Hashimoto's thyroiditis pathophysiology: Difference between revisions
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== Pathophysiology== | == Pathophysiology== | ||
The control, synthesis, and release of the thyroid hormone is usually controlled by hypothalamus and pituitary gland.<ref name="pmid25905405">{{cite journal |vauthors=De Groot LJ, Chrousos G, Dungan K, Feingold KR, Grossman A, Hershman JM, Koch C, Korbonits M, McLachlan R, New M, Purnell J, Rebar R, Singer F, Vinik A, Rousset B, Dupuy C, Miot F, Dumont J |title=Thyroid Hormone Synthesis And Secretion |journal= |volume= |issue= |pages= |year= |pmid=25905405 |doi= |url=}}</ref><ref name="pmid11949270">{{cite journal |vauthors=Kirsten D |title=The thyroid gland: physiology and pathophysiology |journal=Neonatal Netw |volume=19 |issue=8 |pages=11–26 |year=2000 |pmid=11949270 |doi=10.1891/0730-0832.19.8.11 |url=}}</ref> | |||
* [[Thyroid hormone|Thyroid hormones (T3 and T4)]] are regulating [[basal metabolic rate]], influence [[oxygen]] consumption by tissues. They are crucial for normal development of the [[brain]] and growth of the body. | |||
* Secretion of [[thyroid hormones]] follows upper control from the [[hypothalamus]] and the [[pituitary]]. [[Thyrotropin-releasing hormone|Thyroid releasing hormone (TRH)]] acts on [[thyrotropes]] releasing cells in the [[pituitary]] causing them to release [[Thyroid-stimulating hormone|thyroid stimulating hormone (TSH)]]. | |||
* [[TSH]] acts on [[thyroid gland]] by binding to specific membrane receptors and activating an [[intracellular]] pathway involving [[cAMP]] that ends in the formation and secretion of [[thyroid hormones]]. | |||
* [[Iodine]] is essential for the synthesis of [[thyroid hormones]]. [[Iodide]] is up taken through a special Na/I transporter found in the membrane of [[thyroid]] follicular cell. After the [[iodide]] uptake, it goes through a series of organic reactions ending in the formation of the two forms of [[thyroid hormones]]: [[T3]] and [[T4]]. [[T3]] and [[T4]] remain stored in the [[thyroglobulin]] of the follicles and are released in response to further stimulation by [[TSH]] to the [[Thyroid follicle|thyroid follicles]]. | |||
* While [[T3]] is 3 to 5 times more potent than [[T4]], it represents only one-fourth of the total hormone secretion. [[T3]] is thought to be the biologically active form of the hormone. Most of the circulating [[T3]] is due to peripheral conversion of [[T4]] in the liver and peripheral tissues while only a small percentage is secreted directly from the [[thyroid gland]] itself. | |||
* [[T3]] and [[T4]] act on nuclear receptors ([[DNA]] binding [[proteins]]) and cause the regulate the [[transcription]] of many [[proteins]] to regulate the [[metabolic rate]] of the body. | |||
* The higher regulation of [[thyroxine]] secretion follows the [[negative feedback]] role, meaning that high levels of [[T3]] and [[T4]] will suppress [[TRH]] and [[TSH]] secretion and vice versa (Low levels of [[Thyroxin|thyroxine]] will stimulate [[TRH]] and [[TSH]] secretion). This is useful in diagnosing the cause of hyperthyroidism. | |||
* [[TSH]] will be low in primary hyperthyroidism where the gland is the source of the excess hormones. In secondary hyperthyroidism, [[TSH]] will be high as the [[pituitary]] or the [[hypothalamus]] are the sources of the disease. | |||
===Pathogenesis=== | |||
Thyroid cells undergo atrophy or transform into a type of [[follicular cell]] rich in [[mitochondria]] called Hurthle cell. [[Cellular immunity|Cellular]] and [[humoral immunity]] is thought to be involved in the pathophysiology of Hashimoto's thyroiditis:<ref name="pmid26361257">{{cite journal |vauthors=Ajjan RA, Weetman AP |title=The Pathogenesis of Hashimoto's Thyroiditis: Further Developments in our Understanding |journal=Horm. Metab. Res. |volume=47 |issue=10 |pages=702–10 |year=2015 |pmid=26361257 |doi=10.1055/s-0035-1548832 |url=}}</ref><ref name="pmid24434360">{{cite journal |vauthors=Caturegli P, De Remigis A, Rose NR |title=Hashimoto thyroiditis: clinical and diagnostic criteria |journal=Autoimmun Rev |volume=13 |issue=4-5 |pages=391–7 |year=2014 |pmid=24434360 |doi=10.1016/j.autrev.2014.01.007 |url=}}</ref> | Thyroid cells undergo atrophy or transform into a type of [[follicular cell]] rich in [[mitochondria]] called Hurthle cell. [[Cellular immunity|Cellular]] and [[humoral immunity]] is thought to be involved in the pathophysiology of Hashimoto's thyroiditis:<ref name="pmid26361257">{{cite journal |vauthors=Ajjan RA, Weetman AP |title=The Pathogenesis of Hashimoto's Thyroiditis: Further Developments in our Understanding |journal=Horm. Metab. Res. |volume=47 |issue=10 |pages=702–10 |year=2015 |pmid=26361257 |doi=10.1055/s-0035-1548832 |url=}}</ref><ref name="pmid24434360">{{cite journal |vauthors=Caturegli P, De Remigis A, Rose NR |title=Hashimoto thyroiditis: clinical and diagnostic criteria |journal=Autoimmun Rev |volume=13 |issue=4-5 |pages=391–7 |year=2014 |pmid=24434360 |doi=10.1016/j.autrev.2014.01.007 |url=}}</ref> | ||
