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Journal of Pediatric Endocrinology and Metabolism

Editor-in-Chief: Kiess, Wieland

Ed. by Bereket, Abdullah / Darendeliler, Feyza / Dattani, Mehul / Gustafsson, Jan / Luo, Fei Hong / Mericq, Veronica / Toppari, Jorma

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Volume 29, Issue 5


Congenital hypothyroidism and thyroid dyshormonogenesis: a case report of siblings with a newly identified mutation in thyroperoxidase

David P. SparlingORCID iD: http://orcid.org/0000-0001-5940-1544 / Kendra Fabian
  • Division of Pediatric Endocrinology, Diabetes, and Metabolism, Department of Pediatrics, Columbia University, New York, NY, USA
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Lara Harik / Vaidehi Jobanputra / Kwame Anyane-Yeboa / Sharon E. Oberfield
  • Division of Pediatric Endocrinology, Diabetes, and Metabolism, Department of Pediatrics, Columbia University, New York, NY, USA
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Ilene Fennoy
  • Corresponding author
  • Division of Pediatric Endocrinology, Diabetes, and Metabolism, Department of Pediatrics, Columbia University, New York, NY, USA
  • Email
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
Published Online: 2016-02-19 | DOI: https://doi.org/10.1515/jpem-2015-0253


Background: Thyroid dyshormonogenesis continues to be a significant cause of congenital hypothyroidism. Over time, forms of thyroid dyshormonogenesis can result in goiter, which can lead to difficult management decisions as the pathologic changes can both mimic or lead to thyroid cancer.

Methods: Herein we describe the cases of two brothers diagnosed with congenital hypothyroidism, with initial findings consistent with thyroid dyshormonogenesis. One brother eventually developed multinodular goiter with complex pathology on biopsy, resulting in thyroidectomy.

Results: Whole exome sequencing revealed the brothers carry a novel frameshift mutation in thyroperoxidase; the mutation, while not previously described, was likely both deleterious and pathogenic.

Conlcusions: These cases highlight the complex pathology that can occur within thyroid dyshormonogenesis, with similar appearance to possible thyroid cancer, leading to complex management decisions. They also highlight the role that a genetic diagnosis can play in interpreting the impact of dyshormonogenesis on nodular thyroid development, and the need for long-term follow-up in these patients.

Keywords: congenital hypothyroidism; multinodular goiter; thyroid dyshormonogenesis; thyroperoxidase; whole-exome sequencing


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About the article

Corresponding author: Ilene Fennoy, MD, MPH, Division of Pediatric Endocrinology, Diabetes, and Metabolism, Department of Pediatrics, Columbia University Medical Center, 622 West 168th St, PH-5E-522, New York, NY 10032, USA, Phone: +212-305-6559; Fax: +212-305-4778, E-mail:

Received: 2015-06-23

Accepted: 2015-12-14

Published Online: 2016-02-19

Published in Print: 2016-05-01

Citation Information: Journal of Pediatric Endocrinology and Metabolism, Volume 29, Issue 5, Pages 627–631, ISSN (Online) 2191-0251, ISSN (Print) 0334-018X, DOI: https://doi.org/10.1515/jpem-2015-0253.

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