Details of Disease

General Information of Disease (ID: DIS3WGAL)

Disease Name	Hyperaldosteronism
Synonyms	primary hyperaldosteronism
Disease Class	5A72: Hyperaldosteronism
Definition	Overproduction of aldosterone by the adrenal glands, which may lead to hypokalemia and/or hypernatremia.
Disease Hierarchy	DISPP4ZK: Adrenal gland hyperfunction DIS3WGAL: Hyperaldosteronism
ICD Code	ICD-11 ICD-11: 5A72
Disease Identifiers	MONDO ID MONDO_0003009 MESH ID D006929 UMLS CUI C0020428 MedGen ID 6960 HPO ID HP:0000859 SNOMED CT ID 88213004

Drug-Interaction Atlas (DIA) of This Disease

Drug-Interaction Atlas (DIA)

This Disease is Treated as An Indication in 1 Approved Drug(s)

Drug Name	Drug ID	Highest Status	Drug Type	REF
Spironolactone	DM2AQ5N	Approved	Small molecular drug	[1]
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This Disease is Treated as An Indication in 1 Investigative Drug(s)

Drug Name	Drug ID	Highest Status	Drug Type	REF
SL125	DMEIZ20	Investigative	NA	[2]
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Molecular Interaction Atlas (MIA) of This Disease

Molecular Interaction Atlas (MIA)

This Disease Is Related to 19 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
CYP11B1	TTIQUX7	Limited	Altered Expression	[3]
CRH	TTA7YIZ	Disputed	Biomarker	[4]
CYBB	TT5T8MR	Disputed	Biomarker	[5]
DRD2	TTEX248	Disputed	Biomarker	[6]
SERPINA1	TTA7UJC	Disputed	Biomarker	[7]
ATP1A1	TTWK8D0	Strong	Biomarker	[8]
CACNA1D	TT7RGTM	Strong	Genetic Variation	[9]
CACNA1H	TTZPWGN	Strong	Genetic Variation	[10]
CLCN2	TT30NW6	Strong	Genetic Variation	[11]
CRY1	TT5MLZR	Strong	Biomarker	[12]
CRY2	TTAO58M	Strong	Biomarker	[12]
GRK2	TTAZ3MN	Strong	Altered Expression	[13]
HSD11B2	TT9H85R	Strong	Biomarker	[14]
KCNJ1	TTJ13ST	Strong	Genetic Variation	[15]
KCNK9	TTL4FMB	Strong	Biomarker	[16]
PRSS8	TTT4N0Q	Strong	Biomarker	[17]
S100A6	TT716MY	Strong	Altered Expression	[18]
SLC12A1	TTS087L	Strong	Biomarker	[19]
SLC5A1	TT2UE56	Strong	Biomarker	[20]
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⏷ Show the Full List of 19 DTT(s)

This Disease Is Related to 1 DTP Molecule(s)

Gene Name	DTP ID	Evidence Level	Mode of Inheritance	REF
ABCD1	DTKM9DZ	Strong	Altered Expression	[21]
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This Disease Is Related to 1 DME Molecule(s)

Gene Name	DME ID	Evidence Level	Mode of Inheritance	REF
HSD3B1	DERDQWN	Strong	Biomarker	[22]
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This Disease Is Related to 13 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
KCNE1	OTZNQUW9	Limited	Biomarker	[23]
ADD1	OTTF68DC	Strong	Genetic Variation	[24]
APBB3	OTNUTR0N	Strong	Altered Expression	[25]
ARMC5	OTO7IV74	Strong	Biomarker	[26]
ATP2B3	OT9DIEOP	Strong	Genetic Variation	[27]
BSND	OTYWZWPD	Strong	Genetic Variation	[28]
CLSTN3	OTPUFK4C	Strong	Biomarker	[29]
LGALS14	OTOR23GX	Strong	Genetic Variation	[11]
NR5A1	OTOULYR4	Strong	Altered Expression	[30]
PIAS1	OTZVAHZI	Strong	Biomarker	[31]
RBAK	OTYJ6EAU	Strong	Genetic Variation	[32]
RPTOR	OT4TQZ9F	Strong	Altered Expression	[33]
SIAH1	OT29A838	Strong	Biomarker	[31]
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⏷ Show the Full List of 13 DOT(s)