===Cellular immunity=== | ====Cellular immunity==== | ||
*Defects in T suppressor cell response to thyroid-specifc antigens in autoimmune hypothyroidism resulting in failure of T suppressor function. | *Defects in T suppressor cell response to thyroid-specifc antigens in autoimmune hypothyroidism resulting in failure of T suppressor function. | ||
*[[Regulatory T cells]] like T suppressor cells also dampen the [[immune response]]. [[Regulatory T cells]] are high in [[CD25]] expression and have altered activity in Hashimoto thyroiditis. | *[[Regulatory T cells]] like T suppressor cells also dampen the [[immune response]]. [[Regulatory T cells]] are high in [[CD25]] expression and have altered activity in Hashimoto thyroiditis. | ||
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*There is an increased number of follicular [[helper T cells]] in patients Hashimoto's thyroiditis, which correlates with thyroid-specifc antibody levels. | *There is an increased number of follicular [[helper T cells]] in patients Hashimoto's thyroiditis, which correlates with thyroid-specifc antibody levels. | ||
===Humoral immunity=== | ====Humoral immunity==== | ||
*Patients with Hashimoto thyroiditis have positive antibodies against [[thyroglobulin]] (TG) and [[thyroid peroxidase]] (TPO). | *Patients with Hashimoto thyroiditis have positive antibodies against [[thyroglobulin]] (TG) and [[thyroid peroxidase]] (TPO). | ||
*Recently, a distinct variant of HT has been documented where the [[thyroid gland]] is infiltrated with IgG4-positive cells. | *Recently, a distinct variant of HT has been documented where the [[thyroid gland]] is infiltrated with IgG4-positive cells. | ||
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*The [[sodium-iodide symporter]] (NIS) mediates [[iodine]] uptake by the [[thyroid gland]], while [[pendrin]] is responsible for the efflux of [[iodine]] through [[Thyroid follicle|thyroid follicles]]. Antibodies against [[Sodium-iodide symporter|NIS]] and [[pendrin]] are also found in Hashimoto thyroiditis (HT). | *The [[sodium-iodide symporter]] (NIS) mediates [[iodine]] uptake by the [[thyroid gland]], while [[pendrin]] is responsible for the efflux of [[iodine]] through [[Thyroid follicle|thyroid follicles]]. Antibodies against [[Sodium-iodide symporter|NIS]] and [[pendrin]] are also found in Hashimoto thyroiditis (HT). | ||
===Cytokines=== | ====Cytokines==== | ||
*Increased plasma level and expressions of IL-17 and IL-22 are seen in HT. | *Increased plasma level and expressions of IL-17 and IL-22 are seen in HT. | ||
===Micro RNA=== | ===Micro RNA=== | ||
Revision as of 16:42, 6 September 2017
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Furqan M M. M.B.B.S[2]
Overview
Hashimoto's thyroiditis (HT) is characterized by lymphocytic infiltration of the thyroid gland and production of antibodies that recognize thyroid-specific antigens. The pathogenesis is not yet completely understood. Thyroid cells undergo atrophy or transform into a type of follicular cell rich in mitochondria called Hurthle cell. It is currently thought that the disease is caused by abnormalities in cellular and humoral immunity which results in a localized cell-mediated immune response directed toward the thyroid parenchymal cells. This results in the decreased production of thyroid hormones.
Pathophysiology
The control, synthesis, and release of the thyroid hormone is usually controlled by hypothalamus and pituitary gland.[1][2]
- Thyroid hormones (T3 and T4) are regulating basal metabolic rate, influence oxygen consumption by tissues. They are crucial for normal development of the brain and growth of the body.
- Secretion of thyroid hormones follows upper control from the hypothalamus and the pituitary. Thyroid releasing hormone (TRH) acts on thyrotropes releasing cells in the pituitary causing them to release thyroid stimulating hormone (TSH).
- TSH acts on thyroid gland by binding to specific membrane receptors and activating an intracellular pathway involving cAMP that ends in the formation and secretion of thyroid hormones.
