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Congenital viral infection?
Case Report
Congenital viral infection? Lancet 2005; 365: 1110 Neonatal Unit, Forth Park Hospital, Kirkcaldy, KY2 6RA, UK (DN Carroll MRCPCH, P Kamath MRCPCH, L Stewart MRCP) Correspondence to: [email protected]
1110
DN Carroll, P Kamath, L Stewart
In April, 2003, a 17-hour-old girl, born by normal delivery at 36 weeks’ gestation, was admitted to the neonatal unit with tachypnoea, tachycardia, jaundice, hepatosplenomegaly, petechiae, and needing oxygen. She was afebrile and growth was on the 50th centile. Her mother was 33 years old with four now healthy children (two daughters had had brief self-resolving neonatal jaundice); she was on thyroxine and alfacalcidol after a total thyroidectomy 9 years previously. Routine antenatal screening tests were normal. Thyroid function tests (TFTs) at weeks’ 9 and 36 gestation were: thyroid stimulating hormone (TSH) 0·19 and 5·6 (0·5–3·9 mU/L) and free thyroxine (fT4) 17 and 14 (10–19 pmol/L), respectively. The baby had screening tests for sepsis and congenital infection which showed thrombocytopenia (47109/L), polycythaemia (haematocrit 0·72, which resolved without intervention) and unconjugated hyperbilirubinaemia (152 mol/L). Haemoglobin was 21·6 g/dL, white cells 5·7109/L, blood film unremarkable, glucose 3·2 mmol/L, prothrombin time 17 s (9–14), C-reactive protein and capillary gas normal. Cord blood TFTs showed TSH 2·36 mU/L and T4 23 pmol/L. On the presumption of congenital viral infection, intravenous fluids and antibiotics, including treatment for listeriosis (amoxycillin 30 mg/kg, 77 mg, thrice daily and gentamicin 4 mg/kg, 10mg, od) were started, along with phototherapy. Tests for sepsis and congenital infection, cranial ultrasound, chest radiograph, and ophthalmoscopy were normal. Abdominal ultrasound showed hepatosplenomegaly. Antibiotics were stopped when cultures were negative, but she remained unsettled and, losing weight despite being fed formula at the rate of 180 mL/kg/day. Sleeping heart rate was 160–170. On day 10, repeat TFTs showed marked thyrotoxicosis: T4 87 (10–19 pmol/L), tri-iodothyronine 31 (3·3– 5·3 pmol/L), and TSH of 0·1 (0·5–3·9 mU/L). Maternal and infant TSH-receptor antibodies (TRAB) were 27·2 and 9·7, respectively (normal) 1·5 U/L). Further information from the mothers’ general practitioner revealed that her original thyroid disease was a primary thyrotoxicosis with goitre and ophthalmoplegia. A diagnosis of neonatal thyrotoxicosis after trans-placental transfer of TRAB from maternal Graves’ disease was made. Initial management was conservative but biochemical hyperthyroidism, hepatosplenomegaly, and irritability persisted. She responded to Lugol’s iodine solution (KI 10%), one drop per feed, given from day 20 to 46. At last follow-up, in September, 2003, aged 5 months, she was euthyroid, normal on examination and neurodevelopmentally appropriate.
