Endocrine Abstracts

Introduction: Congenital hypothiroidism (CH) is the most common neonatal endocrine disorder, affecting up to one in 1500 to 2000 newborns, if mild forms of hypothyroidism with eutopic and normal-sized thyroid gland are included. It is caused by either dysgenesis or dyshormonogenesis. Recently a novel iodide transporter, SLC26A7 (a member of the SLC26 transporter family), whose dysfunction affects thyroid hormonogenesis in humans, has been identified. The main purpose of this study is to present a case of dyshormonogenic CH due to a homozygous mutation of SLC26A7 gene (c.1883delC, p.P628Qfs*11), which has never been described before.

Case Report: Here we report a case of a 19-year-old young Tunisian male, who presented with severe hypothyroidism and a voluminous diffuse goiter appeared 2 months after his arrive in Italy at the age of 18. No other signs and symptoms of hypothyroidism, mental retardation or delayed growth were observed. Neck US confirmed the presence of diffuse goiter and no nodules or lymphadenopathys were documented. Autoimmune and infiltrative thyroid diseases were excluded and no iatrogenic/toxic causes were detected. The perchlorate discharge test showed a partial organification defect and a hormone replacement therapy was started, leading to an overt reduction of the goiter size (thyroid volume from 93.98 ml to 41.43 ml). With LT4 therapy, a rapid increase of serum FT3 compared to serum FT4 levels was observed. After stopping LT4 therapy for 2 weeks, 1 mg of iodine was administered but worsening of hypothyroidism was observed. NGS analysis showed a not yet identified homozygous mutation of SLC26A7 gene (c.1883delC, p.P628Qfs*11), which results into a stop codon in position 639 and the synthesis of a truncated protein.

Conclusions: In literature, most of CH patients with homozygous mutations of SLC26A7 were detected by neonatal screening or within the first years of life. We describe the first case of CH due to a homozygous mutation of SLC26A7 gene diagnosed during late adolescence, when the patient was 19 years old. Although the neonatal screening test was not available, the absence of intellectual retardation and his harmonic growth suggest a late onset of hypothyroidism. The administration of 1 mg of iodine for 2 weeks did not correct hypothyroidism. We suppose that other environmental factors or genetic polymorphisms of other genes involved in thyroid hormone synthesis might influence the transport of iodine into the lumen of the thyroid follicles and might have a role on the timing of onset and on severity of hypothyroidism.