- William F Young, Jr, MD, MSc
William F Young, Jr, MD, MSc
- Professor of Medicine
- Mayo Clinic College of Medicine
- Section Editors
- Richard H Sterns, MD
Richard H Sterns, MD
- Editor-in-Chief — Nephrology
- Section Editor — Fluid and Electrolytes
- Professor of Medicine
- University of Rochester School of Medicine and Dentistry
- André Lacroix, MD
André Lacroix, MD
- Section Editor — Adrenal Disease
- Professor of Medicine
- University of Montreal, Quebec, Canada
Familial hyperaldosteronism (FH) is an uncommon subset of primary aldosteronism. There are three forms of FH:
●FH type I or glucocorticoid-remediable aldosteronism (GRA) due to a CYP11B1/CYP11B2 chimeric gene
●FH type II, which has been localized to chromosome 7p22, but exact location of mutation(s) is unknown to date
●FH type III caused by germline mutations in the potassium channel subunit KCNJ5
The three forms of FH will be reviewed here. Primary aldosteronism is discussed separately. (See "Diagnosis of primary aldosteronism" and "Pathophysiology and clinical features of primary aldosteronism" and "Treatment of primary aldosteronism".)
- Sutherland DJ, Ruse JL, Laidlaw JC. Hypertension, increased aldosterone secretion and low plasma renin activity relieved by dexamethasone. Can Med Assoc J 1966; 95:1109.
- Lifton RP, Dluhy RG, Powers M, et al. A chimaeric 11 beta-hydroxylase/aldosterone synthase gene causes glucocorticoid-remediable aldosteronism and human hypertension. Nature 1992; 355:262.
- Rich GM, Ulick S, Cook S, et al. Glucocorticoid-remediable aldosteronism in a large kindred: clinical spectrum and diagnosis using a characteristic biochemical phenotype. Ann Intern Med 1992; 116:813.
- McMahon GT, Dluhy RG. Glucocorticoid-remediable aldosteronism. Cardiol Rev 2004; 12:44.
- Torpy DJ, Gordon RD, Lin JP, et al. Familial hyperaldosteronism type II: description of a large kindred and exclusion of the aldosterone synthase (CYP11B2) gene. J Clin Endocrinol Metab 1998; 83:3214.
- Mulatero P, Tizzani D, Viola A, et al. Prevalence and characteristics of familial hyperaldosteronism: the PATOGEN study (Primary Aldosteronism in TOrino-GENetic forms). Hypertension 2011; 58:797.
- Lifton RP, Dluhy RG, Powers M, et al. Hereditary hypertension caused by chimaeric gene duplications and ectopic expression of aldosterone synthase. Nat Genet 1992; 2:66.
- Litchfield WR, Coolidge C, Silva P, et al. Impaired potassium-stimulated aldosterone production: a possible explanation for normokalemic glucocorticoid-remediable aldosteronism. J Clin Endocrinol Metab 1997; 82:1507.
- Fallo F, Pilon C, Williams TA, et al. Coexistence of different phenotypes in a family with glucocorticoid-remediable aldosteronism. J Hum Hypertens 2004; 18:47.
- Litchfield WR, Anderson BF, Weiss RJ, et al. Intracranial aneurysm and hemorrhagic stroke in glucocorticoid-remediable aldosteronism. Hypertension 1998; 31:445.
- Botero-Velez M, Curtis JJ, Warnock DG. Brief report: Liddle's syndrome revisited--a disorder of sodium reabsorption in the distal tubule. N Engl J Med 1994; 330:178.
- Jamieson A, Inglis GC, Campbell M, et al. Rapid diagnosis of glucocorticoid suppressible hyperaldosteronism in infants and adolescents. Arch Dis Child 1994; 71:40.
- Jonsson JR, Klemm SA, Tunny TJ, et al. A new genetic test for familial hyperaldosteronism type I aids in the detection of curable hypertension. Biochem Biophys Res Commun 1995; 207:565.
- Mulatero P, Veglio F, Pilon C, et al. Diagnosis of glucocorticoid-remediable aldosteronism in primary aldosteronism: aldosterone response to dexamethasone and long polymerase chain reaction for chimeric gene. J Clin Endocrinol Metab 1998; 83:2573.
