Upper airway obstruction at birth due to congenital goiter

Topic: GOITROUS CONGENITAL HYPOTHYROIDISM

Title -Goitrous congenital hypothyroidism in a twin pregnancy causing respiratory obstruction at birth: implications for management.

Authors: Reynolds BC, Simpson JH, Macara L, Watt AJB, Kubba H, Donaldson MDC, & Pohlenz J.

Reference: Acta Paediatrica 95: 1345-1348, 2006

Summary

Objectives

Report on a twin pregnancy complicated by fetal goitrous hypothyroidism secondary to dyshormonogenesis caused by a defect in thyroglobulin production.

Patients

Given the late gestational age at diagnosis and the multiple nature of the pregnancy, antenatal treatment with intra-amniotic thyroxine instillation was considered but not performed, Both twins developed airway obstruction at delivery, requiring intubation and ventilation for 2 and 12 days, respectively.

Context and conclusions

The authors review the literature and discuss the practical issues relating to the antenatal assessment and perinatal management of fetal goiter.

Commentary

A dichorionic twin pregnancy was confirmed by ultrasonography (US) at 12 weeks gestation in a healthy, euthyroid, primiparous woman. At 18 weeks of gestation, fetal US revealed no abnormality. Subsequent US, carried out at 24 weeks of gestation, identified a neck mass in one of the twins, assumed to represent fetal goitre. At 31 weeks of gestation, the goiter appeared to be enlarging (AP diameter: 43 mm) and was highly vascular, raising concern about a possible cervical teratoma. One week later, a US control examination showed that the other twin also had a neck mass. MRI was performed at 33 weeks of gestation and allowed to confirm that the neck masses were goiters (no tracheal compression was reported at this stage). The mother had normal thyroid function with slightly positive TPO-Ab titers. In the absence of maternal thyroid disease, provisional diagnosis was goitrous congenital hypothyroidism secondary to dyshormonogenesis. Because of the late gestational age (and presence of twins), therapeutic thyroxine intra-amniotic administration was considered but not pursued. At 36 weeks gestation, one twin developed polyhydramnios and the twins were delivered by caesarian section at 37 weeks gestation.

Twin N-1 was intubated at 2 min of age, because she did not maintain regular respiratory efforts. Clinical examination revealed a moderate goiter. Twin N-2 had clear evidence of airway obstruction with tracheal tug, sternal recession and poor air entry, and was also intubated at 2 min of age. Her clinical examination revealed a large goiter. Both twins were given l-thyroxine (50 -g/day; 19 -g/Kg). One of twins could be extubated successfully on day 2 and a thyroid US on day 5 showed a diffuse bilateral goiter with a thyroid volume (TV) of 6.5 ml (normal: 0.3-1.7 ml). The other twin required external ventilation for a longer period and could only be extubated on day 12. Her TV was 3 ml. Both twins remained well after these initial events and their development proceeded normally. Concerning thyroid function, both twins had a raised serum TSH at birth (46 & 59 mU/L, respectively) with a slightly decreased serum free T4 (8.1 & 8.5 pMol/L, respectively) and, paradoxically, very low serum TG values in the context of prolonged thyroidal stimulation (4 & 5 ng/ml, respectively). Therefore, the presumptive diagnosis was that of a thyroglobulin synthesis defect. This diagnosis was confirmed by molecular genetic studies (performed by J. Pohlenz in Mainz), showing a heterozygous stop mutation in codon 1511 (R1151X), additional heterozygocity for G59S, and presence of a second mutation (S2113L), making these twins compound heterozygotes. Admitting that these twins were dizygotic, this implies that one parent provided one of the mutations, and the other parent the other mutation, and that by statistical chance (1/16) both infants combined the same set of mutations leading to defective Tg production.

Fetal goiters can arise secondary to the transplacental passage of maternal thyroid autoantibodies (for instance, TSH-receptor blocking-type Abs) and also secondary to the inhibitory effects of antithyroid drugs, given to treat maternal Graves- disease. In the absence of maternal thyroid disease, fetal goiter is usually due to dyshormonogenesis.

In the discussion, the authors indicate that, retrospectively, they probably failed to gain maximal information from the antenatal MRI, in particular concerning potential airway obstruction associated with a large fetal goiter. In their assessment (and this is always to criticize afterwards), the obstetric care providers felt that the potential risks of intra-amniotic thyroxine administration outweighed the benefits and such treatment was therefore not given. Perhaps now, with the knowledge that there was tracheal compression, neonatal hypothyroidism (even though not extremely severe), and evolving polyhydramnios, they should have considered antenatal treatment at 34-35 weeks of gestation.

Was there a case for performing cordocentesis or amniocentesis? Such procedures carry a small (but significant risk) but could have provided direct information on fetal thyroid function (serum TSH, free hormone levels, serum Tg levels). Given that the diagnosis of dyshormonogenesis had already been suspected clinically, the additional information would probably not have added much to help clinicians decide on the best therapy. It is usually recommended that cordocentesis or amniocentesis should only be performed if the procedures are considered helpful to decide on the management.

ith regard to imaging of fetal goiter, fetal ultrasonography (US) is obviously the first line test. Its accuracy (largely operator-dependent) can be improved by the use of high-resolution US, three-dimensional US, and color flow Doppler. There is not much reported experience with MRI for the assessment of fetal goiter, but in the present case reports it failed to indicate the possibility of upper airway obstruction.

Finally with regard to therapy, the administration of intra-amniotic thyroxine (alone or combined with triiodothyronine) has been reported in several publications since 1991 already. In all reported cases, thyroxine treatment led to shrinkage of the goiter, reduction in amniotic fluid volume (in cases of polyhydramnios), and normalization of fetal thyroid function. The risks and hazards of intra-amniotic instillation of large doses of thyroxine must be balanced against the risk untreated fetal thyroid function and goiter development (not an easy balance for clinicians). Summary and commentary prepared by Daniel Glinoer )

Present summary and commentary are related to Chapters N- 14 (Section 4) and N- 15 (Section 2) of TDM