Congenital hypothyroidism and thyroid dyshormonogenesis: a case report of siblings with a newly identified mutation in thyroperoxidase

J Pediatr Endocrinol Metab. 2016 May 1;29(5):627-31. doi: 10.1515/jpem-2015-0253.


Background: Thyroid dyshormonogenesis continues to be a significant cause of congenital hypothyroidism. Over time, forms of thyroid dyshormonogenesis can result in goiter, which can lead to difficult management decisions as the pathologic changes can both mimic or lead to thyroid cancer.

Methods: Herein we describe the cases of two brothers diagnosed with congenital hypothyroidism, with initial findings consistent with thyroid dyshormonogenesis. One brother eventually developed multinodular goiter with complex pathology on biopsy, resulting in thyroidectomy.

Results: Whole exome sequencing revealed the brothers carry a novel frameshift mutation in thyroperoxidase; the mutation, while not previously described, was likely both deleterious and pathogenic. Conlcusions: These cases highlight the complex pathology that can occur within thyroid dyshormonogenesis, with similar appearance to possible thyroid cancer, leading to complex management decisions. They also highlight the role that a genetic diagnosis can play in interpreting the impact of dyshormonogenesis on nodular thyroid development, and the need for long-term follow-up in these patients.

Publication types

  • Case Reports

MeSH terms

  • Autoantigens / genetics*
  • Congenital Hypothyroidism / genetics*
  • Congenital Hypothyroidism / pathology
  • Congenital Hypothyroidism / surgery
  • Humans
  • Infant, Newborn
  • Iodide Peroxidase / genetics*
  • Iron-Binding Proteins / genetics*
  • Male
  • Mutation / genetics*
  • Prognosis
  • Siblings
  • Thyroid Gland / abnormalities*
  • Thyroid Gland / metabolism
  • Thyroid Hormones / blood*
  • Thyroidectomy


  • Autoantigens
  • Iron-Binding Proteins
  • Thyroid Hormones
  • TPO protein, human
  • Iodide Peroxidase