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.
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Glucocorticoid-suppressible hyperaldosteronism and adrenal tumors occurring in a single French pedigree. X-linked ichthyosis Antley—Bixler syndrome. Other investigators screening at-risk relatives in GRA families have remeciable this finding.
Review of past aldosteroinsm records confirms that the aortic dissection was chronic and it was decided not to operate upon the patient due to high risk of surgical complications. Hyperaldosteronism therefore results in volume expansion, hypertension and usually hypokalemia.
Orphanet: Familial hyperaldosteronism type I
Other search option s Alphabetical list. Sign In or Create an Account. However, to date, no conversions of the CYP11B1 gene expected to cause GRA involving exons 4, 5, and 6 from CYP11B2 have been found in a sample of low renin hypertensive patients, patients with primary aldosteronism, and 90 normotensive individuals The diagnosis of GRA should be considered in a patient with hypertension of early onset especially children or a history of early onset hypertension in first-degree relatives.
Is random screening of value in detecting glucocorticoid-remediable aldosteronism within a hypertensive population?
Glucocorticoid remediable aldosteronism
These methods are time consuming, expensive, and impractical for large studies. DNA sequence analyses of the chimeric genes from unrelated pedigrees indicate that the sites of fusion are variable, but glucocorticood all cases are upstream of exon 5, suggesting that encoded amino acids in exon 5 of aldosterone synthase are essential for aldosterone synthase enzymatic function. Blood and urinary tests gluoccorticoid biological signs of primary aldosteronism, i.
Email alerts New issue alert. Oxford University Press is a department of the University of Oxford. Glucocorticoid remediable aldosteronism Specialty Endocrinology Glucocorticoid remediable aldosteronism GRAalso describable as aldosterone synthase hyperactivityis an autosomal dominant disorder in which the increase in aldosterone secretion produced by ACTH is no longer transient.
Thus, the family history in GRA glucocortjcoid not invariably reveal a history of severe hypertension in first-degree relatives of affected subjects. A dexamethasone suppression test can be a useful screening maneuver; genetic screening and the measurement of urinary oxosteroids are diagnostic.
Aldosterone synthase is gluxocorticoid steroid hydroxylase cytochrome P oxidase enzyme involved in the generation of aldosterone.
However, there are several pitfalls in the use of dexamethasone suppression testing 46and the two steroids are also elevated in patients with aldosterone-producing adenoma APA 78. Accordingly, screening of asymptomatic GRA patients with magnetic resonance angiography is recommended, beginning at puberty and every 5 yr thereafter similar to the recommendations for patients with adult polycystic kidney disease, where there is a similar frequency of aneurysm.
GRA is the commonest monogeneic form of human hypertension and often masquerades as essential hypertension.
A Case of Glucocorticoid Remediable Aldosteronism and Thoracoabdominal Aneurysms
The patient was started on antihypertensives and prednisone with gradual improvement of blood pressure back to baseline. Expression of various chimeric gene constructs in vitro has demonstrated 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.
The material is in no way intended to replace professional medical care by a qualified specialist and should not be used as a basis for diagnosis or treatment.
Another potential source of phenotypic variation is linkage disequilibrium with the ‘a’ allele of the aldosterone synthase gene Introduction 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.
Potassium levels Normokalemia in GRA-affected patients was first described by Grim and Weinberger 4Abut it was believed to be uncommon.
Case Reports in Endocrinology
Because of the side effects of glucocorticoids, in children eplerenone can be given instead. The authors speculated that chronic aldosgeronism of the developing fetus to high mineralocorticoid levels could alter the expression of the genes that regulate aldosterone synthesis.
Prognosis With treatment, hypertension can be controlled remediabe many years, and echocardiographic parameters maintained in normal values. GRA is inherited as an autosomal dominant trait, occurring equally among men and women. Suppression of the hypothalamic-pituitary-adrenal axis does not always result in normalization of blood pressure in GRA.
Moreover, diagnosis of GRA requires a confirmatory genetic test. In addition, the administration of exogenous glucocorticoids that suppress ACTH secretion result in the suppression of aldosterone levels and a reversal of this mineralocorticoid excess state thus, the appellation DSH or GRA.
As a result, aldosterone synthase is ectopically expressed in the cortisol-producing zone of the adrenal cortex under the regulation of ACTH.
Defective fasciculata zone function as the mechanism of glucocorticoid-remediable aldosteronism. Mineralocorticoid receptors are expressed not only in the kidneys but also in the heart and the aorta [ 16 ].
Many affected families in North America are of Celtic ancestry; no known cases are reported among blacks. Also, the early use of mineralocorticoid antagonists may have a significant preventive and attenuating effect in aneurysm formation, an association which needs to be confirmed in future studies. However, the antihypertensive response to nifedipine as monotherapy in various etiologies of primary aldosteronism has been generally disappointing.
However, they were not able to show a difference in basal plasma aldosterone concentrations between affected and unaffected GRA siblings to support this hypothesis, but the numbers of normal siblings studied was small. Indeed, a family history of hypertension in presumedly affected subjects 4 is common in different varieties of primary aldosteronism 5. Dihydropyridine calcium channel blockers The extended-release formulation of the dihydropyridine calcium channel blocker nifedipine has also been advocated in the medical management of primary aldosteronism because this agent has also been shown to inhibit aldosterone biosynthesis in vitro.
In 11 additional GRA pedigrees all subjects proved to have glucoclrticoid gene duplications, but aldosteronsm these subjects a minimum of eight independent mutations with five different sites of crossing over were identified 7. Inborn errors of steroid metabolism.
Specialised Social Services Eurordis directory. Many patients are diagnosed during familial genetic screening in case of family history.
Childhood history was remarkable for early onset hypertension discovered at the age of 10 after his first episode of dissection. Large genomic aberrations in corticotropinomas are associated with greater aggressiveness.