Endocrine Abstracts (2016) 45 OC2.1 | DOI: 10.1530/endoabs.45.OC2.1

Dyshormonogenesis secondary to two thyroglobulin gene mutations

Elspeth Ferguson & Paul Dimitri


Department of Endocrinology, Sheffield Children’s NHS Foundation Trust, Sheffield, UK.


Introduction: Dyshormonogenesis accounts for approximately 10–15% of cases of congenital hypothyroidism. Although relatively uncommon, the presence of a neonatal goitre should raise suspicion of thyroid dyshormonogenesis. Advances in genomic sequencing have identified errors at all stages of the thyroid hormone synthesis pathway. We present a case of a fetal goitre with the infant subsequently being diagnosed with dyhormonogenesis secondary to two separate thyroglobulin gene mutations.

Case Report: At twenty weeks gestation, routine fetal ultrasonography identified the presence of an anterior neck mass. Fetal goitre was subsequently confirmed on antenatal MRI scan. Maternal history was unremarkable. Maternal thyroid function was normal and maternal thyroid antibodies were negative.

At birth, a goitre was present but there was no evidence of airway compromise. Thyroid function tests performed after delivery revealed TSH >100 mIU/l and T4 1.9 pmol/l. An ultrasound of the neck showed enlargement of the thyroid gland, no mass and no evidence of surrounding vessel or tracheal compression. A diagnosis of congenital hypothyroidism secondary to dyshormonogenesis was made. The infant was commenced on thyroxine and within four weeks thyroid function normalised.

In the first two years of life, TSH proved to be unstable, with T4 in normal range, despite good compliance. Consumption of even small amounts of milk in close proximity to thyroxine dosing were found to have a significant effect on thyroxine absorption in this patient.

Subsequent genetic investigation revealed the patient has a compound heterozygote mutation in the thyroglobulin gene (P.R296X/P.R787X), with both parents confirmed as being a heterozygote for mutations within separate parts of the gene.

Conclusions: This case demonstrates the process of investigation of fetal/neonatal goitres and allows revision of the thyroid hormone synthesis pathway. The diagnosis of dyshormonogenesis is discussed along with highlighting the problems with thyroxine absorption due to consumption of certain foods.

Article tools

My recent searches

No recent searches.

My recently viewed abstracts