Parathyroid adenoma pathophysiology: Difference between revisions
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===Pathogenesis=== | ===Pathogenesis=== | ||
* | *Parathyroid adenoma results in an increase in parathyroid hormone secretion.<ref name="pmid206143002">{{cite journal |vauthors=Wieneke JA, Smith A |title=Parathyroid adenoma |journal=Head Neck Pathol |volume=2 |issue=4 |pages=305–8 |year=2008 |pmid=20614300 |pmc=2807581 |doi=10.1007/s12105-008-0088-8 |url=}}</ref> | ||
*[[Calcium]]-sensing receptor [[expression]] in reduced in [[parathyroid adenoma]] resulting in an increase in [[calcium]] sensing set point.<ref name="pmid8995751">{{cite journal| author=Gogusev J, Duchambon P, Hory B, Giovannini M, Goureau Y, Sarfati E et al.| title=Depressed expression of calcium receptor in parathyroid gland tissue of patients with hyperparathyroidism. | journal=Kidney Int | year= 1997 | volume= 51 | issue= 1 | pages= 328-36 | pmid=8995751 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8995751 }} </ref><ref name="pmid8636374">{{cite journal| author=Kifor O, Moore FD, Wang P, Goldstein M, Vassilev P, Kifor I et al.| title=Reduced immunostaining for the extracellular Ca2+-sensing receptor in primary and uremic secondary hyperparathyroidism. | journal=J Clin Endocrinol Metab | year= 1996 | volume= 81 | issue= 4 | pages= 1598-606 | pmid=8636374 | doi=10.1210/jcem.81.4.8636374 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8636374 }} </ref> | |||
* | ====Calcium-sensing receptors==== | ||
*[[Calcium]]-sensing [[Receptor (biochemistry)|receptors]] are present on [[Parathyroid gland|parathyroid glands]]. They are a type of 7-transmembrane receptors in [[G-protein coupled receptors]] superfamily of receptors.<ref name="pmid8255296">{{cite journal| author=Brown EM, Gamba G, Riccardi D, Lombardi M, Butters R, Kifor O et al.| title=Cloning and characterization of an extracellular Ca(2+)-sensing receptor from bovine parathyroid. | journal=Nature | year= 1993 | volume= 366 | issue= 6455 | pages= 575-80 | pmid=8255296 | doi=10.1038/366575a0 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8255296 }} </ref> | |||
* | *[[Calcium]]-sensing [[Receptor (biochemistry)|receptors]] sense change in [[extracellular]] concentration of ionized [[calcium]].<ref name="pmid7791841">{{cite journal| author=Brown EM, Pollak M, Seidman CE, Seidman JG, Chou YH, Riccardi D et al.| title=Calcium-ion-sensing cell-surface receptors. | journal=N Engl J Med | year= 1995 | volume= 333 | issue= 4 | pages= 234-40 | pmid=7791841 | doi=10.1056/NEJM199507273330407 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7791841 }} </ref> | ||
*[ | *[[Calcium]]-sensing [[Receptor (biochemistry)|receptor]] [[Gene expression|expression]] in reduced in primary hyperparathyroidism ([[parathyroid adenoma]]) and secondary hyperparathyroidism.<ref name="pmid8995751">{{cite journal| author=Gogusev J, Duchambon P, Hory B, Giovannini M, Goureau Y, Sarfati E et al.| title=Depressed expression of calcium receptor in parathyroid gland tissue of patients with hyperparathyroidism. | journal=Kidney Int | year= 1997 | volume= 51 | issue= 1 | pages= 328-36 | pmid=8995751 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8995751 }} </ref> | ||
* | *This reduced [[expression]] of receptor causes an increases in [[calcium]] sensing set point.<ref name="pmid8636374">{{cite journal| author=Kifor O, Moore FD, Wang P, Goldstein M, Vassilev P, Kifor I et al.| title=Reduced immunostaining for the extracellular Ca2+-sensing receptor in primary and uremic secondary hyperparathyroidism. | journal=J Clin Endocrinol Metab | year= 1996 | volume= 81 | issue= 4 | pages= 1598-606 | pmid=8636374 | doi=10.1210/jcem.81.4.8636374 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8636374 }} </ref> | ||
* | *This in turn leads to increase in [[secretion]] of [[parathyroid hormone]] in presence on normal serum concentration of extracellular ionized [[calcium]]. | ||
==Genetics== | ==Genetics== |
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief:
Overview
The exact pathogenesis of [disease name] is not fully understood.
OR
It is thought that [disease name] is the result of / is mediated by / is produced by / is caused by either [hypothesis 1], [hypothesis 2], or [hypothesis 3].
OR
[Pathogen name] is usually transmitted via the [transmission route] route to the human host.
OR
Following transmission/ingestion, the [pathogen] uses the [entry site] to invade the [cell name] cell.
OR
[Disease or malignancy name] arises from [cell name]s, which are [cell type] cells that are normally involved in [function of cells].
OR
The progression to [disease name] usually involves the [molecular pathway].
OR
The pathophysiology of [disease/malignancy] depends on the histological subtype.
