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Fetal thyrotoxicosis associated with nonimmune hydrops
CASE REPORTS Fetal thyrotoxicosis
associated with nonimmune
William
M. Fiegen,
Sioux
J. Watson, Falls,
South
MD, and Michael
MD
Dakota
The reported manifestations of thyrotoxicosis in the fetus include tachycardia, preterm growth retardation, and increased perinatal mortality. Presented is a twin pregnancy in with a history of Graves’ disease and high levels of thyroid-stimulating immunoglobulin which resulted in nonimmune hydrops in one of the twins. (AM J OBSTET GYNECOL 1995;i
Key words:
hydrops
Pregnancy,
thyroid
disease, Graves’ disease, nonimmune
Graves’ disease, an autoimmune disorder of unknown cause, is characterized by the presence of circulating autoantibodies of the immunoglobulin G (IgG) class, which bind to thyroid-stimulating hormone (TSH) receptors and result in production of excess thyroid hormone. The unique significance of this disease in obstetrics lies in the fact that these IgG antibodies are known to cross the placenta and can cause thyrotoxicosis in the fetus. There is a variable spectrum of fetal response to this IgG antibody transfer. Thyrotoxic fetuses have an increased incidence of preterm labor, intrauterine growth retardation, and perinatal mortality.’ Thyrotoxicosis induces in the fetus a hypermetabolic state characterized by fetal tachycardia. This may occur in spite of normal maternal thyroid function. We present a case of a twin pregnancy in a euthyroid mother with known Graves’ disease in which one twin had nonimmune hydrops. Although there are many causes of nonimmune hydrops, fetal thyrotoxicosis is rarely considered in the differential diagnosis. Case report A 28-year-old white woman, gravida 2, para O-O-l-0, had had radioactive ablation of the thyroid for Graves’ disease 10 years before the index pregnancy. She had a known twin gestation and had been followed up for threatened preterm labor. The patient was treated with L-thyroxine, 0.3 mg daily, throughout her pregnancy. Serial thyroid function tests in the mother showed no evidence of hyperthyroidism; at 28 weeks’ gestation the thyroxine level by radioimmunoassay was 8.7 pg/dl (normal 4.3 to 12.0 kg), the TSH level was 1.0 ~IU/ml (normal 0.2 to 7.0 $U), and the total triiodothyronine level was 83 ng/dl (normal 70 to 204 ngidl). From the Division of Perinatal Medicine, Department of Obstetrics and Gynecology, Sioux Valley Hospital. Received for publication May 2 7, 1994; revised August 2, 1994, accepted August 9, 1994. Reprint requests: William J. Watson, MD, Perinatology 1201 S. Euclid Ave., Ste 204, Sioux Falls, SD 57105. Copyright 0 1995 by Mosby-Year Book, Inc. 0002-9378/95 $3.00 + 0 6/l/59690
birth, intrauterine a euthyroid mother G antibodies, 72:1039-40.)
hydrops
In the 2 weeks before delivery the fetal heart tones of both twin A and twin B were noted to be elevated, with a baseline rate of approximately 180 beats/min. The mother was receiving no medications known to increase fetal heart rate. At 31 weeks’ gestation she had spontaneous rupture of membranes. Ultrasonographic evaluation at that time showed that twin B had hydrops with bilateral pleural effusions and ascites. Because of the breech presentation in labor and advanced cervical dilatation, the patient underwent cesarean delivery. Twin A (a male) weighed 1920 gm, and twin B (a female) weighed 1700 gm. Twin B underwent immediate thoracentesis in the delivery room because of pleural effusions noted before delivery and difficulty with ventilation; 90 ml of fluid was obtained from the left side but only 5 ml from the right side. Subsequently chest tubes were placed bilaterally. Both twins had clinical evidence of hyperthyroidism in the neonatal period. No other causes of hydrops were found. In twin A a grade 2 systolic ejection murmur was present. A cardiac echo showed hypertrophic cardiomyopathy with normal cardiac structure. Both had evidence of spontaneous jitteriness in the neonatal period. Free thyroxine and TSH levels were obtained on both twins; twin A had a free thyroxine level of 4.3 ngidl (normal 0.8 to 2.1 ngidl) and a TSH level of 0.7 lJXJ/ml (normal 0.5 to 6.0 tJXJ/ml). The free thyroxine level on twin B was 3.9 ng/dl with a TSH level of 0.7 lJKJ/rnl. A thyroid-stimulating immunoglobin assay performed on the ninth day of life showed 113% activity in twin A and 139% in twin B. The infants were treated with Lugol’s solution and propylthiouracil. The free thyroxine level normalized within 3 days. After delivery a maternal blood test for thyroid stimulation immunoglobin showed the IgG to be at 1109% of basal activity. The mother remained clinically euthyroid throughout the postpartum period. At 2 years of age both infants are clinically normal. Comment It is clear that the fetus may become thyrotoxic even in a mother with normal thyroid function. For this reason direct fetal blood sampling in utero has been 1039
Gerber
et al
rLIarch 1995 4m j Obstet Gynecol
advocated to diagnose and treat fetal thyrotoxicosis in utero.’ Before such blood sampling was technically feasible, only assessment of fetal growth and fetal heart rate were available to the clinician. We were unable to find a previous report of nonimmune hydrops caused by fetal thyrotoxicosis. It is reasonable to postulate that thyrotoxicosis may be a cause of nonimmune hydrops, because high-output cardiac failure may occur in the fetus with thyrotoxicosis and fetal tachyarrhythmias are a known cause of hydrops. It is interesting to note that in this case only one twin in a concordant twin pair had nonimmune hydrops, in spite of both having apparently equal transfer of IgG antibody and similar thyroid tests in the neonatal period. It
is likely that the fetal outcome could have been improved if fetal blood sampling had been undertaken in utero and if the fetuses’ hyperthyroid condition had been treated before birth. In an affected twin pregnancy it would appear unnecessary to sample both fetal circulations, especially if the twins had reasonably concordant growth.
