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Thyroid physiology and screening in preterm infants

Stephen LaFranchi, MD
Section Editors
David S Cooper, MD
Mitchell E Geffner, MD
Deputy Editor
Alison G Hoppin, MD


Congenital hypothyroidism occurs in approximately 1 in 2000 to 1 in 4000 newborns worldwide, with considerable regional and racial/ethnic variation. It is one of the most common treatable causes of intellectual disability (mental retardation). However, most newborn babies with this disorder have few or no clinical manifestations of thyroid deficiency, and the majority of cases are sporadic. As a result, it is not possible to predict which infants are likely to be affected. For these reasons, newborn screening programs in which either thyroxine (T4) or thyrotropin (TSH) are measured in heel-stick blood specimens were developed in the mid-1970s to detect and treat this condition as early as possible. (See "Clinical features and detection of congenital hypothyroidism".)

Interpretation of screening tests requires an understanding of thyroid physiology in newborn babies. This topic will review normal thyroid physiology in the fetus and in preterm and term infants.


The bilobed thyroid shape is evident by seven weeks of gestation, and thyroid follicles containing colloid are seen histologically by 10 weeks. With respect to thyroid function, thyroglobulin synthesis can be detected at four weeks, iodine trapping at 8 to 10 weeks, and thyroxine (T4) and, to a lesser extent, triiodothyronine (T3) synthesis and secretion at 12 weeks. Hypothalamic neurons contain thyrotropin-releasing hormone (TRH) at six to eight weeks, the pituitary-portal vascular system begins to develop at 8 to 10 weeks, and TSH secretion can be detected at 12 weeks. Maturation of the hypothalamic-pituitary-thyroid axis occurs during the second half of gestation, but completely normal feedback relationships are not mature until one to two months of postnatal life. (See "Thyroid hormone synthesis and physiology".)

The pattern of changes during gestation is as follows (figure 1) [1,2]:

During the first trimester, T4 in the circulation is of maternal origin, as the fetal thyroid does not produce significant amounts of T4 until the second half of pregnancy [3]. Thereafter, the rise in serum T4 concentrations is a result of both an increase in hepatic production of serum thyroxine-binding globulin (TBG) and, to a lesser degree, an increase in fetal thyroidal T4 production stimulated by TSH secretion. Fetal serum T4 concentrations rise from a mean of approximately 2 mcg/dL (26 nmol/L) at 12 weeks to 10 mcg/dL (128 nmol/L) at term [1,2]. Fetal serum free T4 concentrations also increase progressively, from a mean value of approximately 0.1 ng/dL (1.3 pmol/L) at 12 weeks to 2.0 ng/dL (25.7 pmol/L) at term.

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Literature review current through: Sep 2017. | This topic last updated: Jan 21, 2016.
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