Glucocorticoid-remediable aldosteronism (GRA) is a monogenic form of human hypertension that predisposes to cerebral hemorrhage. As a result of a chimeric. Glucocorticoid-remediable aldosteronism (GRA), alternatively called dexamethasone-suppressible hyperaldosteronism (DSH) or familial hyperaldosteronism. Aldosterone suppression by dexamethasone, and high hydroxycortisol and oxocortisol levels are used to differentiate glucocorticoid-remediable.

Author: Nabei Mezijar
Country: Tunisia
Language: English (Spanish)
Genre: Art
Published (Last): 11 September 2005
Pages: 456
PDF File Size: 9.13 Mb
ePub File Size: 18.24 Mb
ISBN: 995-4-46672-748-8
Downloads: 80456
Price: Free* [*Free Regsitration Required]
Uploader: Naktilar

Thereafter, the metabolic pathways diverge: Hypokalemia Most patients with GRA have normal potassium levels 8 despite biochemical evidence for primary hyperaldosteronism.

Another clue is a prominent family history of mortality or morbidity aldosterlnism early hemorrhagic stroke. It was with these observations in mind that temediable late Dr.

Receive exclusive offers and updates from Oxford Academic. However, aldosterone responsiveness to Ang II can be restored by chronic therapy with exogenous glucocorticoids.

In a retrospective report, eighty percent of 20 children under the age of 18 who carried the genetic mutation had hypertension by the age of 13 years; blood pressures also correlated within sibling pairs.

Glucocorticoid remediable aldosteronism – Wikipedia

GRA has now been identified across the world, and its molecular etiology is fully characterized. Iodine deficiency Cretinism Congenital hypothyroidism Myxedema Myxedema coma Euthyroid sick syndrome. GRA is the most common monogenetic form of hypertension. A similar syndrome was subsequently reported by New and Peterson 2 1 yr later.

Nat Genet ;2: A new genetic test for familial hyperaldosteronism type I aids in the detection of curable hypertension. Sign In or Create an Account.

Glucocorticoid-remediable aldosteronism.

The enzyme has steroid hydroxylase activity glucicorticoid synthesize aldosterone and other steroids. The product of this hybrid gene is aldosterone synthase that is ACTH-sensitive [2] in the zona fasciculata of the glcocorticoid gland. Can Med Assoc J ; Possible explanations for this incomplete penetrance of hypertension include self-selected dietary salt restriction, concomitant inheritance of blood pressure-lowering genes, or decreased penetrance of the chimeric gene.


Also in our subjects, there was no evidence that differences in baseline aldosterone, PRA, or serum K was involved in the abnormal responsiveness to dexamethasone. Case Report A year-old male presented to our hospital with daily complaints of chest pain and palpitations for the past three months.

The low specificity of dexamethasone suppression testing should also be considered to avoid the risks of giving dexamethasone for a long period of time to patients with primary aldosteronism 31 awaiting confirmation of GRA by genetic test. None of our patients, including 2 pairs of siblings, was positive for the chimeric gene.

Large genomic aberrations in corticotropinomas are associated with greater aggressiveness. Other search option s Alphabetical list. In the presence of a negative genetic test, 1 patient with APA 4.

Aldosterone synthase is a steroid hydroxylase cytochrome P oxidase enzyme involved in the generation of aldosterone.

Negative results obtained by long PCR excluded this disorder in our population, and this was confirmed by Southern blotting in all cases. Informed rrmediable for the study was obtained from all subjects. Glucocorticoid-remediable aldosteronism in a large kindred: Diagnosis GRA can masquerade as essential hypertension because most affected subjects are normokalemic and their blood pressures can range from mildly to severely elevated 5.

Glucocorticoid-remediable aldosteronism in a large kindred: Indeed, a family history of hypertension in presumedly affected subjects 4 is common in different varieties of primary aldosteronism 5.

Glucocorticoid remediable aldosteronism

Elevated levels of these compounds in a timed h urine collection provides a highly sensitive and specific test to diagnose GRA. A PCR-based method of screening individuals of all ages, from neonates to the elderly, for familial hyperaldosteronism type I.

Glucocorticoid remediable aldosteronism is rare familial form of primary aldosteronism characterized by a unique clinical response of hypertension and aldosterone production to the administration of glucocorticoids.


DNA sequence analyses of the chimeric genes from unrelated pedigrees indicate that the sites of fusion are variable, but in all cases are upstream of exon 5, suggesting that encoded amino acids in exon 5 of aldosterone synthase are essential for glucocorticoie synthase enzymatic function.

Glucocorticoid-remediable aldosteronism.

As a result of a chimeric gene duplication, aldosterone is ectopically synthesized in the cortisol-secreting zona fasciculata of the adrenal gland under the control of adrenocorticotropin ACTH. Expression of various chimeric gene constructs in vitro has remediagle that when these genes are fused after exon 3 the expressed product retains aldosterone synthase enzymatic activity, whereas when the fusion is after exon 5 aldosterone synthase enzymatic activity is undetectable.

GRA is inherited as an autosomal dominant trait, occurring equally among men and women.

Aldosterone synthase is found within the zona glomerulosa at the wldosteronism edge of the adrenal cortex. Individuals inheriting the chimera from their mothers also had significantly higher basal mean arterial pressure and basal aldosterone levels compared with individuals with a paternal source of the chimeric gene.

Prognosis With treatment, hypertension can be controlled for many years, and echocardiographic parameters maintained in normal values. Based on this report, screening with magnetic resonance imaging angiography, beginning at puberty aldosteronusm then every five years, has been recommended to detect asymptomatic intra-cranial aneurysms Aldosterone and corticosterone share the first part of their biosynthetic pathway.