Novel heterozygous thyrotropin receptor mutation presenting with neonatal hyperthyrotropinaemia, mild thyroid hypoplasia and absent uptake on radioisotope scan

J Pediatr Endocrinol Metab. 2013;26(5-6):583-6. doi: 10.1515/jpem-2012-0308.


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.

Publication types

  • Case Reports

MeSH terms

  • Heterozygote
  • Humans
  • Infant, Newborn
  • Male
  • Point Mutation
  • Radionuclide Imaging
  • Receptors, Thyrotropin / genetics*
  • Severity of Illness Index
  • Thyroid Dysgenesis / blood
  • Thyroid Dysgenesis / diagnostic imaging*
  • Thyroid Dysgenesis / genetics*
  • Thyroid Gland / diagnostic imaging
  • Thyrotropin / blood*
  • Thyroxine / blood
  • Ultrasonography


  • Receptors, Thyrotropin
  • Thyrotropin
  • Thyroxine