Details of Disease

General Information of Disease (ID: DISOEFNH)

• Disease Name: Primary aldosteronism
• Synonyms: primary hyperaldosteronism; primary aldosteronism; Conn's syndrome; Conn syndrome
• Definition: An endocrine disorder characterized by excessive production of aldosterone by the adrenal glands. Causes include adrenal gland adenoma and adrenal gland hyperplasia. The overproduction of aldosterone results in sodium and water retention and hypokalemia. Patients present with high blood pressure, muscle weakness, and headache.|Editor note: DOID class refers to adenoma-caused Conn syndrome
• Disease Hierarchy:
  DIS3WGAL: Hyperaldosteronism
  DISOEFNH: Primary aldosteronism
• Disease Identifiers:
  MONDO ID: MONDO_0001422
  MESH ID: D006929
  UMLS CUI: C1384514
  MedGen ID: 278002
  HPO ID: HP:0011736
  SNOMED CT ID: 190507007

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 15 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
ATP1A1	TTWK8D0	Limited	Genetic Variation	[1]
CLCN2	TT30NW6	Limited	Genetic Variation	[2]
CLCNKB	TTR68GQ	Limited	Biomarker	[3]
KCNJ5	TTEO25X	Limited	Genetic Variation	[4]
MC2R	TTPWFDX	Limited	Altered Expression	[5]
SLC12A3	TTP362L	Limited	Biomarker	[3]
CACNA1D	TT7RGTM	moderate	Genetic Variation	[6]
CACNA1H	TTZPWGN	moderate	Genetic Variation	[7]
AGTR1	TT8DBY3	Strong	Biomarker	[8]
CPA1	TT3LJ6G	Strong	Biomarker	[9]
ENPEP	TT9PBIL	Strong	Biomarker	[10]
KCNK3	TTGR91N	Strong	Biomarker	[11]
KCNK9	TTL4FMB	Strong	Biomarker	[11]
PRKACA	TT5U49F	Strong	Genetic Variation	[12]
SLC33A1	TTL69WB	Strong	Biomarker	[8]

This Disease Is Related to 1 DTP Molecule(s)

Gene Name	DTP ID	Evidence Level	Mode of Inheritance	REF
SLC26A2	DTFSLX5	Strong	Biomarker	[13]

This Disease Is Related to 2 DME Molecule(s)

Gene Name	DME ID	Evidence Level	Mode of Inheritance	REF
HSD3B1	DERDQWN	Strong	Altered Expression	[14]
HSD3B2	DEN0GVQ	Strong	Altered Expression	[14]

This Disease Is Related to 13 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
ARMC5	OTO7IV74	moderate	Genetic Variation	[15]
ATP2B3	OT9DIEOP	moderate	Genetic Variation	[16]
ADD1	OTTF68DC	Strong	Biomarker	[17]
APBB3	OTNUTR0N	Strong	Altered Expression	[18]
KCNK5	OT68V64E	Strong	Genetic Variation	[19]
LGALS14	OTOR23GX	Strong	Biomarker	[20]
MT3	OTVCZ7HI	Strong	Biomarker	[21]
NGB	OTW0SIUY	Strong	Biomarker	[22]
NR5A1	OTOULYR4	Strong	Biomarker	[23]
PCP4	OTM1XXYX	Strong	Biomarker	[24]
PMPCA	OT5X1G9Q	Strong	Altered Expression	[25]
SCNN1B	OT61QQTL	Strong	Genetic Variation	[26]
SIAH1	OT29A838	Strong	Genetic Variation	[27]

