Objective: Glucocorticoid-remediable aldosteronism (GRA) is caused by the presence of a chimeric gene originating from an unequal cross-over between the CYP11B1 and CYP11B2 genes. Aldosterone suppression by dexamethasone and high 18-hydroxycortisol (18-OHF) levels have been used to differentiate GRA from the other forms of primary aldosteronism. Methods: A dexamethasone suppression test including serum 18-OHF determination and the measurement of urinary excretion of aldosterone, its metabolites and 18-OHF were performed in 3 children of a family with primary aldosteronism. Polymerase chain reactions were performed to identify the chimeric gene. Results: The chimeric gene was identified in 2 children, their mother and grandmother. The affected children had an aldosterone-to-plasma renin activity ratio >30, elevated serum 18-OHF concentration and increased urinary excretion of aldosterone, its metabolites, and 18-OHF. Post-dexamethasone concentrations of serum aldosterone and 18-OHF concentrations were suppressed. Conclusion: Although very rare, the possible diagnosis of GRA should be considered in all children or young adults with low-renin hypertension. Since genetic testing is more specific than biochemical testing, a definitive diagnosis can only be obtained by identification of the CYP11B1/CYP11B2 chimeric gene.

Sutherland DJ, Ruse JL, Laidlaw JC: Hypertension, increased aldosterone secretion and low plasma renin activity relieved by dexamethasone. Can Med Assoc J 1966;95: 1109–1119.
New MI, Peterson RE: A new form of congenital adrenal hyperplasia. J Clin Endocrinol Metab 1967;27:300–305.
Rich GM, Ulick S, Cook S, Wang JZ, Lifton RP, Dluhy RG: Glucocorticoid-remediable aldosteronism in a large kindred: clinical spectrum and diagnosis using a characteristic biochemical phenotype. Ann Intern Med 1992;116:813–820.
Litchfield WR, Dluhy RG: Glucorticoid-remediable aldosteronism. Curr Opin Endocrinol Diabetes 1996;3:265–270.
Grim CE, Weinberger MH: Familial, dexamethasone-suppressible, normokalemic hyperaldosteronism. Pediatrics 1980;65:597– 604.
Litchtfield WR, Coolidge C, Silva P, Lifton RP, Fallo F, Williams GH, et al: Impaired potassium-stimulated aldosterone production: a possible explanation for normokalemic glucocorticoid-remediable aldosteronism. J Clin Endocrinol Metab 1997;82:1507–1510.
Lifton RP, Dluhy RG, Powers M, Rich GM, Cook S, Ulick S, et al: A chimaeric 11β-hydroxylase/aldosterone synthase gene causes glucocorticoid-remediable aldosteronism and human hypertension. Nature 1992;355:262–265.
Lifton RP, Dluhy RG, Powers M, Rich GM, Cook S, Ulick S, et al: Hereditary hypertension caused by chimaeric gene duplications and ectopic expression of aldosterone synthase. Nat Genet 1993;2:66–74.
Pascoe L, Curnow KM, Slutsker L, Connell JM, Speiser PW, New MI, et al: Glucocorticoid-suppressible hyperaldosteronism results from hybrid genes created by unequal crossovers between CYP11B1 and CYP11B2. Proc Natl Acad Sci USA 1992;89:8327–8331.
Curnow KM, Mulatero P, Emeric-Blanchouin N, Aupetit-Faisant B, Corvol P, Pascoe L: The amino acid substitutions Ser288Gly and Val320Ala convert the cortisol-producing enzyme, CYP11B1, into an aldosterone-producing enzyme. Nat Struct Biol 1997;4:32–35.
Mulatero P, Curnow KM, Aupetit-Faisant B, Foekling M, Gomez-Sanchez C, Veglio F, et al: Recombinant CYP11B genes encode enzymes that can catalyze conversion of 11-deoxycortisol to cortisol, 18-hydroxycortisol, and 18-oxocortisol. J Clin Endocrinol Metab 1998;83:3996–4001.
Litchfield WR, New MI, Coolidge C, Lifton RP, Dluhy RG: Evaluation of the dexamethasone suppression test for the diagnosis of glucocorticoid-remediable aldosteronism. J Clin Endocrinol Metab 1997;82:3570–3573.
Mulatero P, Veglio F, Pilon C, Rabbia F, Zocchi C, Limone P, 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;83:2573–2575.
Fardella CE, Mosso L, Gomez-Sanchez C, Soto J, Gómez L, Pinto M, et al: Primary hyperaldosteronism in essential hypertensives: prevalence, biochemical profile, and molecular biology. J Clin Endocrinol Metab 2000;85:1863–1867.
