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[[Image:Parathyroid gland high mag.jpg|thumb|right|280px|[[Micrograph]] of a parathyroid gland. [[H&E stain]].]] | |||
The '''parathyroid glands''' are an endocrine organ that is important in calcium regulation. They often make an appearance in the context of [[thyroid surgery]]. | The '''parathyroid glands''' are an endocrine organ that is important in calcium regulation. They often make an appearance in the context of [[thyroid surgery]]. | ||
They produce parathyroid hormone (PTH). PTH acts to increase serum calcium and is important in the regulation of the calcium balance. | |||
=Clinical= | =Clinical= | ||
== | ==Hyperparathyroidism== | ||
*Definition: increased secretion of ''parathyroid hormone'' (PTH).<ref name=emed_hyperparathyroid>URL: [http://emedicine.medscape.com/article/127351-overview http://emedicine.medscape.com/article/127351-overview]. Accessed on: 24 January 2013.</ref> | |||
What PTH does:<ref name=emed_hyperparathyroid>URL: [http://emedicine.medscape.com/article/127351-overview http://emedicine.medscape.com/article/127351-overview]. Accessed on: 24 January 2013.</ref> | |||
*Increase serum calcium. | |||
*Decrease serum phosphate. | |||
===Classification=== | ===Classification=== | ||
*Primary. | *Primary. | ||
*Secondary. | *Secondary. | ||
*Tertiary. | *Tertiary. | ||
====Overview in a table==== | |||
{| class="wikitable sortable" | |||
! Type | |||
! PTH | |||
! Calcium | |||
! Common causes | |||
|- | |||
| Primary hyperparathyroidism | |||
| high | |||
| high | |||
| [[parathyroid adenoma]] (~85-90% of cases), [[parathyroid hyperplasia]] (~10-15% of cases) | |||
|- | |||
| Secondary hyperparathyroidism | |||
| high | |||
| low or normal | |||
| chronic renal failure, vitamin D deficiency<ref name=emed_hyperparathyroid_2ndary>URL: [http://emedicine.medscape.com/article/127351-overview#aw2aab6b5 http://emedicine.medscape.com/article/127351-overview#aw2aab6b5]. Accessed on: 24 January 2013.</ref> | |||
|- | |||
| Tertiary hyperparathyroidism | |||
| high | |||
| high | |||
| persistent hyperparathyroidism after renal transplant;<ref name=emed_hyperparathyroid_tertiary>URL: [http://emedicine.medscape.com/article/127351-overview#aw2aab6b6 http://emedicine.medscape.com/article/127351-overview#aw2aab6b6]. Accessed on: 24 January 2013.</ref> arises in the context of secondary hyperparathyroidism<ref name=pmid26163537>{{Cite journal | last1 = Duan | first1 = K. | last2 = Gomez Hernandez | first2 = K. | last3 = Mete | first3 = O. | title = Clinicopathological correlates of hyperparathyroidism. | journal = J Clin Pathol | volume = 68 | issue = 10 | pages = 771-87 | month = Oct | year = 2015 | doi = 10.1136/jclinpath-2015-203186 | PMID = 26163537 }}</ref> | |||
|} | |||
====Genetics==== | |||
Genes implicated in hyperparathyroidism:<ref name=pmid22187299>{{Cite journal | last1 = Starker | first1 = LF. | last2 = Akerström | first2 = T. | last3 = Long | first3 = WD. | last4 = Delgado-Verdugo | first4 = A. | last5 = Donovan | first5 = P. | last6 = Udelsman | first6 = R. | last7 = Lifton | first7 = RP. | last8 = Carling | first8 = T. | title = Frequent germ-line mutations of the MEN1, CASR, and HRPT2/CDC73 genes in young patients with clinically non-familial primary hyperparathyroidism. | journal = Horm Cancer | volume = 3 | issue = 1-2 | pages = 44-51 | month = Apr | year = 2012 | doi = 10.1007/s12672-011-0100-8 | PMID = 22187299 }}</ref><ref name=pmid23652676>{{Cite journal | last1 = Hendy | first1 = GN. | last2 = Cole | first2 = DE. | title = Genetic defects associated with familial and sporadic hyperparathyroidism. | journal = Front Horm Res | volume = 41 | issue = | pages = 149-65 | month = | year = 2013 | doi = 10.1159/000345675 | PMID = 23652676 }}</ref> | |||
*MEN1. | |||
*CASR. | |||
*HRPT2/CDC73. | |||
*CDKN1B. | |||
*RET. | |||
====Hypercalcemia DDx==== | |||
