Endocrine Abstracts

Introduction: Dual oxidase 2(DUOX2) is NADPH oxidase complex at the apical membrane of the thyroid follicular cells which produce H2O2 required for thyroid hormone synthesis. DUOX2 gene mutation is a well known cause of congenital hypothyroidism (CH), the phenotype depends on the type of mutation and environmental factors.

Case: We present a case of 29 years old female delivered a male baby with large neonatal goitre and severe CH who was started immediately on levothyroxine.Maternal thyroid function test (TFTs) showed an unusual pattern of TSH being marginally elevated at 6.4 miu/L (0.35–4.5 miu/L), Free T3 in upper normal range at 6.8 pmol/L (range 3.9–6.8 pmol/L) and Low Free T44.8 pmol/L(10.5–26 pmol/L). Similar pattern was seen when confirmed with another laboratory excluding assay interference. Random Cortisol was 579 nmol/L and serum Prolactin was appropriately raised at 1268 mIU/L being post-partum. She had benign goitre for more than 7 years. She was vegetarian and was vegan for 13 years. Subsequent TFTs in both mother and baby showed an elevated free T3/T4 ratio suggesting inadequate iodination either due to lack iodine or dyshormonogenesis. Spot urine Iodine and 24 hours urinary iodine measurement in mother showed profoundly low iodine level (0.05 micromol) suggesting severe iodine deficiency. Gene sequencing showed rare, novel heterozygous DUOX2 missense mutation (c.3956C>G, p.T1319R) in both baby and mother. Three half-brothers of the child had Wild type Variants. She was commenced on oral iodine supplement with dose titration according to urine Iodine excretion.

Discussion: DUOX2 mutation being heterozygous is less likely to cause CH however combined with environmental factor like maternal dietary Iodine deficiency could explain overt dyshormogenesis in the baby and unusual thyroid function tests with longstanding goitre in the mother. Other siblings not carrying the mutation didn’t develop neonatal goitre although they were exposed to similar maternal iodine deficiency.