Intrauterine death following intraamniotic triiodothyronine and thyroxine therapy for fetal goitrous hypothyroidism associated with polyhydramnios and caused by a thyroglobulin mutation

[摘要] In the absence of maternal thyroid disease or iodine deficiency, fetal goitre is rare and usually attributable todyshormonogenesis, for which genetic ascertainment is not always undertaken in the UK. Mechanical complicationsinclude tracheal and oesophageal compression with resultant polyhydramnios, malpresentation at delivery and neonatalrespiratory distress. We report an Indian kindred in which the proband (first-born son) had congenital hypothyroidism(CH) without obvious neonatal goitre. His mother’s second pregnancy was complicated by fetal hypothyroid goitre andpolyhydramnios, prompting amniotic fluid drainage and intraamniotic therapy (with liothyronine, T3 and levothyroxine,T4). Sadly, intrauterine death occurred at 31 weeks. Genetic studies in the proband demonstrated compoundheterozygous novel (c.5178delT, p.A1727Hfs*26) and previously described (c.7123G>A, p.G2375R) thyroglobulin (TG)mutations which are the likely cause of fetal goitre in the deceased sibling. TG mutations rarely cause fetal goitre, andmanagement remains controversial due to the potential complications of intrauterine therapy however an ameliorationin goitre size may be achieved with intraamniotic T4, and intraamniotic T3/T4 combination has achieved a favourableoutcome in one case. A conservative approach, with surveillance, elective delivery and commencement of levothyroxineneonatally may also be justified, although intubation may be required post delivery for respiratory obstruction. Ourobservations highlight the lethality which may be associated with fetal goitre. Additionally, although this complicationmay recur in successive pregnancies, our case highlights the possibility of discordance for fetal goitre in siblingsharbouring the same dyshormonogenesis-associated genetic mutations. Genetic ascertainment may facilitate prenataldiagnosis and assist management in familial cases.

[学科分类] 血液学