Mild TPO deficiency characterized by progressive goiter and normal serum TSH level.

Purpose: Mild thyroid peroxidase (TPO) deficiency is rare and can be extremely occult. This study aimed to replenish the phenotypic and genetic spectrum of mild TPO deficiency.

Methods: Four unrelated patients with progressive goiter were described in this study. Genes associated with congenital hypothyroidism were analyzed and in vitro functional experiments were conducted to evaluate the residual TPO enzyme activities of each mutant.

Results: The four patients (age: 5-27 years old) were characterized by progressive goiter, discordant alteration in thyroid hormones with free triiodothyronine (FT) to free thyroxine (FT) ratio ranging from 0.557 to 1.012, two with slightly elevated TSH level and two with normal TSH level. Six different mutations of TPO gene were identified including three novel mutations (p.Glu337Lys, p.Ala544Val, and p.Glu641Lysfs∗21). Two mutants (p.Asp224del and p.Ala544Val) with residual TPO activity of 41 and 65% may explain the mild TPO-deficient picture in our study. After levothyroxine (L-T) therapy, three patients showed gradual decline of FT3 to FT ratio and two patients showed reduced thyroid size.

Conclusion: Patients with mild TPO deficiency can present with progressive goiter, normal TSH level, and largely reserved TPO activities.