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Cushing syndrome

MedGen UID:
3681
•Concept ID:
C0010481
•
Disease or Syndrome
Synonyms: Adrenal hyperfunction resulting from pituitary acth excess; Cushing's syndrome; Ectopic adrenocorticotropic hormone syndrome; Hyperadrenocorticism; Nodular primary adrenocortical dysplasia
SNOMED CT: Cushing's syndrome (47270006); Cushing's syndrome III (47270006); Suprarenogenic syndrome (47270006); Itsenko-Cushing syndrome (47270006); Itsenko disease (47270006)
Modes of inheritance:
Autosomal dominant inheritance
MedGen UID:
141047
•Concept ID:
C0443147
•
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in heterozygotes. In the context of medical genetics, an autosomal dominant disorder is caused when a single copy of the mutant allele is present. Males and females are affected equally, and can both transmit the disorder with a risk of 50% for each child of inheriting the mutant allele.
Not genetically inherited
MedGen UID:
988794
•Concept ID:
CN307044
•
Finding
Source: Orphanet
clinical entity without genetic inheritance.
See: This record
Autosomal dominant inheritance (Orphanet)
Not genetically inherited (Orphanet)
 
Related genes: ARMC5, USP8, AIP, GNAS
 
Monarch Initiative: MONDO:0018912
Orphanet: ORPHA553

Definition

Cushing's syndrome (CS) encompasses a group of hormonal disorders caused by prolonged and high exposure levels to glucocorticoids that can be of either endogenous (adrenal cortex production) or exogenous (iatrogenic) origin. [from ORDO]

Professional guidelines

PubMed

Prevention and Treatment of Glucocorticoid-Induced Osteoporosis in Adults: Consensus Recommendations From the Belgian Bone Club.
Laurent MR, Goemaere S, Verroken C, Bergmann P, Body JJ, Bruyère O, Cavalier E, Rozenberg S, Lapauw B, Gielen E
Front Endocrinol (Lausanne) 2022;13:908727. Epub 2022 Jun 9 doi: 10.3389/fendo.2022.908727. PMID: 35757436Free PMC Article
Glucocorticoid Withdrawal Syndrome following treatment of endogenous Cushing Syndrome.
He X, Findling JW, Auchus RJ
Pituitary 2022 Jun;25(3):393-403. Epub 2022 Apr 26 doi: 10.1007/s11102-022-01218-y. PMID: 35471718Free PMC Article
New perspectives for mitotane treatment of adrenocortical carcinoma.
Puglisi S, Calabrese A, Basile V, Pia A, Reimondo G, Perotti P, Terzolo M
Best Pract Res Clin Endocrinol Metab 2020 May;34(3):101415. Epub 2020 Mar 5 doi: 10.1016/j.beem.2020.101415. PMID: 32179008

Recent clinical studies

Etiology

Effects of endocrine disorders on lipids and lipoproteins.
Newman CB
Best Pract Res Clin Endocrinol Metab 2023 May;37(3):101667. Epub 2022 May 10 doi: 10.1016/j.beem.2022.101667. PMID: 35654682
The diagnosis and management of Cushing's syndrome in pregnancy.
Hamblin R, Coulden A, Fountas A, Karavitaki N
J Neuroendocrinol 2022 Aug;34(8):e13118. Epub 2022 May 1 doi: 10.1111/jne.13118. PMID: 35491087Free PMC Article
Impact of Cushing's syndrome on fertility and pregnancy.
Castinetti F, Brue T
Ann Endocrinol (Paris) 2022 Jun;83(3):188-190. Epub 2022 Apr 17 doi: 10.1016/j.ando.2022.04.001. PMID: 35443159
Alopecia and the metabolic syndrome.
Lie C, Liew CF, Oon HH
Clin Dermatol 2018 Jan-Feb;36(1):54-61. Epub 2017 Sep 8 doi: 10.1016/j.clindermatol.2017.09.009. PMID: 29241753
Complications of Cushing's syndrome: state of the art.
Pivonello R, Isidori AM, De Martino MC, Newell-Price J, Biller BM, Colao A
Lancet Diabetes Endocrinol 2016 Jul;4(7):611-29. Epub 2016 May 10 doi: 10.1016/S2213-8587(16)00086-3. PMID: 27177728

