MCID: ACT244
MIFTS: 40

Acth-Independent Cushing Syndrome

Categories: Endocrine diseases, Rare diseases, Reproductive diseases

Aliases & Classifications for Acth-Independent Cushing Syndrome

MalaCards integrated aliases for Acth-Independent Cushing Syndrome:

Name: Acth-Independent Cushing Syndrome 59
Adrenocorticotropic Hormone-Independent Cushing Syndrome 59
Corticotropin-Independent Cushing Syndrome 59
Adrenal Cushing Syndrome 59

Classifications:



External Ids:

ICD10 via Orphanet 34 E24.8
Orphanet 59 ORPHA99893

Summaries for Acth-Independent Cushing Syndrome

MalaCards based summary : Acth-Independent Cushing Syndrome, also known as adrenocorticotropic hormone-independent cushing syndrome, is related to acth-independent macronodular adrenal hyperplasia and primary pigmented nodular adrenocortical disease. An important gene associated with Acth-Independent Cushing Syndrome is GNAS (GNAS Complex Locus), and among its related pathways/superpathways are DAG and IP3 signaling and Neuropathic Pain-Signaling in Dorsal Horn Neurons. The drugs Dexamethasone and Dexamethasone acetate have been mentioned in the context of this disorder. Affiliated tissues include skin, testes and cortex, and related phenotypes are failure to thrive and thin skin

Related Diseases for Acth-Independent Cushing Syndrome

Diseases in the Acth-Independent Cushing Syndrome family:

Acth-Independent Cushing Syndrome Due to Rare Cortisol-Producing Adrenal Tumor

Diseases related to Acth-Independent Cushing Syndrome via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 46)
# Related Disease Score Top Affiliating Genes
1 acth-independent macronodular adrenal hyperplasia 33.5 PDE11A GNAS ARMC5
2 primary pigmented nodular adrenocortical disease 31.4 PRKAR1A PRKACA PDE8B PDE11A GNAS
3 cushing syndrome due to macronodular adrenal hyperplasia 30.2 GNAS ARMC5
4 lipoid congenital adrenal hyperplasia 29.4 CYP21A2 CYP11B1
5 adrenal adenoma 29.1 CYP21A2 CYP11B1
6 adrenal carcinoma 29.0 CYP21A2 CYP11B1
7 adrenal cortical adenoma 28.9 PRKAR1A CYP21A2 CYP11B1
8 adrenocortical carcinoma, hereditary 28.7 PRKAR1A GNAS CYP21A2 CYP11B1
9 conn's syndrome 28.6 PRKAR1A PDE11A GNAS CYP21A2 CYP11B1
10 obsolete: acth-independent cushing syndrome due to bilateral adrenocortical hyperplasia 12.7
11 acth-independent cushing syndrome due to rare cortisol-producing adrenal tumor 12.7
12 pigmented nodular adrenocortical disease, primary, 2 11.6
13 pigmented nodular adrenocortical disease, primary, 1 11.6
14 pigmented nodular adrenocortical disease, primary, 3 11.6
15 pigmented nodular adrenocortical disease, primary, 4 11.6
16 acth-independent macronodular adrenal hyperplasia 2 11.6
17 adenoma 10.3
18 hormone producing pituitary cancer 10.2 PRKAR1A GNAS
19 pseudopseudohypoparathyroidism 10.2 PRKAR1A GNAS
20 acrodysostosis 10.2 PRKAR1A GNAS
21 growth hormone secreting pituitary adenoma 10.2 PRKAR1A GNAS
22 lipid metabolism disorder 10.2
23 pituitary tumors 10.2
24 bilateral massive adrenal hemorrhage 10.2
25 pituitary adenoma 4, acth-secreting 10.2
26 acth-secreting pituitary adenoma 10.2
27 neurofibromatosis, type ii 10.1
28 mccune-albright syndrome 10.1
29 adrenal cortical carcinoma 10.1
30 adrenal cortical adenocarcinoma 10.1
31 inherited metabolic disorder 10.1 GNAS CYP21A2
32 hypocalcemia, autosomal dominant 1 10.1 PRKAR1A GNAS
33 precocious puberty 10.1 GNAS CYP21A2
34 cortisone reductase deficiency 10.0 PDE11A CYP21A2
35 pheochromocytoma 9.9
36 myeloma, multiple 9.9
37 adrenal gland pheochromocytoma 9.9
38 ectopic cushing syndrome 9.9
39 glucose intolerance 9.9
40 neuroendocrine carcinoma 9.9
41 pituitary adenoma, prolactin-secreting 9.9 PRKAR1A GNAS
42 steroid inherited metabolic disorder 9.7 CYP21A2 CYP11B1
43 adrenal rest tumor 9.6 CYP21A2 CYP11B1
44 carney complex variant 9.6 PRKAR1A PDE8B PDE11A GNAS
45 adrenal gland disease 9.3 PRKAR1A CYP11B1 ARMC5
46 adrenal cortex disease 9.0 PRKAR1A PDE11A CYP11B1 ARMC5

