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| __NOTOC____NOTOC__
| | __NOTOC__ |
| {{Hyperparathyroidism}}
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| {{CMG}}; {{AE}} {{Anmol}} | | {{CMG}}; {{AE}} {{Anmol}} |
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| == Classification == | | ==Tables== |
| {| class="wikitable" | | {| class="wikitable" |
| ! colspan="4" |Classification of hyperparathyridism | | |+ |
| | !Diagnosis |
| | !Lab findings |
| | ! |
| | ! |
| |- | | |- |
| |Features
| | ! |
| |'''Primary hyperparathyroidism'''
| | ! |
| |'''Secondary hyperparathyroidism'''
| | ! |
| |'''Tertiary hyperparathyroidism'''
| | ! |
| |- | | |- |
| |Pathology | | | |
| |Hyperfunction of parathyroid cells due to hyperplasia, adenoma or carcinoma. | | | |
| |Physiological stimulation of parathyroid in response to hypocalcaemia. | | | |
| |Following long term physiological stimulation leading to hyperplasia. | | | |
| |- | | |- |
| |Cause | | | |
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| |- | | |- |
| |Associations | | | |
| |May be associated with multiple endocrine neoplasia. | | | |
| |Usually due to chronic renal failure or other causes of Vitamin D deficiency. | | | |
| |Seen in chronic renal failure. | | | |
| |-
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| |Serum calcium
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| |High
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| |Low/Normal
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| |High
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| |-
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| |Serum phosphate
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| |Low/Normal
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| |High
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| |High
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| |-
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| |Management
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| |Usually surgery if symptomatic. Cincacalcet can be considered in those not fit for surgery.
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| |Treatment of underlying cause.
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| |Usually cinacalcet or surgery in those that don't respond.
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| |} | | |} |
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| =Causes=
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| ===Genetic causes===
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| *HRPT2 gene mutations:<ref name="pmid14585940">{{cite journal| author=Shattuck TM, Välimäki S, Obara T, Gaz RD, Clark OH, Shoback D et al.| title=Somatic and germ-line mutations of the HRPT2 gene in sporadic parathyroid carcinoma. | journal=N Engl J Med | year= 2003 | volume= 349 | issue= 18 | pages= 1722-9 | pmid=14585940 | doi=10.1056/NEJMoa031237 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=14585940 }} </ref>
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| **HRPT2 gene code for parafibromin protein.
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| **HRPT2 gene mutations are found in a type of familial hyperparathyroidism, hyperparathyroidism-jaw tumor (HPT-JT) syndrome.
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| **HRTP2 gene mutations increases risk of parathyroid carcinoma.
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| *Cyclin D1 gene (CCND1)/PRAD1 gene:<ref name="pmid19373510">{{cite journal| author=Westin G, Björklund P, Akerström G| title=Molecular genetics of parathyroid disease. | journal=World J Surg | year= 2009 | volume= 33 | issue= 11 | pages= 2224-33 | pmid=19373510 | doi=10.1007/s00268-009-0022-6 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19373510 }} </ref><ref name="pmid8626826">{{cite journal| author=Hsi ED, Zukerberg LR, Yang WI, Arnold A| title=Cyclin D1/PRAD1 expression in parathyroid adenomas: an immunohistochemical study. | journal=J Clin Endocrinol Metab | year= 1996 | volume= 81 | issue= 5 | pages= 1736-9 | pmid=8626826 | doi=10.1210/jcem.81.5.8626826 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8626826 }} </ref>
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| **PRAD1 (parathyroid adenoma 1) is a protooncogene located on chromosome 11q13.
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| **Cyclin D1 gene translocation and oncogene action observerd in 8% of adenomas
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| **Cyclin D1 gene overexpression is pbserved in 20% to 40% of parathyroid adenomas
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| *MEN1 gene:<ref name="pmid19373510">{{cite journal| author=Westin G, Björklund P, Akerström G| title=Molecular genetics of parathyroid disease. | journal=World J Surg | year= 2009 | volume= 33 | issue= 11 | pages= 2224-33 | pmid=19373510 | doi=10.1007/s00268-009-0022-6 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19373510 }} </ref><ref name="pmid9215689">{{cite journal| author=Agarwal SK, Kester MB, Debelenko LV, Heppner C, Emmert-Buck MR, Skarulis MC et al.| title=Germline mutations of the MEN1 gene in familial multiple endocrine neoplasia type 1 and related states. | journal=Hum Mol Genet | year= 1997 | volume= 6 | issue= 7 | pages= 1169-75 | pmid=9215689 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9215689 }} </ref>
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| **MEN1 is a tumor supressor gene on chronosome 11q13.
