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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 | | | |
| | | | | |
| | | | | |
| | | | | |
| |- | | |- |
| |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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| ==Overview==
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| Hyperparathyroidism is caused by an increase in concentration of parathyroid hormone in serum. There are three type of hyperparathyroidism including primary, secondary and tertiary hyperparathyroidism. The are an array of different causes for all types of hyperparathyroidism.
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| ==Causes of Primary hyperparathyroidism==
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| Causes of primary hyperparathyroidism are as follows:
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| ===Common causes===
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| *Parathyroid adenoma
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| **Usually single gland affected
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| **Sometimes multiple gland affected
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| ===Less common causes===
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| *Parathyroid hyperplasia
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| *Parathyroid carcinoma
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| *Familial isloated hyperparathyroidism
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| *Radiation exposure (due to development of parathyroid adenoma or parathyroid hyperplasia)<ref name="pmid21848480">{{cite journal| author=Boehm BO, Rosinger S, Belyi D, Dietrich JW| title=The parathyroid as a target for radiation damage. | journal=N Engl J Med | year= 2011 | volume= 365 | issue= 7 | pages= 676-8 | pmid=21848480 | doi=10.1056/NEJMc1104982 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21848480 }} </ref><ref name="pmid18774659">{{cite journal| author=McMullen T, Bodie G, Gill A, Ihre-Lundgren C, Shun A, Bergin M et al.| title=Hyperparathyroidism after irradiation for childhood malignancy. | journal=Int J Radiat Oncol Biol Phys | year= 2009 | volume= 73 | issue= 4 | pages= 1164-8 | pmid=18774659 | doi=10.1016/j.ijrobp.2008.06.1487 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18774659 }} </ref><ref name="pmid890665">{{cite journal| author=Tisell LE, Hansson G, Lindberg S, Ragnhult I| title=Hyperparathyroidism in persons treated with X-rays for tuberculous cervical adenitis. | journal=Cancer | year= 1977 | volume= 40 | issue= 2 | pages= 846-54 | pmid=890665 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=890665 }} </ref>
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| *Celiac disease<ref name="pmid17148709">{{cite journal |vauthors=Maida MJ, Praveen E, Crimmins SR, Swift GL |title=Coeliac disease and primary hyperparathyroidism: an association? |journal=Postgrad Med J |volume=82 |issue=974 |pages=833–5 |year=2006 |pmid=17148709 |pmc=2653933 |doi=10.1136/pgmj.2006.045500 |url=}}</ref><ref name="pmid22238405">{{cite journal |vauthors=Ludvigsson JF, Kämpe O, Lebwohl B, Green PH, Silverberg SJ, Ekbom A |title=Primary hyperparathyroidism and celiac disease: a population-based cohort study |journal=J. Clin. Endocrinol. Metab. |volume=97 |issue=3 |pages=897–904 |year=2012 |pmid=22238405 |pmc=3319223 |doi=10.1210/jc.2011-2639 |url=}}</ref>
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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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| ==Causes of secondary hyperparathyroidism==
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| Causes of secondary hyperparathyroidism are as follows:
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| ===Common causes===
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| *Chronic renal failure (leading to parathyroid hyperplasia)<ref name="pmid15507543">{{cite journal| author=Rodriguez M, Nemeth E, Martin D| title=The calcium-sensing receptor: a key factor in the pathogenesis of secondary hyperparathyroidism. | journal=Am J Physiol Renal Physiol | year= 2005 | volume= 288 | issue= 2 | pages= F253-64 | pmid=15507543 | doi=10.1152/ajprenal.00302.2004 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15507543 }} </ref>
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| *Vitamin D deficiency<ref name="pmid11493580">{{cite journal| author=Lips P| title=Vitamin D deficiency and secondary hyperparathyroidism in the elderly: consequences for bone loss and fractures and therapeutic implications. | journal=Endocr Rev | year= 2001 | volume= 22 | issue= 4 | pages= 477-501 | pmid=11493580 | doi=10.1210/edrv.22.4.0437 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11493580 }} </ref>
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| ===Less common causes===
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| *Severe calcium deficiency<ref name="pmid16512945">{{cite journal| author=Mehrotra M, Gupta SK, Kumar K, Awasthi PK, Dubey M, Pandey CM et al.| title=Calcium deficiency-induced secondary hyperparathyroidism and osteopenia are rapidly reversible with calcium supplementation in growing rabbit pups. | journal=Br J Nutr | year= 2006 | volume= 95 | issue= 3 | pages= 582-90 | pmid=16512945 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16512945 }} </ref>