Graphical network of the top 20 diseases related to Acth-Independent Cushing Syndrome:



Diseases related to Acth-Independent Cushing Syndrome

Symptoms & Phenotypes for Acth-Independent Cushing Syndrome

Human phenotypes related to Acth-Independent Cushing Syndrome:

59 32 (show all 20)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 failure to thrive 59 32 hallmark (90%) Very frequent (99-80%) HP:0001508
2 thin skin 59 32 hallmark (90%) Very frequent (99-80%) HP:0000963
3 round face 59 32 hallmark (90%) Very frequent (99-80%) HP:0000311
4 truncal obesity 59 32 hallmark (90%) Very frequent (99-80%) HP:0001956
5 adrenocortical hypoplasia 59 32 hallmark (90%) Very frequent (99-80%) HP:0008182
6 vestibular areflexia 59 32 hallmark (90%) Very frequent (99-80%) HP:0008568
7 depressivity 59 32 frequent (33%) Frequent (79-30%) HP:0000716
8 diabetes mellitus 59 32 frequent (33%) Frequent (79-30%) HP:0000819
9 hypertension 59 32 frequent (33%) Frequent (79-30%) HP:0000822
10 muscle weakness 59 32 frequent (33%) Frequent (79-30%) HP:0001324
11 hypokalemia 59 32 frequent (33%) Frequent (79-30%) HP:0002900
12 fatigue 59 32 frequent (33%) Frequent (79-30%) HP:0012378
13 generalized hirsutism 59 32 frequent (33%) Frequent (79-30%) HP:0002230
14 acne 59 32 frequent (33%) Frequent (79-30%) HP:0001061
15 anxiety 59 32 frequent (33%) Frequent (79-30%) HP:0000739
16 striae distensae 59 32 frequent (33%) Frequent (79-30%) HP:0001065
17 nephrolithiasis 59 32 frequent (33%) Frequent (79-30%) HP:0000787
18 bruising susceptibility 59 32 frequent (33%) Frequent (79-30%) HP:0000978
19 infertility 59 32 frequent (33%) Frequent (79-30%) HP:0000789
20 menometrorrhagia 59 32 frequent (33%) Frequent (79-30%) HP:0400008

Drugs & Therapeutics for Acth-Independent Cushing Syndrome

Drugs for Acth-Independent Cushing Syndrome (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 26)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Dexamethasone Approved, Investigational, Vet_approved 50-02-2 5743
2
Dexamethasone acetate Approved, Investigational, Vet_approved 1177-87-3
3
Racepinephrine Approved 329-65-7 838
4
Epinephrine Approved, Vet_approved 51-43-4 5816
5
Hydrocortisone Approved, Vet_approved 50-23-7 5754
6
Hydrocortisone acetate Approved, Vet_approved 50-03-3
7 Neurotransmitter Agents
8 Sympathomimetics
9 Adrenergic Agonists
10 Respiratory System Agents
11 Adrenergic alpha-Agonists
12 Hormones
13 Adrenergic beta-Agonists
14 Peripheral Nervous System Agents
15 Epinephryl borate
16 Mydriatics
17 Hormone Antagonists
18 Anti-Asthmatic Agents
19 Adrenergic Agents
20 Hormones, Hormone Substitutes, and Hormone Antagonists
21 Vasoconstrictor Agents
22 Hydrocortisone 17-butyrate 21-propionate
23 Hydrocortisone hemisuccinate
24 Autonomic Agents
25 BB 1101
26 Bronchodilator Agents

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 A Prospective Cohort Study for Patients With Adrenal Diseases Not yet recruiting NCT03474237

Search NIH Clinical Center for Acth-Independent Cushing Syndrome

Genetic Tests for Acth-Independent Cushing Syndrome

Anatomical Context for Acth-Independent Cushing Syndrome

MalaCards organs/tissues related to Acth-Independent Cushing Syndrome:

