Central Hypothyroidism in Infants Who Were Born to Mothers With Thyrotoxicosis Before 32 Weeks' Gestation: 3 Cases

Abstract

ABSTRACT. We describe 3 infants who were born to mothers with Graves' disease and developed central hypothyroidism that persisted for >6 months after birth. Two were preterm infants, and the other was a term infant who was born to a euthyroid mother who had been treated with an antithyroid drug since week 31 of gestation. These cases suggest that passage of thyroid hormones can occur from a thyrotoxic mother to the fetus and that the gestational period earlier than 32 weeks may be the critical time for development of central hypothyroidism. O nly a minority of newborns from mothers with Graves' disease develop central hypothyroidism. 1 In these cases, free thyroxine (T 4 ) levels at birth were higher than those at 5 days of age, suggesting that the fetal T 4 level was higher than that in the period immediately after birth, probably as a result of passive transfer from the mother during the last trimester. 2 The major negative feedback effect of thyroid hormones on thyrotropin (TSH) secretion is mediated by serum free T 4 , which is monodeiodinated to triiodothyronine (T 3 ) by type II deiodinase in the hypothalamus and pituitary thyrotroph cells. Undetectable TSH in the fetal cord serum in the presence of markedly elevated free T 4 (FT 4 ) suggests pituitary negative feedback at as early as 20 weeks' gestation. 3 The exposure of the fetal hypothalamic-pituitary-thyroid system to a higherthan-normal thyroid hormone concentration might impair its physiologic maturation, because there is a continuous significant decrease in the TSH/FT 4 ratio during development from the midgestational fetus to the young adult. 4 Since 1997, we have experienced 3 cases of central hypothyroidism, as described below, and on the basis of these cases, we conclude that the gestational period earlier than 32 weeks may be the critical time for development of central hypothyroidism in offspring. CASE REPORTS Case 1A male infant was born at 27 weeks of gestation with a birth weight of 1152 g (0.3 SD). His 27-year-old gravida 2, para 0 (G2P0) mother had received a diagnosis of Graves' disease at the age of 13 years. However, she had been noncompliant with medication, and premature rupture of membranes occurred at 27 weeks and 2 days of gestation. A nonstress test revealed fetal tachycardia Ͼ200 beats/min. The mother was transferred to our hospital because of the possibility of preterm labor and abruptio placenta. Her thyroid function was as follows: free T 3 (FT 3 ) 21.1 pg/mL, FT 4 8.1 ng/dL, and TSH Ͻ0.03 IU/mL on the day when premature rupture of membranes occurred. The TSH receptor antibody (TRAb) level was 52% (normal: Ͻ15%), and the thyroid-stimulating antibody (TSAb) level was 294% (normal: Ͻ180%).The infant was born via cesarean section on the day the mother was transferred to our hospital. TRAb in the cord blood was 16%, and the infant showed tachycardia at ϳ200 beats per minute after birth, with the following hyperthyroid function 1 hour after birth: FT 3 7.0 pg/mL, FT 4 4.7 ng/dL, and TSH 0.12 IU/mL. Tachycardia and hyperthyroid fu...

Management of Neonates Born to Mothers With Graves’ Disease

“…Treatment duration is most commonly 1 to 2 months. 76 Transient central hypothyroidism, 39,78,79 sometimes followed by hyperthyroidism, [80][81][82] has been reported by others. Recovery from hypothyroidism is usually seen between 3 and 19 months of age.…”

The different requirement of l-T4 therapy in congenital athyreosis compared with adult-acquired hypothyroidism suggests a persisting thyroid hormone resistance at the hypothalamic–pituitary level

“…However, in this human model, a residual thyroid activity in goitrous and ectopic CH and also in patients with adult-onset hypothyroidism was probably present, while in our experimental design, CH patients with agenesis or adult hypothyroid patients with undetectable serum Tg were selected. The maternal thyroid status during pregnancy is also relevant in determining impairment in the hypothalamus-pituitarythyroid axis (30,31,32). In fact, the exposure of this axis to a high thyroid hormone concentration, together with thyroid-stimulating antibodies transferred from mothers with Graves' disease, might alter the axis feedback (31,32) …”

“…The maternal thyroid status during pregnancy is also relevant in determining impairment in the hypothalamus-pituitarythyroid axis (30,31,32). In fact, the exposure of this axis to a high thyroid hormone concentration, together with thyroid-stimulating antibodies transferred from mothers with Graves' disease, might alter the axis feedback (31,32) …”

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