Details of Disease

General Information of Disease (ID: DISOG6P2)

• Disease Name: Cushing disease
• Synonyms: Corticotropinoma; corticotroph adenoma; Cushing disease; Cushing's disease; ACTH-secreting pituitary adenoma; Cushing disease, pituitary; pituitary dependent Cushing syndrome; pituitary adenoma 4, ACTH-secreting, somatic; PITA4; pituitary corticotroph micro-adenoma; pituitary-dependent Cushing syndrome; pituitary adenoma, ACTH-secreting; corticotroph pituitary adenoma; ACTH producing pituitary adenoma; pituitary adenoma 4, ACTH-secreting
• Disease Class: 5A70: Cushing syndrome
• Definition: Cushing's syndrome due to abnormally high secretion of adrenocorticotropic hormone (ACTH) from the pituitary gland.
• Disease Hierarchy:
  DISFK7RF: Adrenal gland neoplasm
  DISNEVYF: Familial isolated pituitary adenoma
  DISS1Q4V: Functioning pituitary gland adenoma
  DIS5TAF4: ACTH-dependent Cushing syndrome
  DISOG6P2: Cushing disease
• ICD Code:
  ICD-11: ICD-11: 5A70
  ICD-10: ICD-10: E24
  ICD-9: ICD-9: 255
  Expand ICD-11: '5A70
  Expand ICD-10: 'E24
  Expand ICD-9: 255
• Disease Identifiers:
  MONDO ID: MONDO_0009050
  MESH ID: D047748
  UMLS CUI: C0221406
  OMIM ID: 219090
  MedGen ID: 66381
  Orphanet ID: 96253
  SNOMED CT ID: 190502001

Drug-Interaction Atlas (DIA) of This Disease

This Disease is Treated as An Indication in 8 Approved Drug(s)

Drug Name	Drug ID	Highest Status	Drug Type	REF
Aminoglutethimide	DMWFHMZ	Approved	Small molecular drug	[1]
Corticotropin	DMP9TWZ	Approved	NA	[2]
Metyrapone	DMI7FVQ	Approved	Small molecular drug	[3]
Mifepristone	DMGZQEF	Approved	Small molecular drug	[4]
Osilodrostat	DMIJC9X	Approved	Small molecular drug	[5]
Ovine corticotropin-releasing hormone	DME0F98	Approved	Small molecular drug	[6]
Pasireotide	DMHM7JS	Approved	Small molecular drug	[6]
Trilostane	DMQZ9GF	Approved	Small molecular drug	[7]

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

Drug Name	Drug ID	Highest Status	Drug Type	REF
COR-003	DMIEOAP	Phase 3	NA	[8]
CORT-125134	DMBS3UG	Phase 3	NA	[9]

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 17 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
PPARG	TTT2SVW	Limited	Genetic Variation	[10]
USP8	TT1J07C	Limited	Biomarker	[11]
GH1	TTT3YKH	moderate	Biomarker	[12]
GHRL	TT1OCL0	moderate	Biomarker	[13]
AVPR1B	TTL9MHW	Strong	Biomarker	[14]
CRH	TTA7YIZ	Strong	Biomarker	[14]
CYP11B1	TTIQUX7	Strong	Biomarker	[15]
GHSR	TTWDC17	Strong	Biomarker	[13]
GIP	TT40HS5	Strong	Biomarker	[16]
HSD11B2	TT9H85R	Strong	Biomarker	[17]
MC2R	TTPWFDX	Strong	Biomarker	[18]
PCSK1	TTED9LZ	Strong	Biomarker	[19]
PCSK2	TT46F0P	Strong	Biomarker	[20]
PRKACA	TT5U49F	Strong	Genetic Variation	[21]
SERPINA6	TTJL8VG	Strong	Biomarker	[22]
SSTR1	TTIND6G	Strong	Altered Expression	[23]
SSTR5	TT2BC4G	Strong	Biomarker	[24]

This Disease Is Related to 1 DTP Molecule(s)

Gene Name	DTP ID	Evidence Level	Mode of Inheritance	REF
SLC20A1	DTMULXV	Strong	Biomarker	[25]

This Disease Is Related to 16 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
CDH23	OTOJGQ7S	Limited	SusceptibilityMutation	[26]
AIP	OTDJ3OSV	Strong	Genetic Variation	[27]
BGLAP	OTK1YLWQ	Strong	Altered Expression	[28]
CABLES1	OTMN4XSX	Strong	Biomarker	[29]
CIRBP	OTXWTPBL	Strong	Biomarker	[30]
CNTN3	OTC1274J	Strong	Altered Expression	[31]
GBA3	OT86XWU2	Strong	Biomarker	[22]
LPXN	OTUNV3CK	Strong	Biomarker	[32]
MED7	OTGF64SM	Strong	Altered Expression	[33]
MOCOS	OT0TL3Q5	Strong	Altered Expression	[31]
NDUFA2	OTNSTATK	Strong	Biomarker	[34]
NR2C2	OTDZWVOJ	Strong	Biomarker	[35]
PAX7	OTDMQRPO	Strong	Altered Expression	[36]
POU1F1	OTXT8A5C	Strong	Biomarker	[25]
SMCP	OTXKY794	Strong	Altered Expression	[31]
TBX19	OTXEMR2U	Strong	Altered Expression	[37]