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| **Somatic loss of single MEN1 allele is observed in 25% to 40% of sporadic parathyroid adenomas.
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| =Pathogenesis=
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| ==Associated conditions==
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| =ECG=
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| =X-ray=
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| =CT scan=
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| =MRI=
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| =Ultrasound=
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| =TC-99m Sestamibi Scintigraphy=
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| =SPECT=
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| =PET=
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| =DXA=
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| *Low bone mineral density (BMD) is caused by primary hyperparathyroidism. Distal forearm is affected most commonly.
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| *DXA of distal forearm should be done in all patients of primary hyperparathyroidism. Worst T-score of distal forearm is observed in patients with primary hyperparathyroidism.<ref name="pmid22258698">{{cite journal| author=Wood K, Dhital S, Chen H, Sippel RS| title=What is the utility of distal forearm DXA in primary hyperparathyroidism? | journal=Oncologist | year= 2012 | volume= 17 | issue= 3 | pages= 322-5 | pmid=22258698 | doi=10.1634/theoncologist.2011-0285 | pmc=3316917 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22258698 }} </ref>
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| =Other diagnostic studies=
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| ==Intraoperative parathyroid hormone (IOPTH)==
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| *Measurement of intraoperative parathyroid hormone (IOPTH) by using a modified sensitive assay (immunoradiometric assay) is beneficial for long term surgical outcomes.Post-surgical success is defined as postoperative normocalcemia.
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| *Patients with hyperparathyroidism due to lesion in a single gland shows a rapid decline of intact parathyroid hormone. The levels of intact parathyroid hormone reached to indetectable levels within hours of resection.<ref name="pmid3194839">{{cite journal| author=Nussbaum SR, Thompson AR, Hutcheson KA, Gaz RD, Wang CA| title=Intraoperative measurement of parathyroid hormone in the surgical management of hyperparathyroidism. | journal=Surgery | year= 1988 | volume= 104 | issue= 6 | pages= 1121-7 | pmid=3194839 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=3194839 }} </ref>
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| *After resection of parathyroid adenoma, intact parathyroid hormone levels decrease by 85% is observed in first 15 minutes. This fall in parathyroid hormone levels is due to short half-life of parathyroid hormone.<ref name="pmid8145618">{{cite journal| author=Bergenfelz A, Isaksson A, Ahrén B| title=Intraoperative monitoring of intact PTH during surgery for primary hyperparathyroidism. | journal=Langenbecks Arch Chir | year= 1994 | volume= 379 | issue= 1 | pages= 50-3 | pmid=8145618 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8145618 }} </ref>
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| *The fall in parathyroid hormone level is significantly more after resection of parathyroid adenoma than after resection of parathyroid hyperplasia.
