The DOI matches its Crossref record; 33 of the 34 references it cites were found in a registry or an index.
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.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“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]
In the citing paper
“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]
In the citing paper
“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).”
In the citing paper
“During pregnancy, TH requirement increases and most LT4-treated women require a dose increase up to 30%.”
In the citing paper
“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]
Citations
Cites
The Colorado Thyroid Disease Prevalence Study
Canaris, G. J., Manowitz, N. R., Mayor, G., & Ridgway, E. C. (2000) · Archives of Internal Medicine · doi:10.1001/archinte.160.4.526 · Cited by 2,824
Haddow, J. E., Palomaki, G. E., Allan, W. C., Williams, J. R., Knight, G. J., Gagnon, J., O'Heir, C. E., Mitchell, M. L., Hermos, R. J., Waisbren, S. E., et al. (1999) · New England Journal of Medicine · doi:10.1056/nejm199908193410801 · Cited by 2,558
The incidence of thyroid disorders in the community: a twenty-year follow-up of the Whickham Survey
Vanderpump, M. P. J., Tunbrldge, W. M. G., French, J. M., Appleton, D., Bates, D., Clark, F., Evans, J. G., Hasan, D. M., Rodgers, H., Tunbridge, F., et al. (1995) · Clinical Endocrinology · doi:10.1111/j.1365-2265.1995.tb01894.x · Cited by 2,432
Glinoer, D. (1997) · Endocrine Reviews · doi:10.1210/edrv.18.3.0300 · Cited by 1,364
Vulsma, T., Gons, M. H., & de Vijlder, J. J. M. (1989) · New England Journal of Medicine · doi:10.1056/nejm198907063210103 · Cited by 795
Regulation of Maternal Thyroid during Pregnancy*
Glinoer, D., Nayer, P. D., Bourdoux, P. P., Lemone, M., Robyn, C., Steirteghem, A. V., KINTHAERT, J., & Lejeune, B. (1990) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem-71-2-276 · Cited by 724
Maternal and Fetal Thyroid Function
Epstein, F. H., Burrow, G. N., Fisher, D. A., & Larsen, P. R. (1994) · New England Journal of Medicine · doi:10.1056/nejm199410203311608 · Cited by 720
Self-citationOvert and Subclinical Hypothyroidism Complicating Pregnancy
Abalovich, M., Gutierrez, S., Alcaraz, G., Maccallini, G., Garcia, A., & Levalle, O. (2002) · Thyroid · doi:10.1089/105072502753451986 · Cited by 714
Maternal thyroid deficiency and pregnancy complications: implications for population screening
Allan, W. C., Haddow, J. E., Palomaki, G. E., Williams, J. R., Mitchell, M. L., Hermos, R. J., Faix, J. D., & Klein, R. (2000) · Journal of Medical Screening · doi:10.1136/jms.7.3.127 · Cited by 643
The Disorders Induced by Iodine Deficiency
DELANGE, F. (1994) · Thyroid · doi:10.1089/thy.1994.4.107 · Cited by 638
Increased need for thyroxine during pregnancy in women with primary hypothyroidism
Mandel, S. J., Larsen, P. R., Seely, E. W., & Brent, G. A. (1990) · New England Journal of Medicine · doi:10.1056/nejm199007123230204 · Cited by 360
Self-citationGlinoer, D. (1997) · Endocrine Reviews · doi:10.1210/er.18.3.404 · Cited by 349
Ain, K. B., MORI, Y., & Refetoff, S. (1987) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem-65-4-689 · Cited by 310
Increased need for thyroxine in women with hypothyroidism during estrogen therapy
Arafah, B. M. (2001) · New England Journal of Medicine · doi:10.1056/nejm200106073442302 · Cited by 267
Sj, V., Martin, J. A., Sc, C., Mathews, T. J., & Park, M. M. (2000) · PubMed · Cited by 247
Huang, S. A., Dorfman, D. M., Genest, D. R., Salvatore, D., & Larsen, P. R. (2003) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2002-021291 · Cited by 211
Self-citationComparison of Thyroid Stimulators and Thyroid Hormone Concentrations in the Sera of Pregnant Women*
Harada, A., Hershman, J. M., REED, A. W., Braunstein, G. D., Dignam, W. J., Derzko, C. M., FRIEDMAN, S., Jewelewicz, R., & Pekary, A. E. (1979) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem-48-5-793 · Cited by 200
Human Placenta Is an Active Site of Thyroxine and 3,3',5-Triiodothyronine Tyrosyl Ring Deiodination*
Roti, E., Fang, S. L., GREEN, K., Emerson, C. H., & Braverman, L. E. (1981) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem-53-3-498 · Cited by 146
Effect of Frequency of Prenatal Care Visits on Perinatal Outcome Among Low-Risk Women
McDuffie, R. S. (1996) · JAMA · doi:10.1001/jama.1996.03530350029030 · Cited by 145
Relation of severity of maternal hypothyroidism to cognitive development of offspring
Klein, R., Sargent, J. D., Larsen, P. R., Waisbren, S. E., Haddow, J. E., & Mitchell, M. L. (2001) · Journal of Medical Screening · doi:10.1136/jms.8.1.18 · Cited by 131
Self-citationMonitoring Thyroxine Treatment During Pregnancy
Kaplan, M. M. (1992) · Thyroid · doi:10.1089/thy.1992.2.147 · Cited by 126
HEMATOLOGIC CHANGES ASSOCIATED WITH PREGNANCY
Peck, T., & Arias, F. (1979) · Clinical Obstetrics & Gynecology · doi:10.1097/00003081-197912000-00002 · Cited by 89
Decrease of Free Thyroxine Levels after Controlled Ovarian Hyperstimulation1
Muller, A. F., Verhoeff, A., Mantel, M. J., de Jong, F. H., & Berghout, A. (2000) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.85.2.6374 · Cited by 78
Glinoer, D., Gershengorn, M. C., Dubois, A., & ROBBINS, J. J. (1977) · Endocrinology · doi:10.1210/endo-100-3-807 · Cited by 69
Revised Nomenclature for Tests of Thyroid Hormones and Thyroid-Related Proteins in Serum.