Neonatal thyrotoxicosis is rare but may be fatal (12–20%).1–5 0·1–0·2% of pregnant women have Graves’ disease, which affects 1–1·5% of their offspring.1–5 1 in 25 000 deliveries are affected in the UK annually.1–5 The diagnosis can be anticipated and the disease easily treated. Anti-thyroid medication can given to the mother ante-natally. Maternal TRAB concentrations should be measured in women at risk of delivering an affected infant to quantify this risk.1–5 Neonatal thyrotoxicosis usually manifests by day 10.1–5 Infants may present with overt hyperthyroidism (tachycardia, goitre, eye signs, heart failure, growth failure, and hypermetabolism) but can present with signs compatible with congenital viral infection (hepatosplenomegaly, thrombocytopenia, petechiae, and hyperviscosity).1,3,4 The mechanism of the latter presentation remains as yet unknown. Normal cord-blood TFTs can occur in the presence of maternal anti-thyroid therapy or “blocking antibodies”.1 Neonatal thyrotoxicosis from transplacental transfer of TRAB is transitory, usually remitting by 8–20 weeks (as seen here) but can last up to 48 weeks.1,4 Iodine, often used in conjunction with thionamides, takes effect rapidly by preventing thyroid- hormone release as well as synthesis.1 Possible reasons for a presentation such as the one described here, include congenital infection, hepatic venous obstruction, leukaemia, Langerhans cell histiocytosis, and osteopetrosis.4 Here no other cause (particularly infective) was identified, and the baby responded to iodine. Neonatal thyrotoxicosis can present in this manner.1,3,4 Earlier diagnosis would have been possible by appreciating the importance of the mother’s thyroidectomy (underlying Graves’ disease), measuring maternal TRAB antenatally, measuring cord blood TRAB, or repeating the infant’s TFTs earlier. We endorse previous recommendations to measure maternal TRAB when there is a history of thyroid disease and to measure TFTs and TRAB on cord blood in infants at high risk and repeat TFTs on day 2–7 and day 10.1 Those at high risk include symptomatic infants or those with a history of maternal Graves’ disease or third trimester thyrotoxicosis.1 References 1 Ogilvy-Stuart A L. Neonatal thyroid disorders. Arch Dis Child Fetal and Neonatal Edition 2002; 87: F165–171.1 2 Skuza K A, Sills I N, Stene M, Rapaport R. Prediction of neonatal hyperthyroidism in infants born to mothers with Graves’ Disease. J Ped 1996; 128: 264–68. 3 Zimmerman D. Fetal and neonatal hyperthyroidism. Thyroid 1999; 9: 727–33. 4 Parker R I, Nguyen P L. Weekly clinicopathological exercises: case 37–1994: a newborn boy with petechiae, hepatosplenomegaly, leukocytosis and thrombocytopenia. NEJM 1994; 331: 1005–12. 5 Smith C M, Gavranich J, A Cotterill, Rodda C P. Congenital neonatal thyrotoxicosis and previous radio-iodine therapy. BMJ 2000; 320: 1260–61.
www.thelancet.com Vol 365 March 19, 2005
Congenital viral infection? Lancet 2005; 365: 1110 Neonatal Unit, Forth Park Hospital, Kirkcaldy, KY2 6RA, UK (DN Carroll MRCPCH, P Kamath MRCPCH, L Stewart MRCP) Correspondence to: [email protected]
1110
DN Carroll, P Kamath, L Stewart
In April, 2003, a 17-hour-old girl, born by normal delivery at 36 weeks’ gestation, was admitted to the neonatal unit with tachypnoea, tachycardia, jaundice, hepatosplenomegaly, petechiae, and needing oxygen. She was afebrile and growth was on the 50th centile. Her mother was 33 years old with four now healthy children (two daughters had had brief self-resolving neonatal jaundice); she was on thyroxine and alfacalcidol after a total thyroidectomy 9 years previously. Routine antenatal screening tests were normal. Thyroid function tests (TFTs) at weeks’ 9 and 36 gestation were: thyroid stimulating hormone (TSH) 0·19 and 5·6 (0·5–3·9 mU/L) and free thyroxine (fT4) 17 and 14 (10–19 pmol/L), respectively. The baby had screening tests for sepsis and congenital infection which showed thrombocytopenia (47109/L), polycythaemia (haematocrit 0·72, which resolved without intervention) and unconjugated hyperbilirubinaemia (152 mol/L). Haemoglobin was 21·6 g/dL, white cells 5·7109/L, blood film unremarkable, glucose 3·2 mmol/L, prothrombin time 17 s (9–14), C-reactive protein and capillary gas normal. Cord blood TFTs showed TSH 2·36 mU/L and T4 23 pmol/L. On the presumption of congenital viral infection, intravenous fluids and antibiotics, including treatment for listeriosis (amoxycillin 30 mg/kg, 77 mg, thrice daily and gentamicin 4 mg/kg, 10mg, od) were started, along with phototherapy. Tests for sepsis and congenital infection, cranial ultrasound, chest radiograph, and ophthalmoscopy were normal. Abdominal ultrasound showed hepatosplenomegaly. Antibiotics were stopped when cultures were negative, but she remained unsettled and, losing weight despite being fed formula at the rate of 180 mL/kg/day. Sleeping heart rate was 160–170. On day 10, repeat TFTs showed marked thyrotoxicosis: T4 87 (10–19 pmol/L), tri-iodothyronine 31 (3·3– 5·3 pmol/L), and TSH of 0·1 (0·5–3·9 mU/L). Maternal and infant TSH-receptor antibodies (TRAB) were 27·2 and 9·7, respectively (normal) 1·5 U/L). Further information from the mothers’ general practitioner revealed that her original thyroid disease was a primary thyrotoxicosis with goitre and ophthalmoplegia. A diagnosis of neonatal thyrotoxicosis after trans-placental transfer of TRAB from maternal Graves’ disease was made. Initial management was conservative but biochemical hyperthyroidism, hepatosplenomegaly, and irritability persisted. She responded to Lugol’s iodine solution (KI 10%), one drop per feed, given from day 20 to 46. At last follow-up, in September, 2003, aged 5 months, she was euthyroid, normal on examination and neurodevelopmentally appropriate.