REFERENCES
I Hollingsworth
DR. Graves’ disease. Clin Obstet
Cynecol
1983;26:615-34.
2. Porreco RP, Bloch CA. Fetal blood sampling in the management of intrauterine thyrotoxicosis. Obstet Gynecol 1990;76:509-12.
Aplasia cutis congenita: A rare cause of elevated wfetoprotein levels Michele Gerber, MD, Margarita Greggory R. Devore, MD Orange,
Long
Beach,
and
de Veciana,
Pasadena,
MD, Craig
V. Towers,
MD, and
California
We present a catastrophic case of aplasia cutis congenita from a pregnancy complicated maternal serum and amniotic fluid a-fetoprotein levels and a positive acetylcholinesterase. occurred at 27 weeks 1 day after premature rupture of membranes with chorioamnionitis. lacked >90% of its skin and died. (AM J OBSTET GYNECOL 1995;172:1040-1.)
Key words:
Aplasia
cutis congenita,
a-fetoprotein,
acetylcholinesterase,
Aplasia cutis congenita is a rare group of disorders usually presenting with isolated scalp defects. We present a unique case of extensive ( > 90%) absence of skin resulting in the neonatal death of a preterm infant from a pregnancy complicated by elevated maternal serum ol-fetoprotein (AFP) and amniotic fluid AFP levels. Case report The patient was a 2 1-year-old woman, gravida 2, para I, whose previous pregnancy was uncomplicated. A maternal serum sample drawn at 19 weeks 4 days
From the Department of Obstetrics and Gynecology Long Beach Medical Center, the Department of Obstetrzcs and Gynecology, University of Calzfornia, Irvine Medical Center, and Aljigen, The Genetics Instztute. Received for publication July I, 1994; accepted September 7, 1994. Re@int reauests: M. de Veciana, MD. Eastern Viwinia Medical School, Deiartment of Obstetrics/&ynecology, Divisiony of MaternalFetal Medicine, 825 Fairfax Ave., Norfolk, VA 23507. Copyright 0 1995 by Mosby-Year Book, Inc. 0002~7378/95 $3.00 + 0 6/l/60432
1040
by elevated Delivery The neonate
pseudocholinesterase
revealed a very high AFP level, 380.6 ngiml (8.7 multiples of the median). An anatomic survey at 20 weeks 6 days was normal yet hindered by oligohydramnios with an amniotic fluid index of 5.0 cm. Amniocentesis revealed a negative amniotic fluid culture and a normal 46,XY karyotype. Amniotic fluid AFP was also markedly elevated at 44.3 kg/ml (7.8 multiples of the median) with a positive acetylcholinesterase and an acetylcholinesterase-to-pseudocholinesterase ratio of 0.03. Concurrently indigo carmine was injected without leakage into a tampon, thus ruling out rupture of membranes. The parents were counseled and desired continuation of the pregnancy. An ultrasonographic examination at 23 weeks 1 day revealed improvement of the amniotic fluid index to 11.0 cm with a normal anatomic survey. At 27 weeks 1 day, the patient presented with ruptured membranes, chorioamnionitis, and a breech presentation. She underwent cesarean deliveq of a 1035 gm male with Apgar scores of 3 at I minute, 7 at 5 minutes, and 7 at 10 minutes, with normal cord blood gases. In the delivery room the infant was noted to have near total absence of skin. He was initially intubated,
associated with nonimmune
William
M. Fiegen,
Sioux
J. Watson, Falls,
South
MD, and Michael
MD
Dakota
The reported manifestations of thyrotoxicosis in the fetus include tachycardia, preterm growth retardation, and increased perinatal mortality. Presented is a twin pregnancy in with a history of Graves’ disease and high levels of thyroid-stimulating immunoglobulin which resulted in nonimmune hydrops in one of the twins. (AM J OBSTET GYNECOL 1995;i
Key words:
hydrops
Pregnancy,
thyroid
disease, Graves’ disease, nonimmune
Graves’ disease, an autoimmune disorder of unknown cause, is characterized by the presence of circulating autoantibodies of the immunoglobulin G (IgG) class, which bind to thyroid-stimulating hormone (TSH) receptors and result in production of excess thyroid hormone. The unique significance of this disease in obstetrics lies in the fact that these IgG antibodies are known to cross the placenta and can cause thyrotoxicosis in the fetus. There is a variable spectrum of fetal response to this IgG antibody transfer. Thyrotoxic fetuses have an increased incidence of preterm labor, intrauterine growth retardation, and perinatal mortality.’ Thyrotoxicosis induces in the fetus a hypermetabolic state characterized by fetal tachycardia. This may occur in spite of normal maternal thyroid function. We present a case of a twin pregnancy in a euthyroid mother with known Graves’ disease in which one twin had nonimmune hydrops. Although there are many causes of nonimmune hydrops, fetal thyrotoxicosis is rarely considered in the differential diagnosis. Case report A 28-year-old white woman, gravida 2, para O-O-l-0, had had radioactive ablation of the thyroid for Graves’ disease 10 years before the index pregnancy. She had a known twin gestation and had been followed up for threatened preterm labor. The patient was treated with L-thyroxine, 0.3 mg daily, throughout her pregnancy. Serial thyroid function tests in the mother showed no evidence of hyperthyroidism; at 28 weeks’ gestation the thyroxine level by radioimmunoassay was 8.7 pg/dl (normal 4.3 to 12.0 kg), the TSH level was 1.0 ~IU/ml (normal 0.2 to 7.0 $U), and the total triiodothyronine level was 83 ng/dl (normal 70 to 204 ngidl). From the Division of Perinatal Medicine, Department of Obstetrics and Gynecology, Sioux Valley Hospital. Received for publication May 2 7, 1994; revised August 2, 1994, accepted August 9, 1994. Reprint requests: William J. Watson, MD, Perinatology 1201 S. Euclid Ave., Ste 204, Sioux Falls, SD 57105. Copyright 0 1995 by Mosby-Year Book, Inc. 0002-9378/95 $3.00 + 0 6/l/59690
birth, intrauterine a euthyroid mother G antibodies, 72:1039-40.)
hydrops
In the 2 weeks before delivery the fetal heart tones of both twin A and twin B were noted to be elevated, with a baseline rate of approximately 180 beats/min. The mother was receiving no medications known to increase fetal heart rate. At 31 weeks’ gestation she had spontaneous rupture of membranes. Ultrasonographic evaluation at that time showed that twin B had hydrops with bilateral pleural effusions and ascites. Because of the breech presentation in labor and advanced cervical dilatation, the patient underwent cesarean delivery. Twin A (a male) weighed 1920 gm, and twin B (a female) weighed 1700 gm. Twin B underwent immediate thoracentesis in the delivery room because of pleural effusions noted before delivery and difficulty with ventilation; 90 ml of fluid was obtained from the left side but only 5 ml from the right side. Subsequently chest tubes were placed bilaterally. Both twins had clinical evidence of hyperthyroidism in the neonatal period. No other causes of hydrops were found. In twin A a grade 2 systolic ejection murmur was present. A cardiac echo showed hypertrophic cardiomyopathy with normal cardiac structure. Both had evidence of spontaneous jitteriness in the neonatal period. Free thyroxine and TSH levels were obtained on both twins; twin A had a free thyroxine level of 4.3 ngidl (normal 0.8 to 2.1 ngidl) and a TSH level of 0.7 lJXJ/ml (normal 0.5 to 6.0 tJXJ/ml). The free thyroxine level on twin B was 3.9 ng/dl with a TSH level of 0.7 lJKJ/rnl. A thyroid-stimulating immunoglobin assay performed on the ninth day of life showed 113% activity in twin A and 139% in twin B. The infants were treated with Lugol’s solution and propylthiouracil. The free thyroxine level normalized within 3 days. After delivery a maternal blood test for thyroid stimulation immunoglobin showed the IgG to be at 1109% of basal activity. The mother remained clinically euthyroid throughout the postpartum period. At 2 years of age both infants are clinically normal. Comment It is clear that the fetus may become thyrotoxic even in a mother with normal thyroid function. For this reason direct fetal blood sampling in utero has been 1039
Gerber
et al
rLIarch 1995 4m j Obstet Gynecol
advocated to diagnose and treat fetal thyrotoxicosis in utero.’ Before such blood sampling was technically feasible, only assessment of fetal growth and fetal heart rate were available to the clinician. We were unable to find a previous report of nonimmune hydrops caused by fetal thyrotoxicosis. It is reasonable to postulate that thyrotoxicosis may be a cause of nonimmune hydrops, because high-output cardiac failure may occur in the fetus with thyrotoxicosis and fetal tachyarrhythmias are a known cause of hydrops. It is interesting to note that in this case only one twin in a concordant twin pair had nonimmune hydrops, in spite of both having apparently equal transfer of IgG antibody and similar thyroid tests in the neonatal period. It
is likely that the fetal outcome could have been improved if fetal blood sampling had been undertaken in utero and if the fetuses’ hyperthyroid condition had been treated before birth. In an affected twin pregnancy it would appear unnecessary to sample both fetal circulations, especially if the twins had reasonably concordant growth.
