Background: Congenital hypothyroidism (CH) is a heterogeneous disorder. While the great majority of cases are considered sporadic, the use of next generation sequencing (NGS) may bring significant advances in elucidating the underlying molecular mechanisms.
Case presentation: We selected a family with three children affected by CH with gland in situ and diagnosed at neonatal screening: the index patient, his sister and his brother. Data at diagnosis and follow-up are listed in the Table 1. They present an important familiarity for thyroid diseases. The mother and her sister have a multinodular goiter in euthyroidism without anti-thyroid antibodies; the mothers thyroglobulin (TG) level is 126 ng/ml (range 060 ng/ml). In addition, the maternal grandfather developed a multinodular goiter with a Plummer adenoma requiring thyroidectomy. All family members have an adequate dietary iodine intake. NGS analysis revealed a heterozygous missense mutation (p.P118L) in the TG gene of the three siblings and of their mother. The other analyzed genes (NKX2-1, PAX8, FOXE1, GLIS3, DUOX2, DUOXA2, SLC26A4, TPO, TSHR, and JAG1) resulted WT.
|Patient||I spot TSH (mcIU/ml)||Serum TSH (mcIU/ml)||Serum FT4 (ng/dl)||Thyroglobulin (ng/ml)||US||L-thyroxine therapy at diagnosis||Re-evaluation||Range of TSH values without therapy (mcIU/ml)|
|Index patient (2013)||10.01||16.911.07||1.21.07||189 (0.255)||Normal||No||No||5.611.7|
|Sister (2005)||12.5||42.8||1.15||148 (0.255)||Normal||Yes||Stopped L-T4||7.3214.71|
|Brother (2002)||10.7||19.51||1.1||34.8 (175)||Normal||Yes||Stopped L-T4||6.3910.25|
Conclusions: According to the identification of the genetic variant in TG with a strong positive family history for multinodular goiter, an adequate ultrasound follow-up and a tailored therapeutic strategy are needed. Indeed, these patients could benefit from hormone replacement therapy with levothyroxine, even in case of a mild increase in TSH concentrations, in order to avoid thyroid surgery in the future.
01 - 03 Oct 2015
European Society for Paediatric Endocrinology