MCID: ACT244
MIFTS: 43

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 58
Adrenocorticotropic Hormone-Independent Cushing Syndrome 58
Corticotropin-Independent Cushing Syndrome 58
Adrenal Cushing Syndrome 58

Classifications:

Orphanet: 58  
Rare infertility disorders
Rare endocrine diseases


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 Metabolism and DAG and IP3 signaling. The drugs Dexamethasone acetate and Epinephrine have been mentioned in the context of this disorder. Affiliated tissues include pituitary, cortex and adrenal gland, 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 top 50) (show all 64)
# Related Disease Score Top Affiliating Genes
1 acth-independent macronodular adrenal hyperplasia 33.5 PDE11A GNAS ARMC5
2 primary pigmented nodular adrenocortical disease 31.0 PRKAR1A PRKACA PDE8B PDE11A GNAS ARMC5
3 acth-secreting pituitary adenoma 30.4 PRKAR1A GNAS
4 adrenocortical carcinoma, hereditary 30.2 PRKAR1A GNAS
5 mccune-albright syndrome 29.6 PRKAR1A PDE8B PDE11A GNAS
6 adrenal cortical carcinoma 29.3 PRKAR1A CYP21A2 CYP11B1
7 lipoid congenital adrenal hyperplasia 29.3 CYP21A2 CYP11B1
8 adenoma 29.2 PRKAR1A GNAS CYP21A2 CYP11B1
9 adrenal cortical adenoma 29.0 PRKAR1A CYP21A2 CYP11B1
10 adrenal carcinoma 28.7 PRKAR1A CYP21A2 CYP11B1 ARMC5
11 adrenal adenoma 28.6 PRKAR1A GNAS CYP21A2 CYP11B1
12 conn's syndrome 28.4 PRKAR1A PDE11A GNAS CYP21A2 CYP11B1 ARMC5
13 obsolete: acth-independent cushing syndrome due to bilateral adrenocortical hyperplasia 12.7
14 acth-independent cushing syndrome due to rare cortisol-producing adrenal tumor 12.7
15 pigmented nodular adrenocortical disease, primary, 2 11.6
16 pigmented nodular adrenocortical disease, primary, 1 11.6
17 pigmented nodular adrenocortical disease, primary, 3 11.6
18 pigmented nodular adrenocortical disease, primary, 4 11.6
19 acth-independent macronodular adrenal hyperplasia 2 11.6
20 lipid metabolism disorder 10.2
21 pituitary tumors 10.2
22 bilateral massive adrenal hemorrhage 10.2
23 pituitary adenoma 4, acth-secreting 10.2
24 hormone producing pituitary cancer 10.2 PRKAR1A GNAS
25 hypothyroidism, congenital, nongoitrous, 1 10.1 PRKAR1A GNAS
26 melanotic neurilemmoma 10.1 PRKAR1A PDE11A
27 hyperpituitarism 10.1 PRKAR1A GNAS
28 pseudopseudohypoparathyroidism 10.1 PRKAR1A GNAS
29 pseudohypoparathyroidism 10.1 PRKAR1A GNAS
30 multiple endocrine neoplasia, type iv 10.1 PRKAR1A GNAS
31 leydig cell tumor 10.1 GNAS CYP21A2
32 neurofibromatosis, type ii 10.1
33 adrenal cortical adenocarcinoma 10.1
34 testicular leydig cell tumor 10.1 PDE11A CYP21A2
35 acrodysostosis 10.1 PRKAR1A GNAS
36 growth hormone secreting pituitary adenoma 10.1 PRKAR1A GNAS
37 pseudohypoparathyroidism, type ia 10.1 PRKAR1A GNAS
38 precocious puberty 10.1 GNAS CYP21A2
39 functioning pituitary adenoma 10.1 PRKAR1A GNAS
40 hypocalcemia, autosomal dominant 1 9.9 PRKAR1A GNAS
41 pheochromocytoma 9.9
42 myeloma, multiple 9.9
43 adrenal gland pheochromocytoma 9.9
44 ectopic cushing syndrome 9.9
45 glucose intolerance 9.9
46 neuroendocrine carcinoma 9.9
47 testicular sex cord-stromal neoplasm 9.9 PRKAR1A PDE11A GNAS
48 sex cord-gonadal stromal tumor 9.9 PRKAR1A PDE11A GNAS
49 basophil adenoma 9.9 PRKAR1A PDE8B PDE11A
50 breast adenoma 9.9 PRKAR1A PDE8B PDE11A

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:

