Case ReportA Case of Glucocorticoid Remediable Aldosteronism andThoracoabdominal Aneurysms
Anahita Shahrrava1 Sunnan Moinuddin1 Prajwal Boddu1 and Rohan Shah2
1Department of Internal Medicine Advocate Illinois Masonic Medical Center 836 West Wellington AvenueChicago IL 60657 USA2Department of Radiology Advocate Illinois Masonic Medical Center 836 West Wellington Avenue Chicago IL 60657 USA
Correspondence should be addressed to Anahita Shahrrava anahitashahrravaadvocatehealthcom
Received 10 March 2016 Accepted 15 May 2016
Academic Editor John Broom
Copyright copy 2016 Anahita Shahrrava et al This is an open access article distributed under the Creative Commons AttributionLicense which permits unrestricted use distribution and reproduction in any medium provided the original work is properlycited
Glucocorticoid remediable aldosteronism (GRA) is rare familial form of primary aldosteronism characterized by a normalization ofhypertension with the administration of glucocorticoids We present a case of GRA and thoracoabdominal aneurysm complicatedby multiple aortic dissections requiring complex surgical and endovascular repairs Registry studies have shown a high rate ofintracranial aneurysms in GRA patients with high case fatality rates The association of thoracoabdominal aneurysms with GRAhas not been described thus far in literature Studies have shown that high tissue aldosterone levels concomitant with salt intakehave a significant role in the pathogenesis of aneurysms and this may explain the formation of aneurysms in the intracranialvasculature and aorta The association of GRA with thoracic aortic aneurysms needs to be further studied to develop screeningrecommendations for early identification and optimal treatment Also the early use of mineralocorticoid antagonists may have asignificant preventive and attenuating effect in aneurysm formation an association which needs to be confirmed in future studies
1 Introduction
Glucocorticoid remediable aldosteronism is rare familialform of primary aldosteronism characterized by a uniqueclinical response of hypertension and aldosterone productionto the administration of glucocorticoids First described in1996 by Sutherland and colleagues in a family of father andson it was observed that the clinical findings of mineralo-corticoid excess including hypertension and hypokalemiareversed dramatically with administration of dexamethasonegiving it the name dexamethasone remediable hyperaldos-teronism also referred to as Familial HyperaldosteronismType 1 [1] GRA has been associated with early onset famil-ial intracranial aneurysms a potentially fatal complicationcarrying high fatality rates The association of GRA withthoracoabdominal aneurysms has not been studied Studiessuggest that high aldosterone levels and high salt intakehave a significant hypertension-independent effect in thepathogenesis of aneurysms [2]
2 Case Report
A 24-year-old male presented to our hospital with dailycomplaints of chest pain and palpitations for the past threemonths He endorsed to not being compliant with hisprednisone and antihypertensives in the recent past Hismedical history was significant for glucocorticoid remedia-ble hyperaldosteronism (GRA) diagnosed at the age of 18HTN depression and anxiety His cardiovascular history wasnotable for 3 aortic dissections at ages of 10 17 and 22 mid-thoracic aortic aneurysm requiring endovascular repair at theage of 18 and abdominal aortic aneurysm which requiredopen surgical repair at the age of 22 Childhood history wasremarkable for early onset hypertension discovered at theage of 10 after his first episode of dissection He also hadsevere headaches during childhood which were attributed tohypertension by his treating physicians He was started thenon amlodipine carvedilol and clonidine for themanagementof his hypertension 8 years later he was diagnosed with
Hindawi Publishing CorporationCase Reports in EndocrinologyVolume 2016 Article ID 2017571 4 pageshttpdxdoiorg10115520162017571
2 Case Reports in Endocrinology
Figure 1
GRAby another physician andwas started on prednisone andspironolactone The biochemical data could not be obtainedas it was done many years ago at an outside hospital butdiagnosis was confirmed by detecting the chimeric gene viaPCR testing Genetic testing was done on parents and thefather was found to have abnormal gene No family history ofaortic aneurysms and negative gene testing ruled out familialthoracic aortic aneurysm anddissectionThepatientrsquosmotherand father were not consanguineous and both parents diedof drug overdoseThe patientrsquos sister has Crohnrsquos diseaseThepatient had a 4 pack-year smoking history
