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Glucocorticoid-remediable aldosteronism(GSH; GRA; HALD1)

MedGen UID:: 824577
•Concept ID:: C3838731
•: Disease or Syndrome

Synonyms:	ACTH-DEPENDENT HYPERALDOSTERONISM SYNDROME; ALDOSTERONISM, SENSITIVE TO DEXAMETHASONE; FH I; GLUCOCORTICOID-SUPPRESSIBLE HYPERALDOSTERONISM; Hyperaldosteronism, familial, type I
SNOMED CT:	Familial hyperaldosteronism type 1 (703232003); Glucocorticoid-sensitive hypertension (703232003); Glucocorticoid-suppressible hyperaldosteronism (703232003); Glucocorticoid-remediable aldosteronism (703232003); Familial hyperaldosteronism type I (703232003); Dexamethasone-sensitive hypertension (703232003); GRA - glucocorticoid-remediable aldosteronism (703232003)
Modes of inheritance:	Autosomal dominant inheritance MedGen UID: 141047 •Concept ID: C0443147 • Intellectual Product Source: Orphanet A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in heterozygotes. In the context of medical genetics, an autosomal dominant disorder is caused when a single copy of the mutant allele is present. Males and females are affected equally, and can both transmit the disorder with a risk of 50% for each child of inheriting the mutant allele. Autosomal dominant inheritance (Orphanet)

Gene (location): Gene(s) directly associated with this condition or phenotype.	CYP11B1 (8q24.3)

Monarch Initiative:	MONDO:0007080
OMIM®:	103900
Orphanet:	ORPHA403

Definition

Familial hyperaldosteronism type I (HALD1), also referred to as glucocorticoid-remediable aldosteronism (GRA), is an autosomal dominant disorder characterized by hypertension, variable hyperaldosteronism, and abnormal adrenal steroid production, including 18-oxocortisol and 18-hydroxycortisol (Lifton et al., 1992). There is significant phenotypic heterogeneity, and some individuals never develop hypertension (Stowasser et al., 2000). Genetic Heterogeneity of Familial Hyperaldosteronism Familial hyperaldosteronism type II (HALD2; 605635) is caused by mutation in the CLCN2 gene (600570) on chromosome 3q27. Familial hyperaldosteronism type III (HALD3; 613677) is caused by mutation in the KCNJ5 gene (600734) on chromosome 11q24. Familial hyperaldosteronism type IV (HALD4; 617027) is caused by mutation in the CACNA1H gene (607904) on chromosome 16p13. [from OMIM]

Clinical features

From HPO

Abnormality of the urinary system

MedGen UID:: 867444
•Concept ID:: C4021821
•: Disease or Syndrome

An abnormality of the urinary system.

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Hypertensive disorder

MedGen UID:: 6969
•Concept ID:: C0020538
•: Disease or Syndrome

The presence of chronic increased pressure in the systemic arterial system.

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Increased circulating aldosterone concentration

MedGen UID:: 6960
•Concept ID:: C0020428
•: Disease or Syndrome

Overproduction of the mineralocorticoid aldosterone by the adrenal cortex.

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Adrenogenital syndrome

MedGen UID:: 86215
•Concept ID:: C0302280
•: Disease or Syndrome

Adrenogenital syndrome is also known as congenital adrenal hyperplasia, which results from disorders of steroid hormone production in the adrenal glands leading to a deficiency of cortisol. The pituitary gland reacts by increased secretion of corticotropin, which in turn causes the adrenal glands to overproduce certain intermediary hormones which have testosterone-like effects.

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Adrenal hyperplasia

MedGen UID:: 301220
•Concept ID:: C1621895
•: Disease or Syndrome

Enlargement of the adrenal gland.

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Decreased circulating renin concentration

MedGen UID:: 337182
•Concept ID:: C1845206
•: Finding

An decreased level of renin in the blood.

