| H01431 | |
| H番号 | H01431 |
| 名称 | クッシング症候群 |
| 概要 | 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). |
| カテゴリ | 内分泌代謝疾患 疾患パスウェイ hsa04934 クッシング症候群 |
| ネットワーク | nt06310 CRH-ACTH-cortisol signaling nt06360 Cushing syndrome |
| 病因遺伝子 | (MEN1) MEN1 [HSA:4221] [KO:K14970] (MEN4) CDKN1B [HSA:1027] [KO:K06624] (CNC1) PRKAR1A [HSA:5573] [KO:K04739] (PITA1) AIP [HSA:9049] [KO:K17767] (PITA2) GPR101 [HSA:83550] [KO:K08423] (PITA3) GNAS [HSA:2778] [KO:K04632] (PITA4) USP8 [HSA:9101] [KO:K11839] (PITA5) CDH23 [HSA:64072] [KO:K06813] (AIMAH2) ARMC5 [HSA:79798] [KO:K22499] (PPNAD1) PRKAR1A [HSA:5573] [KO:K04739] (PPNAD2) PDE11A [HSA:50940] [KO:K13298] (PPNAD3) PDE8B [HSA:8622] [KO:K18437] (PPNAD4) PRKACA [HSA:5566] [KO:K04345] RASD1 [HSA:51655] [KO:K07843] |
| 病原体 | - |
| 環境要因 | - |
| 発癌物質 | - |
| 治療薬 | パシレオチドパモ酸塩 [DR:D10566] トリロスタン [DR:D01180] オシロドロスタットリン酸塩 [DR:D11062] ミトタン [DR:D00420] メチラポン [DR:D00410] |
| コメント | - |
| リンク | ICD-11: 5A70 ICD-10: E24 MeSH: D003480 OMIM: 131100 610755 160980 102200 300943 617686 219090 617540 219080 615954 610489 610475 614190 615830 |
| 文献 | PMID:26004339 著者 Lacroix A, Feelders RA, Stratakis CA, Nieman LK タイトル Cushing's syndrome. 雑誌 Lancet 386:913-27 (2015) DOI:10.1016/S0140-6736(14)61375-1 PMID:25350067 著者 Lecoq AL, Kamenicky P, Guiochon-Mantel A, Chanson P タイトル Genetic mutations in sporadic pituitary adenomas--what to screen for? 雑誌 Nat Rev Endocrinol 11:43-54 (2015) DOI:10.1038/nrendo.2014.181 PMID:28850717 著者 Albani A, Theodoropoulou M, Reincke M タイトル Genetics of Cushing's disease. 雑誌 Clin Endocrinol (Oxf) 88:3-12 (2018) DOI:10.1111/cen.13457 PMID:12791038 (MEN1) 著者 Park JH, Kim IJ, Kang HC, Lee SH, Shin Y, Kim KH, Lim SB, Kang SB, Lee K, Kim SY, Lee MS, Lee MK, Park JH, Moon SD, Park JG タイトル Germline mutations of the MEN1 gene in Korean families with multiple endocrine neoplasia type 1 (MEN1) or MEN1-related disorders. 雑誌 Clin Genet 64:48-53 (2003) DOI:10.1034/j.1399-0004.2003.00091.x PMID:17030811 (CDKN1B) 著者 Pellegata NS, Quintanilla-Martinez L, Siggelkow H, Samson E, Bink K, Hofler H, Fend F, Graw J, Atkinson MJ タイトル Germ-line mutations in p27Kip1 cause a multiple endocrine neoplasia syndrome in rats and humans. 雑誌 Proc Natl Acad Sci U S A 103:15558-63 (2006) DOI:10.1073/pnas.0603877103 PMID:12812976 (PRKAR1A) 著者 Robinson-White A, Hundley TR, Shiferaw M, Bertherat J, Sandrini F, Stratakis CA タイトル Protein kinase-A activity in PRKAR1A-mutant cells, and regulation of mitogen-activated protein kinases ERK1/2. 雑誌 Hum Mol Genet 12:1475-84 (2003) DOI:10.1093/hmg/ddg160 PMID:16728643 (AIP) 著者 Vierimaa O, Georgitsi M, Lehtonen R, Vahteristo P, Kokko A, Raitila A, Tuppurainen K, Ebeling TM, Salmela PI, Paschke R, Gundogdu S, De Menis E, Makinen MJ, Launonen V, Karhu A, Aaltonen LA タイトル Pituitary adenoma predisposition caused by germline mutations in the AIP gene. 雑誌 Science 312:1228-30 (2006) DOI:10.1126/science.1126100 PMID:25470569 (GPR101) 著者 Trivellin G, Daly AF, Faucz FR, Yuan B, Rostomyan L, Larco DO, Schernthaner-Reiter MH, Szarek E, Leal LF, Caberg JH, Castermans E, Villa C, Dimopoulos A, Chittiboina P, Xekouki P, Shah N, Metzger D, Lysy PA, Ferrante E, Strebkova N, Mazerkina N, Zatelli MC, Lodish M, Horvath A, de Alexandre RB, Manning AD, Levy I, Keil MF, Sierra Mde L, Palmeira L, Coppieters W, Georges M, Naves LA, Jamar M, Bours V, Wu TJ, Choong CS, Bertherat J, Chanson P, Kamenicky P, Farrell WE, Barlier A, Quezado M, Bjelobaba I, Stojilkovic SS, Wess J, Costanzi S, Liu P, Lupski JR, Beckers A, Stratakis CA タイトル Gigantism and acromegaly due to Xq26 microduplications and GPR101 mutation. 