References

1	Spironolactone FDA Label
2	Reduction of cell proliferation induced by PD166866: an inhibitor of the basic fibroblast growth factor. J Exp Clin Cancer Res. 2007 Sep;26(3):405-9.
3	Genetics of primary aldosteronism.Front Horm Res. 2014;43:70-8. doi: 10.1159/000360870. Epub 2014 Jun 10.
4	An N-ethyl-N-nitrosourea induced corticotropin-releasing hormone promoter mutation provides a mouse model for endogenous glucocorticoid excess.Endocrinology. 2014 Mar;155(3):908-22. doi: 10.1210/en.2013-1247. Epub 2013 Dec 3.
5	Calcium paradox of aldosteronism and the role of the parathyroid glands.Am J Physiol Heart Circ Physiol. 2006 Jan;290(1):H286-94. doi: 10.1152/ajpheart.00535.2005.
6	Activity, non-selective attention and emotionality in dopamine D2/D3 receptor knock-out mice.Behav Brain Res. 2002 Mar 10;130(1-2):141-8. doi: 10.1016/s0166-4328(01)00428-4.
7	Loss of bone minerals and strength in rats with aldosteronism.Am J Physiol Heart Circ Physiol. 2004 Nov;287(5):H2023-6. doi: 10.1152/ajpheart.00477.2004.
8	Somatic mutations in ATP1A1 and ATP2B3 lead to aldosterone-producing adenomas and secondary hypertension.Nat Genet. 2013 Apr;45(4):440-4, 444e1-2. doi: 10.1038/ng.2550. Epub 2013 Feb 17.
9	Clinical and Steroidogenic Characteristics of Aldosterone-Producing Adenomas With ATPase or CACNA1D Gene Mutations.J Clin Endocrinol Metab. 2016 Feb;101(2):494-503. doi: 10.1210/jc.2015-3284. Epub 2015 Nov 25.
10	CACNA1H(M1549V) Mutant Calcium Channel Causes Autonomous Aldosterone Production in HAC15 Cells and Is Inhibited by Mibefradil.Endocrinology. 2016 Aug;157(8):3016-22. doi: 10.1210/en.2016-1170. Epub 2016 Jun 3.
11	Pathogenesis of Familial Hyperaldosteronism Type II: New Concepts Involving Anion Channels.Curr Hypertens Rep. 2019 Apr 4;21(4):31. doi: 10.1007/s11906-019-0934-y.
12	Role of Cryptochrome-1 and Cryptochrome-2 in Aldosterone-Producing Adenomas and Adrenocortical Cells.Int J Mol Sci. 2018 Jun 5;19(6):1675. doi: 10.3390/ijms19061675.
13	Aldosterone Jeopardizes Myocardial Insulin and -Adrenergic Receptor Signaling via G Protein-Coupled Receptor Kinase 2.Front Pharmacol. 2019 Aug 9;10:888. doi: 10.3389/fphar.2019.00888. eCollection 2019.
14	Aldosterone-sensitive HSD2 neurons in mice.Brain Struct Funct. 2019 Jan;224(1):387-417. doi: 10.1007/s00429-018-1778-y. Epub 2018 Oct 20.
15	Late-onset Bartter syndrome type II.Clin Kidney J. 2017 Oct;10(5):594-599. doi: 10.1093/ckj/sfx033. Epub 2017 May 8.
16	The role of TASK1 in aldosterone production and its expression in normal adrenal and aldosterone-producing adenomas.Clin Endocrinol (Oxf). 2010 Jul;73(1):22-9. doi: 10.1111/j.1365-2265.2009.03738.x. Epub 2009 Oct 28.
17	Adenovirus-mediated human prostasin gene delivery is linked to increased aldosterone production and hypertension in rats.Am J Physiol Regul Integr Comp Physiol. 2003 Apr;284(4):R1031-6. doi: 10.1152/ajpregu.00660.2002. Epub 2002 Dec 19.