58 31 (show all 20)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 failure to thrive 58 31 hallmark (90%) Very frequent (99-80%) HP:0001508
2 thin skin 58 31 hallmark (90%) Very frequent (99-80%) HP:0000963
3 round face 58 31 hallmark (90%) Very frequent (99-80%) HP:0000311
4 truncal obesity 58 31 hallmark (90%) Very frequent (99-80%) HP:0001956
5 adrenocortical hypoplasia 58 31 hallmark (90%) Very frequent (99-80%) HP:0008182
6 vestibular areflexia 58 31 hallmark (90%) Very frequent (99-80%) HP:0008568
7 depressivity 58 31 frequent (33%) Frequent (79-30%) HP:0000716
8 diabetes mellitus 58 31 frequent (33%) Frequent (79-30%) HP:0000819
9 hypertension 58 31 frequent (33%) Frequent (79-30%) HP:0000822
10 muscle weakness 58 31 frequent (33%) Frequent (79-30%) HP:0001324
11 hypokalemia 58 31 frequent (33%) Frequent (79-30%) HP:0002900
12 fatigue 58 31 frequent (33%) Frequent (79-30%) HP:0012378
13 generalized hirsutism 58 31 frequent (33%) Frequent (79-30%) HP:0002230
14 acne 58 31 frequent (33%) Frequent (79-30%) HP:0001061
15 anxiety 58 31 frequent (33%) Frequent (79-30%) HP:0000739
16 striae distensae 58 31 frequent (33%) Frequent (79-30%) HP:0001065
17 nephrolithiasis 58 31 frequent (33%) Frequent (79-30%) HP:0000787
18 infertility 58 31 frequent (33%) Frequent (79-30%) HP:0000789
19 bruising susceptibility 58 31 frequent (33%) Frequent (79-30%) HP:0000978
20 menometrorrhagia 58 31 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 23)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Dexamethasone acetate Approved, Investigational, Vet_approved 1177-87-3
2
Epinephrine Approved, Vet_approved 51-43-4 5816
3
Hydrocortisone acetate Approved, Vet_approved 50-03-3
4
Hydrocortisone Approved, Vet_approved 50-23-7 5754
5
Dexamethasone Approved, Investigational, Vet_approved 50-02-2 5743
6
Racepinephrine Approved 329-65-7 838
7 Neurotransmitter Agents
8 Hydrocortisone hemisuccinate
9 Epinephryl borate
10 Adrenergic Agonists
11 Sympathomimetics
12 Anti-Asthmatic Agents
13 Hydrocortisone 17-butyrate 21-propionate
14 Respiratory System Agents
15 Vasoconstrictor Agents
16 Hormone Antagonists
17 Adrenergic beta-Agonists
18 BB 1101
19 Hormones
20 Autonomic Agents
21 Adrenergic Agents
22 Bronchodilator Agents
23 Mydriatics

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:

40
Pituitary, Cortex, Adrenal Gland, Adrenal Cortex, Breast, Skin, Testes

Publications for Acth-Independent Cushing Syndrome

Articles related to Acth-Independent Cushing Syndrome:

