Details of Disease

General Information of Disease (ID: DISB4U1Q)

• Disease Name: Primary hyperparathyroidism
• Synonyms: primary hyperparathyroidism (disease); primary hyperparathyroidism
• Definition: Hyperfunction of the parathyroid glands resulting in the overproduction of parathyroid hormone. It is caused by parathyroid adenoma, parathyroid hyperplasia, parathyroid carcinoma, and multiple endocrine neoplasia. It is associated with hypercalcemia and hypophosphatemia. Signs and symptoms include weakness, fatigue, nausea, vomiting, constipation, depression, bone pain, osteoporosis, cystic bone lesions, and kidney stones.|Editor note: check relationship to parent and familiar form
• Disease Hierarchy:
  DIS4FVAT: Hyperparathyroidism
  DISB4U1Q: Primary hyperparathyroidism
• Disease Identifiers:
  MONDO ID: MONDO_0010837
  MESH ID: D049950
  UMLS CUI: C0221002
  MedGen ID: 66354
  HPO ID: HP:0008200
  SNOMED CT ID: 36348003

Drug-Interaction Atlas (DIA) of This Disease

This Disease is Treated as An Indication in 1 Approved Drug(s)

Drug Name	Drug ID	Highest Status	Drug Type	REF
Cholecalciferol	DMGU74E	Approved	Small molecular drug	[1]

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 7 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
CDKN1B	TTLGFVW	Strong	Biomarker	[2]
DMD	TTWLFXU	Strong	Biomarker	[3]
FGF23	TT2IZ4K	Strong	Altered Expression	[4]
GNA11	TTSRXJW	Strong	Genetic Variation	[5]
RET	TT4DXQT	Strong	Biomarker	[2]
SLC12A1	TTS087L	Strong	Genetic Variation	[6]
VDR	TTK59TV	Strong	Genetic Variation	[7]

This Disease Is Related to 1 DTP Molecule(s)

Gene Name	DTP ID	Evidence Level	Mode of Inheritance	REF
SLC26A6	DTVGOLN	Strong	Genetic Variation	[8]

This Disease Is Related to 18 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
PTMS	OT9PS4Q0	Limited	Biomarker	[9]
CDC73	OT6JASZ1	moderate	Biomarker	[10]
ADAMTS9	OTV3Q0DS	Strong	Biomarker	[11]
ADGRG2	OTPAD5S1	Strong	Biomarker	[12]
AIP	OTDJ3OSV	Strong	Biomarker	[13]
AP2S1	OTEV2XGW	Strong	Genetic Variation	[5]
BEST1	OTWHE1ZC	Strong	Biomarker	[3]
CRISPLD2	OTVSFHTL	Strong	Genetic Variation	[14]
DERL2	OTI3TUUZ	Strong	Genetic Variation	[15]
DMP1	OTBWBWW7	Strong	Altered Expression	[4]
FZD1	OTZATHVS	Strong	Altered Expression	[16]
GNA12	OT3IRZH3	Strong	Biomarker	[17]
PRSS2	OTOMVUWL	Strong	Genetic Variation	[18]
PTHLH	OTI1JF13	Strong	Biomarker	[19]
RGS5	OTUY0Q2I	Strong	Biomarker	[20]
SDHAF2	OT0UG9H5	Strong	Genetic Variation	[21]
SDHC	OTC8G2MX	Strong	Genetic Variation	[22]
SPINK1	OTSUVAL2	Strong	Genetic Variation	[18]