Diagnosis

Cushing Syndrome: A Review.
Reincke M, Fleseriu M
JAMA 2023 Jul 11;330(2):170-181. doi: 10.1001/jama.2023.11305. PMID: 37432427
Mechanism, diagnosis, and treatment of cyclic Cushing's syndrome: A review.
Cai Y, Ren L, Tan S, Liu X, Li C, Gang X, Wang G
Biomed Pharmacother 2022 Sep;153:113301. Epub 2022 Jun 17 doi: 10.1016/j.biopha.2022.113301. PMID: 35717778
Cushing's syndrome: Treatment and new therapeutic approaches.
Ferriere A, Tabarin A
Best Pract Res Clin Endocrinol Metab 2020 Mar;34(2):101381. Epub 2020 Jan 30 doi: 10.1016/j.beem.2020.101381. PMID: 32035797
Diagnosis of Cushing's Syndrome in the Modern Era.
Nieman LK
Endocrinol Metab Clin North Am 2018 Jun;47(2):259-273. doi: 10.1016/j.ecl.2018.02.001. PMID: 29754631
Cushing's syndrome: from physiological principles to diagnosis and clinical care.
Raff H, Carroll T
J Physiol 2015 Feb 1;593(3):493-506. Epub 2015 Jan 5 doi: 10.1113/jphysiol.2014.282871. PMID: 25480800Free PMC Article

Therapy

Cushing's syndrome.
Gadelha M, Gatto F, Wildemberg LE, Fleseriu M
Lancet 2023 Dec 9;402(10418):2237-2252. Epub 2023 Nov 17 doi: 10.1016/S0140-6736(23)01961-X. PMID: 37984386
Approach to the Patient: Diagnosis of Cushing Syndrome.
Savas M, Mehta S, Agrawal N, van Rossum EFC, Feelders RA
J Clin Endocrinol Metab 2022 Nov 23;107(11):3162-3174. doi: 10.1210/clinem/dgac492. PMID: 36036941Free PMC Article
Glucocorticoid Withdrawal Syndrome following treatment of endogenous Cushing Syndrome.
He X, Findling JW, Auchus RJ
Pituitary 2022 Jun;25(3):393-403. Epub 2022 Apr 26 doi: 10.1007/s11102-022-01218-y. PMID: 35471718Free PMC Article
Cushing's syndrome: Treatment and new therapeutic approaches.
Ferriere A, Tabarin A
Best Pract Res Clin Endocrinol Metab 2020 Mar;34(2):101381. Epub 2020 Jan 30 doi: 10.1016/j.beem.2020.101381. PMID: 32035797
Exogenous Cushing's syndrome and glucocorticoid withdrawal.
Hopkins RL, Leinung MC
Endocrinol Metab Clin North Am 2005 Jun;34(2):371-84, ix. doi: 10.1016/j.ecl.2005.01.013. PMID: 15850848

Prognosis

Hypercoagulability in Cushing's syndrome: incidence, pathogenesis and need for thromboprophylaxis protocols.
Feelders RA, Nieman LK
Pituitary 2022 Oct;25(5):746-749. Epub 2022 Jul 26 doi: 10.1007/s11102-022-01261-9. PMID: 35881275Free PMC Article
Epidemiology and mortality of Cushing's syndrome.
Hakami OA, Ahmed S, Karavitaki N
Best Pract Res Clin Endocrinol Metab 2021 Jan;35(1):101521. Epub 2021 Mar 15 doi: 10.1016/j.beem.2021.101521. PMID: 33766428
Pediatric adrenocortical tumours.
Pinto EM, Zambetti GP, Rodriguez-Galindo C
Best Pract Res Clin Endocrinol Metab 2020 May;34(3):101448. Epub 2020 Jul 3 doi: 10.1016/j.beem.2020.101448. PMID: 32636100
Is Follow-up of Adrenal Incidentalomas Always Mandatory?
Reimondo G, Muller A, Ingargiola E, Puglisi S, Terzolo M
Endocrinol Metab (Seoul) 2020 Mar;35(1):26-35. doi: 10.3803/EnM.2020.35.1.26. PMID: 32207261Free PMC Article
Adrenal mild hypercortisolism.
Goddard GM, Ravikumar A, Levine AC
Endocrinol Metab Clin North Am 2015 Jun;44(2):371-9. doi: 10.1016/j.ecl.2015.02.009. PMID: 26038206

