Backround: Hereditary inborn errors of thyroid hormone synthesis account for 10-15% of congenital hypothyroidism (CH). Thyroid peroxidase (TPO) deficiency is the most common enzymatic defect with a frequency of 50-90%.
Aim: In the present study our objective was to characterize the long-term clinical outcome in patients with TPO deficiency and to assess the association between development of multinodular goiter (MNG) and the adherence to therapy.
Methods: Clinical and genetic data were collected retrospectively from birth up to 44 years. Data was aquired from the medical files of patients with TPO deficiency, followed at the Endocrine clinic at Ha'Emek Medical Center.
Results: 33 patients from 7 core families of Arab-Muslim descent were enrolled. All patients had CH due to TPO deficiency. The main symptoms at presentation were neonatal jaundice (36%), macroglossia (27%) and umbilical hernia (27%). At 1 year follow up 9 patients (27%) showed a delay in developmental milestones, although the majority had normal cognitive achievements at the time of the study. Three different mutations were identified in the TPO gene: 19 patients were homozygous to c.1618C, p. Arg540stop; 4 were homozygous to c.1478G>A, p.Gly493Ser ; 4 were compound heterozygous to both mutations and 2 were homozygous to c.875C, p.Ser292Phe. At diagnosis, 4 patients presented with goiter, however over time, 22 patients developed MNG (61%), at an average of 8.6 years. Eight patients underwent thyroidectomy, one was diagnosed with follicular thyroid carcinoma and the other seven had either follicular hyperplasia or adenoma. When comparing TSH levels between patients who developed goiter to those who did not, no correlation was found between lifetime non-adherence (TSH levels >5mIU/L) and goiter development or the need for thyroidectomy.
Conclusions: This cohort is the largest, long-term follow up of patients with TPO mutations and their clinical manifestation. Our results indicate that elevated TSH alone cannot explain the high rate of goiter development in patients with TPO mutations, suggesting that TPO itself may have a role in thyroid growth suppression. The high rate of MNG development with time and the risk for thyroid carcinoma indicates the need for long-term follow-up in these patients.
19 - 21 Sep 2019
European Society for Paediatric Endocrinology