(show all 46)
# Title Authors PMID Year
1
Somatic PRKACA Mutations: Association With Transition From Pituitary-Dependent to Adrenal-Dependent Cushing Syndrome. 61
31276155 2019
2
High expression of adrenal P450 aromatase (CYP19A1) in association with ARMC5-primary bilateral macronodular adrenocortical hyperplasia. 61
31014964 2019
3
Assay-Specific Spurious ACTH Results Lead to Misdiagnosis, Unnecessary Testing, and Surgical Misadventure-A Case Series. 61
30963134 2019
4
Cushing syndrome: uncovering Carney complex due to novel PRKAR1A mutation. 61
30897549 2019
5
Unilateral Adrenalectomy Could Be a Valid Option for Primary Nodular Adrenal Disease: Evidence From Twins. 61
30591956 2019
6
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. 61
30129786 2018
7
Carney Syndrome Presented as a Pathological Spine Fracture in a 35-Year-Old Male. 61
30442879 2018
8
Niche point-of-care endocrine testing - Reviews of intraoperative parathyroid hormone and cortisol monitoring. 61
29357735 2018
9
Corticotropinoma as a Component of Carney Complex. 61
29264542 2017
10
Coagulation Profile in Patients with Different Etiologies for Cushing Syndrome: A Prospective Observational Study. 61
28226363 2017
11
Three-Quarters Adrenalectomy for Infantile-Onset Cushing Syndrome due to Bilateral Adrenal Hyperplasia in McCune-Albright Syndrome. 61
28528327 2017
12
Reversal of a Blunted Follicle-Stimulating Hormone by Chemotherapy in an Inhibin B-Secreting Adrenocortical Carcinoma. 61
29264444 2017
13
[Comparison of efficacy between the serum cortisol and 24 hour urine free cortisol in combined dexamethasone suppression test in the diagnosis of Cushing syndrome]. 61
27464539 2016
14
Cholesterol Biosynthesis and Trafficking in Cortisol-Producing Lesions of the Adrenal Cortex. 61
26204136 2015
15
Limited Diagnostic Utility of Plasma Adrenocorticotropic Hormone for Differentiation between Adrenal Cushing Syndrome and Cushing Disease. 61
26248856 2015
16
Adrenal venous sampling in a patient with adrenal Cushing syndrome. 61
26309345 2015
17
PRKACA: the catalytic subunit of protein kinase A and adrenocortical tumors. 61
26042218 2015
18
Not all glucocorticoid-induced obesity is the same: differences in adiposity among various diagnostic groups of Cushing syndrome. 61
25295416 2014
19
Bilateral posterior retroperitoneal robotic adrenalectomy for ACTH-independent Cushing syndrome. 61
24710229 2014
20
[A pedigree study of a patient with primary pigmented nodular adrenocortical disease and familial gene mutation]. 61
25146409 2014
21
Differences in adiposity in Cushing syndrome caused by PRKAR1A mutations: clues for the role of cyclic AMP signaling in obesity and diagnostic implications. 61
24248186 2014
22
The role of unilateral adrenalectomy in corticotropin-independent bilateral adrenocortical hyperplasias. 61
23592061 2013
23
Laparoscopic bilateral transperitoneal adrenalectomy for Cushing syndrome: surgical challenges and lessons learnt. 61
23752002 2013
24
Adrenocorticotropic hormone-independent cushing syndrome with bilateral cortisol-secreting adenomas. 61
24396667 2013
25
Differential diagnosis of adrenocorticotropic hormone-independent Cushing syndrome: role of adrenal venous sampling. 61
22982799 2012
26
Glucocorticoid- and androgen-secreting black adrenocortical adenomas: unique cause of corticotropin-independent Cushing syndrome. 61
21700558 2011
27
Glucose-dependent insulinotropic peptide receptor overexpression in adrenocortical hyperplasia in MEN1 syndrome without loss of heterozygosity at the 11q13 locus. 61
21655742 2011
28
MicroRNA signature in massive macronodular adrenocortical disease and implications for adrenocortical tumourigenesis. 61
19849700 2010
29
CT findings of primary pigmented nodular adrenocortical disease: rare cause of ACTH-independent Cushing syndrome. 61
20489078 2010
30
A novel PRKAR1A mutation associated with primary pigmented nodular adrenocortical disease and the Carney complex. 61
19833579 2010
31
Cushing syndrome in a young woman due to primary pigmented nodular adrenal disease. 61
19703806 2010
32
Reversible posterior encephalopathy syndrome associated with micronodular adrenocortical disease and Cushing syndrome. 61
19415327 2010
33
Abnormalities of cAMP signaling are present in adrenocortical lesions associated with ACTH-independent Cushing syndrome despite the absence of mutations in known genes. 61
19429701 2009
34
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. 61
18431404 2008
35
Corticotropin-independent cushing syndrome in a child with an ovarian tumor misdiagnosed as nonclassic congenital adrenal hyperplasia. 61
18996816 2008
36
An unusual variant of Cushing syndrome. 61
18996791 2008
37
Is the adrenal cortex a target for gonadotropins? 61
18691899 2008
38
The clinical conundrum of corticotropin-independent autonomous cortisol secretion in patients with bilateral adrenal masses. 61
18074172 2008
39
Cushing syndrome caused by adrenocortical tumors and hyperplasias (corticotropin- independent Cushing syndrome). 61
18493137 2008
40
[Long-term consequences of surgical excision of cortisol producing adrenocortical adenoma]. 61
17940986 2007
41
A PRKAR1A mutation associated with primary pigmented nodular adrenocortical disease in 12 kindreds. 61
16464939 2006
42
Mutational analysis of PRKAR1A and Gs(alpha) in sporadic adrenocortical tumors. 61
15926108 2005
43
Cyclical Cushing syndrome presenting in infancy: an early form of primary pigmented nodular adrenocortical disease, or a new entity? 61
15240590 2004
44
CT and MR imaging of the adrenal glands in ACTH-independent cushing syndrome. 61
15026592 2004
45
Adrenocorticotropin-independent macronodular adrenal hyperplasia: an uncommon cause of primary adrenal hypercortisolism. 61
10966714 2000
46
The metyrapone and dexamethasone suppression tests for the differential diagnosis of the adrenocorticotropin-dependent Cushing syndrome: a comparison. 61
8042820 1994

