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Establishment of Reference Intervals for Markers of Fetal Thyroid Status in Amniotic Fluid

Washington University School of Medicine, Department of Pathology and Immunology, Division of Laboratory Medicine, St. Louis, Missouri 63110

Address all correspondence and requests for reprints to: Ann Gronowski, Ph.D., Department of Pathology and Immunology, Washington University School of Medicine, 660 South Euclid, Box 8118, St. Louis, Missouri 63110. E-mail: gronowski{at}pathology.wustl.edu.

Fetal goiter can arise as a result of fetal hyper or hypothyroidism. Although this condition is rare, it can be life threatening. Detection of fetal goiter in utero is possible with the aid of ultrasound, but proper prenatal treatment depends on knowledge of hormonal status. Amniotic fluid (AF) sampling is less technically demanding and poses fewer risks to the fetus than cordocentesis for fetal serum sampling, but well-established reference ranges for AF thyroid studies are not available in the literature. We have established reference intervals for AF (TSH), total T₄ (tT₄), and free T₄ using stored AF samples. The reference intervals were: TSH (n = 127), less than 0.1–0.5 mU/liter, with a median of 0.1 mU/liter; tT₄ (n = 129), 2.3–3.9 µg/dl (30–50 nmol/liter), with a median of 3.3 µg/dl (4 nmol/liter); and free T₄ (n = 119) less than 0.4–0.7 ng/dl (5–9 pmol/liter), with a median of 0.4 ng/dl (5 pmol/liter). These intervals represent the largest study done to date on third trimester AF using automated immunoassays. A literature search of fetal goiter revealed a number of cases of hypothyroidism. Seven cases reported AF TSH concentrations (range, 1.1–28.9 mU/liter) and four reported AF tT₄ concentrations [range, 0.98–1.25 µg/ml (13–16 nmol/liter)], all of which fell outside our reference intervals. These data support the use of AF to diagnose fetal hypothyroidism, reducing the need to resort to a riskier procedure such as cordocentesis.

This study has been presented in part at the Academy of Clinical Laboratory Physicians and Scientists Annual Meeting, New York, NY, June 2002. This research was sponsored in part by Abbott Laboratories by supplying reagents.

Abbreviations: AF, Amniotic fluid; fT₄, free T₄; SI, Système Internationale; tT₄, total T₄.

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