Intrauterine Diagnosis and Management of Fetal Goitrous Hypothyroidism: A Report of an Iranian Family with Three Consecutive Pregnancies Complicated by Fetal Goiter

Abstract

The diagnosis and treatment of hypothyroidism during the fetal period may decrease perinatal morbidity and are believed to be important to optimize growth and intellectual development. Herewith a case report of fetal goitrous hypothyroidism is presented in a euthyroid mother, detected at 34 weeks' gestation by ultrasonography, and treated with intra-amniotic levothyroxine injections. The mother had two previous consecutive pregnancies (13 and 8 years ago), also complicated by the occurrence of fetal goiter, resulting in tracheal compression, asphyxia, and early neonatal death in the first and in an emergency cesarean section delivery, because of fetal malpresentation, in the second neonate affected by congenital hypothyroidism (CH). The present male newborn, although born without observable goiter, had a large thyroid on ultrasonography and an early rise of his peripheral venous blood thyrotropin confirmed the diagnosis of CH. Low serum thyroglobulin in the proband and his older brother and parental consanguinity was mostly compatible with a thyroglobulin defective synthesis and secretion as the cause of CH and fetal goiter. Despite apparently sufficient dose of intraamniotic levothyroxine injections repeated weekly from 34-37 weeks' gestation (i.e., four injections of 500 microg levothyroxine), neonatal bone age on the second day of life showed delayed skeletal maturation.

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

“…Although biallelic TG mutations commonly underlie CH due to dyshormonogenesis, their absolute frequency is low, and fetal goitre is a rare complication which may be associated with significant morbidity (3, 7, 8). The proband in this family harboured compound heteroygous TG mutations, and although the stillborn fetus was not genotyped, his goitrous hypothyroidism in utero supports an identical genetic diagnosis.…”

“…Fetal goitre has been reported in association with TG and TPO mutations however both discordance and recurrence in successive pregnancies has been documented (2, 3, 10). A genetic diagnosis in the kindred enabled us to counsel the parents that future offspring had a 25% probability of inheriting biallelic mutations and developing CH with a consequent risk of fetal goitre.…”

“…Treatment response is assessed by monitoring goitre size and resolution of polyhydramnios, sometimes in addition to sequential fetal thyroid hormone measurements. 3D ultrasonography may prove a superior tool to standard techniques in monitoring fetal goitre size in the future (3, 2, 4, 14). The optimal dosing regimen for intraamniotic therapy and effect on neonatal thyroid hormone status remains undefined, and associated complications include premature delivery, intrauterine infection and death.…”

“…Significant fetal hypothyroid goitre is a rare conse­quence of fetal dyshormonogenesis, and complications include polyhydramnios due to oesophageal compression and malpresentation due to neck hyperextension at delivery; additionally, neonatal tracheal compression may cause fatal respiratory compromise (3, 4). The infrequent occurrence of non-autoimmune fetal hypothyroid goitre and the risks associated with intrauterine diagnosis and therapy have precluded large-scale studies of optimal treatment.…”

Iodine-Induced Fetal Hypothyroidism: Diagnosis and Treatment with Intra-Amniotic Levothyroxine

“…A fetal goiter can be diagnosed by antenatal ultrasound[5]. Intra-amniotic levothyroxine injections have been utilized to treat fetal hypothyroidism and goiter [6-8]. However, the impact of intrauterine therapy on neurodevelopmental outcome remains controversial [7, 9].…”