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Cushing syndrome due to macronodular adrenal hyperplasia

MedGen UID:
923388
•Concept ID:
C2062388
•
Disease or Syndrome
Synonyms: ACTH-independent macronodular adrenocortical hyperplasia; adrenocorticotropic hormone-independent macronodular adrenal hyperplasia; AIMAH; corticotropin-independent macronodular adrenal hyperplasia; Hypercortisolism due to macronodular adrenal hyperplasia; massive macronodular adrenocortical disease; MMAD; Primary bilateral macronodular adrenal hyperplasia; primary bilateral macronodular adrenal hyperplasia; primary macronodular adrenal hyperplasia
SNOMED CT: Hypercortisolism due to macronodular adrenal hyperplasia (720459002); Cushing syndrome due to macronodular adrenal hyperplasia (720459002)
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, GNAS
 
Monarch Initiative: MONDO:0009049
Orphanet: ORPHA189427

Definition

Adrenocorticotropic hormone independent macronodular adrenal hyperplasia (AIMAH) is a rare cause of Cushing syndrome with characteristics of nodular enlargement of both adrenal glands that produce excess cortisol. The disease presents a bimodal age distribution with a rare subset presenting in the first years of life, particularly associated to McCune-Albright syndrome. Most patients present in their fifth or sixth decade. The adrenal glands can be massively enlarged bilaterally with the presence of numerous macronodules; however diffuse adrenal enlargement without nodules has been described. AIMAH is most often reported as sporadic but there are increasing reports of familial cases with autosomal dominant transmission. [from SNOMEDCT_US]

Professional guidelines

PubMed

Unilateral Adrenalectomy for Primary Bilateral Macronodular Adrenal Hyperplasia: Analysis of 71 Cases.
Sheikh-Ahmad M, Dickstein G, Matter I, Shechner C, Bejar J, Reut M, Sroka G, Laniado M, Saiegh L
Exp Clin Endocrinol Diabetes 2020 Dec;128(12):827-834. Epub 2019 Oct 21 doi: 10.1055/a-0998-7884. PMID: 31634962
Diagnosis and management of primary bilateral macronodular adrenal hyperplasia.
Vassiliadi DA, Tsagarakis S
Endocr Relat Cancer 2019 Oct 1;26(10):R567-R581. doi: 10.1530/ERC-19-0240. PMID: 32053747
MANAGEMENT OF ENDOCRINE DISEASE: Differential diagnosis, investigation and therapy of bilateral adrenal incidentalomas.
Bourdeau I, El Ghorayeb N, Gagnon N, Lacroix A
Eur J Endocrinol 2018 Aug;179(2):R57-R67. Epub 2018 May 10 doi: 10.1530/EJE-18-0296. PMID: 29748231

Recent clinical studies

Etiology

PPARG dysregulation as a potential molecular target in adrenal Cushing's syndrome.
Vetrivel S, Tamburello M, Oßwald A, Zhang R, Khan A, Jung S, Baker JE, Rainey WE, Nowak E, Altieri B, Detomas M, Watts D, Williams TA, Wielockx B, Beuschlein F, Reincke M, Sbiera S, Riester A
Front Endocrinol (Lausanne) 2023;14:1265794. Epub 2023 Nov 30 doi: 10.3389/fendo.2023.1265794. PMID: 38098864Free PMC Article
Primary bilateral macronodular adrenal hyperplasia: A series of 32 cases and literature review.
Araujo-Castro M, Reincke M
Endocrinol Diabetes Nutr (Engl Ed) 2023 Apr;70(4):229-239. doi: 10.1016/j.endien.2023.04.005. PMID: 37116968
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
Different therapeutic options in patients with Cushing's syndrome due to bilateral macronodular adrenal hyperplasia.
Albiger NM, Regazzo D, Iacobone M, Scaroni C
Minerva Endocrinol 2019 Jun;44(2):205-220. Epub 2017 Nov 3 doi: 10.23736/S0391-1977.17.02771-7. PMID: 29105481
Steroids and hypertension.
Mantero F, Armanini D, Boscaro M, Carpenè G, Fallo F, Opocher G, Rocco S, Scaroni C, Sonino N
J Steroid Biochem Mol Biol 1991;40(1-3):35-44. doi: 10.1016/0960-0760(91)90165-2. PMID: 1958539