Larsen, P. R., Alexander, N. M., CHOPRA, I. J., HAY, I. D., Hershman, J. M., Kaplan, M. M., Mariash, C. N., Nicoloff, J. T., Oppenheimer, J. H., & Solomon, D. H. (1987) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem-64-5-1089 · Cited by 63
Self-citationPostpartum Thyroiditis in Women with Hypothyroidism Antedating Pregnancy?
Caixàs, A., Albareda, M., García‐Patterson, A., Rodrı́guez-Espinosa, J., de Leiva, A., & Corcoy, R. (1999) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.84.11.6144 · Cited by 58
Pekonen, F., Teramo, K. A., Ikonen, E., Österlund, K., Mäkinen, T., & Ba, L. (1984) · PubMed · Cited by 52
Determinants of Iodothyronine Deiodinase Activities in Rodent Uterus
Wasco, E. C., Martinez, E., Grant‐Tschudy, K. S., Germain, E. A. S., Germain, D. L. S., & Galton, V. A. (2003) · Endocrinology · doi:10.1210/en.2003-0490 · Cited by 52
CHOPRA, I. J., & Baber, K. (2003) · Metabolism · doi:10.1053/meta.2003.50019 · Cited by 52
Thyroxine dosage during pregnancy in women with primary hypothyroidism
Girling, J., & de Swiet, M. (1992) · BJOG An International Journal of Obstetrics & Gynaecology · doi:10.1111/j.1471-0528.1992.tb13750.x · Cited by 45
McDuffie, R. S. (1996) · JAMA · doi:10.1001/jama.275.11.847 · Cited by 37
Hypothyroid women need more thyroxine when pregnant.
McDougall, I., & Maclin, N. (1995) · PubMed · Cited by 27
Impact of Thyroxine-Binding Globulin on Thyroid Hormone Economy During Pregnancy
Zigman, J. M., Cohen, S. E., & Garber, J. R. (2003) · Thyroid · doi:10.1089/10507250360731587 · Cited by 15
Flagged first, then by citations
1 of the 34 references couldn’t be matched to a known paper.
Research works printed but not linked: 5
- Ventura SJ, Martin JA, Curtin SC, Menacker F, Hamilton BE. Births: final data for 1999. National vital statistics reports. Vol. 49. No. 1. Hyattsville, Md.: National Center for Health Statistics, March 2001. (DHHS publication no. (PHS) 2001-1120 1-0355.)
- Pekonen F, 1984, Obstet Gynecol, 63, 635
- McDougall IR, 1995, J Fam Pract, 41, 238
- 10.1210/jc.84.11.4000 · DOI
- 10.1210/jc.85.2.545 · DOI · Paper page
Cited by
Sorted by citations
Stagnaro-Green, A., Abalovich, M., Alexander, E., Azizi, F., Mestman, J., Negro, R., Nixon, A., Pearce, E. N., Soldin, O. P., Sullivan, S., et al. (2011) · Thyroid · doi:10.1089/thy.2011.0087 · Cited by 2,942
Self-citationAlexander, E. K., Pearce, E. N., Brent, G. A., Brown, R. S., Chen, H., Dosiou, C., Grobman, W. A., Laurberg, P., Lazarus, J. H., Mandel, S. J., et al. (2017) · Thyroid® · doi:10.1089/thy.2016.0457 · Cited by 2,731
Self-citationJonklaas, J., Bianco, A. C., Bauer, A. J., Burman, K. D., Cappola, A. R., Celi, F. S., Cooper, D. S., Kim, B. W., Peeters, R. P., Rosenthal, M. S., et al. (2014) · Thyroid® · doi:10.1089/thy.2014.0028 · Cited by 1,928
DeGroot, L. J., Abalovich, M., Alexander, E. K., Amino, N., Barbour, L. A., Cobin, R. H., Eastman, C. J., Lazarus, J. H., Luton, D., Mandel, S. J., et al. (2012) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2011-2803 · Cited by 1,885
Self-citationGarber, J. R., Cobin, R. H., Gharib, H., Hennessey, J. V., Klein, I., Mechanick, J. I., Pessah-Pollack, R., Singer, P. A., & Woeber, K. A. (2012) · Endocrine Practice · doi:10.4158/ep12280.gl · Cited by 1,567
Metadata
- 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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review