Thyroid & parathyroid
Thyroid endocrine abnormalities
Congenital hypothyroidism
Last author update: 1 July 2016
Last staff update: 19 February 2021
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PubMed Search: hypothyroidism cretinism
See also Aplasia / hypoplasia, Dyshormonogenetic goiter, Screening - Neonatal hypothyroidism
Table of Contents
Definition / general | Essential features | Epidemiology | Pathophysiology | Etiology | Clinical features | Diagnosis | Laboratory | Radiology description | Case reports | Treatment | Gross description | Microscopic (histologic) description | Cytology description | Differential diagnosis | Additional referencesCite this page: Chi A, Guilmette J. Congenital hypothyroidism. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/thyroidcretinism.html. Accessed April 19th, 2024.
Definition / general
- Also called cretinism
- 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)
- This topic also contains links to its two causes, Aplasia / hypoplasia and Dyshormonogenetic goiter
- 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 U.S. 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
- See also sections in these topics: Aplasia / hypoplasia and Dyshormonogenetic goiter
- 2 million children are affected globally every year (Pediatrics 2015;135:594)
- Affects one per 2,000 - 4,000 newborns (Best Pract Res Clin Endocrinol Metab 2008;22:57)
Pathophysiology
- See also sections in these topics: Aplasia / hypoplasia and Dyshormonogenetic goiter
- 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
- Mutations identified in these genes: TSHR, PAX8, NKX2-1, FOXE1 and NKX2-5
- Thyroid dyshormonogenesis affects overall thyroid hormone synthesis
- Mutations cause iodine organification defects (TPO, DUOX2, DUOXA2, SLC26A4), iodine transport defect (SLC5A5), thyroglobulin (TG) synthesis or transport defect or iodotyrosine deiodinase (IYD / DEHAL1) deficiency
- Thyroid dysgenesis (TD) results in a thyroid organogenesis defect
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
- See also sections in these topics: Aplasia / hypoplasia and Dyshormonogenetic goiter
- 95% of CH neonates are asymptomatic at birth (J Coll Physicians Surg Pak 2013;23:214)
- Unexpected death often occurs in untreated CH due to bronchoaspiration, heart failure or other organ dysfunction with serious infections (Gac Med Mex 1995;131:141)
- Signs / symptoms include impaired development of skeletal system (short, coarse facial features and protruding tongue), severe intellectual disability, GU abnormalities and congenital malformation of the lungs, forebrain and palate (J Pediatr 2009;154:263)
- Rare presenting signs are bradycardia at birth (J Coll Physicians Surg Pak 2013;23:214) or menorrhagia in adulthood (J Assoc Physicians India 2013;61:660)
- Death may occur despite therapy (Am J Dis Child 1979;133:165)
Diagnosis
- See also sections in these topics: Aplasia / hypoplasia and Dyshormonogenetic goiter
- Screening programs for congenital hypothyroidism have been developed in Canada, the United States, parts of Mexico, Western Europe, Japan, Australia and New Zealand and they are under development in parts of many countries in Eastern Europe, Asia, South America and Africa (Iran J Pediatr 2014;24:665, Arq Bras Endocrinol Metabol 2013;57:184, Pediatrics 2006;117:2290)
Laboratory
- See also sections in these topics: Aplasia / hypoplasia and Dyshormonogenetic goiter
- TSH value cut-offs in blood samples vary based on national screening guidelines (Arch Dis Child Educ Pract Ed 2015;100:260, Clin Pediatr Endocrinol 2015;24:107, Klin Padiatr 2015;227:199)
Radiology description
- See also sections in these topics: Aplasia / hypoplasia and Dyshormonogenetic goiter
- Early thyroid ultrasound examination assesses gland volume, athyreosis ("empty thyroid area"), ectopic tissue and thyroid hypoplasia (Radiol Bras 2015;48:220)
Case reports
- See also sections in these topics: Aplasia / hypoplasia and Dyshormonogenetic goiter
- 15 year old girl with congenital dyshormonogenetic hypothyroidism who presents with papillary thyroid carcinoma (Vojnosanit Pregl 2014;71:1078)
- 22 year old man with hypothyroidism and an enlarging thyroid nodule (Arq Bras Endocrinol Metabol 2014;58:958)
- 40 year old woman whose two children had congenital hypothyroidism (J Clin Endocrinol Metab 2011;96:E2039)
- 43 year old Indian man with congenital hypothyroidism treated for an unusual giant pituitary pseudotumor (BMJ Case Rep 2015 Jan 9;2015)
Treatment
- See also sections in these topics: Aplasia / hypoplasia and Dyshormonogenetic goiter
- CH patients die without treatment or despite treatment
- Immediate hormone replacement (Horm Res 2007;68 Suppl 5:107)
- Newborn screening and thyroid therapy started within two weeks of age can normalize cognitive development (Iran J Pediatr 2014;24:665)
- Nationwide salt iodization programs (J Endocrinol Invest 2015;38:185, Pediatrics 2015;135:594)
Gross description
- See also sections in these topics: Aplasia / hypoplasia and Dyshormonogenetic goiter
- 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)
Microscopic (histologic) description
- See also sections in these topics: Aplasia / hypoplasia and Dyshormonogenetic goiter
- 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
- See also sections in these topics: Aplasia / hypoplasia and Dyshormonogenetic goiter
- 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
- See also sections in these topics: Aplasia / hypoplasia and Dyshormonogenetic goiter
- On cytology, CH can mimic follicular neoplasms of the thyroid gland (Diagn Cytopathol 2013;41:720)
Additional references