Mnemonic ''GRIMED'':<ref>{{Ref TN2006| Emerg.}}</ref> | |||
*Granulomatous disease ([[tuberculosis]], [[sarcoidosis]]). | |||
*Renal disease. | |||
*Immobility. | |||
*Malignancy (esp. squamous cell carcinoma, [[plasmacytoma]]). | |||
*Endocrine (primary hyperparathyroidism, tertiary hyperparathyroidism, familial hypocalciuric hypercalcemia (FHH)). | |||
*Drugs (thiazides ... others). | |||
Note: | |||
*Hyperparathyroidism and FHH are assoc. with an increased PTH.<ref name=Ref_PBoD8_1129>{{Ref PBoD8|1129}}</ref> | |||
**Other causes are assoc. with a decreased PTH. | |||
====Primary hyperparathyroidism==== | ====Primary hyperparathyroidism==== | ||
Line 16: | Line 69: | ||
Familial causes of primary hyperparathyroidism: | Familial causes of primary hyperparathyroidism: | ||
*[[MEN 1]]. | *[[MEN 1]]. | ||
*[[MEN | *[[MEN 2A]]. | ||
*Familial hypocalciuric hypercalcemia. | *Familial hypocalciuric hypercalcemia. | ||
**Autosomal dominant. | **Autosomal dominant. | ||
**CASR (calcium sensing receptor) gene defect.<ref name=omim601199>{{OMIM|601199}}</ref> | **CASR (calcium sensing receptor) gene defect.<ref name=omim601199>{{OMIM|601199}}</ref> | ||
=== | Classic manifestations ''moans, stones, bones, (abdominal) groans, psychiatric overtones''.<ref>{{Cite journal | last1 = Lienert | first1 = D. | last2 = Rege | first2 = S. | title = Moans, stones, groans, bones and psychiatric overtones: lithium-induced hyperparathyroidism. | journal = Aust N Z J Psychiatry | volume = 42 | issue = 2 | pages = 171-3 | month = Feb | year = 2008 | doi = | PMID = 18350681 }} | ||
</ref><ref>URL: [http://www.usmleforum.com/files/forum/2010/1/505388.php http://www.usmleforum.com/files/forum/2010/1/505388.php]. Accessed on: 4 December 2011.</ref> | |||
* | *Moans = bone pain. | ||
* | *Stones = [[nephrolithiasis]] (kidney stones). | ||
* | *Bones = bone pathology, e.g. osteitis fibrosa cystica.<ref>{{Cite journal | last1 = França | first1 = TC. | last2 = Griz | first2 = L. | last3 = Pinho | first3 = J. | last4 = Diniz | first4 = ET. | last5 = Andrade | first5 = LD. | last6 = Lucena | first6 = CS. | last7 = Beserra | first7 = SR. | last8 = Asano | first8 = NM. | last9 = Duarte | first9 = AP. | title = Bisphosphonates can reduce bone hunger after parathyroidectomy in patients with primary hyperparathyroidism and osteitis fibrosa cystica. | journal = Rev Bras Reumatol | volume = 51 | issue = 2 | pages = 131-7 | month = Apr | year = 2011 | doi = | PMID = 21584419 }}</ref> | ||
* | *Groans = constipation. | ||
* | *Psychiatric overtones = CNS pathology. | ||
* | **Can include: lethargy, fatigue, depression, memory loss, psychosis, ataxia, delirium, and coma. | ||
==Hypoparathyroidism== | |||
*Rare vis-à-vis hyperparathyroidism. | |||
*Classically iatrogenic, i.e. the surgeon removing 'em.<ref name=Ref_PBoD8_1129>{{Ref PBoD8|1129}}</ref> | |||
Other causes:<ref name=Ref_PBoD8_1130>{{Ref PBoD8|1130}}</ref> | |||
* | *Autoimmune hypoparathyroidism. | ||
*Autosomal dominat hypoparathyroidism. | |||
*Familial isolated hypoparathyroidism. | |||
*Congenital absence ([[DiGeorge syndrome]]). | |||
*Drugs - [[proton pump inhibitors]].<ref name=pmid24736034>{{Cite journal | last1 = Deroux | first1 = A. | last2 = Khouri | first2 = C. | last3 = Chabre | first3 = O. | last4 = Bouillet | first4 = L. | last5 = Casez | first5 = O. | title = Severe acute neurological symptoms related to proton pump inhibitors induced hypomagnesemia responsible for profound hypoparathyroidism with hypocalcemia. | journal = Clin Res Hepatol Gastroenterol | volume = 38 | issue = 5 | pages = e103-5 | month = Oct | year = 2014 | doi = 10.1016/j.clinre.2014.03.005 | PMID = 24736034 }}</ref><ref name=pmid25138239>{{Cite journal | last1 = Toh | first1 = JW. | last2 = Ong | first2 = E. | last3 = Wilson | first3 = R. | title = Hypomagnesaemia associated with long-term use of proton pump inhibitors. | journal = Gastroenterol Rep (Oxf) | volume = | issue = | pages = | month = Aug | year = 2014 | doi = 10.1093/gastro/gou054 | PMID = 25138239 }}</ref> | |||