41
Skin, Testes, Cortex, Adrenal Cortex, Adrenal Gland

Publications for Acth-Independent Cushing Syndrome

Articles related to Acth-Independent Cushing Syndrome:

(show all 45)
# Title Authors PMID Year
1
High expression of adrenal P450 aromatase (CYP19A1) in association with ARMC5-primary bilateral macronodular adrenocortical hyperplasia. 38
31014964 2019
2
Assay-Specific Spurious ACTH Results Lead to Misdiagnosis, Unnecessary Testing, and Surgical Misadventure-A Case Series. 38
30963134 2019
3
Cushing syndrome: uncovering Carney complex due to novel PRKAR1A mutation. 38
30897549 2019
4
Unilateral Adrenalectomy Could Be a Valid Option for Primary Nodular Adrenal Disease: Evidence From Twins. 38
30591956 2019
5
Primary pigmented nodular adrenocortical disease (PPNAD) as an underlying cause of symptoms in a patient presenting with hirsutism and secondary amenorrhea: case report and literature review. 38
30129786 2018
6
Carney Syndrome Presented as a Pathological Spine Fracture in a 35-Year-Old Male. 38
30442879 2018
7
Niche point-of-care endocrine testing - Reviews of intraoperative parathyroid hormone and cortisol monitoring. 38
29357735 2018
8
Corticotropinoma as a Component of Carney Complex. 38
29264542 2017
9
Coagulation Profile in Patients with Different Etiologies for Cushing Syndrome: A Prospective Observational Study. 38
28226363 2017
10
Three-Quarters Adrenalectomy for Infantile-Onset Cushing Syndrome due to Bilateral Adrenal Hyperplasia in McCune-Albright Syndrome. 38
28528327 2017
11
Reversal of a Blunted Follicle-Stimulating Hormone by Chemotherapy in an Inhibin B-Secreting Adrenocortical Carcinoma. 38
29264444 2017
12
[Comparison of efficacy between the serum cortisol and 24 hour urine free cortisol in combined dexamethasone suppression test in the diagnosis of Cushing syndrome]. 38
27464539 2016
13
Cholesterol Biosynthesis and Trafficking in Cortisol-Producing Lesions of the Adrenal Cortex. 38
26204136 2015
14
Limited Diagnostic Utility of Plasma Adrenocorticotropic Hormone for Differentiation between Adrenal Cushing Syndrome and Cushing Disease. 38
26248856 2015
15
Adrenal venous sampling in a patient with adrenal Cushing syndrome. 38
26309345 2015
16
PRKACA: the catalytic subunit of protein kinase A and adrenocortical tumors. 38
26042218 2015
17
Not all glucocorticoid-induced obesity is the same: differences in adiposity among various diagnostic groups of Cushing syndrome. 38
25295416 2014
18
Bilateral posterior retroperitoneal robotic adrenalectomy for ACTH-independent Cushing syndrome. 38
24710229 2014
19
[A pedigree study of a patient with primary pigmented nodular adrenocortical disease and familial gene mutation]. 38
25146409 2014
20
Differences in adiposity in Cushing syndrome caused by PRKAR1A mutations: clues for the role of cyclic AMP signaling in obesity and diagnostic implications. 38
24248186 2014
21
The role of unilateral adrenalectomy in corticotropin-independent bilateral adrenocortical hyperplasias. 38
23592061 2013
22
Laparoscopic bilateral transperitoneal adrenalectomy for Cushing syndrome: surgical challenges and lessons learnt. 38
23752002 2013
23
Adrenocorticotropic hormone-independent cushing syndrome with bilateral cortisol-secreting adenomas. 38
24396667 2013
24
Differential diagnosis of adrenocorticotropic hormone-independent Cushing syndrome: role of adrenal venous sampling. 38
22982799 2012
25
Glucocorticoid- and androgen-secreting black adrenocortical adenomas: unique cause of corticotropin-independent Cushing syndrome. 38
21700558 2011
26
Glucose-dependent insulinotropic peptide receptor overexpression in adrenocortical hyperplasia in MEN1 syndrome without loss of heterozygosity at the 11q13 locus. 38
21655742 2011
27
MicroRNA signature in massive macronodular adrenocortical disease and implications for adrenocortical tumourigenesis. 38
19849700 2010
28
CT findings of primary pigmented nodular adrenocortical disease: rare cause of ACTH-independent Cushing syndrome. 38
20489078 2010
29
A novel PRKAR1A mutation associated with primary pigmented nodular adrenocortical disease and the Carney complex. 38
19833579 2010
30
Cushing syndrome in a young woman due to primary pigmented nodular adrenal disease. 38
19703806 2010
31
Reversible posterior encephalopathy syndrome associated with micronodular adrenocortical disease and Cushing syndrome. 38
19415327 2010
32
Abnormalities of cAMP signaling are present in adrenocortical lesions associated with ACTH-independent Cushing syndrome despite the absence of mutations in known genes. 38
19429701 2009
33
A cAMP-specific phosphodiesterase (PDE8B) that is mutated in adrenal hyperplasia is expressed widely in human and mouse tissues: a novel PDE8B isoform in human adrenal cortex. 38
18431404 2008
34
Corticotropin-independent cushing syndrome in a child with an ovarian tumor misdiagnosed as nonclassic congenital adrenal hyperplasia. 38
18996816 2008
35
An unusual variant of Cushing syndrome. 38
18996791 2008
36
Is the adrenal cortex a target for gonadotropins? 38
18691899 2008
37
The clinical conundrum of corticotropin-independent autonomous cortisol secretion in patients with bilateral adrenal masses. 38
18074172 2008
38
Cushing syndrome caused by adrenocortical tumors and hyperplasias (corticotropin- independent Cushing syndrome). 38
18493137 2008
39
[Long-term consequences of surgical excision of cortisol producing adrenocortical adenoma]. 38
17940986 2007
40
A PRKAR1A mutation associated with primary pigmented nodular adrenocortical disease in 12 kindreds. 38
16464939 2006
41
Mutational analysis of PRKAR1A and Gs(alpha) in sporadic adrenocortical tumors. 38
15926108 2005
42
Cyclical Cushing syndrome presenting in infancy: an early form of primary pigmented nodular adrenocortical disease, or a new entity? 38
15240590 2004
43
CT and MR imaging of the adrenal glands in ACTH-independent cushing syndrome. 38
15026592 2004
44
Adrenocorticotropin-independent macronodular adrenal hyperplasia: an uncommon cause of primary adrenal hypercortisolism. 38
10966714 2000
45
The metyrapone and dexamethasone suppression tests for the differential diagnosis of the adrenocorticotropin-dependent Cushing syndrome: a comparison. 38
8042820 1994

