Background: The familial non-autoimmune hyperthyroidism (FNAH) is a hereditary disease caused by dominant activating mutations of the TSH receptor (TSHR) gene and rare in the paediatric population.
Case presentation: A 20-month girl was referred for tachycardia. In personal history, she was delivered at 35 weeks of gestation by caesarean for fœtal tachycardia; she had been hospitalised at 1 and 5 months for diarrhoea and tachycardia was noticed. Clinically she presented with advanced growth (+2 SDS) and bone age (5 years), hypotrophy, craniostenosis, hyperactivity but motor delay by proximal amyotrophy. Discrete ophthalmopathy was observed. Lab tests revealed severe hyperthyroidism with free T3 >20 pg/ml, free T4: 52 pg/ml and TSH: 0.005 μU/ml. No anti-TSHR antibody was identified. Ultrasonography showed diffuse enlargement of thyroid gland (volume: 4 cm3, normal <2.5 cm3 for age). In familial history, father and fathers mother have been treated for hyperthyroidism: surgery was performed once for father with total thyroidectomy (with papillary microcarcinoma) and twice for grandmother for voluminous and recurrent toxic goiter. Because of similar advanced growth, her 5-year old sister was tested and presented less severe hormonal (fT3: 15.3 pg/ml, fT4 40 pg/ml, TSH 0.006 μU/ml) and ultrasonography presentation. Treatment with thiamazole was initiated (1 mg/kg per day) and hyperthyroidism was partially controlled. We identified in the proband, her sister, father and grandmother a germinal heterozygous mutation in exon 10 of the TSHR gene; mutation C678W resulting for a cysteine to tryptophan substitution. Functional in vitro studies are on-going to explore the role of this residue in the modulation of TSHR activity. Interestingly, these four family members presented with mitral valve prolapse, as previously described in FNAH patients with C639 mutation.
Conclusion: We report a French family with severe FNAH caused by a new germinal mutation in TDM7 of TSHR gene.
01 - 03 Oct 2015
European Society for Paediatric Endocrinology