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| *Gastric bypass surgery, particularly roux-en-Y gastric bypass (RYGBP)<ref name="pmid16633006">{{cite journal |vauthors=Johnson JM, Maher JW, DeMaria EJ, Downs RW, Wolfe LG, Kellum JM |title=The long-term effects of gastric bypass on vitamin D metabolism |journal=Ann. Surg. |volume=243 |issue=5 |pages=701–4; discussion 704–5 |year=2006 |pmid=16633006 |pmc=1570540 |doi=10.1097/01.sla.0000216773.47825.c1 |url=}}</ref>
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| *Malabsorption syndrome<ref name="pmid19836494">{{cite journal |vauthors=Pitt SC, Sippel RS, Chen H |title=Secondary and tertiary hyperparathyroidism, state of the art surgical management |journal=Surg. Clin. North Am. |volume=89 |issue=5 |pages=1227–39 |year=2009 |pmid=19836494 |pmc=2905047 |doi=10.1016/j.suc.2009.06.011 |url=}}</ref>
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| ==Causes of tertiary hyperparathyroidism==
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| Causes of tertiary hyperparathyroidism are as follows:
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| ===Common causes===
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| *Chronic renal failure (leading to parathyroid hyperplasia)
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| *Renal transplant patients<ref name="pmid9780988">{{cite journal |vauthors=Kilgo MS, Pirsch JD, Warner TF, Starling JR |title=Tertiary hyperparathyroidism after renal transplantation: surgical strategy |journal=Surgery |volume=124 |issue=4 |pages=677–83; discussion 683–4 |year=1998 |pmid=9780988 |doi=10.1067/msy.1998.91483 |url=}}</ref>
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| ===Less common cause===
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| *Long standing celiac disease<ref name="pmid17148709">{{cite journal |vauthors=Maida MJ, Praveen E, Crimmins SR, Swift GL |title=Coeliac disease and primary hyperparathyroidism: an association? |journal=Postgrad Med J |volume=82 |issue=974 |pages=833–5 |year=2006 |pmid=17148709 |pmc=2653933 |doi=10.1136/pgmj.2006.045500 |url=}}</ref>
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| =Pathogenesis=
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| ==Associated conditions==
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| *Hypercalcemia
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| *Chronic renal failure
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| *Osteitis fibrous cystica
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| *Osteoporosis
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| *Osteomalacia
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| *Osteoarthritis
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| *Brown tumor
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| *Multiple endocrine neoplasia type 1, type 2A, and type 4
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| *Familial isolated hyperparathyroidism
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| *Neonatal severe hyperparathyroidism
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| *Familial hypocalciuric hypercalcemia
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| *Hyperparathyroid-jaw tumor syndrome
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| *Pancreatitis<ref name="pmid22874807">{{cite journal |vauthors=Bai HX, Giefer M, Patel M, Orabi AI, Husain SZ |title=The association of primary hyperparathyroidism with pancreatitis |journal=J. Clin. Gastroenterol. |volume=46 |issue=8 |pages=656–61 |year=2012 |pmid=22874807 |pmc=4428665 |doi=10.1097/MCG.0b013e31825c446c |url=}}</ref>
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| =Natural history, Prognosis and Complications=
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| ==Natural history==
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| *Primary hyperparathyroidism usually develops in the fifth decade of life, in post-menopausal women and starts as asymptomatic hypercalcemia in presence of increased parathyroid hormone.
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| *If left untreated, some of patients with hyperparathyroidism may develop marked hypercalcemia, marked hypercalciuria, cortical bone demineralization and nephrolithiasis.
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| *These complications resolves after the treatment.
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| *Untreated complication may be fatal.<ref name="pmid3878002">{{cite journal |vauthors=Corlew DS, Bryda SL, Bradley EL, DiGirolamo M |title=Observations on the course of untreated primary hyperparathyroidism |journal=Surgery |volume=98 |issue=6 |pages=1064–71 |year=1985 |pmid=3878002 |doi= |url=}}</ref>
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| ==Complications==
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| Complications of primary hyperparathyroidism are due to hypercalcemia. Common complications of primary hyperparathyroidism include:
