Fetal Thyroid Function

Abstract

Cordocentesis has permitted the study of fetal thyroid function in utero. In normal fetuses, fetal TSH, TBG, and thyroid hormone concentrations increase progressively throughout intrauterine life. Fetal TSH concentrations are always high compared to nonpregnant adult values. TBG concentrations reach adult levels at term. TT4 and FT4 concentrations reach adult levels at approximately 36 weeks gestation, but TT3 and FT3 are always below adult concentrations. There are no significant associations between fetal and maternal concentrations of TSH, TBG, or thyroid hormones. The maternal administration of TRH from at least 25 weeks gestation stimulates the fetal pituitary gland to produce TSH. The response is rapid, unrelated to gestational age, and much greater than that of the mother. These findings suggest that in intrauterine life there is independent and autonomous maturation of the pituitary, thyroid, and liver. The fetal pituitary is able to respond to the maternal administration of TRH and appears to be more sensitive than in the adult. In small-for-gestational-age fetuses, the concentrations of TSH are higher and the concentrations of TT4 and FT4 are lower than in appropriately grown fetuses. The degrees of elevation of TSH and fall in thyroid hormones are significantly related to the degree of fetal hypoxemia and acidemia, respectively. Although the low concentrations of thyroid hormones may have some beneficial effects by reducing oxygen requirements, they may adversely affect brain development.

Thyroid Allostasis–Adaptive Responses of Thyrotropic Feedback Control to Conditions of Strain, Stress, and Developmental Programming

“…In the first half of pregnancy, the fetus is largely dependent on maternal supply with thyroid hormones, probably explaining, why production of iodothyronines is upregulated in the mother (230). Despite this anti-NTIS-like pattern in the maternal metabolism, which is mainly mediated via human chorionic gonadotropin (hCG) and estrogens (230), concentrations of free and total T3 are low in the fetus throughout gestation, and concentrations of TBG, free and total T4 are, although rising with increasing gestational age (230), lower in the fetal than in the maternal circulation (Figure 8) (232). TSH levels attain a maximum of about 15 mIU/L in the 20th week, when the feedback loop maturates, and then again at birth (29).…”

European Society for Paediatric Endocrinology Consensus Guidelines on Screening, Diagnosis, and Management of Congenital Hypothyroidism

“…Several interventions have also been proposed for improving the fetal outcomes of fetal hypothyroid disorders by considering the fetus as the patient to be treated and gaining direct access to the amniotic cavity. These approaches range from public health interventions with clear benefits and negligible risks, such as increasing the iodine intake of all pregnant women, to procedures with a much less clear benefit-to-risk ratio, such as cordocentesis for determining thyroid function in a fetus with goiter and repeated intra-amniotic injections of L-T 4 [146,147,148,149,150,151,152] (table 4). …”

Iodine-Induced Fetal Hypothyroidism: Diagnosis and Treatment with Intra-Amniotic Levothyroxine

“…A fetal blood sample to assess fetal thyroid status and a genetic amniocentesis was performed at 21 4/7 weeks’ gestation. Fetal TSH was 94.4 mIU/L and FT4 0.5 ng/dL, consistent with severe fetal hypothyroidism [18, 19] (Table 1). Amniocentesis revealed a 46,XX karyotype and a normal prenatal microarray.…”

“…During this time, the fetal goiter remained stable in size. Immediately following the third injection, a repeat fetal blood sample was performed at 26 4/7 weeks’ gestation and demonstrated fetal euthyroidism [18, 19] (Table 1). At 30 4/7 weeks’ gestational age, the fetal goiter had decreased in size, and the tracheal compression and polyhydramnios had resolved.…”