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Abnormality of the cardiovascular system
- Hypertensive disorder
Abnormality of the endocrine system
Abnormality of the genitourinary system
- Abnormality of the urinary system

Term Hierarchy

GTR
MeSH

CClinical test, RResearch test, OOMIM, GGeneReviews, VClinVar

Familial hyperaldosteronism
- CROGVFamilial hyperaldosteronism type II
- CROGVFamilial hyperaldosteronism type III
- CROGVGlucocorticoid-remediable aldosteronism

Phenotypic abnormality
- Abnormality of the endocrine system
  - Abnormality of renin-angiotensin system
    - Abnormal circulating aldosterone concentration
      - Increased circulating aldosterone concentration
        Familial hyperaldosteronism
        Glucocorticoid-remediable aldosteronism

Professional guidelines

PubMed

DIAGNOSIS OF ENDOCRINE DISEASE: 18-Oxocortisol and 18-hydroxycortisol: is there clinical utility of these steroids?

Lenders JWM, Williams TA, Reincke M, Gomez-Sanchez CE
Eur J Endocrinol 2018 Jan;178(1):R1-R9. Epub 2017 Sep 13 doi: 10.1530/EJE-17-0563. PMID: 28904009 Free PMC Article

AN INDIVIDUALIZED APPROACH TO THE EVALUATION AND MANAGEMENT OF PRIMARY ALDOSTERONISM.

Vaidya A, Malchoff CD, Auchus RJ; AACE Adrenal Scientific Committee
Endocr Pract 2017 Jun;23(6):680-689. Epub 2017 Mar 23 doi: 10.4158/EP161717.RA. PMID: 28332881

Diagnosis and management of primary aldosteronism.

Wheeler MH, Harris DA
World J Surg 2003 Jun;27(6):627-31. Epub 2003 May 13 doi: 10.1007/s00268-003-7069-6. PMID: 12732984

See all (11)

Recent clinical studies

Etiology

Genetic testing for familial hyperaldosteronism type 1 in Aotearoa/New Zealand.

Elston MS, Tamatea JAU, King RI, Florkowski CM, Boyle V
Intern Med J 2024 Nov;54(11):1814-1820. Epub 2024 Aug 31 doi: 10.1111/imj.16511. PMID: 39215608

Inherited forms of mineralocorticoid hypertension.

Hassan-Smith Z, Stewart PM
Curr Opin Endocrinol Diabetes Obes 2011 Jun;18(3):177-85. doi: 10.1097/MED.0b013e3283469444. PMID: 21494136

Glucocorticoid-remediable aldosteronism.

McMahon GT, Dluhy RG
Arq Bras Endocrinol Metabol 2004 Oct;48(5):682-6. Epub 2005 Mar 7 doi: 10.1590/s0004-27302004000500014. PMID: 15761539

Glucocorticoid-remediable aldosteronism and pregnancy.

Wyckoff JA, Seely EW, Hurwitz S, Anderson BF, Lifton RP, Dluhy RG
Hypertension 2000 Feb;35(2):668-72. doi: 10.1161/01.hyp.35.2.668. PMID: 10679515

Genetic determinants of human hypertension.

Lifton RP
Proc Natl Acad Sci U S A 1995 Sep 12;92(19):8545-51. doi: 10.1073/pnas.92.19.8545. PMID: 7567973 Free PMC Article

See all (35)

Diagnosis

Glucocorticoid-remediable aldosteronism.

McMahon GT, Dluhy RG
Arq Bras Endocrinol Metabol 2004 Oct;48(5):682-6. Epub 2005 Mar 7 doi: 10.1590/s0004-27302004000500014. PMID: 15761539

Glucocorticoid-remediable aldosteronism.

McMahon GT, Dluhy RG
Cardiol Rev 2004 Jan-Feb;12(1):44-8. doi: 10.1097/01.crd.0000096417.42861.ce. PMID: 14667264

Hypertension.

Warnock DG
Semin Nephrol 1999 Jul;19(4):374-80. PMID: 10435675

Primary aldosteronism.

Holland OB
Semin Nephrol 1995 Mar;15(2):116-25. PMID: 7777722

Genetic determinants of human hypertension.

Lifton RP
Proc Natl Acad Sci U S A 1995 Sep 12;92(19):8545-51. doi: 10.1073/pnas.92.19.8545. PMID: 7567973 Free PMC Article

See all (86)

Therapy

Familial hyperaldosteronism type 1 and pregnancy: successful treatment with low dose dexamethasone.