On initial exam patient was hypertensive with a bloodpressure of 206109 Physical exam was unremarkable exceptfor a 46 systolic murmur most prominent in the aortic areawith radiation to the apex The patient did not have morpho-logical features of related conditions like Marfanrsquos syndromeEhlers-Danlos syndrome or Loeys-Dietz syndrome Labseither were within normal limits or were unremarkableTransthoracic echocardiogram revealed concentric hypertro-phy with an ejection fraction of 60 and an intimal flapsuggestive of aortic dissection There was no evidence ofcardiac anomalies of bicuspid valve on echocardiograph CTangiogram (Figure 1) demonstrated chronic dissection of theaortic arch (not shown in figure) terminating at thoracicstent and extending into the innominate and common carotidarteries and a pseudoaneurysm of the distal thoracic aortajust above the celiac artery (Figures 1 and 2) The patient wasstarted on antihypertensives and prednisone with gradualimprovement of blood pressure back to baseline Review ofpast medical records confirms that the aortic dissection waschronic and it was decided not to operate upon the patientdue to high risk of surgical complications Interventionalradiology was consulted and an endovascular repair of thepseudoaneurysm was planned An endovascular aortic stentwas placed successfully without complications (Figures 2and 3) and the patient was transferred to ICU for closemonitoring
Figure 2
Figure 3
3 Discussion
Glucocorticoid remediable aldosteronism is a rare formof familial hyperaldosteronism characterized by an auto-somal dominant pattern of inheritance [3] GRA is themost common monogenetic form of hypertension Molec-ular studies have characterized the genetic basis of GRAto be from the unequal crossing over between CYP11B1(11120573-hydroxylase) and CYP11B2 (aldosterone synthase) lociresulting in chimeric gene involving the 51015840 ACTH-responsivepromoter of the 11120573-hydroxylase gene to the 31015840 codingsequences of the aldosterone synthase [4 5] This results inectopic expression of aldosterone synthase in zona fasciculataunder themodulation of ACTH resulting in ACTHmediatedaldosteronism [4 6]
GRA is characterized by early onset severe hypertensionstarting in early childhood with up to 80 of the affectedpresenting before the age of 13 [7] However associatedstudies have observed a large variation in the expressionof phenotype among affected family members with somehaving only mild hypertension and others being normoten-sive [8] Most patients with GRA are normokalemic in salt
Case Reports in Endocrinology 3
restricted state making potassium levels an insensitive toolfor evaluating GRA indicating PHA [9 10] GRA is a lowrenin hypertension characterized by high aldosteronereninratio failure to suppress aldosterone with salt loading andelevated 18-hydroxycortisol 18-hydroxycorticosterone and18-oxocortisol levels [11 12] However definitive diagnosis isbest accomplished by genetic testing for the chimeric geneby PCR in the peripheral blood DNA [13] Physicians shouldmaintain a high degree of suspicion for GRA in children withearly onset severe hypertension especially with a supportingfamily history of early onset hypertension [7]
Early cerebrovascular complications in GRA were sys-temically reviewed in a cohort of 376 patients from 27GRA pedigrees which showed the presence of intracranialaneurysms in 48 of all GRA pedigrees and case fatality ratesof up to 61 [14] leading to screening recommendations forintracranial aneurysms every 5 years after puberty [15] How-ever the incidence of thoracoabdominal aneurysms in GRAhas not been studied to date Mineralocorticoid receptorsare expressed not only in the kidneys but also in the heartand the aorta [16] It has been proven that aldosterone exertswidespread cardiovascular effects including left ventricularhypertrophy hypertension and heart failure independent ofchanges in systemic blood pressure indicating a potentialremodeling role for mineralocorticoid antagonists [17] Acase report of successful treatment of a pseudoaneurysm in atype 2 diabetes mellitus patient while treating primary aldos-teronismwith spironolactone has been described [18] Mousemodels of aortic aneurysms have identified a significantrole of aldosterone in the pathogenesis of aortic aneurysmsHigh aldosterone concomitant with increased salt intakeleads to age-dependent aneurysmal changes in the aortawhich do not correlate with blood pressure increases andreduce in size with mineralocorticoid receptor antagonistslike spironolactone [2] The results of this study lend tothe proposal that early use of mineralocorticoid antagonistsmay have a significant preventative and remodeling effect ofaneurysm formation inGRApatients and that early diagnosisof GRA remains pivotal to allow for prompt screening andearly initiation of these agents Also case studies of aortic dis-section in hyperaldosteronism suggest that high aldosteronelevelsmay exert structural alterations in the aorta beyond andindependent of aldosteronism-induced hypertension [19 20]The combined risk factor profile of hypertension smokingand hyperaldosteronism may well explain early onset ofdissection and aneurysms in our patient