=Normal parathyroid glands= | =Normal parathyroid glands= | ||
:The [[cytology]] is dealt with in ''[[normal parathyroid cytology]]''. | |||
===General=== | ===General=== | ||
*Identification of normal can be tricky. | *Identification of normal can be tricky. | ||
Line 53: | Line 114: | ||
***Chief cells - predominant cell type, small, cytoplasm has variable staining (hyperchromatic-clear-eosinophilic). | ***Chief cells - predominant cell type, small, cytoplasm has variable staining (hyperchromatic-clear-eosinophilic). | ||
***Oxyphil cells (''acid staining'' cells<ref>[http://dictionary.reference.com/search?q=oxyphil%20cell http://dictionary.reference.com/search?q=oxyphil%20cell]</ref>) - abundant cytoplasm. | ***Oxyphil cells (''acid staining'' cells<ref>[http://dictionary.reference.com/search?q=oxyphil%20cell http://dictionary.reference.com/search?q=oxyphil%20cell]</ref>) - abundant cytoplasm. | ||
***Adipocytes - | ***Adipocytes - dependent on age, body habitus, PT hormone, size of gland.<ref name=pmid7551007>{{Cite journal | last1 = Iwasaki | first1 = A. | last2 = Shan | first2 = L. | last3 = Kawano | first3 = I. | last4 = Nakamura | first4 = M. | last5 = Utsuno | first5 = H. | last6 = Kobayashi | first6 = A. | last7 = Kuma | first7 = K. | last8 = Kakudo | first8 = K. | title = Quantitative analysis of stromal fat content of human parathyroid glands associated with thyroid diseases using computer image analysis. | journal = Pathol Int | volume = 45 | issue = 7 | pages = 483-6 | month = Jul | year = 1995 | doi = | PMID = 7551007 }}</ref> | ||
****Increased with age, may be used to help differentiate from thyroid - '''key feature'''. | |||
====Images==== | |||
<gallery> | |||
Image:Parathyroid_gland_intermed_mag.jpg | Parathyroid gland - intermed. mag. (WC) | |||
Image:Parathyroid_gland_high_mag.jpg | Parathyroid gland - cropped - high mag. (WC) | |||
Image:Parathyroid_gland_high_mag_cropped.jpg | Parathyroid gland - high mag. (WC) | |||
</gallery> | |||
www: | |||
*[http://library.med.utah.edu/WebPath/ENDOHTML/ENDO031.html Parathyroid - med.utah.edu]. | |||
*[http://pathology.mc.duke.edu/research/PTH225.html Histology - several images. - pathology.mc.duke.edu]. | |||
====Parathyroid cell types==== | |||
{| class="wikitable" | {| class="wikitable" | ||
! Name | |||
! Staining (cytoplasm) | |||
! Quantity of cells | |||
! Cytoplasm (quantity) | |||
! Function | |||
! Image | |||
|- | |||
| (parathyroid) chief cells | |||
| intense hyperchromatic to eosinophilic (see note) | |||
| abundant | |||
| moderate | |||
| manufacture parathyroid <br>hormone (PTH) | |||
| [[Image:Parathyroid adenoma - chief cells -- high mag.jpg|thumb|center|85px|Chief cells (WC)]] | |||
|- | |||
| oxyphil cells | |||
| moderate/light hyperchromatic to eosinophilic | |||
| rare | |||
| abundant | |||
| ? | |||
| [[Image:Parathyroid adenoma - oxyphil cells -- high mag.jpg|thumb|center|85px|Oxyphil cells (WC)]] | |||
|} | |} | ||
Notes: | Notes: | ||
*Cytoplasmic staining varies considerably on H&E preparations - it may vary from hyperchromatic<ref>[http://www.deltagen.com/target/histologyatlas/atlas_files/endocrine/parathyroid_and_thyroid_glands_20x.jpg http://www.deltagen.com/target/histologyatlas/atlas_files/endocrine/parathyroid_and_thyroid_glands_20x.jpg]</ref> to clear to eosinophilic<ref>[http://instruction.cvhs.okstate.edu/Histology/HistologyReference/hrendo.htm http://instruction.cvhs.okstate.edu/Histology/HistologyReference/hrendo.htm]</ref> | *Cytoplasmic staining varies considerably on H&E preparations - it may vary from hyperchromatic<ref>[http://www.deltagen.com/target/histologyatlas/atlas_files/endocrine/parathyroid_and_thyroid_glands_20x.jpg http://www.deltagen.com/target/histologyatlas/atlas_files/endocrine/parathyroid_and_thyroid_glands_20x.jpg]</ref> to clear to eosinophilic.<ref>[http://instruction.cvhs.okstate.edu/Histology/HistologyReference/hrendo.htm http://instruction.cvhs.okstate.edu/Histology/HistologyReference/hrendo.htm]</ref> | ||