References

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• [2] 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: 3633).
• [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: 5224).
• [4] 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: 2805).
• [5] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2020
• [6] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [7] 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: 6850).
• [8] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [9] ClinicalTrials.gov (NCT03697109) A Study of the Efficacy and Safety of Relacorilant in Patients With Endogenous Cushing Syndrome (GRACE). U.S. National Institutes of Health.
• [10] Inhibitory Effects of a Novel PPAR- Agonist MEKT1 on Pomc Expression/ACTH Secretion in AtT20 Cells.PPAR Res. 2018 Apr 23;2018:5346272. doi: 10.1155/2018/5346272. eCollection 2018.
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• [20] Possible relevance between prohormone convertase 2 expression and tumor growth in human adrenocorticotropin-producing pituitary adenoma.J Clin Endocrinol Metab. 2010 Aug;95(8):4003-11. doi: 10.1210/jc.2009-2716. Epub 2010 May 25.
• [21] Somatic PRKACA Mutations: Association With Transition From Pituitary-Dependent to Adrenal-Dependent Cushing Syndrome.J Clin Endocrinol Metab. 2019 Nov 1;104(11):5651-5657. doi: 10.1210/jc.2018-02209.
• [22] LONG-TERM OUTCOME OF THE DIFFERENT TREATMENT ALTERNATIVES FOR RECURRENT AND PERSISTENT CUSHING DISEASE.Endocr Pract. 2017 Jul;23(7):759-767. doi: 10.4158/EP171756.OR. Epub 2017 Mar 23.
• [23] High Expression of Somatostatin Receptors 2A, 3, and 5 in Corticotroph Pituitary Adenoma.Int J Endocrinol. 2018 Dec 9;2018:1763735. doi: 10.1155/2018/1763735. eCollection 2018.
• [24] Somatostatin receptor ligands and resistance to treatment in pituitary adenomas.J Mol Endocrinol. 2014 Jun;52(3):R223-40. doi: 10.1530/JME-14-0011. Epub 2014 Mar 19.
• [25] Multihormonal pituitary adenoma concomitant with Pit-1 and Tpit lineage cells causing acromegaly associated with subclinical Cushing's disease: a case report.BMC Endocr Disord. 2017 Sep 2;17(1):54. doi: 10.1186/s12902-017-0203-5.
• [26] Germline Mutations in CDH23, Encoding Cadherin-Related 23, Are Associated with Both Familial and Sporadic Pituitary Adenomas.Am J Hum Genet. 2017 May 4;100(5):817-823. doi: 10.1016/j.ajhg.2017.03.011. Epub 2017 Apr 13.
• [27] Germline AIP mutations in apparently sporadic pituitary adenomas: prevalence in a prospective single-center cohort of 443 patients.J Clin Endocrinol Metab. 2012 Apr;97(4):E663-70. doi: 10.1210/jc.2011-2291. Epub 2012 Feb 8.
• [28] Beyond the metabolic syndrome: Visceral and marrow adipose tissues impair bone quantity and quality in Cushing's disease.PLoS One. 2019 Oct 15;14(10):e0223432. doi: 10.1371/journal.pone.0223432. eCollection 2019.
• [29] PATHOGENESIS OF CUSHING DISEASE: AN UPDATE ON THE GENETICS OF CORTICOTROPINOMAS.Endocr Pract. 2018 Oct 2;24(10):907-914. doi: 10.4158/EP-2018-0111. Epub 2018 Aug 7.
• [30] Cold inducible RNA binding protein upregulation in pituitary corticotroph adenoma induces corticotroph cell proliferation via Erk signaling pathway.Oncotarget. 2016 Feb 23;7(8):9175-87. doi: 10.18632/oncotarget.7037.
• [31] Quality of life is significantly impaired in both secretory and non-functioning pituitary adenomas.Clin Endocrinol (Oxf). 2019 Mar;90(3):457-467. doi: 10.1111/cen.13915. Epub 2019 Jan 15.
• [32] Lipoprotein particles in patients with pediatric Cushing disease and possible cardiovascular risks.Pediatr Res. 2019 Sep;86(3):375-381. doi: 10.1038/s41390-019-0438-0. Epub 2019 May 21.
• [33] The Sp transcription factors are involved in the cellular expression of the human glucose-dependent insulinotropic polypeptide receptor gene and overexpressed in adrenals of patients with Cushing's syndrome.J Mol Endocrinol. 2005 Aug;35(1):61-71. doi: 10.1677/jme.1.01765.
• [34] Volumetric magnetic resonance imaging analysis in patients with short-term remission of Cushing's disease.Clin Endocrinol (Oxf). 2017 Oct;87(4):367-374. doi: 10.1111/cen.13381. Epub 2017 Jun 14.
• [35] Targeting the ERK pathway for the treatment of Cushing's disease.Oncotarget. 2016 Oct 25;7(43):69149-69158. doi: 10.18632/oncotarget.12381.
• [36] The selector gene Pax7 dictates alternate pituitary cell fates through its pioneer action on chromatin remodeling.Genes Dev. 2012 Oct 15;26(20):2299-310. doi: 10.1101/gad.200436.112.
• [37] Differential gene expression in ACTH -secreting and non-functioning pituitary tumors.Eur J Endocrinol. 2007 Dec;157(6):717-24. doi: 10.1530/EJE-07-0428.