雑誌 N Engl J Med 371:2363-74 (2014) DOI:10.1056/NEJMoa1408028 PMID:7737262 (GNAS) 著者 Williamson EA, Ince PG, Harrison D, Kendall-Taylor P, Harris PE タイトル G-protein mutations in human pituitary adrenocorticotrophic hormone-secreting adenomas. 雑誌 Eur J Clin Invest 25:128-31 (1995) DOI:10.1111/j.1365-2362.1995.tb01537.x PMID:25485838 (USP8) 著者 Reincke M, Sbiera S, Hayakawa A, Theodoropoulou M, Osswald A, Beuschlein F, Meitinger T, Mizuno-Yamasaki E, Kawaguchi K, Saeki Y, Tanaka K, Wieland T, Graf E, Saeger W, Ronchi CL, Allolio B, Buchfelder M, Strom TM, Fassnacht M, Komada M タイトル Mutations in the deubiquitinase gene USP8 cause Cushing's disease. 雑誌 Nat Genet 47:31-8 (2015) DOI:10.1038/ng.3166 PMID:28413019 (CDH23) 著者 Zhang Q, Peng C, Song J, Zhang Y, Chen J, Song Z, Shou X, Ma Z, Peng H, Jian X, He W, Ye Z, Li Z, Wang Y, Ye H, Zhang Z, Shen M, Tang F, Chen H, Shi Z, Chen C, Chen Z, Shen Y, Wang Y, Lu S, Zhang J, Li Y, Li S, Mao Y, Zhou L, Yan H, Shi Y, Huang C, Zhao Y タイトル Germline Mutations in CDH23, Encoding Cadherin-Related 23, Are Associated with Both Familial and Sporadic Pituitary Adenomas. 雑誌 Am J Hum Genet 100:817-823 (2017) DOI:10.1016/j.ajhg.2017.03.011 PMID:24601692 (ARMC5) 著者 Faucz FR, Zilbermint M, Lodish MB, Szarek E, Trivellin G, Sinaii N, Berthon A, Libe R, Assie G, Espiard S, Drougat L, Ragazzon B, Bertherat J, Stratakis CA タイトル Macronodular adrenal hyperplasia due to mutations in an armadillo repeat containing 5 (ARMC5) gene: a clinical and genetic investigation. 雑誌 J Clin Endocrinol Metab 99:E1113-9 (2014) DOI:10.1210/jc.2013-4280 PMID:12213893 (PRKAR1A) 著者 Groussin L, Jullian E, Perlemoine K, Louvel A, Leheup B, Luton JP, Bertagna X, Bertherat J タイトル Mutations of the PRKAR1A gene in Cushing's syndrome due to sporadic primary pigmented nodular adrenocortical disease. 雑誌 J Clin Endocrinol Metab 87:4324-9 (2002) DOI:10.1210/jc.2002-020592 PMID:16767104 (PDE11A) 著者 Horvath A, Boikos S, Giatzakis C, Robinson-White A, Groussin L, Griffin KJ, Stein E, Levine E, Delimpasi G, Hsiao HP, Keil M, Heyerdahl S, Matyakhina L, Libe R, Fratticci A, Kirschner LS, Cramer K, Gaillard RC, Bertagna X, Carney JA, Bertherat J, Bossis I, Stratakis CA タイトル A genome-wide scan identifies mutations in the gene encoding phosphodiesterase 11A4 (PDE11A) in individuals with adrenocortical hyperplasia. 雑誌 Nat Genet 38:794-800 (2006) DOI:10.1038/ng1809 PMID:18272904 (PDE8B) 著者 Horvath A, Mericq V, Stratakis CA タイトル Mutation in PDE8B, a cyclic AMP-specific phosphodiesterase in adrenal hyperplasia. 雑誌 N Engl J Med 358:750-2 (2008) DOI:10.1056/NEJMc0706182 PMID:24571724 (PRKACA) 著者 Beuschlein F, Fassnacht M, Assie G, Calebiro D, Stratakis CA, Osswald A, Ronchi CL, Wieland T, Sbiera S, Faucz FR, Schaak K, Schmittfull A, Schwarzmayr T, Barreau O, Vezzosi D, Rizk-Rabin M, Zabel U, Szarek E, Salpea P, Forlino A, Vetro A, Zuffardi O, Kisker C, Diener S, Meitinger T, Lohse MJ, Reincke M, Bertherat J, Strom TM, Allolio B タイトル Constitutive activation of PKA catalytic subunit in adrenal Cushing's syndrome. 雑誌 N Engl J Med 370:1019-28 (2014) DOI:10.1056/NEJMoa1310359 PMID:28487882 (RASD1) 著者 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 タイトル Identification of a novel RASD1 somatic mutation in a USP8-mutated corticotroph adenoma. 雑誌 Cold Spring Harb Mol Case Stud 3:a001602 (2017) DOI:10.1101/mcs.a001602 |