Long-Term Outcome of Patients with TPO Mutations

Abstract

Introduction: Thyroid peroxidase (TPO) deficiency is the most common enzymatic defect causing congenital hypothyroidism (CH). We aimed to characterize the long-term outcome of patients with TPO deficiency. Methods: Clinical and genetic data were collected retrospectively. Results: Thirty-three patients with primary CH caused by TPO deficiency were enrolled. The follow-up period was up to 43 years. Over time, 20 patients (61%) developed MNG. Eight patients (24%) underwent thyroidectomy: one of them had minimal invasive follicular thyroid carcinoma. No association was found between elevated lifetime TSH levels and the development of goiter over the years. Conclusions: This cohort represents the largest long-term follow up of patients with TPO deficiency. Our results indicate that elevated TSH alone cannot explain the high rate of goiter occurrence in patients with TPO deficiency, suggesting additional factors in goiter development. The high rate of MNG development and the risk for thyroid carcinoma indicate a need for long-term follow up with annual ultrasound scans.

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

“…analysing the long-term outcome of 33 CH patients with TPO mutations showed that 61% of them developed MNG over time at an average age of 8,6 years ( 19 ) without an association with higher TSH levels. In this case series, thyroidectomy was performed in eight patients (24%) leading to the diagnosis of a minimally invasive follicular carcinoma and seven cases of follicular hyperplasia or adenoma ( 19 ). Thus, the high rate of MNG development and the risk for thyroid carcinoma indicates the need for regular ultrasound and a long-term follow up in these patients ( 19 ).…”

“…In this case series, thyroidectomy was performed in eight patients (24%) leading to the diagnosis of a minimally invasive follicular carcinoma and seven cases of follicular hyperplasia or adenoma ( 19 ). Thus, the high rate of MNG development and the risk for thyroid carcinoma indicates the need for regular ultrasound and a long-term follow up in these patients ( 19 ). Although most patients affected by PTHS develop benign nodular goiter ( 3 , 20 , 21 ), our patient underwent total thyroidectomy at the age of seven without previously performing a cytological investigation by fine-needle aspiration.…”