The diagnosis and monitoring of thyroid disease necessitates the knowledge of thyroid pathophysiology and of the technical limitations of current thyroid-related biochemical tests. Thyroid disease diagnosis and monitoring are further complicated during pregnancy and lactation, due to pregnancy-related changes in thyroid hormone metabolism. Dramatic changes that occur in thyroxine and triiodothyronine ranges during pregnancy pose challenges for hypothyroid gravidas. Very early in pregnancy, levothyroxine replacement needs to be increased. Moreover, increases in thyroid hormone replacement need to be conducted individually and on a timely basis. For reasons that are still not entirely clear, although dependent in part on changes in thyroxine binding, free thyroxine (FT4) levels decrease as pregnancy progresses necessitating the use of trimester-specific reference intervals for appropriate replacement. Thyroxine binding protein levels vary by hormonal status, inheritance, and disease states and are higher in pregnancy; hence, FT4 assays became popular because they measure the unbound hormone. However, current FT4 immunoassays are estimate tests that do not reliably measure FT4 and are known to be sensitive to alterations in binding proteins and therefore are method-specific. The need to reliably identify hypothyroxinemic pregnant patients, especially in the first trimester, is of prime importance for early fetal brain development before the fetal thyroid functions. This article addresses 1) the current limitations of laboratory-free thyroxine immunoassay methodologies and especially during pregnancy; 2) trimester-specific reference intervals for thyroid function tests; and 3) the study of levothyroxine pharmacokinetics in pregnant and nonpregnant women.
From the Department of Oncology, Lombardi Comprehensive Cancer Center, Washington, DC; and Department of Medicine and Physiology and Biophysics, Georgetown University Medical Center, Washington, DC.
Received for publication March 16, 2010; accepted March 16, 2010.
Dr. Soldin is partially supported by 5U10HD047890 NIH/NICHD Obstetrics Pharmacology Research Unit (OPRU) and by the Office of Research on Women's Health.
The author declares no competing financial interests.
Correspondence: Offie P. Soldin, PhD, MBA, Director, PregnaTox, Associate Professor of Oncology, Medicine, Physiology and Biophysics, Lombardi Comprehensive Cancer Center, LL S-166, Georgetown University Medical Center, 3800 Reservoir Road, NW, Washington, DC 20057 (e-mail: firstname.lastname@example.org).