Cretinism pathophysiology: Difference between revisions
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===Pathogenesis=== | ===Pathogenesis=== | ||
*It is thought that cretinism is caused by a congenital anomaly in the thyroid gland. | *It is thought that cretinism is caused by a [[congenital anomaly]] in the [[thyroid gland]]. | ||
*Different mechanisms causing congenital hypothyroidism include the following: | *Different mechanisms causing congenital hypothyroidism include the following: | ||
** Thyroid dysgenesis:<ref name="pmid11232006">{{cite journal| author=Vilain C, Rydlewski C, Duprez L, Heinrichs C, Abramowicz M, Malvaux P et al.| title=Autosomal dominant transmission of congenital thyroid hypoplasia due to loss-of-function mutation of PAX8. | journal=J Clin Endocrinol Metab | year= 2001 | volume= 86 | issue= 1 | pages= 234-8 | pmid=11232006 | doi=10.1210/jcem.86.1.7140 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11232006 }}</ref> | ** [[Thyroid dysgenesis]]:<ref name="pmid11232006">{{cite journal| author=Vilain C, Rydlewski C, Duprez L, Heinrichs C, Abramowicz M, Malvaux P et al.| title=Autosomal dominant transmission of congenital thyroid hypoplasia due to loss-of-function mutation of PAX8. | journal=J Clin Endocrinol Metab | year= 2001 | volume= 86 | issue= 1 | pages= 234-8 | pmid=11232006 | doi=10.1210/jcem.86.1.7140 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11232006 }}</ref> | ||
*** Thyroid dysgenesis is the most common cause of congenital hypothyroidism. It is due to the absence of the thyroid gland, ectopic growth of the gland, or hypoplastic gland. | *** 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 is caused by a mutation in some genes responsible for thyroid formation and function. These genes include the following: | *** It is believed that thyroid dysgenesis is 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. | **** 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 [[PAX8 gene|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. | **** [[Mutations]] in the [[Homeobox gene|transcription factors NK2 homeobox 1,]] [[transcription factor]]-2, and [[Homeobox gene|NK2 homeobox 5 genes]] also lead to thyroid dysgenesis. | ||
** Thyroid dyshormonogenesis: | ** Thyroid dyshormonogenesis: | ||
*** It is believed also that the defect in the synthesis of the thyroid hormone itself is another way of the pathogenesis of cretinism. | *** It is believed also that the defect in the synthesis of the [[thyroid hormone]] itself is another way of the pathogenesis of cretinism. | ||
*** The most common mechanism involved in decreasing thyroid hormone synthesis and secretion is the impairment of thyroid peroxidase enzyme. This impairment will lead to defect in the iodide oxidation and organification. | *** The most common mechanism involved in decreasing thyroid hormone synthesis and secretion is the impairment of thyroid peroxidase enzyme. This impairment will lead to defect in the [[iodide]] [[oxidation]] and organification. | ||
==Genetics== | ==Genetics== | ||
*Cretinism can occur due to genetic defects | *Cretinism can occur due to [[genetic defects]]. <ref name="pmid11717564">{{cite journal| author=Gillam MP, Kopp P| title=Genetic defects in thyroid hormone synthesis. | journal=Curr Opin Pediatr | year= 2001 | volume= 13 | issue= 4 | pages= 364-72 | pmid=11717564 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11717564 }}</ref> | ||
*Mutation in sodium-iodide symporter gene can impede the iodine transportation into the thyroid follicles. This mutation will decrease the synthesis of the thyroid hormone.<ref name="pmid9486973">{{cite journal| author=Pohlenz J, Rosenthal IM, Weiss RE, Jhiang SM, Burant C, Refetoff S| title=Congenital hypothyroidism due to mutations in the sodium/iodide symporter. Identification of a nonsense mutation producing a downstream cryptic 3' splice site. | journal=J Clin Invest | year= 1998 | volume= 101 | issue= 5 | pages= 1028-35 | pmid=9486973 | doi=10.1172/JCI1504 | pmc=508654 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9486973 }}</ref> | *Mutation in sodium-iodide symporter gene can impede the [[iodine]] transportation into the thyroid follicles. This mutation will decrease the synthesis of the [[thyroid hormone]].<ref name="pmid9486973">{{cite journal| author=Pohlenz J, Rosenthal IM, Weiss RE, Jhiang SM, Burant C, Refetoff S| title=Congenital hypothyroidism due to mutations in the sodium/iodide symporter. Identification of a nonsense mutation producing a downstream cryptic 3' splice site. | journal=J Clin Invest | year= 1998 | volume= 101 | issue= 5 | pages= 1028-35 | pmid=9486973 | doi=10.1172/JCI1504 | pmc=508654 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9486973 }}</ref> | ||
==Associated Conditions== | ==Associated Conditions== | ||
* Cretinism may be associated with the following conditions: <ref name="pmid23647375">{{cite journal| author=Carvalho A, Hermanns P, Rodrigues AL, Sousa I, Anselmo J, Bikker H et al.| title=A new PAX8 mutation causing congenital hypothyroidism in three generations of a family is associated with abnormalities in the urogenital tract. | journal=Thyroid | year= 2013 | volume= 23 | issue= 9 | pages= 1074-8 | pmid=23647375 | doi=10.1089/thy.2012.0649 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23647375 }}</ref> | * Cretinism may be associated with the following conditions: <ref name="pmid23647375">{{cite journal| author=Carvalho A, Hermanns P, Rodrigues AL, Sousa I, Anselmo J, Bikker H et al.| title=A new PAX8 mutation causing congenital hypothyroidism in three generations of a family is associated with abnormalities in the urogenital tract. | journal=Thyroid | year= 2013 | volume= 23 | issue= 9 | pages= 1074-8 | pmid=23647375 | doi=10.1089/thy.2012.0649 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23647375 }}</ref> | ||
** Horseshoe kidney | ** [[Horseshoe kidney]] | ||
** Ureterocele | ** [[Ureterocele]] | ||
** Undescended testes | ** [[Undescended testes]] | ||
** Hydrocele | ** [[Hydrocele]] | ||
** Cleft palate | ** [[Cleft palate]] | ||
** Bilateral choanal atresia | ** [[Choanal atresia|Bilateral choanal atresia]] | ||
** Neurologic manifestations as ataxia | ** Neurologic manifestations as [[ataxia]] | ||
==Gross Pathology== | ==Gross Pathology== | ||
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Ahmed Elsaiey, MBBCH [2]
Overview
It is thought that cretinism is 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
- It is thought that cretinism is caused by a congenital anomaly in the thyroid gland.
- Different mechanisms causing congenital hypothyroidism include the following:
- 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 is 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 also that the defect in the synthesis of the thyroid hormone itself is another way of the pathogenesis of cretinism.
- The most common mechanism involved in decreasing thyroid hormone synthesis and secretion is the impairment of thyroid peroxidase enzyme. This impairment will lead 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 will decrease the synthesis of the thyroid hormone.[3]
Associated Conditions
- Cretinism may be associated with the following conditions: [4]
- Horseshoe kidney
- Ureterocele
- Undescended testes
- Hydrocele
- Cleft palate
- Bilateral choanal atresia
- Neurologic manifestations as ataxia
Gross Pathology
- There are no gross 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.