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Peer-reviewedCC BY 4.0Metabolites

First-Trimester Thyroid-Stimulating Hormone Levels and Gestational Diabetes Mellitus: A Retrospective Cohort Study

  • Büşra Şahin1
  • Tansu Bahar Gürbüz2
  • Fazilet Tatar3
  • Rümeysa Uzun4
  • Melike Özyurt Topuzoğlu5
  • Ramazan Erda Pay6
  • Yaprak Üstün7
7 affiliations
  1. 1Department of Obstetrics and Gynecology, Kocaeli City Hospital, University of Health Sciences, Kocaeli 41060, Türkiye
  2. 2Department of Obstetrics and Gynecology, Cerrahpaşa Faculty of Medicine, Istanbul University-Cerrahpaşa, Istanbul 34098, Türkiye
  3. 3Department of Obstetrics and Gynecology, Ankara Bilkent City Hospital, Ankara 06800, Türkiye
  4. 4Department of Obstetrics and Gynecology, Samsun City Hospital, Samsun 55080, Türkiye
  5. 5Department of Obstetrics and Gynecology, Yozgat Boğazlıyan State Hospital, Yozgat 66400, Türkiye
  6. 6Department of Obstetrics and Gynecology, Ankara Etlik City Hospital, Ankara 06800, Türkiye
  7. 7Department of Obstetrics and Gynecology, İzmir City Hospital, İzmir 35540, Türkiye
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Abstract

Background: The clinical relevance of a mildly elevated first-trimester thyroid-stimulating hormone (TSH) concentration is uncertain, recent meta-analyses disagree, and few studies have directly contrasted a TSH of 2.5–4.0 mIU/L with a TSH above 4.0 mIU/L. Methods: In this single-centre retrospective cohort study, 218 singleton pregnancies with a first-trimester TSH ≥ 2.5 and ≤10.0 mIU/L and a concurrent free thyroxine (fT4) measurement were classified as high-normal TSH (2.5–4.0 mIU/L; n = 168) or elevated TSH (>4.0–10.0 mIU/L; n = 50; subclinical hypothyroidism in 47 and biochemically overt hypothyroidism in 3). The primary outcome was gestational diabetes mellitus (GDM); secondary outcomes were a composite obstetric complication, individual obstetric and neonatal outcomes, and first- and second-trimester screening markers. Two logistic regression models adjusted for maternal age were fitted; because levothyroxine was started after the index TSH measurement, it was treated as a potential intermediate and examined only in post hoc sensitivity analyses. Results: GDM occurred in 7/50 (14.0%) women with TSH > 4.0 mIU/L versus 6/168 (3.6%) with TSH 2.5–4.0 mIU/L (Fisher’s exact test, p = 0.013; unadjusted odds ratio (OR) 4.40, 95% confidence interval (CI) 1.40–13.76; risk difference 10.4 percentage points, 95% CI 0.4–20.4). After adjustment for maternal age, TSH > 4.0 mIU/L remained associated with GDM (adjusted OR 5.24, 95% CI 1.60–17.16; p = 0.006), an estimate based on only 13 events; additional adjustment for levothyroxine use gave a similar estimate (adjusted OR 4.51, 95% CI 1.33–15.22). The composite obstetric complication did not differ (32.0% vs. 20.2%; χ2(1) = 3.02, p = 0.082; adjusted OR 1.95, 95% CI 0.96–3.98), nor did individual obstetric outcomes, neonatal outcomes or screening markers. Conclusions: First-trimester TSH > 4.0 mIU/L was associated with a higher frequency of GDM. Given the few events, the wide confidence interval, unmeasured body-mass index and thyroid-peroxidase-antibody status and the absence of a TSH < 2.5 mIU/L comparison group, the finding is hypothesis-generating and does not establish 4.0 mIU/L as a clinically discriminatory threshold.

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Cite

BibTeXRIS
BibTeX
@article{sahin2026firsttrimester,
  title = {{First-Trimester Thyroid-Stimulating Hormone Levels and Gestational Diabetes Mellitus: A Retrospective Cohort Study}},
  author = {Büşra Şahin and Tansu Bahar Gürbüz and Fazilet Tatar and Rümeysa Uzun and Melike Özyurt Topuzoğlu and Ramazan Erda Pay and Yaprak Üstün},
  journal = {Metabolites},
  year = {2026},
  month = oct,
  doi = {10.3390/metabo16100772},
  url = {https://www.mdpi.com/2218-1989/16/10/772},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - First-Trimester Thyroid-Stimulating Hormone Levels and Gestational Diabetes Mellitus: A Retrospective Cohort Study
AU  - Büşra Şahin
AU  - Tansu Bahar Gürbüz
AU  - Fazilet Tatar
AU  - Rümeysa Uzun
AU  - Melike Özyurt Topuzoğlu
AU  - Ramazan Erda Pay
AU  - Yaprak Üstün
PY  - 2026
DA  - 2026/10/01
JO  - Metabolites
DO  - 10.3390/metabo16100772
UR  - https://www.mdpi.com/2218-1989/16/10/772
AB  - Background: The clinical relevance of a mildly elevated first-trimester thyroid-stimulating hormone (TSH) concentration is uncertain, recent meta-analyses disagree, and few studies have directly contrasted a TSH of 2.5–4.0 mIU/L with a TSH above 4.0 mIU/L. Methods: In this single-centre retrospective cohort study, 218 singleton pregnancies with a first-trimester TSH ≥ 2.5 and ≤10.0 mIU/L and a concurrent free thyroxine (fT4) measurement were classified as high-normal TSH (2.5–4.0 mIU/L; n = 168) or elevated TSH (>4.0–10.0 mIU/L; n = 50; subclinical hypothyroidism in 47 and biochemically overt hypothyroidism in 3). The primary outcome was gestational diabetes mellitus (GDM); secondary outcomes were a composite obstetric complication, individual obstetric and neonatal outcomes, and first- and second-trimester screening markers. Two logistic regression models adjusted for maternal age were fitted; because levothyroxine was started after the index TSH measurement, it was treated as a potential intermediate and examined only in post hoc sensitivity analyses. Results: GDM occurred in 7/50 (14.0%) women with TSH > 4.0 mIU/L versus 6/168 (3.6%) with TSH 2.5–4.0 mIU/L (Fisher’s exact test, p = 0.013; unadjusted odds ratio (OR) 4.40, 95% confidence interval (CI) 1.40–13.76; risk difference 10.4 percentage points, 95% CI 0.4–20.4). After adjustment for maternal age, TSH > 4.0 mIU/L remained associated with GDM (adjusted OR 5.24, 95% CI 1.60–17.16; p = 0.006), an estimate based on only 13 events; additional adjustment for levothyroxine use gave a similar estimate (adjusted OR 4.51, 95% CI 1.33–15.22). The composite obstetric complication did not differ (32.0% vs. 20.2%; χ2(1) = 3.02, p = 0.082; adjusted OR 1.95, 95% CI 0.96–3.98), nor did individual obstetric outcomes, neonatal outcomes or screening markers. Conclusions: First-trimester TSH > 4.0 mIU/L was associated with a higher frequency of GDM. Given the few events, the wide confidence interval, unmeasured body-mass index and thyroid-peroxidase-antibody status and the absence of a TSH < 2.5 mIU/L comparison group, the finding is hypothesis-generating and does not establish 4.0 mIU/L as a clinically discriminatory threshold.
SN  - 2218-1989
ER  -