Pathophysiology
Physiology
The effect of parathyroid hormone on mineral metabolism is as follows:[1][2]
- Effect of parathyroid hormone on inorganic phosphate metabolism:
- Increases excretion of inorganic phosphate from kidney resulting in decreased serum concentration of phosphate.
- Effect on parathyroid hormone on calcium metabolism:
- Direct effect:
- Increased resorption of bones.
- Decreases excretion from kidney.
- Indirect effect:
- Increases conversion of inactive 25-hydroxy vitamin D to the active 1,25-dihydroxy vitamin D which increases absorption of calcium from gut. Decreased phosphate concentration also increases this conversion process. Vitamin D shows synergism with parathyroid hormone action on bone.
- Decreased serum inorganic phosphate concentration prevents precipitation of calcium phosphate in bones.
- Both these direct and indirect mechanism results in an increased serum calcium concentration.
- Direct effect:
- Effect of parathyroid hormone on magnesium concentration:
Effect of minerals and vitamin D on parathyroid hormone:
- Decrease in serum calcium concentration stimulates parathyroid hormone.
- Calcium provides negative feedback on parathyroid hormone.
- Magnesium provides negative feedback on parathyroid hormone.
- Vitamin D decreases the concentration of parathyroid hormone.
Parathyroid hormone | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Kidney | Bone | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Decreased excretion of magnesium | Increasead conversion of inactive 25-hydroxy vitamin D to the active 1,25-dihydroxy vitamin D | Increase excretion of inorganic phosphate | Decrease excretion of calcium | Increased resorption of bone | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Increased serum concentration of magnesium | Increased absorption of calcium from gut | Decreased serum concentration of inorganic phosphate | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Prevents precipitation of calcium phosphate in bones | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Increased serum concentration of calcium | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Pathogenesis
- Parathyroid adenoma results in an increase in parathyroid hormone secretion.[3]
- Calcium-sensing receptor expression in reduced in parathyroid adenoma resulting in an increase in calcium sensing set point.[4][5]
Calcium-sensing receptors
- Calcium-sensing receptors are present on parathyroid glands. They are a type of 7-transmembrane receptors in G-protein coupled receptors superfamily of receptors.[6]
- Calcium-sensing receptors sense change in extracellular concentration of ionized calcium.[7]
- Calcium-sensing receptor expression in reduced in primary hyperparathyroidism (parathyroid adenoma) and secondary hyperparathyroidism.[4]
- This reduced expression of receptor causes an increases in calcium sensing set point.[5]
- This in turn leads to increase in secretion of parathyroid hormone in presence on normal serum concentration of extracellular ionized calcium.
Genetics
[Disease name] is transmitted in [mode of genetic transmission] pattern.
OR
Genes involved in the pathogenesis of [disease name] include:
- [Gene1]
- [Gene2]
- [Gene3]
OR
The development of [disease name] is the result of multiple genetic mutations such as:
- [Mutation 1]
- [Mutation 2]
- [Mutation 3]
Associated Conditions
Conditions associated with [disease name] include:
- [Condition 1]
- [Condition 2]
- [Condition 3]
Gross Pathology
On gross pathology, [feature1], [feature2], and [feature3] are characteristic findings of [disease name].
Microscopic Pathology
On microscopic histopathological analysis, [feature1], [feature2], and [feature3] are characteristic findings of [disease name].
References
- ↑ HARRISON MT (1964). "INTERRELATIONSHIPS OF VITAMIN D AND PARATHYROID HORMONE IN CALCIUM HOMEOSTASIS". Postgrad Med J. 40: 497–505. PMC 2482768. PMID 14184232.
- ↑ Nussey, Stephen (2001). Endocrinology : an integrated approach. Oxford, UK Bethesda, Md: Bios NCBI. ISBN 1-85996-252-1.
- ↑ Wieneke JA, Smith A (2008). "Parathyroid adenoma". Head Neck Pathol. 2 (4): 305–8. doi:10.1007/s12105-008-0088-8. PMC 2807581. PMID 20614300.
- ↑ 4.0 4.1 Gogusev J, Duchambon P, Hory B, Giovannini M, Goureau Y, Sarfati E; et al. (1997). "Depressed expression of calcium receptor in parathyroid gland tissue of patients with hyperparathyroidism". Kidney Int. 51 (1): 328–36. PMID 8995751.
- ↑ 5.0 5.1 Kifor O, Moore FD, Wang P, Goldstein M, Vassilev P, Kifor I; et al. (1996). "Reduced immunostaining for the extracellular Ca2+-sensing receptor in primary and uremic secondary hyperparathyroidism". J Clin Endocrinol Metab. 81 (4): 1598–606. doi:10.1210/jcem.81.4.8636374. PMID 8636374.
- ↑ Brown EM, Gamba G, Riccardi D, Lombardi M, Butters R, Kifor O; et al. (1993). "Cloning and characterization of an extracellular Ca(2+)-sensing receptor from bovine parathyroid". Nature. 366 (6455): 575–80. doi:10.1038/366575a0. PMID 8255296.
- ↑ Brown EM, Pollak M, Seidman CE, Seidman JG, Chou YH, Riccardi D; et al. (1995). "Calcium-ion-sensing cell-surface receptors". N Engl J Med. 333 (4): 234–40. doi:10.1056/NEJM199507273330407. PMID 7791841.