Neonatal thyrotoxicosis is rare but may be fatal (12–20%).1–5 0·1–0·2% of pregnant women have Graves’ disease, which affects 1–1·5% of their offspring.1–5 1 in 25 000 deliveries are affected in the UK annually.1–5 The diagnosis can be anticipated and the disease easily treated. Anti-thyroid medication can given to the mother ante-natally. Maternal TRAB concentrations should be measured in women at risk of delivering an affected infant to quantify this risk.1–5 Neonatal thyrotoxicosis usually manifests by day 10.1–5 Infants may present with overt hyperthyroidism (tachycardia, goitre, eye signs, heart failure, growth failure, and hypermetabolism) but can present with signs compatible with congenital viral infection (hepatosplenomegaly, thrombocytopenia, petechiae, and hyperviscosity).1,3,4 The mechanism of the latter presentation remains as yet unknown. Normal cord-blood TFTs can occur in the presence of maternal anti-thyroid therapy or “blocking antibodies”.1 Neonatal thyrotoxicosis from transplacental transfer of TRAB is transitory, usually remitting by 8–20 weeks (as seen here) but can last up to 48 weeks.1,4 Iodine, often used in conjunction with thionamides, takes effect rapidly by preventing thyroid- hormone release as well as synthesis.1 Possible reasons for a presentation such as the one described here, include congenital infection, hepatic venous obstruction, leukaemia, Langerhans cell histiocytosis, and osteopetrosis.4 Here no other cause (particularly infective) was identified, and the baby responded to iodine. Neonatal thyrotoxicosis can present in this manner.1,3,4 Earlier diagnosis would have been possible by appreciating the importance of the mother’s thyroidectomy (underlying Graves’ disease), measuring maternal TRAB antenatally, measuring cord blood TRAB, or repeating the infant’s TFTs earlier. We endorse previous recommendations to measure maternal TRAB when there is a history of thyroid disease and to measure TFTs and TRAB on cord blood in infants at high risk and repeat TFTs on day 2–7 and day 10.1 Those at high risk include symptomatic infants or those with a history of maternal Graves’ disease or third trimester thyrotoxicosis.1 References 1 Ogilvy-Stuart A L. Neonatal thyroid disorders. Arch Dis Child Fetal and Neonatal Edition 2002; 87: F165–171.1 2 Skuza K A, Sills I N, Stene M, Rapaport R. Prediction of neonatal hyperthyroidism in infants born to mothers with Graves’ Disease. J Ped 1996; 128: 264–68. 3 Zimmerman D. Fetal and neonatal hyperthyroidism. Thyroid 1999; 9: 727–33. 4 Parker R I, Nguyen P L. Weekly clinicopathological exercises: case 37–1994: a newborn boy with petechiae, hepatosplenomegaly, leukocytosis and thrombocytopenia. NEJM 1994; 331: 1005–12. 5 Smith C M, Gavranich J, A Cotterill, Rodda C P. Congenital neonatal thyrotoxicosis and previous radio-iodine therapy. BMJ 2000; 320: 1260–61.
www.thelancet.com Vol 365 March 19, 2005