The first-line treatment of GRA is the nightly use ofdexamethasone or prednisone in doses sufficient to suppressearlymorning surges in ACTH and normalize blood pressure[21] The initiation of mineralocorticoid antagonists in thetreatment regimen is less clear and is generally consideredin patients whose blood pressure is not normalized onglucocorticoids or if there is coexisting essential hypertension[22] As discussed above early use of mineralocorticoidantagonists may have far reaching benefits in preventingandor attenuating aneurysm formation and should be con-sidered early in the course of therapy even in normotensives
To our knowledge thoracoabdominal aneurysms inGRAhave not been described in literatureThe association of GRA
with thoracic aortic aneurysms needs to be further studiedto inform screening recommendations for early detectionand optimal management of aortic aneurysms in theseselect groups of patients The early use of mineralocorticoidantagonists may have a significant preventive and attenuatingeffect in aneurysm formation an effect which needs to beconfirmed in future studies
Competing Interests
The authors declare that they have no competing interests
References
[1] V M Vehaskari ldquoHeritable forms of hypertensionrdquo PediatricNephrology vol 24 no 10 pp 1929ndash1937 2009
[2] S Liu Z Xie A Daugherty et al ldquoMineralocorticoid receptoragonists induce mouse aortic aneurysm formation and rupturein the presence of high saltrdquo Arteriosclerosis Thrombosis andVascular Biology vol 33 no 7 pp 1568ndash1579 2013
[3] D J Sutherland J L Ruse and J C Laidlaw ldquoHypertensionincreased aldosterone secretion and low plasma renin activityrelieved by dexamethasonerdquo Canadian Medical AssociationJournal vol 95 no 22 pp 1109ndash1119 1966
[4] R V Jackson A Lafferty D J Torpy and C Stratakis ldquoNewgenetic insights in familial hyperaldosteronismrdquo Annals of theNew York Academy of Sciences vol 970 pp 77ndash88 2002
[5] L Pascoe K M Curnow L Slutsker et al ldquoGlucocorticoid-suppressible hyperaldosteronism results from hybrid genescreated by unequal crossovers between CYP11B1 and CYP11B2rdquoProceedings of the National Academy of Sciences of the UnitedStates of America vol 89 no 17 pp 8327ndash8331 1992
[6] R P Lifton R G Dluhy M Powers S Ulick and J MLalouel ldquoThe molecular basis of glucocorticoid-remediablealdosteronism a mendelian cause of human hypertensionrdquoTransactions of the Association of American Physicians vol 105pp 64ndash71 1992
[7] R G Dluhy B Anderson B Harlin J Ingelfinger and RLifton ldquoGlucocorticoid-remediable aldosteronism is associatedwith severe hypertension in early childhoodrdquo The Journal ofPediatrics vol 138 no 5 pp 715ndash720 2001
[8] F Fallo C Pilon T A Williams et al ldquoCoexistence of differentphenotypes in a family with glucocorticoid-remediable aldos-teronismrdquo Journal of HumanHypertension vol 18 no 1 pp 47ndash51 2004
[9] G M Rich S Ulick S Cook J Z Wang R P Lifton and RG Dluhy ldquoGlucocorticoid-remediable aldosteronism in a largekindred cinical spectrum and diagnosis using a characteristicbiochemical phenotyperdquo Annals of Internal Medicine vol 116no 10 pp 813ndash820 1992
[10] E A Espiner and R A Donald ldquoAldosterone regulation inprimary aldosteronism influence of salt balance posture andACTHrdquo Clinical Endocrinology vol 12 no 3 pp 277ndash286 1980
[11] O Vonend C Altenhenne N J Buchner et al ldquoAGerman fam-ily with glucocorticoid-remediable aldosteronismrdquo NephrologyDialysis Transplantation vol 22 no 4 pp 1123ndash1130 2007
[12] P Mulatero S M di Cella S Monticone et al ldquo18-Hydroxycorticosterone 18-hydroxycortisol and 18-oxocortisolin the diagnosis of primary aldosteronism and its subtypesrdquoJournal of Clinical Endocrinology and Metabolism vol 97 no3 pp 881ndash889 2012
4 Case Reports in Endocrinology
[13] J R Jonsson S A Klemm T J Tunny M Stowasser and RD Gordon ldquoA new genetic test for familial hyperaldosteronismtype I AIDS in the detection of curable hypertensionrdquo Biochem-ical and Biophysical Research Communications vol 207 no 2pp 565ndash571 1995
[14] W R Litchfield B F Anderson R J Weiss R P Lifton andR G Dluhy ldquoIntracranial aneurysm and hemorrhagic stroke inglucocorticoid- remediable aldosteronismrdquo Hypertension vol31 no 1 pp 445ndash450 1998
[15] F Crawley A Clifton and M M Brown ldquoShould we screen forfamilial intracranial aneurysmrdquo Stroke vol 30 no 2 pp 312ndash316 1999
