A New Family With Dexamethasone‐suppressible Hyperaldosteronism: Aldosterone Unresponsiveness to Angiotensin Ii

Fallo, Francesco; Sonino, Nicoletta; Armanini, Decio; Luzzi, T; Pedini, F.; Pasini, C; Mantero, Franco

doi:10.1111/j.1365-2265.1985.tb00168.x

Cited by 41 publications

(16 citation statements)

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“…The B/aldosterone ratio was also not different from normal in baseline conditions (15 vs 13, expressed on an equimolar basis), but was greatly lower than normal after ACTH (30 vs 84), reflecting the hyper-responsiveness of aldosterone to ACTH stimulation typical of this disease. 8,17 Moreover, a similar marked ACTH-induced decrease of B/aldosterone ratio due to aldosterone hyperresponse also occurred in the younger sister and in the father with GRA (45 and 20 vs 84, respectively). This steroid hormone pattern is in disagreement with findings in other studies of a deficient 11b- Different phenotypes in GRAhydroxylation in GRA, 18 but is in accordance with an increased aldosterone synthase activity in this condition.…”

Section: Discussionmentioning

confidence: 84%

“…6,7 Scarce data are available on the intrafamily variation of phenotype in patients with genetically proved GRA. While in the family previously reported by us 8 and in that described by Rich et al, 9 the penetrance of hypertension and aldosteronism was high in all affected pedigree members, in the family of Gates et al 10 and in another one more recently reported by us, 11 the great majority of affected members had mild hypertension and normal biochemistry, including serum potassium. Here we report a new family of six members in which three subjects have been identified as possessing the same type of CYP11B1/CYP11B2 chimaeric fusion, but display diverse biochemical and clinical phenotypes.…”

Section: Introductionmentioning

confidence: 76%

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Coexistence of different phenotypes in a family with glucocorticoid-remediable aldosteronism

et al. 2003

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In glucocorticoid-remediable aldosteronism (GRA), there is a large interfamily variation of phenotype. We report three subjects with GRA in a single family (parents, two brothers and two sisters), of whom only one (proband) displayed classical features of the mineralocorticoid excess. The proband was a man found to be hypertensive and hypokalaemic at the age of 24 years. Plasma renin activity was suppressed and plasma aldosterone was repeatedly elevated. Blood pressure and aldosterone levels normalized within 5 days of dexamethasone therapy. The presence of a chimaeric CYP11B1/CYP11B2 gene was demonstrated by long-PCR and Southern blotting (crossover site at the end of intron 3) in the proband, in the younger sister (sibling 1) and in the father. In these patients, sequencing of the chimaeric portion of CYP11B1 did not reveal any mutation, while sequencing of the chimaeric portion of CYP11B2 showed a V386A polymorphism in exon 7, known to cause only a minimal impairment of enzymatic activity. Sibling 1 was normotensive, normokalaemic and had normal PRA and aldosterone. The father had normal blood pressure and potassium, low-normal PRA and normal aldosterone. All three subjects had elevated levels of urinary 18-hydroxycortisol and 18-oxocortisol. Baseline 11-deoxycorticosterone (DOC), corticosterone (B) and aldosterone were high in the proband and normal in the father and sibling 1; 11-deoxycortisol (S) and cortisol (F) were normal. ACTH induced a normal increase of B, DOC, S and F, and an excessive aldosterone increase in all three patients. Abnormalities in the chimaeric portions of CYB11B1 or CYP11B2 genes did not account for the phenotypic disparity of the different members in a single GRA family. Altered regulation of the chimaeric gene may be responsible for differences in its activity.

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Section: Discussionmentioning

confidence: 84%

Section: Introductionmentioning

confidence: 76%

Coexistence of different phenotypes in a family with glucocorticoid-remediable aldosteronism

et al. 2003

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“…23 With dexamethasone treatment, however, plasma aldosterone did rise as a function of plasma ANG II levels. The lack of response without dexamethasone treatment is compatible with indirect evidence that aldosterone does not rise during ambulation in subjects with dexamethasone-suppressible hyperaldosteronism 24 and is explained by down-regulation of adrenal ANG II receptor number as a consequence of suppression of renin and angiotensin due to sodium retention.…”

Section: Figure 5 Relationship Between Plasma Concentrations Of Angimentioning

confidence: 99%

Dexamethasone-suppressible hyperaldosteronism. Adrenal transition cell hyperplasia?

