AIMAH2
MCID: ACT202
MIFTS: 34

Acth-Independent Macronodular Adrenal Hyperplasia 2 (AIMAH2)

Categories: Bone diseases, Cardiovascular diseases, Endocrine diseases, Genetic diseases, Metabolic diseases, Rare diseases, Reproductive diseases

Aliases & Classifications for Acth-Independent Macronodular Adrenal Hyperplasia 2

MalaCards integrated aliases for Acth-Independent Macronodular Adrenal Hyperplasia 2:

Name: Acth-Independent Macronodular Adrenal Hyperplasia 2 57 12 72 29 6 39 17 70
Primary Macronodular Adrenal Hyperplasia 57 43 72
Aimah2 57 12 72
Acth-Independent Macronodular Adrenal Hyperplasia 43 70
Adrenocorticotropic Hormone-Independent Macronodular Adrenal Hyperplasia 43
Corticotropin-Independent Macronodular Adrenal Hyperplasia 43
Acth-Independent Macronodular Adrenocortical Hyperplasia 43
Primary Bilateral Macronodular Adrenal Hyperplasia 43
Adrenal Cushing Syndrome Due to Aimah 43
Aimah 43
Pmah 43

Characteristics:

OMIM®:

57 (Updated 20-May-2021)
Inheritance:
somatic mutation
autosomal dominant


HPO:

31
acth-independent macronodular adrenal hyperplasia 2:
Inheritance autosomal dominant inheritance somatic mutation
Onset and clinical course adult onset


Classifications:



Summaries for Acth-Independent Macronodular Adrenal Hyperplasia 2

MedlinePlus Genetics : 43 Primary macronodular adrenal hyperplasia (PMAH) is a disorder characterized by multiple lumps (nodules) in the adrenal glands, which are small hormone-producing glands located on top of each kidney. These nodules, which usually are found in both adrenal glands (bilateral) and vary in size, cause adrenal gland enlargement (hyperplasia) and result in the production of higher-than-normal levels of the hormone cortisol. Cortisol is an important hormone that suppresses inflammation and protects the body from physical stress such as infection or trauma through several mechanisms including raising blood sugar levels.PMAH typically becomes evident in a person's forties or fifties. It is considered a form of Cushing syndrome, which is characterized by increased levels of cortisol resulting from one of many possible causes. These increased cortisol levels lead to weight gain in the face and upper body, fragile skin, bone loss, fatigue, and other health problems. However, some people with PMAH do not experience these signs and symptoms and are said to have subclinical Cushing syndrome.

MalaCards based summary : Acth-Independent Macronodular Adrenal Hyperplasia 2, also known as primary macronodular adrenal hyperplasia, is related to acth-independent macronodular adrenal hyperplasia 1 and acth-independent macronodular adrenal hyperplasia, and has symptoms including agitation and generalized fatigue. An important gene associated with Acth-Independent Macronodular Adrenal Hyperplasia 2 is ARMC5 (Armadillo Repeat Containing 5). Affiliated tissues include adrenal gland, brain and heart, and related phenotypes are abdominal obesity and decreased circulating acth level

Disease Ontology : 12 An ACTH-independent macronodular adrenal hyperplasia that has material basis in a combination of autosomal dominant and second hit somatic mutation in ARMC5 on chromosome 16p11.2.

OMIM® : 57 ACTH-independent macronodular adrenal hyperplasia-2 is an autosomal dominant tumor susceptibility with syndromic incomplete penetrance, as a second hit to the ARMC5 gene is required to develop macronodular hyperplasia (Assie et al., 2013). (615954) (Updated 20-May-2021)

UniProtKB/Swiss-Prot : 72 ACTH-independent macronodular adrenal hyperplasia 2: A form of macronodular adrenal hyperplasia characterized by multiple, bilateral, non-pigmented, benign, adrenocortical nodules. It results in excessive production of cortisol leading to ACTH-independent Cushing syndrome. Clinical manifestations of Cushing syndrome include facial and truncal obesity, abdominal striae, muscular weakness, osteoporosis, arterial hypertension, diabetes.

