher failure-to-conceive rate compared with euthyroid women (adjusted RR 2.02 [1.56-2.62]; P < 0.001). The LBR ≥ 34 weeks was similar in the treated SCH/OH and euthyroid groups (adjusted RR 1.09 [0.77-1.55]; P = 0.6).CONCLUSION: Approximately 7% of euthyroid TPOAb-positive women will develop hypothyroidism within 1 year preconception or in pregnancy. Conception rates are lower in women with treated SCH/OH compared with euthyroid women, but LBR are comparable. Thyroid function in TPOAb-positive women should be monitored regularly, when trying to conceive, to ensure prompt diagnosis and appropriate treatment initiation.

KW - Female

KW - Humans

KW - Pregnancy

KW - Abortion, Spontaneous

KW - Autoantibodies

KW - Hypothyroidism/drug therapy

KW - Iodide Peroxidase

KW - Thyroid Diseases/complications

KW - Thyrotropin

KW - Thyroxine/therapeutic use

KW - Adolescent

KW - Young Adult

KW - Adult

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DO - 10.1210/clinem/dgac525

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JO - The Journal of clinical endocrinology and metabolism

JF - The Journal of clinical endocrinology and metabolism

IS - 1

ER -

Evaluating the Progression to Hypothyroidism in Preconception Euthyroid Thyroid Peroxidase Antibody-Positive Women

Abstract

Bibliographical note

Keywords

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