[16] M J Young and A J Rickard ldquoMechanisms of mineralocorti-coid salt-induced hypertension and cardiac fibrosisrdquoMolecularand Cellular Endocrinology vol 350 no 2 pp 248ndash255 2012
[17] H V Joffe and G K Adler ldquoEffect of aldosterone andmineralo-corticoid receptor blockade on vascular inflammationrdquo HeartFailure Reviews vol 10 no 1 pp 31ndash37 2005
[18] Y Ito K Yoshimura Y Matsuzawa et al ldquoSuccessful treatmentof a mycotic aortic pseudoaneurysm in a patient with type 2diabetes mellitus while treating primary aldosteronism withspironolactonerdquo Journal of Atherosclerosis and Thrombosis vol17 no 7 pp 771ndash775 2010
[19] K L Harvey C V Riga M OrsquoConnor M S Hamady NChapman and R G J Gibbs ldquoA rare case of aortic dissectionand primary hyperaldosteronismrdquo EJVES Extra vol 20 no 3pp e22ndashe24 2010
[20] J-M Tartiere L Kesri J-J Mourad M Safar and J BlacherldquoPrimary aldosteronism a risk factor for aortic dissectionrdquoJournal des Maladies Vasculaires vol 28 no 4 pp 185ndash1892003
[21] M Stowasser A W Bachmann P R Huggard T R Rossettiand R D Gordon ldquoTreatment of familial hyperaldosteronismtype I only partial suppression of adrenocorticotropin requiredto correct hypertensionrdquo Journal of Clinical Endocrinology andMetabolism vol 85 no 9 pp 3313ndash3318 2000
[22] F Halperin and R G Dluhy ldquoGlucocorticoid-remediableAldosteronismrdquo Endocrinology andMetabolism Clinics of NorthAmerica vol 40 no 2 pp 333ndash341 2011
GRAby another physician andwas started on prednisone andspironolactone The biochemical data could not be obtainedas it was done many years ago at an outside hospital butdiagnosis was confirmed by detecting the chimeric gene viaPCR testing Genetic testing was done on parents and thefather was found to have abnormal gene No family history ofaortic aneurysms and negative gene testing ruled out familialthoracic aortic aneurysm anddissectionThepatientrsquosmotherand father were not consanguineous and both parents diedof drug overdoseThe patientrsquos sister has Crohnrsquos diseaseThepatient had a 4 pack-year smoking history
On initial exam patient was hypertensive with a bloodpressure of 206109 Physical exam was unremarkable exceptfor a 46 systolic murmur most prominent in the aortic areawith radiation to the apex The patient did not have morpho-logical features of related conditions like Marfanrsquos syndromeEhlers-Danlos syndrome or Loeys-Dietz syndrome Labseither were within normal limits or were unremarkableTransthoracic echocardiogram revealed concentric hypertro-phy with an ejection fraction of 60 and an intimal flapsuggestive of aortic dissection There was no evidence ofcardiac anomalies of bicuspid valve on echocardiograph CTangiogram (Figure 1) demonstrated chronic dissection of theaortic arch (not shown in figure) terminating at thoracicstent and extending into the innominate and common carotidarteries and a pseudoaneurysm of the distal thoracic aortajust above the celiac artery (Figures 1 and 2) The patient wasstarted on antihypertensives and prednisone with gradualimprovement of blood pressure back to baseline Review ofpast medical records confirms that the aortic dissection waschronic and it was decided not to operate upon the patientdue to high risk of surgical complications Interventionalradiology was consulted and an endovascular repair of thepseudoaneurysm was planned An endovascular aortic stentwas placed successfully without complications (Figures 2and 3) and the patient was transferred to ICU for closemonitoring
Figure 2
Figure 3
3 Discussion
Glucocorticoid remediable aldosteronism is a rare formof familial hyperaldosteronism characterized by an auto-somal dominant pattern of inheritance [3] GRA is themost common monogenetic form of hypertension Molec-ular studies have characterized the genetic basis of GRAto be from the unequal crossing over between CYP11B1(11120573-hydroxylase) and CYP11B2 (aldosterone synthase) lociresulting in chimeric gene involving the 51015840 ACTH-responsivepromoter of the 11120573-hydroxylase gene to the 31015840 codingsequences of the aldosterone synthase [4 5] This results inectopic expression of aldosterone synthase in zona fasciculataunder themodulation of ACTH resulting in ACTHmediatedaldosteronism [4 6]
GRA is characterized by early onset severe hypertensionstarting in early childhood with up to 80 of the affectedpresenting before the age of 13 [7] However associatedstudies have observed a large variation in the expressionof phenotype among affected family members with somehaving only mild hypertension and others being normoten-sive [8] Most patients with GRA are normokalemic in salt
Case Reports in Endocrinology 3