Related Diseases for Acth-Independent Macronodular Adrenal Hyperplasia 2

Diseases in the Acth-Independent Macronodular Adrenal Hyperplasia family:

Acth-Independent Macronodular Adrenal Hyperplasia 2 Acth-Independent Macronodular Adrenal Hyperplasia 1

Diseases related to Acth-Independent Macronodular Adrenal Hyperplasia 2 via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 48)
# Related Disease Score Top Affiliating Genes
1 acth-independent macronodular adrenal hyperplasia 1 11.9
2 acth-independent macronodular adrenal hyperplasia 11.6
3 conn's syndrome 10.4
4 hypokalemia 10.3
5 bilateral massive adrenal hemorrhage 10.3
6 allergic disease 10.3
7 meningioma, familial 10.3
8 intracranial meningioma 10.3
9 secretory meningioma 10.3
10 lymphoplasmacyte-rich meningioma 10.3
11 adrenal cortical adenoma 10.3
12 adrenal adenoma 10.3
13 hyperinsulinism 10.3
14 insulinoma 10.3
15 nelson syndrome 10.3
16 hypoglycemia 10.3
17 tremor 10.3
18 multiple endocrine neoplasia, type i 10.3
19 mccune-albright syndrome 10.3
20 adrenocortical carcinoma, hereditary 10.3
21 alacrima, achalasia, and mental retardation syndrome 10.3
22 adrenal cortical carcinoma 10.3
23 primary pigmented nodular adrenocortical disease 10.3
24 polycystic kidney disease 10.3
25 glucose intolerance 10.3
26 hemiplegia 10.3
27 infant gynecomastia 10.3
28 gynecomastia 10.3
29 impotence 10.3
30 multiple endocrine neoplasia 10.3
31 adrenal cortical adenocarcinoma 10.3
32 hyperglycemia 10.3
33 adenoma 10.3
34 pulmonary embolism 10.3
35 aldosterone-producing adenoma 10.3
36 overgrowth syndrome 10.3
37 pheochromocytoma 10.2
38 body mass index quantitative trait locus 1 10.2
39 adrenal gland pheochromocytoma 10.2
40 hypogonadism 10.2
41 exophthalmos 10.2
42 acth-independent cushing syndrome 10.2
43 brain meningioma 10.1
44 coloboma, congenital heart disease, ichthyosiform dermatosis, mental retardation, and ear anomalies syndrome 9.9
45 gallbladder disease 1 9.9
46 primary hyperparathyroidism 9.9
47 hyperparathyroidism 9.9
48 muscular atrophy 9.9

Graphical network of the top 20 diseases related to Acth-Independent Macronodular Adrenal Hyperplasia 2:



Diseases related to Acth-Independent Macronodular Adrenal Hyperplasia 2

Symptoms & Phenotypes for Acth-Independent Macronodular Adrenal Hyperplasia 2

Human phenotypes related to Acth-Independent Macronodular Adrenal Hyperplasia 2:

31 (show all 11)
# Description HPO Frequency HPO Source Accession
1 abdominal obesity 31 occasional (7.5%) HP:0012743
2 decreased circulating acth level 31 very rare (1%) HP:0002920
3 increased urinary cortisol level 31 very rare (1%) HP:0012030
4 increased circulating cortisol level 31 very rare (1%) HP:0003118
5 depressivity 31 HP:0000716
6 hypertension 31 HP:0000822
7 fatigue 31 HP:0012378
8 osteoporosis 31 HP:0000939
9 round face 31 HP:0000311
10 hyperglycemia 31 HP:0003074
11 macronodular adrenal hyperplasia 31 HP:0008231

Symptoms via clinical synopsis from OMIM®:

57 (Updated 20-May-2021)
Skeletal:
osteoporosis

Laboratory Abnormalities:
hyperglycemia

Metabolic Features:
generalized fatigue

Growth Weight:
central obesity (in some patients)
weight gain (in some patients)

Head And Neck Face:
round face

Endocrine Features:
macronodular adrenal hyperplasia
high plasma cortisol
low adrenocorticotropic hormone (acth)

Neurologic Behavioral Psychiatric Manifestations:
depression
cognitive changes

Cardiovascular Vascular:
hypertension (in all patients)

Clinical features from OMIM®:

615954 (Updated 20-May-2021)

UMLS symptoms related to Acth-Independent Macronodular Adrenal Hyperplasia 2:


agitation; generalized fatigue

Drugs & Therapeutics for Acth-Independent Macronodular Adrenal Hyperplasia 2

Search Clinical Trials , NIH Clinical Center for Acth-Independent Macronodular Adrenal Hyperplasia 2

