title: Minimally invasive follicular thyroid carcinoma developed in dyshormonogenetic multinodular goiter due to thyroid peroxidase gene mutation.
abstract: BACKGROUND
  The occurrence of thyroid carcinoma in patients with congenital hypothyroidism (CH) caused by dyshormonogenesis is very rare, and has only been reported in one patient harboring mutations in the thyroid peroxidase (TPO) gene.
  
  
  METHODS
  We report on a 29-year follow-up of two consanguineous siblings with CH due to total iodide organification defect who also had sensorineural hearing loss. Molecular analysis revealed a novel biallelic mutation of the TPO gene in which phenylalanine substitutes serine at codon 292 (c.875C>T, p.S292F) in exon 8. Despite early initiation, adequate doses of levothyroxine treatment and consequently normal thyrotropin (TSH) levels, the proposita developed a huge multinodular goiter (MNG) and underwent total thyroidectomy due to tracheal compression. Pathological examination revealed a unifocal follicular thyroid carcinoma without vascular invasion in the left lobe of the thyroid gland.
  
  
  CONCLUSIONS
  Our finding of follicular thyroid carcinoma arising from dyshormonogenetic MNG in a patient without elevated serum TSH levels indicates that genetic and environmental factors other than TSH level might be involved in the development of thyroid carcinoma in dyshormonogenetic MNG.
  
  
  CONCLUSIONS
  Despite the rare occurrence of thyroid carcinoma in dyshormonogenetic MNG, we recommend long-term follow-up and regular neck ultrasound imaging to prevent delayed diagnosis of thyroid carcinoma.
authors.affiliation: Institute of Endocrinology, Ha'Emek Medical Center, Afula, Israel.
authors.forename: Elena
authors.initials: E
authors.lastname: Chertok Shacham
authors.forename: Avraham
authors.initials: A
authors.lastname: Ishay
authors.forename: Elmalah
authors.initials: E
authors.lastname: Irit
authors.forename: Joachim
authors.initials: J
authors.lastname: Pohlenz
authors.forename: Yardena
authors.initials: Y
authors.lastname: Tenenbaum-Rakover
mesh_terms: D018263:Adenocarcinoma, Follicular; D000328:Adult; D000483:Alleles; D003062:Codon; D005192:Family Health; D005260:Female; D005500:Follow-Up Studies; D006044:Goiter, Nodular / Q000150:complications* / Q000175:diagnosis* / Q000235:genetics; D006801:Humans; D007453:Iodide Peroxidase / Q000235:genetics*; D008297:Male; D009154:Mutation; D010649:Phenylalanine / Q000235:genetics; D035781:Siblings; D013964:Thyroid Neoplasms / Q000201:enzymology / Q000235:genetics*; D013965:Thyroidectomy / Q000379:methods; D013997:Time Factors; D014463:Ultrasonography / Q000379:methods
chemical_list: D003062:Codon; D010649:Phenylalanine; D007453:Iodide Peroxidase