References

• [1] Na/K Pump Mutations Associated with Primary Hyperaldosteronism Cause Loss of Function.Biochemistry. 2019 Apr 2;58(13):1774-1785. doi: 10.1021/acs.biochem.9b00051. Epub 2019 Mar 14.
• [2] 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.
• [3] Coexistence of normotensive primary aldosteronism in two patients with Gitelman's syndrome and novel thiazide-sensitive Na-Cl cotransporter mutations.Eur J Endocrinol. 2009 Aug;161(2):275-83. doi: 10.1530/EJE-09-0271. Epub 2009 May 18.
• [4] Mosaicism for KCNJ5 Causing Early-Onset Primary Aldosteronism due to Bilateral Adrenocortical Hyperplasia.Am J Hypertens. 2020 Feb 22;33(2):124-130. doi: 10.1093/ajh/hpz172.
• [5] Expression of aldosterone synthase and adrenocorticotropic hormone receptor in adrenal incidentalomas from normotensive and hypertensive patients: Distinguishing subclinical or atypical primary aldosteronism from adrenal incidentaloma.Int J Mol Med. 2012 Dec;30(6):1396-402. doi: 10.3892/ijmm.2012.1144. Epub 2012 Sep 27.
• [6] Cellular and Genetic Causes of Idiopathic Hyperaldosteronism.Hypertension. 2018 Oct;72(4):874-880. doi: 10.1161/HYPERTENSIONAHA.118.11086.
• [7] Splice-variant-specific effects of primary aldosteronism point mutations on human Ca(V)3.2 calcium channels.Cell Calcium. 2019 Dec;84:102104. doi: 10.1016/j.ceca.2019.102104. Epub 2019 Nov 1.
• [8] Effects of mineralocorticoid and AT-1 receptor antagonism on the aldosterone-renin ratio (ARR) in primary aldosteronism patients (EMIRA Study): rationale and design.J Hum Hypertens. 2019 Feb;33(2):167-171. doi: 10.1038/s41371-018-0139-x. Epub 2018 Dec 5.
• [9] Sporadic solitary aldosterone- and cortisol-co-secreting adenomas: endocrine, histological and genetic findings in a subtype of primary aldosteronism.Hypertens Res. 2010 May;33(5):467-72. doi: 10.1038/hr.2010.18. Epub 2010 Feb 26.
• [10] Speckle-Tracking Echocardiographic Layer-Specific Strain Analysis on Subclinical Left Ventricular Dysfunction in Patients With Primary Aldosteronism.Am J Hypertens. 2019 Jan 15;32(2):155-162. doi: 10.1093/ajh/hpy175.
• [11] Potassium channels related to primary aldosteronism: Expression similarities and differences between human and rat adrenals.Mol Cell Endocrinol. 2015 Dec 5;417:141-8. doi: 10.1016/j.mce.2015.09.011. Epub 2015 Sep 12.
• [12] PRKACA Somatic Mutations Are Rare Findings in Aldosterone-Producing Adenomas.J Clin Endocrinol Metab. 2016 Aug;101(8):3010-7. doi: 10.1210/jc.2016-1700. Epub 2016 Jun 7.
• [13] Diastrophic dysplasia sulfate transporter (SLC26A2) is expressed in the adrenal cortex and regulates aldosterone secretion.Hypertension. 2014 May;63(5):1102-9. doi: 10.1161/HYPERTENSIONAHA.113.02504. Epub 2014 Mar 3.
• [14] 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.
• [15] ARMC5 mutations in familial and sporadic primary bilateral macronodular adrenal hyperplasia.PLoS One. 2018 Jan 25;13(1):e0191602. doi: 10.1371/journal.pone.0191602. eCollection 2018.
• [16] Clinicopathologic Correlates of Primary Aldosteronism.Arch Pathol Lab Med. 2015 Jul;139(7):948-54. doi: 10.5858/arpa.2014-0156-RS.
• [17] 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.
• [18] 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.
• [19] Mutations of the Twik-Related Acid-Sensitive K+ Channel 2 Promoter in Human Primary Aldosteronism.Endocrinology. 2018 Mar 1;159(3):1352-1359. doi: 10.1210/en.2017-03119.
• [20] Pathogenesis of hypertension in a mouse model for human CLCN2 related hyperaldosteronism.Nat Commun. 2019 Oct 15;10(1):4678. doi: 10.1038/s41467-019-12113-9.
• [21] Metallothionein-3 (MT-3) in the human adrenal cortex and its disorders.Endocr Pathol. 2014 Sep;25(3):229-35. doi: 10.1007/s12022-013-9280-9.
• [22] Neuroglobin correlates with cryptochrome-1 in obstructive sleep apnea with primary aldosteronism.PLoS One. 2018 Sep 20;13(9):e0204390. doi: 10.1371/journal.pone.0204390. eCollection 2018.
• [23] Elementary studies on elevated steroidogenic factor-1 expression in aldosterone-producing adenoma.Urol Oncol. 2012 Jul-Aug;30(4):457-62. doi: 10.1016/j.urolonc.2010.03.001. Epub 2010 Sep 26.
• [24] PCP4: a regulator of aldosterone synthesis in human adrenocortical tissues.J Mol Endocrinol. 2014 Feb 24;52(2):159-67. doi: 10.1530/JME-13-0248. Print 2014 Apr.
• [25] Evidence for a potential role for HDL as an important source of cholesterol in human adrenocortical tumors via the CLA-1 pathway.Endocr J. 1999 Feb;46(1):27-34. doi: 10.1507/endocrj.46.27.
• [26] Liddle syndrome misdiagnosed as primary aldosteronism resulting from a novel frameshift mutation of SCNN1B.Endocr Connect. 2018 Dec;7(12):1528-1534. doi: 10.1530/EC-18-0484.
• [27] 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.