Genetic Tests for Acth-Independent Macronodular Adrenal Hyperplasia 2

Genetic tests related to Acth-Independent Macronodular Adrenal Hyperplasia 2:

# Genetic test Affiliating Genes
1 Acth-Independent Macronodular Adrenal Hyperplasia 2 29 ARMC5

Anatomical Context for Acth-Independent Macronodular Adrenal Hyperplasia 2

MalaCards organs/tissues related to Acth-Independent Macronodular Adrenal Hyperplasia 2:

40
Adrenal Gland, Brain, Heart, Kidney

Publications for Acth-Independent Macronodular Adrenal Hyperplasia 2

Articles related to Acth-Independent Macronodular Adrenal Hyperplasia 2:

(show all 27)
# Title Authors PMID Year
1
ARMC5 mutations are common in familial bilateral macronodular adrenal hyperplasia. 6 57
24905064 2014
2
Macronodular adrenal hyperplasia due to mutations in an armadillo repeat containing 5 (ARMC5) gene: a clinical and genetic investigation. 6 57
24601692 2014
3
ARMC5 mutations in macronodular adrenal hyperplasia with Cushing's syndrome. 6 57
24283224 2013
4
ARMC5 mutations are a frequent cause of primary macronodular adrenal Hyperplasia. 61 57
24708098 2014
5
Familial vasopressin-sensitive ACTH-independent macronodular adrenal hyperplasia (VPs-AIMAH): clinical studies of three kindreds. 57
19018784 2009
6
Genetic alteration of ARMC5 in a patient diagnosed with meningioma and primary macronodular adrenal hyperplasia: a case report. 61
33105102 2020
7
Primary macronodular adrenal hyperplasia (PMAH) can be generated by a new ARMC5 germline variant (c.52C>T (p.Gln18X)). 61
32713866 2020
8
A New Insight into the Surgical Treatment of Primary Macronodular Adrenal Hyperplasia. 61
32724871 2020
9
ARMC5 mutations are associated with high levels of proliferating cell nuclear antigen and the presence of the serotonin receptor 5HT4R in PMAH nodules. 61
32267363 2020
10
Allelic Variants of ARMC5 in Patients With Adrenal Incidentalomas and in Patients With Cushing's Syndrome Associated With Bilateral Adrenal Nodules. 61
32117062 2020
11
ARMC5 Alterations in Primary Macronodular Adrenal Hyperplasia (PMAH) and the Clinical State of Variant Carriers. 61
31555754 2019
12
Adrenal tumors: when to search for a germline abnormality? 61
30985498 2019
13
Genetics of primary macronodular adrenal hyperplasia. 61
30075949 2018
14
Genomic insights into Cushing syndrome. 61
29735160 2018
15
Whole-genome sequencing revealed armadillo repeat containing 5 (ARMC5) mutation in a Chinese family with ACTH-independent macronodular adrenal hyperplasia. 61
29279458 2018
16
Age-dependent effects of Armc5 haploinsufficiency on adrenocortical function. 61
28911199 2017
17
Long-term Results after CT-Guided Percutaneous Ethanol Ablation for the Treatment of Hyperfunctioning Adrenal Disorders. 61
27759849 2016
18
The Use of Three-dimensional Printers for Partial Adrenalectomy: Estimating the Resection Limits. 61
26775074 2016
19
High 18F-FDG uptake in PMAH correlated with normal expression of Glut1, HK1, HK2, and HK3. 61
25766729 2016
20
Etiopathogeny of Primary Adrenal Hypercortisolism. 61
27212135 2016
21
The ARMC5 gene shows extensive genetic variance in primary macronodular adrenocortical hyperplasia. 61
26162405 2015
22
GERMLINE DELETION OF ARMC5 IN FAMILIAL PRIMARY MACRONODULAR ADRENAL HYPERPLASIA. 61
26214113 2015
23
Primary Aldosteronism and ARMC5 Variants. 61
25822102 2015
24
ARMC5 Mutations in a Large Cohort of Primary Macronodular Adrenal Hyperplasia: Clinical and Functional Consequences. 61
25853793 2015
25
Molecular and clinical evidence for an ARMC5 tumor syndrome: concurrent inactivating germline and somatic mutations are associated with both primary macronodular adrenal hyperplasia and meningioma. 61
25279498 2015
26
Genetics of primary macronodular adrenal hyperplasia. 61
25472909 2015
27
Familial ACTH-independent Cushing's syndrome with bilateral macronodular adrenal hyperplasia clinically affecting only female family members. 61
12373631 2002

