Defining gestational thyroid dysfunction through modified non-pregnancy reference intervals: an individual participant meta-analysis.

Pregnancy Reference values Thyroid Function Tests Thyroid Gland Thyrotropin Thyroxine

Journal

The Journal of clinical endocrinology and metabolism
ISSN: 1945-7197
Titre abrégé: J Clin Endocrinol Metab
Pays: United States
ID NLM: 0375362

Informations de publication

Date de publication:
31 Jul 2024
Historique:
received: 19 04 2024
revised: 17 06 2024
accepted: 29 07 2024
medline: 31 7 2024
pubmed: 31 7 2024
entrez: 31 7 2024
Statut: aheadofprint

Résumé

Establishing local trimester-specific reference intervals for gestational TSH and FT4 is often not feasible, necessitating alternative strategies. We aimed to systematically quantify the diagnostic performance of standardized modifications of center-specific non-pregnancy reference intervals as compared to trimester-specific reference intervals. We included prospective cohorts participating in the Consortium on Thyroid and Pregnancy. After relevant exclusions, reference intervals were calculated per cohort in thyroperoxidase antibody-negative women. Modifications to the non-pregnancy reference intervals included an absolute modification (per 0.1 mU/L TSH or 1 pmol/L FT4), relative modification (in steps of 5%) and fixed limits (upper TSH limit between 3.0 to 4.5 mU/L and lower FT4 limit 5-15 pmol/L). We compared (sub)clinical hypothyroidism prevalence, sensitivity and positive predictive value (PPV) of aforementioned methodologies with population-based trimester-specific reference intervals. The final study population comprised 52,496 participants in 18 cohorts. Optimal modifications of standard reference intervals to diagnose gestational overt hypothyroidism were -5% for the upper limit of TSH and +5% for the lower limit of FT4 (sensitivity 0.70, confidence interval [CI] 0.47-0.86; PPV 0.64, CI 0.54-0.74). For subclinical hypothyroidism, these were -20% for the upper limit of TSH and -15% for the lower limit of FT4 (sensitivity 0.91, CI 0.67-0.98; PPV 0.71, CI 0.58-0.80). Absolute and fixed modifications yielded similar results. Confidence intervals were wide, limiting generalizability. We could not identify modifications of non-pregnancy TSH and FT4 reference intervals that would enable centers to adequately approximate trimester-specific reference intervals. Future efforts should be turned towards studying the meaningfulness of trimester-specific reference intervals and risk-based decision limits.

Sections du résumé

BACKGROUND BACKGROUND
Establishing local trimester-specific reference intervals for gestational TSH and FT4 is often not feasible, necessitating alternative strategies. We aimed to systematically quantify the diagnostic performance of standardized modifications of center-specific non-pregnancy reference intervals as compared to trimester-specific reference intervals.
METHODS METHODS
We included prospective cohorts participating in the Consortium on Thyroid and Pregnancy. After relevant exclusions, reference intervals were calculated per cohort in thyroperoxidase antibody-negative women. Modifications to the non-pregnancy reference intervals included an absolute modification (per 0.1 mU/L TSH or 1 pmol/L FT4), relative modification (in steps of 5%) and fixed limits (upper TSH limit between 3.0 to 4.5 mU/L and lower FT4 limit 5-15 pmol/L). We compared (sub)clinical hypothyroidism prevalence, sensitivity and positive predictive value (PPV) of aforementioned methodologies with population-based trimester-specific reference intervals.
RESULTS RESULTS
The final study population comprised 52,496 participants in 18 cohorts. Optimal modifications of standard reference intervals to diagnose gestational overt hypothyroidism were -5% for the upper limit of TSH and +5% for the lower limit of FT4 (sensitivity 0.70, confidence interval [CI] 0.47-0.86; PPV 0.64, CI 0.54-0.74). For subclinical hypothyroidism, these were -20% for the upper limit of TSH and -15% for the lower limit of FT4 (sensitivity 0.91, CI 0.67-0.98; PPV 0.71, CI 0.58-0.80). Absolute and fixed modifications yielded similar results. Confidence intervals were wide, limiting generalizability.
CONCLUSION CONCLUSIONS
We could not identify modifications of non-pregnancy TSH and FT4 reference intervals that would enable centers to adequately approximate trimester-specific reference intervals. Future efforts should be turned towards studying the meaningfulness of trimester-specific reference intervals and risk-based decision limits.

