Details of Disease

General Information of Disease (ID: DIS4FVAT)

• Disease Name: Hyperparathyroidism
• Synonyms: hyperparathyroidism
• Disease Class: 5A51: Hyper-parathyroidism
• Definition: Hyperfunction of the parathyroid glands resulting in the overproduction of parathyroid hormone. It may be primary or secondary; primary hyperparathyroidism 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. Secondary hyperparathyroidism is caused by the chronic stimulation of the parathyroid glands in patients with chronic renal failure, rickets, and malabsorption syndromes.
• Disease Hierarchy:
  DISJKZDC: Parathyroid disease
  DIS4FVAT: Hyperparathyroidism
• ICD Code:
  ICD-11: ICD-11: 5A51
  ICD-9: ICD-9: 252.02, 588.81
  Expand ICD-11: '5A51
  Expand ICD-10: 'E21; 'E21.2; 'E21.3
  Expand ICD-9: 252.02,588.81
• Disease Identifiers:
  MONDO ID: MONDO_0001741
  MESH ID: D006961
  UMLS CUI: C0020502
  MedGen ID: 6967
  HPO ID: HP:0000843
  SNOMED CT ID: 66999008

Drug-Interaction Atlas (DIA) of This Disease

This Disease is Treated as An Indication in 4 Approved Drug(s)

Drug Name	Drug ID	Highest Status	Drug Type	REF
Cinacalcet	DMCX0K3	Approved	Small molecular drug	[1]
Falecalcitrol	DMBI9ZJ	Approved	Small molecular drug	[2]
Paricalcitol	DMYBV3G	Approved	Small molecular drug	[3]
Alfacalcidol	DM1237M	Phase 4	NA	[4]

This Disease is Treated as An Indication in 2 Clinical Trial Drug(s)

Drug Name	Drug ID	Highest Status	Drug Type	REF
ASP7991	DM3TN1A	Phase 2	NA	[5]
CTAP-201	DMHBK6L	Phase 1	NA	[6]

This Disease is Treated as An Indication in 2 Investigative Drug(s)

Drug Name	Drug ID	Highest Status	Drug Type	REF
CTA-091	DMNGNRE	Investigative	NA	[7]
CTA-192	DM3D9E3	Investigative	NA	[7]

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 11 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
CCND1	TTFCJ7S	Limited	Biomarker	[8]
RET	TT4DXQT	Limited	Biomarker	[9]
ATRAID	TTFLIKM	Strong	Altered Expression	[10]
CDKN1B	TTLGFVW	Strong	Genetic Variation	[11]
CDKN2C	TTBRUGA	Strong	Altered Expression	[10]
FECH	TTQ6VF4	Strong	Biomarker	[12]
GNA11	TTSRXJW	Strong	Genetic Variation	[13]
PPY	TTIB95A	Strong	Biomarker	[14]
PTGER2	TT1ZAVI	Strong	Biomarker	[15]
PTH1R	TTFPD47	Strong	Biomarker	[16]
SLC12A1	TTS087L	Strong	Genetic Variation	[17]

This Disease Is Related to 19 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
AMELX	OTIN26MM	Strong	Biomarker	[18]
AP2S1	OTEV2XGW	Strong	Genetic Variation	[13]
CDC73	OT6JASZ1	Strong	Genetic Variation	[19]
CORO7	OTG7MEAJ	Strong	Biomarker	[20]
EEF1E1	OTRA6XOB	Strong	Altered Expression	[10]
GCM2	OTSKNPTI	Strong	Genetic Variation	[21]
LAMTOR1	OTIBJBW9	Strong	Altered Expression	[10]
MAFK	OTZJUE4P	Strong	Altered Expression	[10]
MEN1	OTN6U6V0	Strong	Genetic Variation	[22]
PDSS1	OTXGVHAB	Strong	Biomarker	[23]
PHEX	OTG7N3J7	Strong	Genetic Variation	[24]
PLCB3	OT0OMDEM	Strong	Altered Expression	[25]
PTRH1	OTOAOS93	Strong	Biomarker	[26]
RGS5	OTUY0Q2I	Strong	Altered Expression	[27]
SEMA3D	OTD5TJV1	Strong	Biomarker	[28]
SEPHS1	OTZ19I59	Strong	Biomarker	[23]
SPAG11A	OTNQ9UB0	Strong	Biomarker	[15]
TBX4	OTW58FG4	Strong	Biomarker	[23]
TPPP2	OTI3WA6X	Strong	Altered Expression	[10]

