Timing and Magnitude of Increases in Levothyroxine Requirements during Pregnancy in Women with Hypothyroidism
Abstract
BACKGROUND: Hypothyroidism during pregnancy has been associated with impaired cognitive development and increased fetal mortality. During pregnancy, maternal thyroid hormone requirements increase. Although it is known that women with hypothyroidism should increase their levothyroxine dose during pregnancy, biochemical hypothyroidism occurs in many. In this prospective study we attempted to identify precisely the timing and amount of levothyroxine adjustment required during pregnancy. METHODS: Women with hypothyroidism who were planning pregnancy were observed prospectively before and throughout their pregnancies. Thyroid function, human chorionic gonadotropin, and estradiol were measured before conception, approximately every two weeks during the first trimester, and monthly thereafter. The dose of levothyroxine was increased to maintain the thyrotropin concentration at preconception values throughout pregnancy. RESULTS: Twenty pregnancies occurred in 19 women and resulted in 17 full-term births. An increase in the levothyroxine dose was necessary during 17 pregnancies. The mean levothyroxine requirement increased 47 percent during the first half of pregnancy (median onset of increase, eight weeks of gestation) and plateaued by week 16. This increased dose was required until delivery. CONCLUSIONS: Levothyroxine requirements increase as early as the fifth week of gestation. Given the importance of maternal euthyroidism for normal fetal cognitive development, we propose that women with hypothyroidism increase their levothyroxine dose by approximately 30 percent as soon as pregnancy is confirmed. Thereafter, serum thyrotropin levels should be monitored and the levothyroxine dose adjusted accordingly.
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Women being treated for hypothyroidism typically require an increase in their LT4 dose early in the first trimester of pregnancy.
“Women being treated for hypothyroidism typically require an increase in their LT4 dose early in the first trimester of pregnancy (228).”
From Guidelines for the Treatment of Hypothyroidism: Prepared by the American Thyroid Association Task Force on Thyroid Hormone Replacement (2014) · cites this paper as [228]
During normal pregnancy, women experience increased thyroxine requirements that may approach 50%.
“As mentioned above, during normal pregnancy, women experience increased thyroxine requirements that may approach 50% [41, 60].”
From Diagnosis and management of treatment-refractory hypothyroidism: an expert consensus report (2017) · cites this paper as [60]
Women with athyreosis, the most severe form of congenital hypothyroidism, require the highest LT4 doses.
“Women with athyreosis, the most severe form of CH, require the highest doses and treatment should aim to keep TSH concentrations <2.5 mU/L throughout pregnancy (154,155,158).”
During pregnancy, thyroid hormone requirement increases and most LT4-treated women require a dose increase up to 30%.
“During pregnancy, TH requirement increases and most LT4-treated women require a dose increase up to 30%.”
The sharp rise in oestrogen levels during the first weeks of pregnancy leads to elevation of TBG levels and thus contributes to a greater requirement for LT4.
“The sharp rise in oestrogen levels during the first weeks of pregnancy leads to an elevation of TBG levels and thus contributes to a greater requirement for LT4 [ 91 ].”
From Factors influencing the levothyroxine dose in the hormone replacement therapy of primary hypothyroidism in adults (2022) · cites this paper as [91]
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- Authors
- Alexander, E. K., Marqusee, E., Lawrence, J., Jarolim, P., Fischer, G. A., & Larsen, P. R.
- Affiliations
- Brigham and Women's Hospital (US)
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2004-07-15
- Volume
- 351
- Issue
- 3
- Pages
- 241-249
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- OpenAlex
- W2088262036
- Cited by
- 633
- References
- 34
- Citations by year
- 2026: 6 · 2025: 15 · 2024: 15 · 2023: 10 · 2022: 35 · 2021: 17 · 2020: 19 · 2019: 25 · 2018: 25 · 2017: 25 · 2016: 37 · 2015: 28 · 2014: 33 · 2013: 36 · 2012: 41
- FWCI
- 21.91
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Heart, Lung, and Blood Institute (HL07609)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK044128, DK-44128, T32DK007529, DK-07529)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
- Health Sciences › Medicine › Surgery › Thyroid and Parathyroid Surgery
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Cancer Diagnosis and Treatment
- Keywords
- levothyroxine dose adjustment, maternal thyroid function, human chorionic gonadotropin, estradiol
- MeSH terms
- Adult, Drug Administration Schedule, Estradiol, Female, Chorionic Gonadotropin, Humans, Hypothyroidism, Pregnancy, Pregnancy Complications, Prospective Studies, Thyrotropin, Thyroxine
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