Clinical prediction guides

Cushing Syndrome: A Review.
Reincke M, Fleseriu M
JAMA 2023 Jul 11;330(2):170-181. doi: 10.1001/jama.2023.11305. PMID: 37432427
Approach to the Patient: Diagnosis of Cushing Syndrome.
Savas M, Mehta S, Agrawal N, van Rossum EFC, Feelders RA
J Clin Endocrinol Metab 2022 Nov 23;107(11):3162-3174. doi: 10.1210/clinem/dgac492. PMID: 36036941Free PMC Article
Overview of the 2022 WHO Classification of Adrenal Cortical Tumors.
Mete O, Erickson LA, Juhlin CC, de Krijger RR, Sasano H, Volante M, Papotti MG
Endocr Pathol 2022 Mar;33(1):155-196. Epub 2022 Mar 14 doi: 10.1007/s12022-022-09710-8. PMID: 35288842Free PMC Article
Hirsutism in Women.
Matheson E, Bain J
Am Fam Physician 2019 Aug 1;100(3):168-175. PMID: 31361105
Cushing's Syndrome: Screening and Diagnosis.
Ceccato F, Boscaro M
High Blood Press Cardiovasc Prev 2016 Sep;23(3):209-15. Epub 2016 May 9 doi: 10.1007/s40292-016-0153-4. PMID: 27160717

Recent systematic reviews

Diagnostic challenges in cyclic Cushing's syndrome: a systematic review.
Nowak E, Vogel F, Albani A, Braun L, Rubinstein G, Zopp S, Ritzel K, Beuschlein F, Theodoropoulou M, Reincke M
Lancet Diabetes Endocrinol 2023 Aug;11(8):593-606. Epub 2023 Jul 7 doi: 10.1016/S2213-8587(23)00150-X. PMID: 37429301
Dynamic Testing for Differential Diagnosis of ACTH-Dependent Cushing Syndrome: A Systematic Review and Meta-analysis.
Ceccato F, Barbot M, Mondin A, Boscaro M, Fleseriu M, Scaroni C
J Clin Endocrinol Metab 2023 Apr 13;108(5):e178-e188. doi: 10.1210/clinem/dgac686. PMID: 36453141
Time to Diagnosis in Cushing's Syndrome: A Meta-Analysis Based on 5367 Patients.
Rubinstein G, Osswald A, Hoster E, Losa M, Elenkova A, Zacharieva S, Machado MC, Hanzu FA, Zopp S, Ritzel K, Riester A, Braun LT, Kreitschmann-Andermahr I, Storr HL, Bansal P, Barahona MJ, Cosaro E, Dogansen SC, Johnston PC, Santos de Oliveira R, Raftopoulos C, Scaroni C, Valassi E, van der Werff SJA, Schopohl J, Beuschlein F, Reincke M
J Clin Endocrinol Metab 2020 Mar 1;105(3) doi: 10.1210/clinem/dgz136. PMID: 31665382
Effectiveness of medical treatment for Cushing's syndrome: a systematic review and meta-analysis.
Broersen LHA, Jha M, Biermasz NR, Pereira AM, Dekkers OM
Pituitary 2018 Dec;21(6):631-641. doi: 10.1007/s11102-018-0897-z. PMID: 29855779Free PMC Article
Cushing's syndrome and pregnancy outcomes: a systematic review of published cases.
Caimari F, Valassi E, Garbayo P, Steffensen C, Santos A, Corcoy R, Webb SM
Endocrine 2017 Feb;55(2):555-563. Epub 2016 Oct 4 doi: 10.1007/s12020-016-1117-0. PMID: 27704478

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