restricted state making potassium levels an insensitive toolfor evaluating GRA indicating PHA [9 10] GRA is a lowrenin hypertension characterized by high aldosteronereninratio failure to suppress aldosterone with salt loading andelevated 18-hydroxycortisol 18-hydroxycorticosterone and18-oxocortisol levels [11 12] However definitive diagnosis isbest accomplished by genetic testing for the chimeric geneby PCR in the peripheral blood DNA [13] Physicians shouldmaintain a high degree of suspicion for GRA in children withearly onset severe hypertension especially with a supportingfamily history of early onset hypertension [7]
Early cerebrovascular complications in GRA were sys-temically reviewed in a cohort of 376 patients from 27GRA pedigrees which showed the presence of intracranialaneurysms in 48 of all GRA pedigrees and case fatality ratesof up to 61 [14] leading to screening recommendations forintracranial aneurysms every 5 years after puberty [15] How-ever the incidence of thoracoabdominal aneurysms in GRAhas not been studied to date Mineralocorticoid receptorsare expressed not only in the kidneys but also in the heartand the aorta [16] It has been proven that aldosterone exertswidespread cardiovascular effects including left ventricularhypertrophy hypertension and heart failure independent ofchanges in systemic blood pressure indicating a potentialremodeling role for mineralocorticoid antagonists [17] Acase report of successful treatment of a pseudoaneurysm in atype 2 diabetes mellitus patient while treating primary aldos-teronismwith spironolactone has been described [18] Mousemodels of aortic aneurysms have identified a significantrole of aldosterone in the pathogenesis of aortic aneurysmsHigh aldosterone concomitant with increased salt intakeleads to age-dependent aneurysmal changes in the aortawhich do not correlate with blood pressure increases andreduce in size with mineralocorticoid receptor antagonistslike spironolactone [2] The results of this study lend tothe proposal that early use of mineralocorticoid antagonistsmay have a significant preventative and remodeling effect ofaneurysm formation inGRApatients and that early diagnosisof GRA remains pivotal to allow for prompt screening andearly initiation of these agents Also case studies of aortic dis-section in hyperaldosteronism suggest that high aldosteronelevelsmay exert structural alterations in the aorta beyond andindependent of aldosteronism-induced hypertension [19 20]The combined risk factor profile of hypertension smokingand hyperaldosteronism may well explain early onset ofdissection and aneurysms in our patient
The first-line treatment of GRA is the nightly use ofdexamethasone or prednisone in doses sufficient to suppressearlymorning surges in ACTH and normalize blood pressure[21] The initiation of mineralocorticoid antagonists in thetreatment regimen is less clear and is generally consideredin patients whose blood pressure is not normalized onglucocorticoids or if there is coexisting essential hypertension[22] As discussed above early use of mineralocorticoidantagonists may have far reaching benefits in preventingandor attenuating aneurysm formation and should be con-sidered early in the course of therapy even in normotensives
To our knowledge thoracoabdominal aneurysms inGRAhave not been described in literatureThe association of GRA
with thoracic aortic aneurysms needs to be further studiedto inform screening recommendations for early detectionand optimal management of aortic aneurysms in theseselect groups of patients The early use of mineralocorticoidantagonists may have a significant preventive and attenuatingeffect in aneurysm formation an effect which needs to beconfirmed in future studies
Competing Interests
The authors declare that they have no competing interests
References
[1] V M Vehaskari ldquoHeritable forms of hypertensionrdquo PediatricNephrology vol 24 no 10 pp 1929ndash1937 2009
[2] S Liu Z Xie A Daugherty et al ldquoMineralocorticoid receptoragonists induce mouse aortic aneurysm formation and rupturein the presence of high saltrdquo Arteriosclerosis Thrombosis andVascular Biology vol 33 no 7 pp 1568ndash1579 2013
[3] D J Sutherland J L Ruse and J C Laidlaw ldquoHypertensionincreased aldosterone secretion and low plasma renin activityrelieved by dexamethasonerdquo Canadian Medical AssociationJournal vol 95 no 22 pp 1109ndash1119 1966
[4] R V Jackson A Lafferty D J Torpy and C Stratakis ldquoNewgenetic insights in familial hyperaldosteronismrdquo Annals of theNew York Academy of Sciences vol 970 pp 77ndash88 2002
[5] L Pascoe K M Curnow L Slutsker et al ldquoGlucocorticoid-suppressible hyperaldosteronism results from hybrid genescreated by unequal crossovers between CYP11B1 and CYP11B2rdquoProceedings of the National Academy of Sciences of the UnitedStates of America vol 89 no 17 pp 8327ndash8331 1992