- Iodine is essential for the synthesis of thyroid hormones. Iodide is up taken through a special Na/I transporter found in the membrane of thyroid follicular cell. After the iodide uptake, it goes through a series of organic reactions ending in the formation of the two forms of thyroid hormones: T3 and T4. T3 and T4 remain stored in the thyroglobulin of the follicles and are released in response to further stimulation by TSH to the thyroid follicles.
- While T3 is 3 to 5 times more potent than T4, it represents only one-fourth of the total hormone secretion. T3 is thought to be the biologically active form of the hormone. Most of the circulating T3 is due to peripheral conversion of T4 in the liver and peripheral tissues while only a small percentage is secreted directly from the thyroid gland itself.
- T3 and T4 act on nuclear receptors (DNA binding proteins) and cause the regulate the transcription of many proteins to regulate the metabolic rate of the body.
- The higher regulation of thyroxine secretion follows the negative feedback role, meaning that high levels of T3 and T4 will suppress TRH and TSH secretion and vice versa (Low levels of thyroxine will stimulate TRH and TSH secretion). This is useful in diagnosing the cause of hyperthyroidism.
- TSH will be low in primary hyperthyroidism where the gland is the source of the excess hormones. In secondary hyperthyroidism, TSH will be high as the pituitary or the hypothalamus are the sources of the disease.
Pathogenesis
Thyroid cells undergo atrophy or transform into a type of follicular cell rich in mitochondria called Hurthle cell. Cellular and humoral immunity is thought to be involved in the pathophysiology of Hashimoto's thyroiditis:[3][4]
Cellular immunity
- Defects in T suppressor cell response to thyroid-specifc antigens in autoimmune hypothyroidism resulting in failure of T suppressor function.
- Regulatory T cells like T suppressor cells also dampen the immune response. Regulatory T cells are high in CD25 expression and have altered activity in Hashimoto thyroiditis.
- CD4+ cells are less sensitive to the inhibitory effect of TGFβ in Hashimoto thyroiditis.
- There is an increased number of follicular helper T cells in patients Hashimoto's thyroiditis, which correlates with thyroid-specifc antibody levels.
Humoral immunity
- Patients with Hashimoto thyroiditis have positive antibodies against thyroglobulin (TG) and thyroid peroxidase (TPO).
- Recently, a distinct variant of HT has been documented where the thyroid gland is infiltrated with IgG4-positive cells.
- Thyroid hormone receptor antibodies might be involved in the disease presentation as sometimes thyroiditis presents as hyperthyroidism. The balance between the thyroid stimulating antibodies (TSAb) and thyroid blocking antibodies (TBAb) explains the fluctuating hormone levels in patients with Hashimoto's thyroiditis. It should also be noted that thyroid stimulating antibodies (TSAb) might have a minor blocking action.
- The sodium-iodide symporter (NIS) mediates iodine uptake by the thyroid gland, while pendrin is responsible for the efflux of iodine through thyroid follicles. Antibodies against NIS and pendrin are also found in Hashimoto thyroiditis (HT).
Cytokines
- Increased plasma level and expressions of IL-17 and IL-22 are seen in HT.
Micro RNA
- MicroRNAs (miRNA), which are small noncoding RNA regions, have also been implicated in the pathogenesis of thyroid immunity. In HT tissue, a decreased level of miR-155_2 and an increase in miR-200a1 was found.
Genetics
- A family history of thyroid disorders is common, with HLA-B* 46:01 confers an increased risk of HT developing in Han Chinese children. HLA-A* 02:07 and HLA-DRB4 conferred susceptibility. The genes implicated vary in different groups and the incidence is increased in patients with chromosomal disorders, including Down's syndrome and Turner syndrome.[3][5]
References
- ↑ De Groot LJ, Chrousos G, Dungan K, Feingold KR, Grossman A, Hershman JM, Koch C, Korbonits M, McLachlan R, New M, Purnell J, Rebar R, Singer F, Vinik A, Rousset B, Dupuy C, Miot F, Dumont J. "Thyroid Hormone Synthesis And Secretion". PMID 25905405.
- ↑ Kirsten D (2000). "The thyroid gland: physiology and pathophysiology". Neonatal Netw. 19 (8): 11–26. doi:10.1891/0730-0832.19.8.11. PMID 11949270.
- ↑ 3.0 3.1 Ajjan RA, Weetman AP (2015). "The Pathogenesis of Hashimoto's Thyroiditis: Further Developments in our Understanding". Horm. Metab. Res. 47 (10): 702–10. doi:10.1055/s-0035-1548832. PMID 26361257.
- ↑ Caturegli P, De Remigis A, Rose NR (2014). "Hashimoto thyroiditis: clinical and diagnostic criteria". Autoimmun Rev. 13 (4–5): 391–7. doi:10.1016/j.autrev.2014.01.007. PMID 24434360.
- ↑ Barbesino G, Chiovato L (2000). "The genetics of Hashimoto's disease". Endocrinol. Metab. Clin. North Am. 29 (2): 357–74. PMID 10874534.