*Chief cells tend to stain more intensely than oxyphil cells. | *Chief cells tend to stain more intensely than oxyphil cells. | ||
Thyroid | ====Thyroid versus parathyroid==== | ||
*Parathyroid cytoplasm: | *Parathyroid cytoplasm: | ||
**Hyperchromatic. | **Hyperchromatic. | ||
Notes: | |||
*Thyroid often has birefringent (calcium oxalate) crystals (60 of 80 cases) whereas parathyroid less often does (2 or 20 cases).<ref name=pmid24618617>{{cite journal |authors=Wong KS, Lewis JS, Gottipati S, Chernock RD |title=Utility of birefringent crystal identification by polarized light microscopy in distinguishing thyroid from parathyroid tissue on intraoperative frozen sections |journal=Am J Surg Pathol |volume=38 |issue=9 |pages=1212–9 |date=September 2014 |pmid=24618617 |doi=10.1097/PAS.0000000000000204 |url=}}</ref> | |||
*Thyroid usually follicular - though parathyroid occasionally is pseudofollicular. | |||
====Parathyroid versus lymphoid tissue==== | |||
*Parathyroid: | *Parathyroid: | ||
**No germinal centres. | **No germinal centres. | ||
**Gland-like/follicular-like arrangement | **Gland-like/follicular-like arrangement may be present but usually much smaller than normal thyroid follicles. | ||
***May be confused with thyroid microfollicules. | |||
**Occasional cell with rim of clear cytoplasm (oxyphil?). | **Occasional cell with rim of clear cytoplasm (oxyphil?). | ||
**Nuclei are different: | |||
***Slightly larger than in lymphocytes (1.2-1.5x the size) | |||
***Stippled chromatin (unlike lymphocytes). | |||
Images: | Images: | ||
*[http:// | *[http://www.deltagen.com/target/histologyatlas/atlas_files/endocrine/parathyroid_and_thyroid_glands_20x.jpg Parathyroid image (deltagen.com)]. | ||
*[http:// | *[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1770637/figure/f1/ Parathyroid gland (nih.gov)].<ref name=pmid15790694>{{Cite journal | last1 = Johnson | first1 = SJ. | last2 = Sheffield | first2 = EA. | last3 = McNicol | first3 = AM. | title = Best practice no 183. Examination of parathyroid gland specimens. | journal = J Clin Pathol | volume = 58 | issue = 4 | pages = 338-42 | month = Apr | year = 2005 | doi = 10.1136/jcp.2002.002550 | PMID = 15790694 | pmc = 1770637 }}</ref> | ||
===IHC=== | |||
*GATA3 +ve (>98%<ref name=pmid27097544>{{Cite journal | last1 = Takada | first1 = N. | last2 = Hirokawa | first2 = M. | last3 = Suzuki | first3 = A. | last4 = Higuchi | first4 = M. | last5 = Kuma | first5 = S. | last6 = Miyauchi | first6 = A. | title = Diagnostic value of GATA-3 in cytological identification of parathyroid tissues. | journal = Endocr J | volume = 63 | issue = 7 | pages = 621-6 | month = Jul | year = 2016 | doi = 10.1507/endocrj.EJ15-0700 | PMID = 27097544 }}</ref>). | |||
*PTH -ve/+ve (~33%<ref name=pmid27097544/>). | |||
*Chromogranin A +ve (~80%<ref name=pmid27097544/>). | |||
*AE1/AE3 +ve.{{fact}}<!-- {{Cite journal | last1 = Piciu | first1 = D. | last2 = Irimie | first2 = A. | last3 = Kontogeorgos | first3 = G. | last4 = Piciu | first4 = A. | last5 = Buiga | first5 = R. | title = Highly aggressive pathology of non-functional parathyroid carcinoma. | journal = Orphanet J Rare Dis | volume = 8 | issue = | pages = 115 | month = Aug | year = 2013 | doi = 10.1186/1750-1172-8-115 | PMID = 23915575 }} --> | |||
=Specific entities= | =Specific entities= | ||
==Parathyroid hyperplasia== | ==Parathyroid hyperplasia== | ||
{{Main|Parathyroid hyperplasia}} | |||
==Parathyroid adenoma== | ==Parathyroid adenoma== | ||
{{Main|Parathyroid adenoma}} | |||
==Parathyroid carcinoma== | ==Parathyroid carcinoma== | ||
{{Main|Parathyroid carcinoma}} | |||
=See also= | =See also= |
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