KEGG   DISEASE: Cushing syndromeHelp
Entry
H01431                      Disease                                

Name
Cushing syndrome
  Subgroup
Pituitary adenoma [DS:H01102]
Non-pituitary tumor
CRH-producing tumor
Adrenocortical tumor
McCane Albright
Birateral macronodular adrenal hyperplasia [DS:H02049]
Primary pigmented nodular adrenal disease [DS:H00260]
Description
Cushing syndrome (CS) is a rare disorder resulting from prolonged exposure to excess glucocorticoids via exogenous and endogenous sources. The typical clinical features of CS are related to hypercortisolism and include accumulation of central fat, moon facies, neuromuscular weakness, osteoporosis or bone fractures, metabolic complications, and mood changes. Traditionally, endogenous CS is classified as adrenocorticotropic hormone (ACTH)-dependent (about 80%) or ACTH- independent (about 20%). Among ACTH-dependent forms, pituitary corticotroph adenoma (Cushing's disease) is most common. Most pituitary tumors are sporadic, resulting from monoclonal expansion of a single mutated cell. Recently recurrent activating somatic driver mutations in the ubiquitin-specific protease 8 gene (USP8) were identified in almost half of corticotroph adenoma. Germline mutations in MEN1 (encoding menin), AIP (encoding aryl-hydrocarbon receptor-interacting protein), PRKAR1A (encoding cAMP-dependent protein kinase type I alpha regulatory subunit) and CDKN1B (encoding cyclin-dependent kinase inhibitor 1B; also known as p27 Kip1) have been identified in familial forms of pituitary adenomas. However, the frequency of familial pituitary adenomas is less than 5% in patients with pituitary adenomas. Among ACTH-independent CS, adrenal adenoma is most common. Rare adrenal causes of CS include primary bilateral macronodular adrenal hyperplasia (BMAH) or primary pigmented nodular adrenocortical disease (PPNAD).
Category
Endocrine and metabolic disease
Brite
Human diseases [BR:br08402]
 Endocrine and metabolic diseases
  Adrenal gland diseases
   H01431  Cushing syndrome
Human diseases in ICD-11 classification [BR:br08403]
 05 Endocrine, nutritional or metabolic diseases
  Endocrine diseases
   Disorders of the adrenal glands or adrenal hormone system
    5A70  Cushing syndrome
     H01431  Cushing syndrome
BRITE hierarchy
Pathway
hsa04934  Cushing syndrome
Network
N00290  Mutation-inactivated MEN1 to transcription
N00315  Mutation-inactivated AIP to AhR-mediated transcription
N00316  Mutation-inactivated CDKN1B to p27-cell cycle G1/S
N00319  Mutation-activated USP8 to EGFR-ERK-ACTH signaling pathway
N00320  Mutation-activated PRKACA to ACTH-cortisol signaling pathway
N00321  Mutation-activated GNAS to ACTH-cortisol signaling pathway
N00322  Mutation-inactivated PRKAR1A to ACTH-cortisol signaling pathway
N00323  Mutation-inactivated PDE11A/PDE8B to ACTH-cortisol signaling pathway
N00325  Mutation-inactivated RASD1 to CRHR-PKA-ACTH signaling pathway
N00326  Mutation-activated GNAS to CRHR-PKA-ACTH signaling pathway
N00327  Mutation-inactivated PRKAR1A to CRHR-PKA-ACTH signaling pathway
 » show all
Gene
MEN1 [HSA:4221] [KO:K14970]
CDKN1B [HSA:1027] [KO:K06624]
PRKAR1A [HSA:5573] [KO:K04739]
AIP [HSA:9049] [KO:K17767]
GPR101 [HSA:83550] [KO:K08423]
GNAS [HSA:2778] [KO:K04632]
USP8 [HSA:9101] [KO:K11839]
PIK3CA [HSA:5290] [KO:K00922]
DICER1 [HSA:23405] [KO:K11592]
RASD1 [HSA:51655] [KO:K07843]
ARMC5 [HSA:79798] [KO:K22499]
FH [HSA:2271] [KO:K01679]
PDE11A [HSA:50940] [KO:K13298]
APC [HSA:324] [KO:K02085]
MC2R [HSA:4158] [KO:K04200]
PRKACA [HSA:5566] [KO:K04345]
PRKAR1A [HSA:5573] [KO:K04739]
PDE11A [HSA:50940] [KO:K13298]
PDE8B [HSA:8622] [KO:K18437]
Drug
Pasireotide diaspartate [DR:D10497]
Other DBs
ICD-11: 5A70
ICD-10: E24
MeSH: D003480
OMIM: 600634 610755 160980 102200 300943 617686 219090 219080 615954 610489 610475 603390
Reference
  Authors
Lacroix A, Feelders RA, Stratakis CA, Nieman LK
  Title
Cushing's syndrome.
  Journal
Lancet 386:913-27 (2015)
DOI:10.1016/S0140-6736(14)61375-1
Reference
  Authors
Lecoq AL, Kamenicky P, Guiochon-Mantel A, Chanson P
  Title
Genetic mutations in sporadic pituitary adenomas--what to screen for?
  Journal
Nat Rev Endocrinol 11:43-54 (2015)
DOI:10.1038/nrendo.2014.181
Reference
  Authors
Albani A, Theodoropoulou M, Reincke M
  Title
Genetics of Cushing's disease.
  Journal
Clin Endocrinol (Oxf) 88:3-12 (2018)
DOI:10.1111/cen.13457
Reference
  Authors
Uzilov AV, Cheesman KC, Fink MY, Newman LC, Pandya C, Lalazar Y, Hefti M, Fowkes M, Deikus G, Lau CY, Moe AS, Kinoshita Y, Kasai Y, Zweig M, Gupta A, Starcevic D, Mahajan M, Schadt EE, Post KD, Donovan MJ, Sebra R, Chen R, Geer EB
  Title
Identification of a novel RASD1 somatic mutation in a USP8-mutated corticotroph adenoma.
  Journal
Cold Spring Harb Mol Case Stud 3:a001602 (2017)
DOI:10.1101/mcs.a001602

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