Thyroid gland
Endocrine abnormalities
Hypothyroidism - cretinism

Author: Julie Guilmette, M.D. and Anthony Chi, M.D., Ph.D. (see Authors page)

Revised: 26 July 2016, last major update July 2016

Copyright: (c) 2002-2016, PathologyOutlines.com, Inc.

PubMed Search: Hypothyroidism [title] cretinism

Definition / General
  • Congenital hypothyroidism (CH) is a clinical condition characterized by absence of thyroid hormone secondary to abnormal thyroid gland developmental or biosynthesis disorders (J Coll Physicians Surg Pak 2013;23:214)
  • Congenital hypothyroidism is now treatable due to newborn testing, iodine supplementation and hormone replacement therapy (Pediatrics 2006;117:2290)
  • The consequence of untreated CH is a constellation of physical and mental conditions, called cretinism
  • The incidence of congenital hypothyroidism has been increasing in the US since mandated screening began (Mol Genet Metab 2007;91:268)
Essential Features
  • Congenital hypothyroidism (CH) is a preventable cause of intellectual disability (formerly mental retardation), usually caused by thyroid gland dysgenesis or agenesis
  • Rarely, CH may result from a pituitary or hypothalamic abnormality (Pediatrics 2006;117:2290)
  • Occasionally newborn thyroid abnormalities, including CH, are due to transplacental passage of medication, blocking antibodies or iodine excess / deficiency from the mother; in these cases, the abnormality is often transient (Pediatrics 2006;117:2290)
  • National screening programs allow early diagnosis and treatment (Iran J Pediatr 2014;24:665)
  • Clinically, signs and symptoms related to CH arise in early infancy and include impaired skeletal development, dwarfism, intellectual disability and GU congenital malformation (J Pediatr 2009;154:263)
  • Histological examination reveals variably size nodules with microfollicular, solid predominant and macrofollicular patterns
  • Follicular cytological atypia may be observed (Diagn Cytopathol 2013;41:720, Ann Transl Med 2013;1:21)
Epidemiology
Pathophysiology
  • Maternal hypothyroidism may cause severe mental retardation, because maternal T3 / T4 crosses the placenta and is critical to support fetal brain development before the fetal thyroid gland develops
  • Two types of congenital hypothyroidism are described (Endocr Dev 2014;26:60):
    • Thyroid dysgenesis (TD) results in a thyroid organogenesis defect
      • Five mutations identified in TSHR, PAX8, NKX2-1, FOXE1 and NKX2-5
    • Thyroid dyshormonogenesis affects overall thyroid hormone synthesis
      • Seven mutations identified causing iodine organification defect (TPO, DUOX2, DUOXA2, SLC26A4), iodine transport defect (SLC5A5), thyroglobulin (TG) synthesis or transport defect or iodotyrosine deiodinase (IYD / DEHAL1) deficiency
Etiology
  • Usually due to thyroid dysgenesis / agenesis, rarely due to inborn errors of metabolism
  • 2% of patients with CH have a positive family history
  • This disorder is usually considered to be sporadic (J Clin Endocrinol Metab 2001;86:2009)
Clinical Features
Diagnosis
Laboratory
Radiology Description
  • Early thyroid ultrasound examination assesses gland volume, athyreosis (‘empty thyroid area’), ectopic tissue and thyroid hypoplasia (Radiol Bras 2015;48:220)
Case Reports
Treatment
Gross Description
  • Enlarged multinodular thyroid gland may occur (Arq Bras Endocrinol Metabol 2014;58:958)
  • Nodules of varying size, fibrosis and occasionally hemorrhagic / cystic degenerative changes in a case of dyshormonogenetic goiter in a patient with CH and on thyroid hormone replacement therapy since early childhood (Ann Transl Med 2013;1:21)
Micro Description
  • CH patients treated with hormone replacement therapy:
    • Prominent bridging fibrosis surrounding thyroid nodules
    • Multiple thyroid nodules with different architectures, including a hypercellular microfollicular arrangement with scant colloid, hypercellular solid / trabecular nodules and macrofollicles containing colloid (Diagn Cytopathol 2013;41:720, Ann Transl Med 2013;1:21)
    • Some follicular cells may contain vacuolated cytoplasm (Phlebologie 1990;43:319)
    • Follicular cells may have bizarre, markedly enlarged hyperchromatic nuclei (Ann Transl Med 2013;1:21)
Cytology Description
  • Large syncytial aggregates of follicular cells intermixed with smaller microfollicles, some with slightly enlarged hyperchromatic nuclei
  • No intranuclear grooves or pseudoinclusions ( Diagn Cytopathol 2013;41:720)
Differential Diagnosis
Additional References