[6] R P Lifton R G Dluhy M Powers S Ulick and J MLalouel ldquoThe molecular basis of glucocorticoid-remediablealdosteronism a mendelian cause of human hypertensionrdquoTransactions of the Association of American Physicians vol 105pp 64ndash71 1992
[7] R G Dluhy B Anderson B Harlin J Ingelfinger and RLifton ldquoGlucocorticoid-remediable aldosteronism is associatedwith severe hypertension in early childhoodrdquo The Journal ofPediatrics vol 138 no 5 pp 715ndash720 2001
[8] F Fallo C Pilon T A Williams et al ldquoCoexistence of differentphenotypes in a family with glucocorticoid-remediable aldos-teronismrdquo Journal of HumanHypertension vol 18 no 1 pp 47ndash51 2004
[9] G M Rich S Ulick S Cook J Z Wang R P Lifton and RG Dluhy ldquoGlucocorticoid-remediable aldosteronism in a largekindred cinical spectrum and diagnosis using a characteristicbiochemical phenotyperdquo Annals of Internal Medicine vol 116no 10 pp 813ndash820 1992
[10] E A Espiner and R A Donald ldquoAldosterone regulation inprimary aldosteronism influence of salt balance posture andACTHrdquo Clinical Endocrinology vol 12 no 3 pp 277ndash286 1980
[11] O Vonend C Altenhenne N J Buchner et al ldquoAGerman fam-ily with glucocorticoid-remediable aldosteronismrdquo NephrologyDialysis Transplantation vol 22 no 4 pp 1123ndash1130 2007
[12] P Mulatero S M di Cella S Monticone et al ldquo18-Hydroxycorticosterone 18-hydroxycortisol and 18-oxocortisolin the diagnosis of primary aldosteronism and its subtypesrdquoJournal of Clinical Endocrinology and Metabolism vol 97 no3 pp 881ndash889 2012
4 Case Reports in Endocrinology
[13] J R Jonsson S A Klemm T J Tunny M Stowasser and RD Gordon ldquoA new genetic test for familial hyperaldosteronismtype I AIDS in the detection of curable hypertensionrdquo Biochem-ical and Biophysical Research Communications vol 207 no 2pp 565ndash571 1995
[14] W R Litchfield B F Anderson R J Weiss R P Lifton andR G Dluhy ldquoIntracranial aneurysm and hemorrhagic stroke inglucocorticoid- remediable aldosteronismrdquo Hypertension vol31 no 1 pp 445ndash450 1998
[15] F Crawley A Clifton and M M Brown ldquoShould we screen forfamilial intracranial aneurysmrdquo Stroke vol 30 no 2 pp 312ndash316 1999
[16] M J Young and A J Rickard ldquoMechanisms of mineralocorti-coid salt-induced hypertension and cardiac fibrosisrdquoMolecularand Cellular Endocrinology vol 350 no 2 pp 248ndash255 2012
[17] H V Joffe and G K Adler ldquoEffect of aldosterone andmineralo-corticoid receptor blockade on vascular inflammationrdquo HeartFailure Reviews vol 10 no 1 pp 31ndash37 2005
[18] Y Ito K Yoshimura Y Matsuzawa et al ldquoSuccessful treatmentof a mycotic aortic pseudoaneurysm in a patient with type 2diabetes mellitus while treating primary aldosteronism withspironolactonerdquo Journal of Atherosclerosis and Thrombosis vol17 no 7 pp 771ndash775 2010
[19] K L Harvey C V Riga M OrsquoConnor M S Hamady NChapman and R G J Gibbs ldquoA rare case of aortic dissectionand primary hyperaldosteronismrdquo EJVES Extra vol 20 no 3pp e22ndashe24 2010
[20] J-M Tartiere L Kesri J-J Mourad M Safar and J BlacherldquoPrimary aldosteronism a risk factor for aortic dissectionrdquoJournal des Maladies Vasculaires vol 28 no 4 pp 185ndash1892003
[21] M Stowasser A W Bachmann P R Huggard T R Rossettiand R D Gordon ldquoTreatment of familial hyperaldosteronismtype I only partial suppression of adrenocorticotropin requiredto correct hypertensionrdquo Journal of Clinical Endocrinology andMetabolism vol 85 no 9 pp 3313ndash3318 2000
[22] F Halperin and R G Dluhy ldquoGlucocorticoid-remediableAldosteronismrdquo Endocrinology andMetabolism Clinics of NorthAmerica vol 40 no 2 pp 333ndash341 2011
restricted state making potassium levels an insensitive toolfor evaluating GRA indicating PHA [9 10] GRA is a lowrenin hypertension characterized by high aldosteronereninratio failure to suppress aldosterone with salt loading andelevated 18-hydroxycortisol 18-hydroxycorticosterone and18-oxocortisol levels [11 12] However definitive diagnosis isbest accomplished by genetic testing for the chimeric geneby PCR in the peripheral blood DNA [13] Physicians shouldmaintain a high degree of suspicion for GRA in children withearly onset severe hypertension especially with a supportingfamily history of early onset hypertension [7]