Variations for Acth-Independent Macronodular Adrenal Hyperplasia 2

ClinVar genetic disease variations for Acth-Independent Macronodular Adrenal Hyperplasia 2:

6
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 ARMC5 NM_001105247.2(ARMC5):c.799C>T (p.Arg267Ter) SNV Pathogenic 144052 rs369721476 GRCh37: 16:31473667-31473667
GRCh38: 16:31462346-31462346
2 ARMC5 NM_001105247.2(ARMC5):c.2692C>T (p.Arg898Trp) SNV Pathogenic 144053 rs587777659 GRCh37: 16:31478094-31478094
GRCh38: 16:31466773-31466773
3 ARMC5 NM_001105247.2(ARMC5):c.256C>T (p.Gln86Ter) SNV Pathogenic 144054 rs587777660 GRCh37: 16:31471101-31471101
GRCh38: 16:31459780-31459780
4 ARMC5 NM_001105247.2(ARMC5):c.1643T>C (p.Leu548Pro) SNV Pathogenic 144055 rs587777661 GRCh37: 16:31475987-31475987
GRCh38: 16:31464666-31464666
5 ARMC5 ARMC5, 1-BP DEL, G Deletion Pathogenic 144056 GRCh37:
GRCh38:
6 ARMC5 NM_001105247.2(ARMC5):c.1777C>T (p.Arg593Trp) SNV Pathogenic 144057 rs587777662 GRCh37: 16:31476121-31476121
GRCh38: 16:31464800-31464800
7 ARMC5 NM_001105247.2(ARMC5):c.1094T>C (p.Leu365Pro) SNV Pathogenic 144058 rs587777663 GRCh37: 16:31473962-31473962
GRCh38: 16:31462641-31462641
8 ARMC5 NM_001105247.2(ARMC5):c.1762_1766GGCGC[3] (p.Leu591fs) Microsatellite Likely pathogenic 666958 rs1596605496 GRCh37: 16:31476105-31476106
GRCh38: 16:31464784-31464785
9 ARMC5 NM_001105247.2(ARMC5):c.1864+198T>A SNV Uncertain significance 1032625 GRCh37: 16:31476406-31476406
GRCh38: 16:31465085-31465085
10 ARMC5 NM_001105247.2(ARMC5):c.2657G>A (p.Arg886His) SNV Uncertain significance 1032626 GRCh37: 16:31478059-31478059
GRCh38: 16:31466738-31466738

UniProtKB/Swiss-Prot genetic disease variations for Acth-Independent Macronodular Adrenal Hyperplasia 2:

72 (show all 17)
# Symbol AA change Variation ID SNP ID
1 ARMC5 p.Leu156Phe VAR_072354 rs114930262
2 ARMC5 p.Arg315Gln VAR_072355 rs141597457
3 ARMC5 p.Arg315Trp VAR_072356
4 ARMC5 p.Arg593Trp VAR_072358 rs587777662
5 ARMC5 p.Arg898Trp VAR_072360 rs587777659
6 ARMC5 p.Cys139Arg VAR_079100
7 ARMC5 p.Leu331Pro VAR_079104
8 ARMC5 p.Arg362Leu VAR_079105
9 ARMC5 p.Arg362Trp VAR_079106 rs138539760
10 ARMC5 p.Leu365Pro VAR_079108 rs587777663
11 ARMC5 p.Cys657Arg VAR_079118
12 ARMC5 p.Cys657Trp VAR_079119
13 ARMC5 p.Ile664Ser VAR_079120
14 ARMC5 p.Pro731Arg VAR_079123 rs200951744
15 ARMC5 p.Tyr736Ser VAR_079124
16 ARMC5 p.Leu754Pro VAR_079125
17 ARMC5 p.His808Pro VAR_079128

Expression for Acth-Independent Macronodular Adrenal Hyperplasia 2

Search GEO for disease gene expression data for Acth-Independent Macronodular Adrenal Hyperplasia 2.

Pathways for Acth-Independent Macronodular Adrenal Hyperplasia 2

GO Terms for Acth-Independent Macronodular Adrenal Hyperplasia 2

Sources for Acth-Independent Macronodular Adrenal Hyperplasia 2

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
20 GARD
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 20-May-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
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