Identifiants

DOI: 10.1210/clinem/dgae528 PMID: 39083675
pubmed: 39083675
pii: 7724966
doi: 10.1210/clinem/dgae528
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society.

Auteurs

Joris A J Osinga (JAJ)

Department of Internal Medicine, Erasmus University Medical Center, 3000 CA Rotterdam, the Netherlands.
Academic Center for Thyroid Diseases, Erasmus University Medical Center, 3000 CA, Rotterdam, the Netherlands.
ORCID: 0000-0003-2527-5150

Scott M Nelson (SM)

School of Medicine, Dentistry and Nursing, University of Glasgow, G12 8QQ Glasgow, UK.

John P Walsh (JP)

Department of Endocrinology and Diabetes, Sir Charles Gairdner Hospital, Nedlands 6009, Western Australia, Australia.
Medical School, University of Western Australia, Crawley 6009, Western Australia, Australia.
ORCID: 0000-0002-1766-2612

Ghalia Ashoor (G)

Harris Birthright Research Center for Fetal Medicine, King's College Hospital, SE5 9RS London, United Kingdom.

Glenn E Palomaki (GE)

Department of Pathology and Laboratory Medicine, Women & Infants Hospital and Alpert Medical School at Brown University, RI 02903 Providence, Rhode Island.
ORCID: 0000-0001-6154-8449

Abel López-Bermejo (A)

Pediatric Endocrinology Research Group, Girona Biomedical Research Institute (IDIBGI), Dr. Josep Trueta Hospital, 17007 Girona, Spain.
Departament de Ciències Mèdiques. Universitat de Girona, 17003, Girona, Spain.
ORCID: 0000-0002-5828-8911

Judit Bassols (J)

Maternal-Fetal Metabolic Research Group, Girona Biomedical Research Institute (IDIBGI), Dr. Josep Trueta Hospital, 17007 Girona, Spain.

Ashraf Aminorroaya (A)

Isfahan Endocrine and Metabolism Research Center, Isfahan University of Medical Sciences, 81745-33871 Isfahan, Iran.

Maarten A C Broeren (MAC)

Laboratory of Clinical Chemistry and Haematology, Máxima Medical Centre, 5504 DB Veldhoven, Netherlands.

Liangmiao Chen (L)

Department of Endocrinology and Rui'an Center of the Chinese-American Research Institute for Diabetic Complications, Third Affiliated Hospital of Wenzhou Medical University, 325035 Wenzhou, China.

Xuemian Lu (X)

Department of Endocrinology and Rui'an Center of the Chinese-American Research Institute for Diabetic Complications, Third Affiliated Hospital of Wenzhou Medical University, 325035 Wenzhou, China.

Suzanne J Brown (SJ)

Department of Endocrinology and Diabetes, Sir Charles Gairdner Hospital, Nedlands 6009, Western Australia, Australia.
ORCID: 0000-0002-8413-561X

Flora Veltri (F)

Endocrine Unit, Centre Hospitalier Universitaire Saint-Pierre, Université Libre de Bruxelles (ULB), Brussels, Belgium.

Kun Huang (K)

Department of Maternal, Child and Adolescent Health, Scientific Research Center in Preventive Medicine; School of Public Health; Anhui Medical University, 230032 Anhui, China.

Tuija Männistö (T)

NordLab, Oulu and Translational Medicine Research Unit, University of Oulu, 90570 Oulu, Finland.

Marina Vafeiadi (M)

Department of Social Medicine, School of Medicine, University of Crete, 710 03 Heraklion, Crete, Greece.

Peter N Taylor (PN)

Thyroid Research Group, Systems Immunity Research Institute, Cardiff University School of Medicine, CF10 3EU Cardiff, UK.

