Jie Zhang1, Rulai Han1, Liyun Shen1, Jing Xie2, Yuan Xiao3, Lei Jiang1, Weiwei Zhou1, Haorong Li1, Ziyuan Liu1, Yulin Zhou1, Shu Wang1, Lei Ye4, Weiqing Wang1. 1. Shanghai Key Laboratory for Endocrine Tumors, Shanghai Clinical Center for Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases and Shanghai E-institute for Endocrinology, Ruijin Hospital, Shanghai Jiao Tong University, School of Medicine, 197 Ruijin 2nd Road, Shanghai, 200025, PR China. 2. Department of Pathology, Ruijin Hospital, Shanghai Jiao Tong University, School of Medicine, 197 Ruijin 2nd Road, Shanghai, 200025, PR China. 3. Department of Pediatrics, Ruijin Hospital, Shanghai Jiao Tong University, School of Medicine, 197 Ruijin 2nd Road, Shanghai, 200025, PR China. 4. Shanghai Key Laboratory for Endocrine Tumors, Shanghai Clinical Center for Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases and Shanghai E-institute for Endocrinology, Ruijin Hospital, Shanghai Jiao Tong University, School of Medicine, 197 Ruijin 2nd Road, Shanghai, 200025, PR China. lei_yelei@163.com.
Abstract
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 (FT3) to free thyroxine (FT4) 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-T4) therapy, three patients showed gradual decline of FT3 to FT4 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.
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 (FT3) to free thyroxine (FT4) 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-T4) therapy, three patients showed gradual decline of FT3 to FT4 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.
Authors: S Pannain; R E Weiss; C E Jackson; D Dian; J C Beck; V C Sheffield; N Cox; S Refetoff Journal: J Clin Endocrinol Metab Date: 1999-03 Impact factor: 5.958