Connell¹,

Kenyon²,

Corrie³

et al. 1986

Hypertension

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SUMMARY Dexamethasone-suppressible hyperaldosteronism is a rare familial syndrome in which hypokalemia, suppression of plasma renin concentration, and elevated aldosterone secretion are corrected by treatment with glucocorticoids. Regulation of adrenocortical function and body electrolytes was studied in two affected brothers. Both were hypertensive (210/128 and 160/106 mm Hg) with hypokalemia (3.3 and 3.5 mM) and low plasma renin concentrations. Aldosterone was elevated intermittently with levels as high as 45 ng/dl (normal range, 4-16 ng/dl). Cortisol concentrations were normal but were correlated with aldosterone levels (r = 0.9 and 0.7). Concentrations of 11-deoxycorticosterone (19 and 21 ng/dl; normal range, 4-16 ng/dl) and 18-hydroxycortisol (1000 and 950 ng/dl; normal range, 34-150 ng/dl) were elevated, and diurnal changes in both were the same as those seen with aldosterone. Infusion of adrenocorticotropic hormone,_ 24 (ACTH) caused exaggerated increases of aldosterone, 11-deoxycorticosterone, and 18-hydroxycortisol; cortisol response was normal. A 4-week trial of dexamethasone normalized blood pressure and caused a natriuresis, a fall in aldosterone, and a rise in plasma renin. Administration of ACTH after dexamethasone treatment again caused exaggerated increases of aldosterone. Aldosterone did not respond to angiotensin II before dexamethasone therapy (r = 0.01), but it showed a normal response after therapy (r = 0.8, p<0.01). Neither administration of dopamine (1 /xg/kg/min) nor long-term therapy with bromocriptine (2.5 mg t.i.d. for 4 weeks) affected aldosterone biosynthesis. Thus, loss of dopaminergic inhibition of mineralocorticoid biosynthesis does not account for hyperaldosteronism in this condition. The abnormal pattern of steroid secretion in these brothers is consistent with a population of adrenocortical transition-type cells that secrete aldosterone in response to ACTH but not to angiotensin II and have biosynthetic characteristics of both zona glomerulosa and zona fasciculata cell types. These properties would explain the excess synthesis of 18-hydroxycortisol from a cell type that can uniquely hydroxylate steroid at both the 17 and 18 positions. (Hypertension 8: 669-676, 1986) KEY WORDS • hyperaldosteronism • cortisol • 18-hydroxycortisol 11-deoxycorticosterone * corticosterone EXAMETHASONE-suppressible hyperaldo-I I steronism is a familial form of hypertension A.^^ in which features of mineralocorticoid excess (hypokalemia, low plasma renin concentration) and elevated blood pressure remit during glucocorticoid treatment.13 Basal aldosterone secretion is increased 2 and aldosterone response to adrenocorticotropic hormone (ACTH) is exaggerated, 4 but the exact cause of these biochemical abnormalities, and indeed of the Received September 18, 1985; accepted January 28, 1986. hypertension itself, remains a matter for speculation. 56We studied two brothers with this condition and examined the effect of dexamethasone therapy on body sodium and potassium content. We also examined the effe...

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“…2 Subsequently it was shown to be inherited in an autosomal dominant fashion and approximately 100 cases were reported in the world literature up to the early 1990's. [3][4][5][6][7][8][9] The most common presentation of GRA used to be the discovery of asymptomatic severe hypertension, especially in infancy or early adulthood. With the ability to identify individuals by genetic or biochemical testing, much milder or earlier clinical forms are being described.…”

mentioning

confidence: 99%

“…As a result, plasma aldosterone levels do not increase and plasma renin activity (PRA) remains suppressed in response to upright posture or to an infusion of angiotensin II. 6,8,[11][12][13][14] In establishing the differential diagnosis of primary aldosteronism, patients should have supine PRA, aldosterone and cortisol measured at 08.00 h and again erect at 12.00 h. A fall in plasma cortisol (and by inference ACTH) together with a concomitant fall in plasma aldosterone across the same period is highly suggestive of GRA. A single measurement may not be representative, and this procedure should be repeated on at least two occasions.…”

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confidence: 99%

Monogenic forms of mineralocorticoid hypertension: insights into the pathogenesis of ‘essential’ hypertension?

Petrelli

Stewart

1998

J Hum Hypertens

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Hypertension is a common condition, which, depending on its definition, affects 10-25% of the population. Because it is an established risk factor for coronary and cerebrovascular disease, hypertension has, quite rightly, been targeted as an important factor in determining the health of the nation. Despite this we can explain the underlying cause of a patient's hypertension in Ͻ5% of cases; the remainder are labelled 'essential' hypertension, an elegant way of stating that the aetiology is unknown. As a result, in the vast majority of cases treatment is given on an empirical basis.In the last 5 years, significant advances have been made in our understanding of the pathogenesis of hypertension with the characterisation of three forms of inherited hypertension. All arise because of distinct, single gene mutations but can result in the same phenotype, that of mineralocorticoid hypertension. The purpose of this article is to review these 'monogenic' forms of mineralocorticoid hypertension, glucocorticoid-remediable hyperaldosteronism, Liddle's syndrome and apparent mineralocorticoid excess, and to discuss their significance to the broader population with essential hypertension.Glucocorticoid remediable aldosteronism (GRA) (also referred to as dexamethasone suppressible hyperaldosteronism or glucocorticoidsuppressible hyperaldosteronism)In 1966 a hypertensive father and son were described with a new disorder that mimicked priCorrespondence: PM Stewart, Professor

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A New Family With Dexamethasone‐suppressible Hyperaldosteronism: Aldosterone Unresponsiveness to Angiotensin Ii

Cited by 41 publications

References 23 publications

Coexistence of different phenotypes in a family with glucocorticoid-remediable aldosteronism

Coexistence of different phenotypes in a family with glucocorticoid-remediable aldosteronism

Dexamethasone-suppressible hyperaldosteronism. Adrenal transition cell hyperplasia?

Monogenic forms of mineralocorticoid hypertension: insights into the pathogenesis of ‘essential’ hypertension?

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