Sanga V, Lenzini L, Seccia TM, Rossi GP
Blood Press 2021 Apr;30(2):133-137. Epub 2021 Jan 4 doi: 10.1080/08037051.2020.1863771. PMID: 33390031

Glucocorticoid-remediable aldosteronism.

McMahon GT, Dluhy RG
Arq Bras Endocrinol Metabol 2004 Oct;48(5):682-6. Epub 2005 Mar 7 doi: 10.1590/s0004-27302004000500014. PMID: 15761539

Glucocorticoid-remediable aldosteronism.

McMahon GT, Dluhy RG
Cardiol Rev 2004 Jan-Feb;12(1):44-8. doi: 10.1097/01.crd.0000096417.42861.ce. PMID: 14667264

Glucocorticoid-remediable aldosteronism.

Dluhy RG, Lifton RP
J Clin Endocrinol Metab 1999 Dec;84(12):4341-4. doi: 10.1210/jcem.84.12.6256. PMID: 10599685

The genetics of hypertension.

Thibonnier M, Schork NJ
Curr Opin Genet Dev 1995 Jun;5(3):362-70. doi: 10.1016/0959-437x(95)80052-2. PMID: 7549432

See all (47)

Prognosis

Clinical and Molecular Perspectives of Monogenic Hypertension.

Levanovich PE, Diaczok A, Rossi NF
Curr Hypertens Rev 2020;16(2):91-107. doi: 10.2174/1573402115666190409115330. PMID: 30963979 Free PMC Article

Glucocorticoid-remediable aldosteronism is associated with severe hypertension in early childhood.

Dluhy RG, Anderson B, Harlin B, Ingelfinger J, Lifton R
J Pediatr 2001 May;138(5):715-20. doi: 10.1067/mpd.2001.112648. PMID: 11343049

Glucocorticoid-remediable aldosteronism and pregnancy.

Wyckoff JA, Seely EW, Hurwitz S, Anderson BF, Lifton RP, Dluhy RG
Hypertension 2000 Feb;35(2):668-72. doi: 10.1161/01.hyp.35.2.668. PMID: 10679515

Intracranial aneurysm and hemorrhagic stroke in glucocorticoid-remediable aldosteronism.

Litchfield WR, Anderson BF, Weiss RJ, Lifton RP, Dluhy RG
Hypertension 1998 Jan;31(1 Pt 2):445-50. doi: 10.1161/01.hyp.31.1.445. PMID: 9453343

Primary aldosteronism.

Holland OB
Semin Nephrol 1995 Mar;15(2):116-25. PMID: 7777722

See all (12)

Clinical prediction guides

Prediction of successful outcome in patients with primary aldosteronism.

Moo TA, Zarnegar R, Duh QY
Curr Treat Options Oncol 2007 Aug;8(4):314-21. doi: 10.1007/s11864-007-0039-8. PMID: 18058076

Molecular genetics of adrenocortical tumours, from familial to sporadic diseases.

Libé R, Bertherat J
Eur J Endocrinol 2005 Oct;153(4):477-87. doi: 10.1530/eje.1.02004. PMID: 16189167

Glucocorticoid remediable aldosteronism: low morbidity and mortality in a four-generation italian pedigree.

Mulatero P, di Cella SM, Williams TA, Milan A, Mengozzi G, Chiandussi L, Gomez-Sanchez CE, Veglio F
J Clin Endocrinol Metab 2002 Jul;87(7):3187-91. doi: 10.1210/jcem.87.7.8647. PMID: 12107222

Glucocorticoid-remediable aldosteronism (GRA): diagnosis, variability of phenotype and regulation of potassium homeostasis.

Dluhy RG, Lifton RP
Steroids 1995 Jan;60(1):48-51. doi: 10.1016/0039-128x(94)00010-a. PMID: 7792815

A chimaeric 11 beta-hydroxylase/aldosterone synthase gene causes glucocorticoid-remediable aldosteronism and human hypertension.

Lifton RP, Dluhy RG, Powers M, Rich GM, Cook S, Ulick S, Lalouel JM
Nature 1992 Jan 16;355(6357):262-5. doi: 10.1038/355262a0. PMID: 1731223

See all (12)