Early cerebrovascular complications in GRA were sys-temically reviewed in a cohort of 376 patients from 27GRA pedigrees which showed the presence of intracranialaneurysms in 48 of all GRA pedigrees and case fatality ratesof up to 61 [14] leading to screening recommendations forintracranial aneurysms every 5 years after puberty [15] How-ever the incidence of thoracoabdominal aneurysms in GRAhas not been studied to date Mineralocorticoid receptorsare expressed not only in the kidneys but also in the heartand the aorta [16] It has been proven that aldosterone exertswidespread cardiovascular effects including left ventricularhypertrophy hypertension and heart failure independent ofchanges in systemic blood pressure indicating a potentialremodeling role for mineralocorticoid antagonists [17] Acase report of successful treatment of a pseudoaneurysm in atype 2 diabetes mellitus patient while treating primary aldos-teronismwith spironolactone has been described [18] Mousemodels of aortic aneurysms have identified a significantrole of aldosterone in the pathogenesis of aortic aneurysmsHigh aldosterone concomitant with increased salt intakeleads to age-dependent aneurysmal changes in the aortawhich do not correlate with blood pressure increases andreduce in size with mineralocorticoid receptor antagonistslike spironolactone [2] The results of this study lend tothe proposal that early use of mineralocorticoid antagonistsmay have a significant preventative and remodeling effect ofaneurysm formation inGRApatients and that early diagnosisof GRA remains pivotal to allow for prompt screening andearly initiation of these agents Also case studies of aortic dis-section in hyperaldosteronism suggest that high aldosteronelevelsmay exert structural alterations in the aorta beyond andindependent of aldosteronism-induced hypertension [19 20]The combined risk factor profile of hypertension smokingand hyperaldosteronism may well explain early onset ofdissection and aneurysms in our patient
The first-line treatment of GRA is the nightly use ofdexamethasone or prednisone in doses sufficient to suppressearlymorning surges in ACTH and normalize blood pressure[21] The initiation of mineralocorticoid antagonists in thetreatment regimen is less clear and is generally consideredin patients whose blood pressure is not normalized onglucocorticoids or if there is coexisting essential hypertension[22] As discussed above early use of mineralocorticoidantagonists may have far reaching benefits in preventingandor attenuating aneurysm formation and should be con-sidered early in the course of therapy even in normotensives
To our knowledge thoracoabdominal aneurysms inGRAhave not been described in literatureThe association of GRA
with thoracic aortic aneurysms needs to be further studiedto inform screening recommendations for early detectionand optimal management of aortic aneurysms in theseselect groups of patients The early use of mineralocorticoidantagonists may have a significant preventive and attenuatingeffect in aneurysm formation an effect which needs to beconfirmed in future studies
Competing Interests
The authors declare that they have no competing interests
References
[1] V M Vehaskari ldquoHeritable forms of hypertensionrdquo PediatricNephrology vol 24 no 10 pp 1929ndash1937 2009
[2] S Liu Z Xie A Daugherty et al ldquoMineralocorticoid receptoragonists induce mouse aortic aneurysm formation and rupturein the presence of high saltrdquo Arteriosclerosis Thrombosis andVascular Biology vol 33 no 7 pp 1568ndash1579 2013
[3] D J Sutherland J L Ruse and J C Laidlaw ldquoHypertensionincreased aldosterone secretion and low plasma renin activityrelieved by dexamethasonerdquo Canadian Medical AssociationJournal vol 95 no 22 pp 1109ndash1119 1966
[4] R V Jackson A Lafferty D J Torpy and C Stratakis ldquoNewgenetic insights in familial hyperaldosteronismrdquo Annals of theNew York Academy of Sciences vol 970 pp 77ndash88 2002
[5] L Pascoe K M Curnow L Slutsker et al ldquoGlucocorticoid-suppressible hyperaldosteronism results from hybrid genescreated by unequal crossovers between CYP11B1 and CYP11B2rdquoProceedings of the National Academy of Sciences of the UnitedStates of America vol 89 no 17 pp 8327ndash8331 1992
[6] R P Lifton R G Dluhy M Powers S Ulick and J MLalouel ldquoThe molecular basis of glucocorticoid-remediablealdosteronism a mendelian cause of human hypertensionrdquoTransactions of the Association of American Physicians vol 105pp 64ndash71 1992
[7] R G Dluhy B Anderson B Harlin J Ingelfinger and RLifton ldquoGlucocorticoid-remediable aldosteronism is associatedwith severe hypertension in early childhoodrdquo The Journal ofPediatrics vol 138 no 5 pp 715ndash720 2001
[8] F Fallo C Pilon T A Williams et al ldquoCoexistence of differentphenotypes in a family with glucocorticoid-remediable aldos-teronismrdquo Journal of HumanHypertension vol 18 no 1 pp 47ndash51 2004
[9] G M Rich S Ulick S Cook J Z Wang R P Lifton and RG Dluhy ldquoGlucocorticoid-remediable aldosteronism in a largekindred cinical spectrum and diagnosis using a characteristicbiochemical phenotyperdquo Annals of Internal Medicine vol 116no 10 pp 813ndash820 1992