Variations for Acth-Independent Cushing Syndrome

ClinVar genetic disease variations for Acth-Independent Cushing Syndrome:

6 ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 GNAS NM_001077488.4(GNAS):c.604C>A (p.Arg202Ser)SNV Pathogenic 15937 rs11554273 20:57484420-57484420 20:58909365-58909365
2 GNAS NM_001077488.4(GNAS):c.85C>T (p.Gln29Ter)SNV Pathogenic 374113 rs1057518907 20:57466866-57466866 20:58891811-58891811
3 GNAS NM_001077488.4(GNAS):c.1A>G (p.Met1Val)SNV Pathogenic/Likely pathogenic 15927 rs137854530 20:57466782-57466782 20:58891727-58891727
4 GNAS NM_001077488.4(GNAS):c.604C>T (p.Arg202Cys)SNV Pathogenic/Likely pathogenic 15933 rs11554273 20:57484420-57484420 20:58909365-58909365
5 GNAS NM_001077488.4(GNAS):c.605G>A (p.Arg202His)SNV Pathogenic/Likely pathogenic 15934 rs121913495 20:57484421-57484421 20:58909366-58909366
6 GNAS NM_080425.3(GNAS):c.1200C>A (p.Ala400=)SNV Uncertain significance 417934 rs908810796 20:57429520-57429520 20:58854465-58854465
7 GNAS NM_080425.3(GNAS):c.1455C>A (p.Ala485=)SNV Benign 417936 rs55890501 20:57429775-57429775 20:58854720-58854720

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 42)
# Super pathways Score Top Affiliating Genes
1
Show member pathways
13.76 PRKAR1A PRKACA PDE8B PDE11A GNAS CYP21A2
2
Show member pathways
12.83 PRKAR1A PRKACA PDE8B GNAS
3
Show member pathways
12.45 PRKAR1A PRKACA GNAS
4
Show member pathways
12.45 PRKAR1A PRKACA GNAS
5
Show member pathways
12.39 PRKAR1A PRKACA GNAS
6
Show member pathways
12.36 PRKAR1A PRKACA GNAS
7
Show member pathways
12.32 PRKAR1A PRKACA GNAS
8
Show member pathways
12.3 PRKAR1A PRKACA GNAS
9
Show member pathways
12.2 PRKAR1A PRKACA GNAS
10
Show member pathways
12.13 PRKAR1A PRKACA GNAS
11
Show member pathways
12.12 PRKAR1A PRKACA GNAS
12 12.11 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
11.94 PRKACA PDE8B PDE11A GNAS CYP21A2 CYP11B1
17
Show member pathways
11.91 PRKAR1A PRKACA GNAS
18 11.89 PRKAR1A PRKACA GNAS
19
Show member pathways
11.83 PRKAR1A PRKACA GNAS
20 11.8 PDE8B PDE11A GNAS
21
Show member pathways
11.7 PRKAR1A PRKACA GNAS
22 11.55 GNAS CYP21A2 CYP11B1
23 11.53 PRKACA GNAS
24 11.51 PRKAR1A PRKACA GNAS
25
Show member pathways
11.5 CYP21A2 CYP11B1
26
Show member pathways
11.5 PRKAR1A PRKACA GNAS
27 11.44 PRKAR1A PRKACA GNAS
28 11.41 PRKACA GNAS
29 11.39 PRKACA GNAS
30 11.38 PRKAR1A PRKACA
31 11.36 PRKACA GNAS
32 11.34 PRKACA GNAS
33 11.34 PRKAR1A PRKACA
34 11.3 PRKAR1A PRKACA
35 11.27 PRKACA GNAS
36 11.24 PRKAR1A PRKACA
37 11.16 PRKAR1A PRKACA
38 11.1 PRKAR1A PRKACA
39 10.92 PRKAR1A PRKACA GNAS
40 10.91 PRKACA GNAS
41
Show member pathways
10.88 CYP21A2 CYP11B1
42 10.49 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 activation of protein kinase A activity GO:0034199 9.26 PRKAR1A PRKACA
5 glucocorticoid biosynthetic process GO:0006704 9.16 CYP21A2 CYP11B1
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 8.96 PDE8B PDE11A
2 3',5'-cyclic-GMP phosphodiesterase activity GO:0047555 8.62 PRKAR1A PDE11A

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 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
53 NINDS
54 Novoseek
56 OMIM
57 OMIM via Orphanet
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
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