- Gates LJ, Benjamin N, Haites NE, et al. Is random screening of value in detecting glucocorticoid-remediable aldosteronism within a hypertensive population? J Hum Hypertens 2001; 15:173.
- Dluhy RG, Anderson B, Harlin B, et al. Glucocorticoid-remediable aldosteronism is associated with severe hypertension in early childhood. J Pediatr 2001; 138:715.
- Funder JW, Carey RM, Fardella C, et al. Case detection, diagnosis, and treatment of patients with primary aldosteronism: an endocrine society clinical practice guideline. J Clin Endocrinol Metab 2008; 93:3266.
- Stowasser M, Bachmann AW, Huggard PR, et al. Treatment of familial hyperaldosteronism type I: only partial suppression of adrenocorticotropin required to correct hypertension. J Clin Endocrinol Metab 2000; 85:3313.
- Pallauf A, Schirpenbach C, Zwermann O, et al. The prevalence of familial hyperaldosteronism in apparently sporadic primary aldosteronism in Germany: a single center experience. Horm Metab Res 2012; 44:215.
- Sukor N, Mulatero P, Gordon RD, et al. Further evidence for linkage of familial hyperaldosteronism type II at chromosome 7p22 in Italian as well as Australian and South American families. J Hypertens 2008; 26:1577.
- Carss KJ, Stowasser M, Gordon RD, O'Shaughnessy KM. Further study of chromosome 7p22 to identify the molecular basis of familial hyperaldosteronism type II. J Hum Hypertens 2011; 25:560.
- Young WF. Primary aldosteronism: renaissance of a syndrome. Clin Endocrinol (Oxf) 2007; 66:607.
- Geller DS, Zhang J, Wisgerhof MV, et al. A novel form of human mendelian hypertension featuring nonglucocorticoid-remediable aldosteronism. J Clin Endocrinol Metab 2008; 93:3117.
- Choi M, Scholl UI, Yue P, et al. K+ channel mutations in adrenal aldosterone-producing adenomas and hereditary hypertension. Science 2011; 331:768.
- Charmandari E, Sertedaki A, Kino T, et al. A novel point mutation in the KCNJ5 gene causing primary hyperaldosteronism and early-onset autosomal dominant hypertension. J Clin Endocrinol Metab 2012; 97:E1532.
- Mussa A, Camilla R, Monticone S, et al. Polyuric-polydipsic syndrome in a pediatric case of non-glucocorticoid remediable familial hyperaldosteronism. Endocr J 2012; 59:497.
- Mulatero P, Tauber P, Zennaro MC, et al. KCNJ5 mutations in European families with nonglucocorticoid remediable familial hyperaldosteronism. Hypertension 2012; 59:235.
- Scholl UI, Nelson-Williams C, Yue P, et al. Hypertension with or without adrenal hyperplasia due to different inherited mutations in the potassium channel KCNJ5. Proc Natl Acad Sci U S A 2012; 109:2533.
- Scholl UI, Goh G, Stölting G, et al. Somatic and germline CACNA1D calcium channel mutations in aldosterone-producing adenomas and primary aldosteronism. Nat Genet 2013; 45:1050.
- Scholl UI, Stölting G, Nelson-Williams C, et al. Recurrent gain of function mutation in calcium channel CACNA1H causes early-onset hypertension with primary aldosteronism. Elife 2015; 4:e06315.
- FAMILIAL HYPERALDOSTERONISM TYPE I (FH TYPE I) OR GLUCOCORTICOID-REMEDIABLE ALDOSTERONISM (GRA)
- Clinical characteristics
- FAMILIAL HYPERALDOSTERONISM TYPE II (FH TYPE II)
- Possible mutations
- Clinical features
- Approach to diagnosis
- FAMILIAL HYPERALDOSTERONISM TYPE III (FH TYPE III)
- Mutations in KCNJ5 gene
- Clinical findings
- Evaluation and diagnosis
- SUMMARY AND RECOMMENDATIONS