References

• [1] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 3308).
• [2] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [3] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 2791).
• [4] X-Linked Hypophosphatemia. 2012 Feb 9 [updated 2023 Dec 14]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews(?) [Internet]. Seattle (WA): University of Washington, Seattle; 1993C2024.
• [5] ClinicalTrials.gov (NCT02133404) A Study to Evaluate the Effect of ASP7991 in Secondary Hyperparathyroidism Patients Undergoing Hemodialysis. U.S. National Institutes of Health.
• [6] ClinicalTrials.gov (NCT00792857) Comparison of I.V. CTAP201 and Doxercalciferol (Hectorol) in Subjects With Chronic Kidney Disease (CKD) and Secondary Hyperparathyroidism (SHPT). U.S. National Institutes of Health.
• [7] The ChEMBL database in 2017. Nucleic Acids Res. 2017 Jan 4;45(D1):D945-D954.
• [8] Cinacalcet HCl suppresses Cyclin D1 oncogene-derived parathyroid cell proliferation in a murine model for primary hyperparathyroidism.Calcif Tissue Int. 2011 Jul;89(1):29-35. doi: 10.1007/s00223-011-9490-4. Epub 2011 May 4.
• [9] Genotypic characteristics and their association with phenotypic characteristics of hereditary medullary thyroid carcinoma in Korea.Surgery. 2018 Aug;164(2):312-318. doi: 10.1016/j.surg.2018.03.018. Epub 2018 May 17.
• [10] Reduced p18INK4c, p21CIP1/WAF1 and p27KIP1 mRNA levels in tumours of primary and secondary hyperparathyroidism.Clin Endocrinol (Oxf). 2004 Mar;60(3):389-93. doi: 10.1111/j.1365-2265.2004.01995.x.
• [11] A heterozygous frameshift mutation in exon 1 of CDKN1B gene in a patient affected by MEN4 syndrome.Eur J Endocrinol. 2014 Aug;171(2):K7-K17. doi: 10.1530/EJE-14-0080. Epub 2014 May 12.
• [12] Diagnostic performance of choline PET for detection of hyperfunctioning parathyroid glands in hyperparathyroidism: a systematic review and meta-analysis.Eur J Nucl Med Mol Imaging. 2019 Mar;46(3):751-765. doi: 10.1007/s00259-018-4123-z. Epub 2018 Aug 9.
• [13] Diseases associated with calcium-sensing receptor.Orphanet J Rare Dis. 2017 Jan 25;12(1):19. doi: 10.1186/s13023-017-0570-z.
• [14] Genetic screening for MEN1 mutations in families presenting with familial primary hyperparathyroidism.World J Surg. 2002 Aug;26(8):907-13. doi: 10.1007/s00268-002-6617-9. Epub 2002 May 21.
• [15] Prostaglandin E2 receptor EP2 mediates the effect of cyclooxygenase 2 on secondary parathyroid hyperplasia in end-stage renal disease.Nephrol Dial Transplant. 2019 Apr 1;34(4):606-617. doi: 10.1093/ndt/gfy194.
• [16] 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.
• [17] A novel SLC12A1 gene mutation associated with hyperparathyroidism, hypercalcemia, nephrogenic diabetes insipidus, and nephrocalcinosis in four patients.Bone. 2017 Apr;97:121-125. doi: 10.1016/j.bone.2017.01.011. Epub 2017 Jan 14.
• [18] Recent advances in nephrology: highlights from the 35th annual meeting of the American society of nephrology.Drugs Today (Barc). 2002 Dec;38(12):797-805.
• [19] 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.
• [20] Primary hyperparathyroidism: Dynamic postoperative metabolic changes.Clin Endocrinol (Oxf). 2018 Jan;88(1):129-138. doi: 10.1111/cen.13476. Epub 2017 Oct 1.
• [21] Specifying the molecular pattern of sporadic parathyroid tumorigenesis-The Y282D variant of the GCM2 gene.Biomed Pharmacother. 2017 Aug;92:843-848. doi: 10.1016/j.biopha.2017.05.028. Epub 2017 Jun 9.
• [22] Perioperative Hypotensive Crisis in an Adolescent with a Pancreatic VIPoma and MEN1-Gene Variant.Horm Res Paediatr. 2019;91(4):285-289. doi: 10.1159/000493396. Epub 2018 Oct 16.
• [23] Compared effects of calcium and sodium polystyrene sulfonate on mineral and bone metabolism and volume overload in pre-dialysis patients with hyperkalemia.Clin Exp Nephrol. 2018 Feb;22(1):35-44. doi: 10.1007/s10157-017-1412-y. Epub 2017 Apr 18.
• [24] The enigma of hyperparathyroidism in hypophosphatemic rickets.Pediatr Nephrol. 2004 May;19(5):473-7. doi: 10.1007/s00467-004-1443-y. Epub 2004 Mar 11.
• [25] Hyperparathyroidism of multiple endocrine neoplasia type 1: candidate gene and parathyroid calcium sensing protein expression.Surgery. 1995 Dec;118(6):924-30; discussion 930-1. doi: 10.1016/s0039-6060(05)80095-9.
• [26] Catabolic Effects of Human PTH (1-34) on Bone: Requirement of Monocyte Chemoattractant Protein-1 in Murine Model of Hyperparathyroidism.Sci Rep. 2017 Nov 10;7(1):15300. doi: 10.1038/s41598-017-15563-7.
• [27] 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.
• [28] Deficiency in the secreted protein Semaphorin3d causes abnormal parathyroid development in mice.J Biol Chem. 2019 May 24;294(21):8336-8347. doi: 10.1074/jbc.RA118.007063. Epub 2019 Apr 12.