18	A novel missense mutation of mineralocorticoid receptor gene in one Japanese family with a renal form of pseudohypoaldosteronism type 1.J Clin Endocrinol Metab. 2000 Dec;85(12):4690-4. doi: 10.1210/jcem.85.12.7078.
19	Loop disorders: insights derived from defined genotypes.Nephron Physiol. 2011;118(1):p7-14. doi: 10.1159/000320882. Epub 2010 Nov 11.
20	Fecal stream is essential for adaptive induction of glucose-coupled sodium transport in the remnant ileum after total proctocolectomy.J Gastrointest Surg. 2006 Jul-Aug;10(7):1051-9. doi: 10.1016/j.gassur.2005.12.003.
21	Genetic polymorphism of CYP11B2 gene and hypertension in Japanese.Hypertension. 1999 Jan;33(1 Pt 2):266-70. doi: 10.1161/01.hyp.33.1.266.
22	Development of monoclonal antibodies against the human 3-hydroxysteroid dehydrogenase/isomerase isozymes.Steroids. 2017 Nov;127:56-61. doi: 10.1016/j.steroids.2017.08.011. Epub 2017 Aug 31.
23	Expression of potassium channel isoforms mRNA in normal human adrenals and aldosterone-secreting adenomas.J Endocrinol Invest. 2006 Feb;29(2):147-53. doi: 10.1007/BF03344088.
24	Blood pressure in patients with primary aldosteronism is influenced by bradykinin B(2) receptor and alpha-adducin gene polymorphisms.J Clin Endocrinol Metab. 2002 Jul;87(7):3337-43. doi: 10.1210/jcem.87.7.8666.
25	AN INDIVIDUALIZED APPROACH TO THE EVALUATION AND MANAGEMENT OF PRIMARY ALDOSTERONISM.Endocr Pract. 2017 Jun;23(6):680-689. doi: 10.4158/EP161717.RA. Epub 2017 Mar 23.
26	ARMC5 mutations are common in familial bilateral macronodular adrenal hyperplasia.J Clin Endocrinol Metab. 2014 Sep;99(9):E1784-92. doi: 10.1210/jc.2014-1265. Epub 2014 Jun 6.
27	A Novel Somatic Deletion Mutation of ATP2B3 in Aldosterone-Producing Adenoma.Endocr Pathol. 2015 Dec;26(4):328-33. doi: 10.1007/s12022-015-9400-9.
28	Two novel homozygous missense mutations identified in the BSND gene in Moroccan patients with Bartter's syndrome.Int J Pediatr Otorhinolaryngol. 2018 Oct;113:46-50. doi: 10.1016/j.ijporl.2018.07.010. Epub 2018 Jul 10.
29	Genetic characterization of a mouse line with primary aldosteronism.J Mol Endocrinol. 2017 Feb;58(2):67-78. doi: 10.1530/JME-16-0200. Epub 2016 Dec 13.
30	Insulin Regulates Adrenal Steroidogenesis by Stabilizing SF-1 Activity.Sci Rep. 2018 Mar 22;8(1):5025. doi: 10.1038/s41598-018-23298-2.
31	The E3 ubiquitin ligase Siah1 regulates adrenal gland organization and aldosterone secretion.JCI Insight. 2017 Dec 7;2(23):e97128. doi: 10.1172/jci.insight.97128.
32	Examination of chromosome 7p22 candidate genes RBaK, PMS2 and GNA12 in familial hyperaldosteronism type II.Clin Exp Pharmacol Physiol. 2008 Apr;35(4):380-5. doi: 10.1111/j.1440-1681.2008.04882.x.
33	Up-regulation of the mammalian target of rapamycin complex 1 subunit Raptor by aldosterone induces abnormal pulmonary artery smooth muscle cell survival patterns to promote pulmonary arterial hypertension.FASEB J. 2016 Jul;30(7):2511-27. doi: 10.1096/fj.201500042. Epub 2016 Mar 22.