Diagnosis

Adrenal Cushing's syndrome in children.
Guarnotta V, Emanuele F, Salzillo R, Giordano C
Front Endocrinol (Lausanne) 2023;14:1329082. Epub 2023 Dec 12 doi: 10.3389/fendo.2023.1329082. PMID: 38192416Free 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
Update on primary bilateral macronodular adrenal hyperplasia (PBMAH).
Bouys L, Chiodini I, Arlt W, Reincke M, Bertherat J
Endocrine 2021 Mar;71(3):595-603. Epub 2021 Feb 15 doi: 10.1007/s12020-021-02645-w. PMID: 33587256
Diagnosis and management of primary bilateral macronodular adrenal hyperplasia.
Vassiliadi DA, Tsagarakis S
Endocr Relat Cancer 2019 Oct 1;26(10):R567-R581. doi: 10.1530/ERC-19-0240. PMID: 32053747
Cushing's disease.
Bertagna X, Guignat L, Groussin L, Bertherat J
Best Pract Res Clin Endocrinol Metab 2009 Oct;23(5):607-23. doi: 10.1016/j.beem.2009.06.001. PMID: 19945026

Therapy

Primary bilateral macronodular adrenal hyperplasia: A series of 32 cases and literature review.
Araujo-Castro M, Reincke M
Endocrinol Diabetes Nutr (Engl Ed) 2023 Apr;70(4):229-239. doi: 10.1016/j.endien.2023.04.005. PMID: 37116968
MicroRNA expression signature and target prediction in familial and sporadic primary macronodular adrenal hyperplasia (PMAH).
Tan XG, Zhu J, Cui L
BMC Endocr Disord 2022 Jan 5;22(1):11. doi: 10.1186/s12902-021-00910-7. PMID: 34986816Free PMC Article
Diagnosis and management of primary bilateral macronodular adrenal hyperplasia.
Vassiliadi DA, Tsagarakis S
Endocr Relat Cancer 2019 Oct 1;26(10):R567-R581. doi: 10.1530/ERC-19-0240. PMID: 32053747
Pharmacologic management of Cushing syndrome : new targets for therapy.
Sonino N, Boscaro M, Fallo F
Treat Endocrinol 2005;4(2):87-94. doi: 10.2165/00024677-200504020-00003. PMID: 15783246
Classic and recent etiologies of Cushing's syndrome: diagnosis and therapy.
Beauregard C, Dickstein G, Lacroix A
Treat Endocrinol 2002;1(2):79-94. doi: 10.2165/00024677-200201020-00002. PMID: 15765624

Prognosis

Characterization of Adrenal miRNA-Based Dysregulations in Cushing's Syndrome.
Vetrivel S, Zhang R, Engel M, Oßwald A, Watts D, Chen A, Wielockx B, Sbiera S, Reincke M, Riester A
Int J Mol Sci 2022 Jul 12;23(14) doi: 10.3390/ijms23147676. PMID: 35887024Free 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
Genomic insights into Cushing syndrome.
Assié G
Ann Endocrinol (Paris) 2018 Jun;79(3):119-122. Epub 2018 May 4 doi: 10.1016/j.ando.2018.03.011. PMID: 29735160
Clinicopathological correlates of adrenal Cushing's syndrome.
Duan K, Gomez Hernandez K, Mete O
J Clin Pathol 2015 Mar;68(3):175-86. Epub 2014 Nov 25 doi: 10.1136/jclinpath-2014-202612. PMID: 25425660
Cushing's disease.
Bertagna X, Guignat L, Groussin L, Bertherat J
Best Pract Res Clin Endocrinol Metab 2009 Oct;23(5):607-23. doi: 10.1016/j.beem.2009.06.001. PMID: 19945026

Clinical prediction guides

Characterization of Adrenal miRNA-Based Dysregulations in Cushing's Syndrome.
Vetrivel S, Zhang R, Engel M, Oßwald A, Watts D, Chen A, Wielockx B, Sbiera S, Reincke M, Riester A
Int J Mol Sci 2022 Jul 12;23(14) doi: 10.3390/ijms23147676. PMID: 35887024Free 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
Update of Genetic and Molecular Causes of Adrenocortical Hyperplasias Causing Cushing Syndrome.
Berthon A, Bertherat J
Horm Metab Res 2020 Aug;52(8):598-606. Epub 2020 Feb 25 doi: 10.1055/a-1061-7349. PMID: 32097969
Genetics of primary bilateral macronodular adrenal hyperplasia: a model for early diagnosis of Cushing's syndrome?
Drougat L, Espiard S, Bertherat J
Eur J Endocrinol 2015 Oct;173(4):M121-31. Epub 2015 Aug 11 doi: 10.1530/EJE-15-0532. PMID: 26264719
Clinicopathological correlates of adrenal Cushing's syndrome.
Duan K, Gomez Hernandez K, Mete O
J Clin Pathol 2015 Mar;68(3):175-86. Epub 2014 Nov 25 doi: 10.1136/jclinpath-2014-202612. PMID: 25425660

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