Case Report - Multinodular goiter in a patient with Congenital Hypothyroidism and Bannayan-Riley-Ruvalcaba syndrome: the possible synergic role of TPO and PTEN mutation

Front Endocrinol (Lausanne). 2023 Jun 8:14:1205785. doi: 10.3389/fendo.2023.1205785. eCollection 2023.


We report the case of a paediatric female patient affected by Bannayan-Riley-Ruvalcaba syndrome (BRRS) and congenital hypothyroidism (CH) with homozygous mutation of the TPO gene. She underwent total thyroidectomy at the age of seven years because of the development of a multinodular goiter. BRRS patients present an increased risk of benign and malignant thyroid disease since childhood because of inactivating mutation of PTEN, an onco-suppressor gene. Instead, homozygous mutations in the TPO gene can be associated with severe forms of hypothyroidism with goiter; previous studies have described cases of follicular and papillary thyroid cancer in CH patients with TPO mutation despite a perfectly controlled thyroid function with Levothyroxine therapy. To our knowledge, this is the first case that describes the possible synergic role of coexisting mutation of both TPO and PTEN in the development of multinodular goiter underlining the importance of a tailored surveillance program in these patients, especially during childhood.

Keywords: PTEN hamartoma tumor syndrome; TPO; case report; congenital hypothyroidism; goiter.

Publication types

  • Case Reports

MeSH terms

  • Child
  • Congenital Hypothyroidism* / complications
  • Congenital Hypothyroidism* / genetics
  • Female
  • Goiter* / complications
  • Goiter* / genetics
  • Goiter* / surgery
  • Hamartoma Syndrome, Multiple* / complications
  • Hamartoma Syndrome, Multiple* / genetics
  • Hamartoma Syndrome, Multiple* / pathology
  • Humans
  • Mutation
  • PTEN Phosphohydrolase / genetics
  • Thyroid Neoplasms*


  • PTEN protein, human
  • PTEN Phosphohydrolase