References

• [1] Cholecalciferol FDA Label
• [2] Primary Hyperparathyroidism.Front Horm Res. 2019;51:1-12. doi: 10.1159/000491034. Epub 2018 Nov 19.
• [3] Clinical Impact of p27(Kip1) and CaSR Expression on Primary Hyperparathyroidism.Endocr Pathol. 2018 Sep;29(3):250-258. doi: 10.1007/s12022-018-9524-9.
• [4] Attenuated Dentin Matrix Protein 1 Enhances Fibroblast Growth Factor 23 in Calvaria in a Primary Hyperparathyroidism Model.Endocrinology. 2019 May 1;160(5):1348-1358. doi: 10.1210/en.2019-00017.
• [5] AP2S1 and GNA11 mutations - not a common cause of familial hypocalciuric hypercalcemia.Eur J Endocrinol. 2017 Feb;176(2):177-185. doi: 10.1530/EJE-16-0842. Epub 2016 Nov 15.
• [6] Association of Mutations in SLC12A1 Encoding the NKCC2 Cotransporter With Neonatal Primary Hyperparathyroidism.J Clin Endocrinol Metab. 2016 May;101(5):2196-200. doi: 10.1210/jc.2016-1211. Epub 2016 Mar 10.
• [7] Effects of genetic variants on serum parathyroid hormone in hyperparathyroidism and end-stage renal disease patients: A systematic review and meta-analysis.Medicine (Baltimore). 2018 May;97(21):e10834. doi: 10.1097/MD.0000000000010834.
• [8] Analysis of the 206M polymorphic variant of the SLC26A6 gene encoding a Cl- oxalate transporter in patients with primary hyperparathyroidism.Eur J Endocrinol. 2009 Feb;160(2):283-8. doi: 10.1530/EJE-08-0623. Epub 2008 Nov 24.
• [9] MANAGEMENT OF ENDOCRINE DISEASE: Unmet therapeutic, educational and scientific needs in parathyroid disorders.Eur J Endocrinol. 2019 Sep 1;181(3):P1-P19. doi: 10.1530/EJE-19-0316. Epub 2019 Jun 1.
• [10] Whole exome sequencing in familial isolated primary hyperparathyroidism.J Endocrinol Invest. 2020 Feb;43(2):231-245. doi: 10.1007/s40618-019-01107-5. Epub 2019 Sep 5.
• [11] Association of ADAMTS4 and ADAMTS9 levels with cardiovascular risk in patients with primary hyperparathyroidism.Endocr Res. 2018 Feb;43(1):15-20. doi: 10.1080/07435800.2017.1368543. Epub 2017 Sep 22.
• [12] Orphan Adhesion GPCR GPR64/ADGRG2 Is Overexpressed in Parathyroid Tumors and Attenuates Calcium-Sensing Receptor-Mediated Signaling.J Bone Miner Res. 2017 Mar;32(3):654-666. doi: 10.1002/jbmr.3023. Epub 2016 Nov 25.
• [13] Mutation analysis of MEN1, HRPT2, CASR, CDKN1B, and AIP genes in primary hyperparathyroidism patients with features of genetic predisposition.J Endocrinol Invest. 2009 Jun;32(6):512-8. doi: 10.1007/BF03346498. Epub 2009 Mar 26.
• [14] Pancreatitis risk in primary hyperparathyroidism: relation to mutations in the SPINK1 trypsin inhibitor (N34S) and the cystic fibrosis gene.Am J Gastroenterol. 2008 Feb;103(2):368-74. doi: 10.1111/j.1572-0241.2007.01695.x. Epub 2007 Dec 12.
• [15] MIL-125-NH(2)@TiO(2) Core-Shell Particles Produced by a Post-Solvothermal Route for High-Performance Photocatalytic H(2) Production.ACS Appl Mater Interfaces. 2018 May 16;10(19):16418-16423. doi: 10.1021/acsami.8b01462. Epub 2018 May 2.
• [16] Evidence of a stabilizing mutation of -catenin encoded by CTNNB1 exon 3 in a large series of sporadic parathyroid adenomas.Endocrine. 2012 Dec;42(3):612-5. doi: 10.1007/s12020-012-9690-3. Epub 2012 May 11.
• [17] Multiple endocrine neoplasia type 1 in Poland: a two-centre experience.Endokrynol Pol. 2019;70(5):385-391. doi: 10.5603/EP.a2019.0031. Epub 2019 Jul 5.
• [18] Multifactorial genesis of pancreatitis in primary hyperparathyroidism: evidence for "protective" (PRSS2) and "destructive" (CTRC) genetic factors.Exp Clin Endocrinol Diabetes. 2011 Jan;119(1):26-9. doi: 10.1055/s-0030-1255106. Epub 2010 Jul 12.
• [19] Association between parathyroid hormone (PTH)/PTH-related peptide receptor gene polymorphism and the extent of bone mass reduction in primary hyperparathyroidism.Horm Metab Res. 2000 Sep;32(9):355-8. doi: 10.1055/s-2007-978652.
• [20] Parathyroid-Targeted Overexpression of Regulator of G-Protein Signaling 5 (RGS5) Causes Hyperparathyroidism in Transgenic Mice.J Bone Miner Res. 2019 May;34(5):955-963. doi: 10.1002/jbmr.3674. Epub 2019 Feb 28.
• [21] Expression and somatic mutations of SDHAF2 (SDH5), a novel endocrine tumor suppressor gene in parathyroid tumors of primary hyperparathyroidism.Endocrine. 2010 Dec;38(3):397-401. doi: 10.1007/s12020-010-9399-0. Epub 2010 Oct 23.
• [22] AN AGGRESSIVE TEMPORAL BONE SDHC PARAGANGLIOMA ASSOCIATED WITH INCREASED HIF-2 SIGNALING.Endocr Pract. 2016 Feb;22(2):190-5. doi: 10.4158/EP15889.OR. Epub 2015 Oct 22.