Short-Term Hyperthyroidism Followed by Transient Pituitary Hypothyroidism in a Very Low Birth Weight Infant Born to a Mother With Uncontrolled Graves' Disease

Abstract

ABSTRACT. Transient hypothyroxinemia in infants born to mothers with poorly controlled Graves' disease was first reported in 1988. We report that short-term hyperthyroidism followed by hypothyroidism with low basal thyroid-stimulating hormone (TSH) levels developed in a very low birth weight infant born at 27 weeks of gestation to a noncompliant mother with thyrotoxicosis attributable to Graves' disease. We performed serial thyrotropin-releasing hormone (TRH) tests in this infant and demonstrated that TSH unresponsiveness to TRH disappeared at 6.5 months of age.The maternal thyroid function was free triiodothyronine (FT 3 ), 21.1 pg/mL; free thyroxine (FT 4 ), 8.1 ng/dL; TSH, <0.03 U/mL; thyroid-stimulating hormone receptor antibody, 52% (normal: <15%); thyroid-stimulating antibody, 294% (normal: <180%); and thyroid-stimulation blocking antibody, 9% (normal: <25%) on the day of delivery. A nonstress test revealed fetal tachycardia >200 beats per minute, and a male infant weighing 1152 g was born by emergency cesarean section. Thyroid-stimulating hormone receptor antibody was 16% and thyroidstimulating antibody was 370% in the cord blood. We administered 10 mg/kg per day of oral propylthiouracil from day 1. Tachycardia along with elevated FT 4 and FT 3 levels in the infant decreased from 200/minute to 170/ minute, 4.7 ng/dL to 2.9 ng/dL, 7.0 pg/mL to 4.8 pg/mL, respectively, in the first 33 hours. At 5 days, FT 4 and FT 3 were 1.1 ng/dL and 2.9 pg/mL, respectively, and we stopped propylthiouracil administration. Although FT 4 decreased to 0.4 ng/dL, TSH was quite low and did not respond to intravenous TRH by 14 days of age. We began daily levothyroxine 5-/kg supplementation. The responsiveness of TSH to TRH did not become significant until 4 months old and normalized at 6.5 months old. At this time, levothyroxine was stopped.We conclude that placental transfer of thyroid hormones may cause hyperthyroidism in the fetal and early neonatal periods and lead to transient pituitary hypothyroidism in an infant born to a mother with uncontrolled Graves' disease. Pediatrics 2001;107(4). URL: http://www. pediatrics.org/cgi/content/full/107/4/e57; pituitary hypothyroidism, Graves' disease, thyroxine, triiodothyronine, placental transfer.ABBREVIATIONS. FT 3, free triiodothyronine; FT 4, free thyroxine; TSH, thyroid-stimulating hormone; TRAb, thyroid-stimulating hormone receptor antibody; TSAb, thyroid-stimulating antibody; TRH, thyrotropin-releasing hormone; T 4 , thyroxine; T 3, triiodothyronine. CASE REPORTA male infant was born at 27 weeks 2 days of gestational age to a 27-year-old G2P0 mother who was diagnosed at age 13 years with thyrotoxicosis attributable to Graves' disease. She was noncompliant with medication and had an elective abortion at age 26 years because of thyrotoxicosis. Premature rupture of the membranes occurred at 27 weeks 2 days of the second gestation and a nonstress test revealed fetal tachycardia Ͼ200 beats per minute. The mother was transferred to our hospital because of threatened premature labor a...

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

“…We hypothesize that maternal hyperthyroidism during pregnancy leads to a hyperthyroid fetal environment, as seen in case 1, which has previously been reported as "short-term hyperthyroidism followed by transient pituitary hypothyroidism in a very low birth weight infant born to a mother with uncontrolled Graves' disease." 6 Another report describes an infant in whom central hyperthyroidism developed after neonatal hyperthyroidism and persisted for only a few days after birth, with the condition thought to be attributable to passive transfer of maternal thyroxine from a mother with thyrotoxicosis. 7 However, in case 3, a term normal birth weight infant was born to a mother who had euthyroid function at the time of delivery, and in case 2, maternal thyroid function was improving at the time of delivery after antithyroid drug therapy had been introduced in week 31 of gestation.…”

One Case of Fetal and Neonatal Variable Thyroid Dysfunction in the Context of Graves’ Disease

“…Thus, this transient hypothyroidism could be the result of the simultaneous action of blocking and stimulating antibodies. Cases with a reverse course in which a transient neonatal hyperthyroidism was followed by hypothyroidism have been described [19]. During pregnancy, a transfer of stimulating antibodies took place during pregnancy and the fetal TSH synthesis was inhibited by their negative biofeedback.…”

“…These autoantibodies bind to the fetal thyroid TSH receptors and mimic their action by increasing the secretion of the thyroid hormones [20]. In the mother, antibodies blocking the binding of TSH to its receptors may also be observed [19]. These antibodies also go through the placental barrier.…”

Fetal neonatal hyperthyroidism: diagnostic and therapeutic approachment

“…Other problems found in the babies of mothers with Graves' disease include transient central hypothyroidism, primary hypothyroidism, and isolated hyperthyrotropinemia (28,30,(48)(49)(50). This condition may be observed in the early postnatal period, following a short-term picture of hyperthyroidism or euthyroidism, or the picture of hypothyroidism may be observed before the stage of hyperthyroidism (8,30).…”