Nicod J, Dick B, Frey FJ, Ferrari P: Mutation analysis of CYP11B1 and CYP11B2 in patients with increased 18-hydroxycortisol production.Mol Cell Endocrinol 2004;214:167–174.
Vecsei P, Abdelhamid S, Mittelstadt GV, Lichtwald K, Haack D, Lewicka S: Aldosterone metabolites and possible aldosterone precursors in hypertension. J Steroid Biochem 1983;19:345–351.
Seeman T, Widimsky J, Hampf M, Bernhardt R: Abolished nocturnal blood pressure fall in a boy with glucocorticoid-remediable aldosteronism. J Hum Hypertens 1999;13:823–828.
Peters J, Hampf M, Peters B, Bernhardt R: Molekularbiologie, Klinik und Therapie steroidbedingter Hypertonien; in Ganten D, Ruckpaul K (eds): Handbuch der molekularen Medizin. Berlin, Springer, 1998, pp 432–437.
Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo JL Jr, et al, and the National High Blood Pressure Education Program Coordinating Committee: Seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Hypertension 2003;42:1206–1252.
Pizzolo F, Trabetti E, Guarini P, Mulatero P, Ciacciarelli A, Blengio GS, et al: Glucocorticoid remediable aldosteronism screening in hypertensive patients from a primary care setting. J Hum Hypertens 2005;19:325–327.
Adler G, Widecka K, Peczkowska M, Dobrucki T, Placha G, Drozd R, et al: Genetic screening for glucocorticoid-remediable aldosteronism: experience of three clinical centres in Poland. J Appl Genet 2005;46:329–332.
Stowasser M, Gordon RD, Gunasekera TG, Cowley DC, Ward G, Archibald C, et al: High rate of detection of primary aldosteronism, including surgically treatable forms, after ‘non-selective’ screening of hypertensive patients. J Hypertens 2003;21:2149–2157.
Seiler L, Rump LC, Schulte-Mönting J, Slawik M, Borm K, Pavenstädt H, et al: Diagnosis of primary aldosteronism: value of different screening parameters and influence of antihypertensive medication. Eur J Endocrinol 2004;150:329–337.
Mulatero P, Stowasser M, Loh KC, Fardella CE, Gordon RD, Mosso L, et al: Increased diagnosis of primary aldosteronism, including surgically correctable forms, in centers from five continents. J Clin Endocrinol Metab 2004;89:1045–1050.
Fogari R, Preti P, Zoppi A, Rinaldi A, Fogari E, Mugellini A: Prevalence of primary aldosteronism among unselected hypertensive patients: a prospective study based on the use of an aldosterone/renin ratio above 25 as a screening test. Hypertens Res 2007;30:111–117.
Funder JW, Carey RM, Fardella C, Gomez-Sanchez CE, Mantero F, Stowasser M, et al: Case detection, diagnosis, and treatment of patients with primary aldosteronism: an endocrine society clinical practice guideline. J Clin Endocrinol Metab 2008;93:3266–3281.
Stowasser M, Bachmann AW, Tunny TJ, Gordon RD: Production of 18-oxocortisol in subtypes of primary aldosteronism. Clin Exp Pharmacol Physiol 1998;23:591–593.
Reynolds RM, Shakerdi LA, Sandhu K, Wallace AM, Wood PJ, Walker BR: The utility of three different methods for measuring urinary 18-hydroxycortisol in the differential diagnosis of suspected primary hyperaldosteronism. Eur J Endocrinol 2005;152:903–907.
Mosso L, Gomez-Sanchez CE, Foecking MF, Fardella C: Serum 18-hydroxycortisol in primary aldosteronism, hypertension, and normotensives. Hypertension 2001;38:688–691.
Gomez-Sanchez CE, Upcavage RJ, Zager PG, Foecking MF, Holland OB, Ganguly A: Urinary 18-hydroxycortisol and its relationship to the excretion of other adrenal steroids. J Clin Endocrinol Metab 1987;65:310–314.
Rohatagi S, Barth J, Möllmann H, Hochhaus G, Soldner A, Möllmann C, et al: Pharmacokinetics of methylprednisolone and prednisolone after single and multiple oral administration. J Clin Pharmacol 1997;37:916–925.
Donnelly R, Seale JP: Clinical pharmacokinetics of inhaled budesonide. Clin Pharmacokinet 2001;40:427–440.
Dluhy RG, Anderson BF, Harlin B, Ingelfinger J, Lifton RP: Glucocorticoid-remediable aldosteronism is associated with severe hypertension in early childhood. J Pediatr 2001;138:715–720.
Litchfield WR, Anderson BF, Weiss RJ, Lifton RP, Dluhy RG: Intracranial aneurysm and hemorrhagic stroke in glucocorticoid-remediable aldosteronism. Hypertension 1998;31:445–450.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.