| Entry |
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| Name |
Cushing syndrome |
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| 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] |
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| 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).
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| Category |
Endocrine and metabolic disease
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| 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
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| Pathway |
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| Network |
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| Element |
| 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 |
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| Gene |
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| Drug |
Pasireotide diaspartate [DR: D10497]
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| Other DBs |
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| Reference |
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| Authors |
Lacroix A, Feelders RA, Stratakis CA, Nieman LK |
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| Title |
Cushing's syndrome. |
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| Journal |
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| Reference |
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| Authors |
Lecoq AL, Kamenicky P, Guiochon-Mantel A, Chanson P |
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| Title |
Genetic mutations in sporadic pituitary adenomas--what to screen for? |
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| Journal |
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| Reference |
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| Authors |
Albani A, Theodoropoulou M, Reincke M |
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| Title |
Genetics of Cushing's disease. |
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| Journal |
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| Reference |
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| 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 |
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| Title |
Identification of a novel RASD1 somatic mutation in a USP8-mutated corticotroph adenoma. |
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| Journal |
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| LinkDB |
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