title: Novel heterozygous thyrotropin receptor mutation presenting with neonatal hyperthyrotropinaemia, mild thyroid hypoplasia and absent uptake on radioisotope scan.
abstract: Hyperthyrotropinaemia [mildly elevated thyrotropin (TSH) with normal thyroxine (T4) levels] demands a full assessment, including clinical examination, thyroid imaging and, where indicated, molecular genetic investigations. A male infant, both of whose parents were on T4 treatment, was referred at age 57 days with mild but persistent TSH elevation (12.7 mU/L) and normal free T4 (19.6 pmol/L), following notification by the screening laboratory of a capillary TSH of 10.7 mU/L (reference range, 1.7-9.1 mU/L) on day 8. Assessment showed a venous free T4 level of 15 pmol/L, venous TSH of 20.9 mU/L, serum thyroglobulin of 63 μg/L (reference range, <50 μg/L), and negative thyroglobulin and thyroid peroxidase antibodies. Thyroid ultrasound showed a eutopic, slightly small gland with heterogeneous texture; however, there was no uptake on radioisotope scan. Molecular genetic studies demonstrated a novel missense heterozygous mutation in the TSH receptor (TSHR) gene (c.1169G>T;p.Cys390Phe) in the child, mother and maternal grandmother, but not in the father. The infant was treated with T4 but this was discontinued at age 3 years when repeat testing showed a free T4 of 16.7 pmol/L (reference range, 9-23 pmol/L) and TSH of 8.5 mU/L (reference range, 0.3-5.5 mU/L). A heterozygous TSHR mutation should be considered in the context of hyperthyrotropinaemia and reduced/absent uptake on radioisotope scan. Detection of this mutation has allowed our patient to discontinue T4 treatment for the moment, with a view to staying off treatment in the long-term.
authors: Child Health Unit, School of Medicine, Royal Hospital for Sick Children, Glasgow G3 8SJ, UK.
authors: Angela
authors: A
authors: Lucas-Herald
authors: Therese
authors: T
authors: Bradley
authors: Pia
authors: P
authors: Hermanns
authors: Jeremy
authors: J
authors: Jones
authors: Morag
authors: M
authors: Attaie
authors: Elaine
authors: E
authors: Thompson
authors: Joachim
authors: J
authors: Pohlenz
authors: Malcolm
authors: M
authors: Donaldson
mesh_terms: D006579:Heterozygote; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D017354:Point Mutation; D011877:Radionuclide Imaging; D011989:Receptors, Thyrotropin / Q000235:genetics*; D012720:Severity of Illness Index; D050033:Thyroid Dysgenesis / Q000097:blood / Q000000981:diagnostic imaging* / Q000235:genetics*; D013961:Thyroid Gland / Q000000981:diagnostic imaging; D013972:Thyrotropin / Q000097:blood*; D013974:Thyroxine / Q000097:blood; D014463:Ultrasonography
chemical_list: D011989:Receptors, Thyrotropin; D013972:Thyrotropin; D013974:Thyroxine