Variations for Acth-Independent Cushing Syndrome

ClinVar genetic disease variations for Acth-Independent Cushing Syndrome:

6
# Gene Variation Type Significance SNP ID GRCh37 Pos GRCh38 Pos
1 GNAS NM_001077488.4(GNAS): c.85C> T (p.Gln29Ter) single nucleotide variant Pathogenic rs1057518907 20:57466866-57466866 20:58891811-58891811
2 GNAS NM_001077488.4(GNAS): c.604C> A (p.Arg202Ser) single nucleotide variant Pathogenic rs11554273 20:57484420-57484420 20:58909365-58909365
3 GNAS NM_001077488.4(GNAS): c.605G> A (p.Arg202His) single nucleotide variant Pathogenic/Likely pathogenic rs121913495 20:57484421-57484421 20:58909366-58909366
4 GNAS NM_001077488.4(GNAS): c.604C> T (p.Arg202Cys) single nucleotide variant Pathogenic/Likely pathogenic rs11554273 20:57484420-57484420 20:58909365-58909365
5 GNAS NM_001077488.4(GNAS): c.1A> G (p.Met1Val) single nucleotide variant Pathogenic/Likely pathogenic rs137854530 20:57466782-57466782 20:58891727-58891727
6 GNAS NM_080425.3(GNAS): c.1455C> A (p.Ala485=) single nucleotide variant Uncertain significance rs55890501 20:57429775-57429775 20:58854720-58854720
7 GNAS NM_080425.3(GNAS): c.1200C> A (p.Ala400=) single nucleotide variant Uncertain significance rs908810796 20:57429520-57429520 20:58854465-58854465

Expression for Acth-Independent Cushing Syndrome

Search GEO for disease gene expression data for Acth-Independent Cushing Syndrome.

