Differential levels of thyroid peroxidase and thyroglobulin messenger ribonucleic acids in congenital goiter with defective thyroglobulin synthesis

J Endocrinol Invest. 1990 Nov;13(10):797-806. doi: 10.1007/BF03349625.


The biosynthesis of thyroid hormones requires iodide, thyroid peroxidase (TPO), thyroglobulin (Tg) and H2O2. We have studied two sisters with congenital large goiters and hypothyroidism. Perchlorate tests were negative. Serum T3 and T4 were decreased, TSH was increased and Tg was within the lower limit of normal. Biochemical and molecular studies were performed on goiter samples obtained after surgery. Tg content in both tissues was negligible. Paper chromatography of labeled iodocompounds showed a decrease in T4, and the presence of a pronase/pancreatin-resistant iodoprotein. TPO activity was normal in the tissues. Sephacryl S-300 gel filtration demonstrated labeled iodoalbumin-like protein and the absence of a Tg peak. Salting out studies of soluble protein fraction gave an abnormal pattern. Agarose gel electrophoresis showed the presence of an iodoalbumin-like protein and the absence of Tg in the tissues. This last finding was confirmed by immunoelectrophoresis. The Tg and TPO mRNAs levels were also analyzed. Dot-blot hybridization studies with pM5 (TPO cDNA) and phTgM2 (Tg cDNA) probes showed increased and decreased signals, respectively. The increase in TPO mRNA can be explained as a compensatory mechanism vis a vis an increase in serum TSH caused by decreased serum T3 and T4 due to the impairment in Tg mRNA. The Tg mRNA of both patients was further studied with four different probes covering 5' and 3' regions (phTgM1, phTgB1, phTgB2 and phTgB3). Hybridization was observed with all four probes, thus excluding a dramatic deletion defect. Northern transfer showed a clear signal of hybridization with the phTgB1 probe in the 8-9 Kb range. We may conclude that the biochemical and molecular abnormality of these patients is characterized by a decrease of Tg mRNA and of Tg translation.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Blotting, Western
  • Child
  • DNA Probes
  • Female
  • Goiter / congenital*
  • Goiter / genetics
  • Humans
  • Iodide Peroxidase / genetics*
  • Iodine Radioisotopes
  • Nucleic Acid Hybridization
  • RNA, Messenger / metabolism*
  • Thyroglobulin / biosynthesis
  • Thyroglobulin / genetics*
  • Thyrotropin / blood
  • Thyroxine / blood
  • Triiodothyronine / blood


  • DNA Probes
  • Iodine Radioisotopes
  • RNA, Messenger
  • Triiodothyronine
  • Thyrotropin
  • Thyroglobulin
  • Iodide Peroxidase
  • Thyroxine