Introduction:
Hyperaldosteronism-induced arterial hypertension is uncommon and can be treated with glucosecorticoid-remediable aldosteronism (GRA). Adrenocorticotropic hormone regulates the synthesis of aldosterone in GRA, an autosomal dominant feature that is passed down across families. While essential hypertension accounts for the majority of occurrences, some cases can be traced back to a specific cause. Primary aldosteronism is the most prevalent kind of secondary hypertension. Bilateral idiopathic hyperaldosteronism (IHA, relative frequency 65 percent) and aldosterone-producing adenoma (Conn's syndrome, 30 percent) are the two main subtypes of primary aldosteronism, while less than one percent of cases of primary aldosteronism are caused by glucocorticoid-remediable aldosteronism (GRA, familial hyperaldosteronism type I).
What Are the Causes Behind IHA Idiopathic Hyperaldosteronism?
Although the causes of IHA are unknown, different mutations in the KCNJ5 gene that control the function of a potassium channel inside the adrenal gland have been found in certain people with Conn's syndrome. Due to these alterations, the potassium channel becomes less selective, allowing other ions—mostly sodium—to get through as well and increasing the synthesis of aldosterone. Conversely, Lifton et al. have shown the underlying genetic rearrangement responsible for the development of GRA. Uneven crossing over between the genes encoding aldosterone synthase (CYP11B2) and 11β-hydroxylase (CYP11B1) results in a chimeric gene duplication that causes GRA: The 5′ adrenocorticotropin-responsive promotor region of the 11β hydroxylase gene and the 3′ coding regions of the aldosterone synthase gene are combined to form the chimeric gene.
The first summary of the typical clinical appearance was provided by Sutherland et al. Aldosterone synthase is generally only expressed in the zona glomerulosa of the adrenal gland, while steroid 11-hydroxylase, which is regulated by ACTH, is normally only expressed in the zona fasciculata of the adrenal gland. While one- or both-sided zona glomerulosa hyperplasia characterizes Conn's syndrome and IHA, the gene duplication in GRA causes ectopic production of aldosterone synthase activity in the zona fasciculata, which produces cortisol. GRA is a dominant, autosomal trait that is inherited. Unlike Conn's syndrome, the symptoms of arterial hypertension in GRA usually appear before the age of 21. GRA is an uncommon monogenic form of primary aldosteronism, with the majority of cases reported from the USA, China, Japan, Italy, and Germany having few instances to date.
What Are the Signs and Symptoms of Glucocorticoid-Remediable Hyperaldosteronism?
While some GRA patients may not exhibit any symptoms at all, they may experience the following ones:
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Exhaustion headache.
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Elevated blood pressure.
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Low potassium.
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Sporadic or transient paralysis.
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Tense muscles.
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Weakened muscles.
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Multidipsia.
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Tingling.
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Overindulgence in nutrition.
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Alkalosis metabolism.
How Is GRA Different from Other Types of Primary Aldosteronism?
GRA is distinguished from other types of primary aldosteronism by high levels of 18-hydroxycortisol and 18-oxocortisol, as well as by aldosterone suppression caused by dexamethasone. These techniques are costly, time-consuming, and unsuitable for large-scale research. Furthermore, a confirmatory genetic test is necessary for the diagnosis of GRA.
Aldosterone production is only controlled by ACTH in Glucocorticoid-remediable aldosteronism (GRA), a rare kind of hereditary primary aldosteronism. The first clue to look into the potential of GRA is still evidence of a mineralocorticoid excess condition, even though the presentation of the disease varies and some people have normotension and normokalemia. Indeed, several forms of primary aldosteronism frequently have a family history of hypertension in assumed affected people. Biochemical indicators specific to GRA have been identified as hardly detectable aldosterone levels following a brief dexamethasone trial and abnormally high secretion of two hormones, 18-hydroxycortisol and 18-oxocortisol). Dexamethasone suppression testing, however, has a number of drawbacks), and patients' levels of the two steroids are also raised.
Only genetic testing demonstrating a hybrid gene resulting from a fusion of the aldosterone synthase and steroid 11β-hydroxylase genes can provide a definitive diagnosis. Recently, a PCR method that enables quick identification of a chimeric gene in GRA patients has been made available.
What Are the Glucocorticoid-Remediable Hyperaldosteronism?
The satisfying drop in blood pressure that follows focused treatment emphasizes how critical it is to diagnose GRA properly. Furthermore, a sodium-restricted diet (less than two g/day) is advised in addition to medication because GRA is a volume-expanded mineralocorticoid excess syndrome. This will minimize potassium waste and possibly lower blood pressure. Randomized research comparing different pharmacological treatment regimens in GRA have not yet been carried out.
Suppression of Glucocorticoids:
In patients with GRA, blood pressure does not always return to normal once the hypothalamic-pituitary-adrenal axis is suppressed. This could be related to how long the patient has had high blood pressure, end-organ damage from untreated hypertension, concurrent essential hypertension, or, in rare cases, autonomous aldosterone production in patients with chronic GRA.
Mineralocorticoids Antagonism:
When used as a monotherapy, spirolactone, a competitive antagonist of aldosterone for the mineralocorticoid receptor, is frequently highly successful in treating people with GRA. When starting treatment, adult patients should take 50 mg twice a day with meals. After that, their dosage should be increased to 400 mg daily until their blood pressure is under control. In an effort to further deplete sodium, potassium-wasting diuretics (25 to 25 mg hydrochlorothiazide or 20 to 40 mg furosemide) may be given; if these diuretics are taken, careful monitoring of serum potassium is crucial. In addition to its antiandrogenic effects, spirolactone also causes erectile dysfunction, diminished libido, and gynecomastia in adult men; in women, it is associated with irregular menstruation. If the medication is taken with food, it may lessen symptoms related to the stomach, such as nausea.
Blockers of Calcium Channels by Dihydropyridine:
Since the dihydropyridine calcium channel blocker nifedipine has also been demonstrated to reduce aldosterone production in vitro, its extended-release formulation has also been recommended for the medical therapy of primary aldosteronism. On the other hand, Nifedipine as monotherapy has often failed to provide an antihypertensive effect in cases of primary aldosteronism. Although dihydropyridine calcium channel blockers, such Amlodipine and Nifedipine, can have a satisfying antihypertensive effect in GRA patients (Dluhy R.G., unpublished data), these drugs should only be used as a last resort.
Conclusion:
The most prevalent monogenic cause of hypertension is glucocorticoid-remediable aldosteronism (GRA), a genetic type of primary hyperaldosteronism. Under the control of adrenocorticotropin (ACTH), a chimeric gene duplication causes ectopic aldosterone synthase activity in the zona fasciculata of the adrenal cortex, which produces cortisol. Usually starting in childhood, hypertension can be resistant to conventional treatments. When diuretics are not used for treatment, hypokalemia is rare. Accurate diagnostic tests have been made possible by the identification of the disorder's genetic basis. The mainstay of treatment is glucocorticoid inhibition of ACTH; antagonists of the mineralocorticoid receptor are other options.