Pathways for Acth-Independent Cushing Syndrome

Pathways related to Acth-Independent Cushing Syndrome according to GeneCards Suite gene sharing:

(show all 44)
# Super pathways Score Top Affiliating Genes
1
Show member pathways
12.83 PRKAR1A PRKACA PDE8B GNAS
2
Show member pathways
12.45 PRKAR1A PRKACA GNAS
3
Show member pathways
12.45 PRKAR1A PRKACA GNAS
4
Show member pathways
12.39 PRKAR1A PRKACA GNAS
5
Show member pathways
12.36 PRKAR1A PRKACA GNAS
6
Show member pathways
12.33 PRKAR1A PRKACA GNAS
7
Show member pathways
12.31 PRKAR1A PRKACA GNAS
8
Show member pathways
12.2 PRKAR1A PRKACA GNAS
9
Show member pathways
12.13 PRKAR1A PRKACA GNAS
10
Show member pathways
12.12 PRKACA PDE8B GNAS CYP21A2 CYP11B1
11
Show member pathways
12.11 PRKAR1A PRKACA GNAS
12 12.1 PRKAR1A PRKACA GNAS
13
Show member pathways
12.07 PRKACA PDE8B PDE11A GNAS
14
Show member pathways
12.06 PRKAR1A PRKACA GNAS
15
Show member pathways
11.94 PRKAR1A PRKACA GNAS
16
Show member pathways
11.91 PRKAR1A PRKACA GNAS
17 11.89 PRKAR1A PRKACA GNAS
18
Show member pathways
11.83 PRKAR1A PRKACA GNAS
19 11.8 PDE8B PDE11A GNAS
20
Show member pathways
11.7 PRKAR1A PRKACA GNAS
21 11.56 PRKAR1A PRKACA
22 11.55 PRKACA GNAS
23 11.55 GNAS CYP21A2 CYP11B1
24 11.52 PRKACA GNAS
25
Show member pathways
11.5 CYP21A2 CYP11B1
26 11.5 PRKAR1A PRKACA GNAS
27
Show member pathways
11.5 PRKAR1A PRKACA GNAS
28 11.44 PRKAR1A PRKACA GNAS
29 11.41 PRKACA GNAS
30 11.39 PRKAR1A PRKACA
31 11.36 PRKACA GNAS
32 11.35 PRKACA GNAS
33 11.35 PRKACA GNAS
34 11.34 PRKAR1A PRKACA
35 11.3 PRKAR1A PRKACA
36 11.27 PRKACA GNAS
37 11.24 PRKAR1A PRKACA
38 11.17 PRKAR1A PRKACA GNAS
39 11.15 PRKAR1A PRKACA
40 11.1 PRKAR1A PRKACA
41 10.92 PRKAR1A PRKACA GNAS
42 10.91 PRKACA GNAS
43
Show member pathways
10.86 CYP21A2 CYP11B1
44 10.16 PRKAR1A PRKACA GNAS

GO Terms for Acth-Independent Cushing Syndrome

Cellular components related to Acth-Independent Cushing Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 ciliary base GO:0097546 9.16 PRKAR1A PRKACA
2 plasma membrane raft GO:0044853 8.96 PRKAR1A PRKACA
3 cAMP-dependent protein kinase complex GO:0005952 8.62 PRKAR1A PRKACA

Biological processes related to Acth-Independent Cushing Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 steroid biosynthetic process GO:0006694 9.4 CYP21A2 CYP11B1
2 mesoderm formation GO:0001707 9.37 PRKAR1A PRKACA
3 sterol metabolic process GO:0016125 9.32 CYP21A2 CYP11B1
4 glucocorticoid biosynthetic process GO:0006704 9.26 CYP21A2 CYP11B1
5 activation of protein kinase A activity GO:0034199 9.16 PRKAR1A PRKACA
6 renal water homeostasis GO:0003091 9.13 PRKAR1A PRKACA GNAS
7 cellular response to glucagon stimulus GO:0071377 8.8 PRKAR1A PRKACA GNAS

Molecular functions related to Acth-Independent Cushing Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 phosphoric diester hydrolase activity GO:0008081 9.16 PDE8B PDE11A
2 3',5'-cyclic-GMP phosphodiesterase activity GO:0047555 8.96 PRKAR1A PDE11A
3 3',5'-cyclic-AMP phosphodiesterase activity GO:0004115 8.32 PDE8B

Sources for Acth-Independent Cushing Syndrome

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
40 LOVD
42 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
54 NINDS
55 Novoseek
57 OMIM
58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 TGDB
71 Tocris
72 UMLS
73 UMLS via Orphanet
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