Fang-Biao Tao (FB)

Department of Maternal, Child and Adolescent Health, Scientific Research Center in Preventive Medicine; School of Public Health; Anhui Medical University, 230032 Anhui, China.

Lida Chatzi (L)

Department of Preventive Medicine, Keck School of Medicine, University of Southern California, 90089 CA, USA.

Maryam Kianpour (M)

Isfahan Endocrine and Metabolism Research Center, Isfahan University of Medical Sciences, 81745-33871 Isfahan, Iran.

Eila Suvanto (E)

Department of Obstetrics and Gynecology and Medical Research Center Oulu, University of Oulu, 90570 Oulu, Finland.

Elena N Grineva (EN)

Institute of Endocrinology, Almazov National Medical Research Centre, 197341 Saint Petersburg, Russia.

Kypros H Nicolaides (KH)

Department of Women and Children's Health, Faculty of Life Sciences and Medicine King's College London, SE5 9RS London, United Kingdom.

Mary E D'Alton (ME)

Department of Obstetrics and Gynecology, Columbia University Irving Medical Center, NY 10032 New York, USA.

Kris G Poppe (KG)

Endocrine Unit, Centre Hospitalier Universitaire Saint-Pierre, Université Libre de Bruxelles (ULB), Brussels, Belgium.

Erik Alexander (E)

Division of Endocrinology, Hypertension and Diabetes, Brigham and Women's Hospital, Harvard Medical School, Boston, 02115 MA, USA.

Ulla Feldt-Rasmussen (U)

Department of Medical Endocrinology and Metabolism, Copenhagen University Hospital, Rigshospitalet, and Department od Clinical Medicine, Faculty of Health and clinical Sciences, Copenhagen University, 2100 Copenhagen, Denmark.

Sofie Bliddal (S)

Department of Medical Endocrinology and Metabolism, Copenhagen University Hospital, Rigshospitalet, and Department od Clinical Medicine, Faculty of Health and clinical Sciences, Copenhagen University, 2100 Copenhagen, Denmark.
ORCID: 0000-0002-2456-1019

Polina V Popova (PV)

Institute of Endocrinology, Almazov National Medical Research Centre, 197341 Saint Petersburg, Russia.

Layal Chaker (L)

Department of Internal Medicine, Erasmus University Medical Center, 3000 CA Rotterdam, the Netherlands.
Academic Center for Thyroid Diseases, Erasmus University Medical Center, 3000 CA, Rotterdam, the Netherlands.
Department of Epidemiology, Erasmus University Medical Center, 3000 CA Rotterdam, the Netherlands.

W Edward Visser (WE)

Department of Internal Medicine, Erasmus University Medical Center, 3000 CA Rotterdam, the Netherlands.
Academic Center for Thyroid Diseases, Erasmus University Medical Center, 3000 CA, Rotterdam, the Netherlands.

Robin P Peeters (RP)

Department of Internal Medicine, Erasmus University Medical Center, 3000 CA Rotterdam, the Netherlands.
Academic Center for Thyroid Diseases, Erasmus University Medical Center, 3000 CA, Rotterdam, the Netherlands.
ORCID: 0000-0001-7732-9371

Arash Derakhshan (A)

Department of Internal Medicine, Erasmus University Medical Center, 3000 CA Rotterdam, the Netherlands.
Academic Center for Thyroid Diseases, Erasmus University Medical Center, 3000 CA, Rotterdam, the Netherlands.
ORCID: 0000-0001-7335-1918

Tanja G M Vrijkotte (TGM)

Department of Public and Occupational Health, Amsterdam UMC, University of Amsterdam, Amsterdam Public Health Research Institute, 1081 HV Amsterdam, the Netherlands.

Victor J M Pop (VJM)

Department of Medical and Clinical Psychology, Tilburg University, 5000 LE Tilburg, The Netherlands.

Tim I M Korevaar (TIM)

Department of Internal Medicine, Erasmus University Medical Center, 3000 CA Rotterdam, the Netherlands.
Academic Center for Thyroid Diseases, Erasmus University Medical Center, 3000 CA, Rotterdam, the Netherlands.

Classifications MeSH