[10] E A Espiner and R A Donald ldquoAldosterone regulation inprimary aldosteronism influence of salt balance posture andACTHrdquo Clinical Endocrinology vol 12 no 3 pp 277ndash286 1980
[11] O Vonend C Altenhenne N J Buchner et al ldquoAGerman fam-ily with glucocorticoid-remediable aldosteronismrdquo NephrologyDialysis Transplantation vol 22 no 4 pp 1123ndash1130 2007
[12] P Mulatero S M di Cella S Monticone et al ldquo18-Hydroxycorticosterone 18-hydroxycortisol and 18-oxocortisolin the diagnosis of primary aldosteronism and its subtypesrdquoJournal of Clinical Endocrinology and Metabolism vol 97 no3 pp 881ndash889 2012
4 Case Reports in Endocrinology
[13] J R Jonsson S A Klemm T J Tunny M Stowasser and RD Gordon ldquoA new genetic test for familial hyperaldosteronismtype I AIDS in the detection of curable hypertensionrdquo Biochem-ical and Biophysical Research Communications vol 207 no 2pp 565ndash571 1995
[14] W R Litchfield B F Anderson R J Weiss R P Lifton andR G Dluhy ldquoIntracranial aneurysm and hemorrhagic stroke inglucocorticoid- remediable aldosteronismrdquo Hypertension vol31 no 1 pp 445ndash450 1998
[15] F Crawley A Clifton and M M Brown ldquoShould we screen forfamilial intracranial aneurysmrdquo Stroke vol 30 no 2 pp 312ndash316 1999
[16] M J Young and A J Rickard ldquoMechanisms of mineralocorti-coid salt-induced hypertension and cardiac fibrosisrdquoMolecularand Cellular Endocrinology vol 350 no 2 pp 248ndash255 2012
[17] H V Joffe and G K Adler ldquoEffect of aldosterone andmineralo-corticoid receptor blockade on vascular inflammationrdquo HeartFailure Reviews vol 10 no 1 pp 31ndash37 2005
[18] Y Ito K Yoshimura Y Matsuzawa et al ldquoSuccessful treatmentof a mycotic aortic pseudoaneurysm in a patient with type 2diabetes mellitus while treating primary aldosteronism withspironolactonerdquo Journal of Atherosclerosis and Thrombosis vol17 no 7 pp 771ndash775 2010
[19] K L Harvey C V Riga M OrsquoConnor M S Hamady NChapman and R G J Gibbs ldquoA rare case of aortic dissectionand primary hyperaldosteronismrdquo EJVES Extra vol 20 no 3pp e22ndashe24 2010
[20] J-M Tartiere L Kesri J-J Mourad M Safar and J BlacherldquoPrimary aldosteronism a risk factor for aortic dissectionrdquoJournal des Maladies Vasculaires vol 28 no 4 pp 185ndash1892003
[21] M Stowasser A W Bachmann P R Huggard T R Rossettiand R D Gordon ldquoTreatment of familial hyperaldosteronismtype I only partial suppression of adrenocorticotropin requiredto correct hypertensionrdquo Journal of Clinical Endocrinology andMetabolism vol 85 no 9 pp 3313ndash3318 2000
[22] F Halperin and R G Dluhy ldquoGlucocorticoid-remediableAldosteronismrdquo Endocrinology andMetabolism Clinics of NorthAmerica vol 40 no 2 pp 333ndash341 2011
[13] J R Jonsson S A Klemm T J Tunny M Stowasser and RD Gordon ldquoA new genetic test for familial hyperaldosteronismtype I AIDS in the detection of curable hypertensionrdquo Biochem-ical and Biophysical Research Communications vol 207 no 2pp 565ndash571 1995
[14] W R Litchfield B F Anderson R J Weiss R P Lifton andR G Dluhy ldquoIntracranial aneurysm and hemorrhagic stroke inglucocorticoid- remediable aldosteronismrdquo Hypertension vol31 no 1 pp 445ndash450 1998
[15] F Crawley A Clifton and M M Brown ldquoShould we screen forfamilial intracranial aneurysmrdquo Stroke vol 30 no 2 pp 312ndash316 1999
[16] M J Young and A J Rickard ldquoMechanisms of mineralocorti-coid salt-induced hypertension and cardiac fibrosisrdquoMolecularand Cellular Endocrinology vol 350 no 2 pp 248ndash255 2012
[17] H V Joffe and G K Adler ldquoEffect of aldosterone andmineralo-corticoid receptor blockade on vascular inflammationrdquo HeartFailure Reviews vol 10 no 1 pp 31ndash37 2005
[18] Y Ito K Yoshimura Y Matsuzawa et al ldquoSuccessful treatmentof a mycotic aortic pseudoaneurysm in a patient with type 2diabetes mellitus while treating primary aldosteronism withspironolactonerdquo Journal of Atherosclerosis and Thrombosis vol17 no 7 pp 771ndash775 2010
[19] K L Harvey C V Riga M OrsquoConnor M S Hamady NChapman and R G J Gibbs ldquoA rare case of aortic dissectionand primary hyperaldosteronismrdquo EJVES Extra vol 20 no 3pp e22ndashe24 2010
[20] J-M Tartiere L Kesri J-J Mourad M Safar and J BlacherldquoPrimary aldosteronism a risk factor for aortic dissectionrdquoJournal des Maladies Vasculaires vol 28 no 4 pp 185ndash1892003
[21] M Stowasser A W Bachmann P R Huggard T R Rossettiand R D Gordon ldquoTreatment of familial hyperaldosteronismtype I only partial suppression of adrenocorticotropin requiredto correct hypertensionrdquo Journal of Clinical Endocrinology andMetabolism vol 85 no 9 pp 3313ndash3318 2000
[22] F Halperin and R G Dluhy ldquoGlucocorticoid-remediableAldosteronismrdquo Endocrinology andMetabolism Clinics of NorthAmerica vol 40 no 2 pp 333ndash341 2011
