Cretinism pathophysiology
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Ahmed Elsaiey, MBBCH [2]
Overview
Cretinism is believed to be the result of a congenital anomaly in the thyroid gland. Cretinism can be caused by thyroid dysgenesis which is the most common cause of cretinism. Thyroid dysgenesis may be due to the absence of the thyroid gland, ectopic growth of the gland, or hypoplastic gland. Thyroid dysgenesis can be also due to mutations in genes as the TSH receptor gene, PAX8 gene, and NK2 homeobox 1. It is thought also that cretinism may be due to thyroid dyshormonogenesis. The decrease of thyroid hormone synthesis and secretion is due to impairment of thyroid peroxidase enzyme. Cretinism may be associated with some congenital anomalies like horseshoe kidney, ureterocele, hydrocele, and undescended testes.
Pathophysiology
Pathogenesis
- Cretinism is believed to be caused by a congenital anomaly in the thyroid gland.
- Different mechanisms causing congenital hypothyroidism include:
- Thyroid dysgenesis:[1]
- Thyroid dysgenesis is the most common cause of congenital hypothyroidism. It is due to the absence of the thyroid gland, ectopic growth of the thyroid gland, or hypoplastic gland.
- It is believed that thyroid dysgenesis may be caused by a mutation in some genes responsible for thyroid formation and function. These genes include the following:
- Mutation in the TSH receptor is responsible for the hypoplastic thyroid gland.
- Mutations in the paired box 8 (PAX8) gene leads to thyroid dysgenesis.
- Mutations in the transcription factors NK2 homeobox 1, transcription factor-2, and NK2 homeobox 5 genes also lead to thyroid dysgenesis.
- Thyroid dyshormonogenesis:
- It is believed that the defect in the synthesis of the thyroid hormone is another mechanism for pathogenesis of cretinism.
- The most common mechanism involved in decreased thyroid hormone synthesis and secretion is the impairment of thyroid peroxidase enzyme. This impairment leads to defect in the iodide oxidation and organification.
- Thyroid dysgenesis:[1]
Genetics
- Cretinism can occur due to genetic defects. [2]
- Mutation in sodium-iodide symporter gene can impede the iodine transportation into the thyroid follicles. This mutation decreases the synthesis of the thyroid hormone.[3]
Associated Conditions
- Cretinism may be associated with the following conditions: [4]
Gross Pathology
- There are no gross findings associated with cases of cretinism.
Microscopic Pathology
- There are no microscopic findings associated with cases of cretinism.
References
- ↑ Vilain C, Rydlewski C, Duprez L, Heinrichs C, Abramowicz M, Malvaux P; et al. (2001). “Autosomal dominant transmission of congenital thyroid hypoplasia due to loss-of-function mutation of PAX8”. J Clin Endocrinol Metab. 86 (1): 234–8. doi:10.1210/jcem.86.1.7140. PMID 11232006.
- ↑ Gillam MP, Kopp P (2001). “Genetic defects in thyroid hormone synthesis”. Curr Opin Pediatr. 13 (4): 364–72. PMID 11717564.
- ↑ Pohlenz J, Rosenthal IM, Weiss RE, Jhiang SM, Burant C, Refetoff S (1998). “Congenital hypothyroidism due to mutations in the sodium/iodide symporter. Identification of a nonsense mutation producing a downstream cryptic 3′ splice site”. J Clin Invest. 101 (5): 1028–35. doi:10.1172/JCI1504. PMC 508654. PMID 9486973.
- ↑ Carvalho A, Hermanns P, Rodrigues AL, Sousa I, Anselmo J, Bikker H; et al. (2013). “A new PAX8 mutation causing congenital hypothyroidism in three generations of a family is associated with abnormalities in the urogenital tract”. Thyroid. 23 (9): 1074–8. doi:10.1089/thy.2012.0649. PMID 23647375.
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