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| *A fall in level of parathyroid hormone 15 minutes after resection of hyper-functioning parathyroid glands may help differentiating sigle gland disease from multi gland disease.<ref>{{cite journal |last1=Irvin III |first1=George L. |last2=Dembrow |first2=Victor D. |last3=Prudhomme |first3=David L. |date= December 1993 |title=Clinical usefulness of an intraoperative “quick parathyroid hormone” assay |url=http://www.surgjournal.com/article/0039-6060(93)90317-7/abstract |journal=Surgery |volume=114 |issue=6 |pages=1019 - 1023 |doi= |access-date= }}</ref><ref name="pmid9718013">{{cite journal| author=Bergenfelz A, Isaksson A, Lindblom P, Westerdahl J, Tibblin S| title=Measurement of parathyroid hormone in patients with primary hyperparathyroidism undergoing first and reoperative surgery. | journal=Br J Surg | year= 1998 | volume= 85 | issue= 8 | pages= 1129-32 | pmid=9718013 | doi=10.1046/j.1365-2168.1998.00824.x | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9718013 }} </ref>
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| *IOPTH monitoring has a predictive accuracy of 97%. <ref name="pmid8957480">{{cite journal| author=Boggs JE, Irvin GL, Molinari AS, Deriso GT| title=Intraoperative parathyroid hormone monitoring as an adjunct to parathyroidectomy. | journal=Surgery | year= 1996 | volume= 120 | issue= 6 | pages= 954-8 | pmid=8957480 | doi=10.1016/S0039-6060(96)80040-7 | pmc= | url=http://ac.els-cdn.com/S0039606096800407/1-s2.0-S0039606096800407-main.pdf?_tid=99caa004-930c-11e7-92b8-00000aab0f01&acdnat=1504706978_12ba7c16e03bb28c66dc1c17a05074c4}} </ref>
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| ===Technique for intraoperative parathyroid hormone (IOPTH) monitoring===
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| *When the enlarged parathyroid gland is first visualized intraoperatively, the baseline sample should be obtained.<ref name="pmid11822958">{{cite journal| author=Westerdahl J, Lindblom P, Bergenfelz A| title=Measurement of intraoperative parathyroid hormone predicts long-term operative success. | journal=Arch Surg | year= 2002 | volume= 137 | issue= 2 | pages= 186-90 | pmid=11822958 | doi=10.1001/archsurg.137.2.186 | pmc= | url=http://jamanetwork.com/journals/jamasurgery/fullarticle/212128 }} </ref>
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| *The baseline samples should never be obtained before induction of anesthesia. It is due to the fact that an increase in parathyroid hormone level may be observed after general anesthesia.
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| *After excision of enlarged gland, 2nd and 3rd samples are collected at 5 and 10 minutes respectively.
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| *Several criteria are used for predicting post-operative normocalcemia including:
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| **A decline in parathyroid hormone levels of ≥60% from baseline value at 15 minutes.
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| **A decline in parathyroid hormone levels of ≥50% from baseline value at 10 minutes.
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| ==Super Selective Venous Sampling==
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| ==Selective arteriography==
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| *Selective transarterial hypocalcemic stimulation is combined with nonselective venous sampling to perform selective arteriography.<ref name="pmid19958942">{{cite journal| author=Powell AC, Alexander HR, Chang R, Marx SJ, Skarulis M, Pingpank JF et al.| title=Reoperation for parathyroid adenoma: a contemporary experience. | journal=Surgery | year= 2009 | volume= 146 | issue= 6 | pages= 1144-55 | pmid=19958942 | doi=10.1016/j.surg.2009.09.015 | pmc=3467310 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19958942 }} </ref>
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| *Sodium citrate is injected to induce hypocalcemia. Simultaneous arteriography is performed.
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| *Samples are taken for superior vena cava at basaeline and timed intervals (20 sec, 40 sec, and 60 sec).
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| *An increase in the parathyroid hormone level to 1.4 times above the baseline or a clear blush observed on arteriography is considered as positive localization.
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| * Arterial stimulation venous sampling is performed simultaneously with arteriogram due to similarly high PPV.
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| ==Angiography==
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| *Superselective arterial digital subtraction angiography (DSA) and superselective conventional angiography (CA) may be used for preoperative localization of hyper-functioning parathyroid glands in which noninvasive imaging modalities are negative or inconclusive.<ref name="pmid2644666">{{cite journal| author=Miller DL, Chang R, Doppman JL, Norton JA| title=Localization of parathyroid adenomas: superselective arterial DSA versus superselective conventional angiography. | journal=Radiology | year= 1989 | volume= 170 | issue= 3 Pt 2 | pages= 1003-6 | pmid=2644666 | doi=10.1148/radiology.170.3.2644666 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=2644666 }} </ref>
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| *Sensitivity of superselective digital subtraction angiography appears to be similar to conventional angiography.
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| *Superselective arterial digital subtraction angiography may be more sensitive than conventional angiography for preoperative localization of mediastinal hyper-functioning parathyroid glands.
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| ==References== | | ==References== |
| | {{reflist|2}} |