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| *Bone related complication:<ref name="pmid25166047">{{cite journal |vauthors=Bandeira F, Cusano NE, Silva BC, Cassibba S, Almeida CB, Machado VC, Bilezikian JP |title=Bone disease in primary hyperparathyroidism |journal=Arq Bras Endocrinol Metabol |volume=58 |issue=5 |pages=553–61 |year=2014 |pmid=25166047 |pmc=4315357 |doi= |url=}}</ref><ref name="pmid9801732">{{cite journal |vauthors=Mazzuoli GF, D'Erasmo E, Pisani D |title=Primary hyperparathyroidism and osteoporosis |journal=Aging (Milano) |volume=10 |issue=3 |pages=225–31 |year=1998 |pmid=9801732 |doi= |url=}}</ref><ref name="pmid11493580">{{cite journal| author=Lips P| title=Vitamin D deficiency and secondary hyperparathyroidism in the elderly: consequences for bone loss and fractures and therapeutic implications. | journal=Endocr Rev | year= 2001 | volume= 22 | issue= 4 | pages= 477-501 | pmid=11493580 | doi=10.1210/edrv.22.4.0437 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11493580 }} </ref><ref name="pmid20305774">{{cite journal |vauthors=Michael JW, Schlüter-Brust KU, Eysel P |title=The epidemiology, etiology, diagnosis, and treatment of osteoarthritis of the knee |journal=Dtsch Arztebl Int |volume=107 |issue=9 |pages=152–62 |year=2010 |pmid=20305774 |pmc=2841860 |doi=10.3238/arztebl.2010.0152 |url=}}</ref>
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| **Brown tumor
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| **Osteitis fibrous cystica
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| **Osteoarthritis
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| **Osteomalacia
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| **Osteoporosis
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| *Cardiac complications:<ref name="pmid8989242">{{cite journal |vauthors=Stefenelli T, Abela C, Frank H, Koller-Strametz J, Globits S, Bergler-Klein J, Niederle B |title=Cardiac abnormalities in patients with primary hyperparathyroidism: implications for follow-up |journal=J. Clin. Endocrinol. Metab. |volume=82 |issue=1 |pages=106–12 |year=1997 |pmid=8989242 |doi=10.1210/jcem.82.1.3666 |url=}}</ref>
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| **Left ventricular hypertrophy
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| **Cardiac calcific deposits in the myocardium
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| **Aortic and mitral valve calcification
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| *Endocrine complications:<ref name="pmid22874807">{{cite journal |vauthors=Bai HX, Giefer M, Patel M, Orabi AI, Husain SZ |title=The association of primary hyperparathyroidism with pancreatitis |journal=J. Clin. Gastroenterol. |volume=46 |issue=8 |pages=656–61 |year=2012 |pmid=22874807 |pmc=4428665 |doi=10.1097/MCG.0b013e31825c446c |url=}}</ref>
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| **Pancreatitis
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| *Gastrointestinal complications:<ref name="pmid3878002">{{cite journal |vauthors=Corlew DS, Bryda SL, Bradley EL, DiGirolamo M |title=Observations on the course of untreated primary hyperparathyroidism |journal=Surgery |volume=98 |issue=6 |pages=1064–71 |year=1985 |pmid=3878002 |doi= |url=}}</ref>
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| **Peptic ulcer disease
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| *Metabolic complications:<ref name="pmid3812520">{{cite journal |vauthors=Fitzpatrick LA, Bilezikian JP |title=Acute primary hyperparathyroidism |journal=Am. J. Med. |volume=82 |issue=2 |pages=275–82 |year=1987 |pmid=3812520 |doi= |url=}}</ref><ref name="pmid25447624">{{cite journal |vauthors=Ahmad S, Kuraganti G, Steenkamp D |title=Hypercalcemic crisis: a clinical review |journal=Am. J. Med. |volume=128 |issue=3 |pages=239–45 |year=2015 |pmid=25447624 |doi=10.1016/j.amjmed.2014.09.030 |url=}}</ref><ref name="pmid3878002">{{cite journal |vauthors=Corlew DS, Bryda SL, Bradley EL, DiGirolamo M |title=Observations on the course of untreated primary hyperparathyroidism |journal=Surgery |volume=98 |issue=6 |pages=1064–71 |year=1985 |pmid=3878002 |doi= |url=}}</ref>
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| **Hypercalcemic crisis
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| *Pregnancy related complications:
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| **Neonatal hypoparathyroidism
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| *Psychiatric complications:<ref name="pmid21917870">{{cite journal |vauthors=Espiritu RP, Kearns AE, Vickers KS, Grant C, Ryu E, Wermers RA |title=Depression in primary hyperparathyroidism: prevalence and benefit of surgery |journal=J. Clin. Endocrinol. Metab. |volume=96 |issue=11 |pages=E1737–45 |year=2011 |pmid=21917870 |doi=10.1210/jc.2011-1486 |url=}}</ref>
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| **Depression
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| *Renal complications:<ref name="pmid12412783">{{cite journal |vauthors=Peacock M |title=Primary hyperparathyroidism and the kidney: biochemical and clinical spectrum |journal=J. Bone Miner. Res. |volume=17 Suppl 2 |issue= |pages=N87–94 |year=2002 |pmid=12412783 |doi= |url=}}</ref><ref name="pmid22470864">{{cite journal |vauthors=Lila AR, Sarathi V, Jagtap V, Bandgar T, Menon PS, Shah NS |title=Renal manifestations of primary hyperparathyroidism |journal=Indian J Endocrinol Metab |volume=16 |issue=2 |pages=258–62 |year=2012 |pmid=22470864 |pmc=3313745 |doi=10.4103/2230-8210.93745 |url=}}</ref>
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| **Nephrolithiasis
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| **Nephrocalcinosis
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| ==References== | | ==References== |
| | {{reflist|2}} |