REFERENCES
I Hollingsworth
DR. Graves’ disease. Clin Obstet
Cynecol
1983;26:615-34.
2. Porreco RP, Bloch CA. Fetal blood sampling in the management of intrauterine thyrotoxicosis. Obstet Gynecol 1990;76:509-12.
Aplasia cutis congenita: A rare cause of elevated wfetoprotein levels Michele Gerber, MD, Margarita Greggory R. Devore, MD Orange,
Long
Beach,
and
de Veciana,
Pasadena,
MD, Craig
V. Towers,
MD, and
California
We present a catastrophic case of aplasia cutis congenita from a pregnancy complicated maternal serum and amniotic fluid a-fetoprotein levels and a positive acetylcholinesterase. occurred at 27 weeks 1 day after premature rupture of membranes with chorioamnionitis. lacked >90% of its skin and died. (AM J OBSTET GYNECOL 1995;172:1040-1.)
Key words:
Aplasia
cutis congenita,
a-fetoprotein,
acetylcholinesterase,
Aplasia cutis congenita is a rare group of disorders usually presenting with isolated scalp defects. We present a unique case of extensive ( > 90%) absence of skin resulting in the neonatal death of a preterm infant from a pregnancy complicated by elevated maternal serum ol-fetoprotein (AFP) and amniotic fluid AFP levels. Case report The patient was a 2 1-year-old woman, gravida 2, para I, whose previous pregnancy was uncomplicated. A maternal serum sample drawn at 19 weeks 4 days
From the Department of Obstetrics and Gynecology Long Beach Medical Center, the Department of Obstetrzcs and Gynecology, University of Calzfornia, Irvine Medical Center, and Aljigen, The Genetics Instztute. Received for publication July I, 1994; accepted September 7, 1994. Re@int reauests: M. de Veciana, MD. Eastern Viwinia Medical School, Deiartment of Obstetrics/&ynecology, Divisiony of MaternalFetal Medicine, 825 Fairfax Ave., Norfolk, VA 23507. Copyright 0 1995 by Mosby-Year Book, Inc. 0002~7378/95 $3.00 + 0 6/l/60432
1040
by elevated Delivery The neonate
pseudocholinesterase
revealed a very high AFP level, 380.6 ngiml (8.7 multiples of the median). An anatomic survey at 20 weeks 6 days was normal yet hindered by oligohydramnios with an amniotic fluid index of 5.0 cm. Amniocentesis revealed a negative amniotic fluid culture and a normal 46,XY karyotype. Amniotic fluid AFP was also markedly elevated at 44.3 kg/ml (7.8 multiples of the median) with a positive acetylcholinesterase and an acetylcholinesterase-to-pseudocholinesterase ratio of 0.03. Concurrently indigo carmine was injected without leakage into a tampon, thus ruling out rupture of membranes. The parents were counseled and desired continuation of the pregnancy. An ultrasonographic examination at 23 weeks 1 day revealed improvement of the amniotic fluid index to 11.0 cm with a normal anatomic survey. At 27 weeks 1 day, the patient presented with ruptured membranes, chorioamnionitis, and a breech presentation. She underwent cesarean deliveq of a 1035 gm male with Apgar scores of 3 at I minute, 7 at 5 minutes, and 7 at 10 minutes, with normal cord blood gases. In the delivery room the infant was noted to have near total absence of skin. He was initially intubated,