Glucocorticoid remediable aldosteronism ( GRA ), also can be described as aldosteron synthase hyperactivity , is an autosomal dominant disorder in which increased secretion of aldosterone produced by ACTH is no longer while.
This is the cause of primary hyperaldosteronism.
Video Glucocorticoid remediable aldosteronism
Symptoms
Patients with GRA may be asymptomatic, but the following symptoms can be found:
- Fatigue
- Headaches
- High blood pressure
- Hypokalemia
- Intermittent or intermittent paralysis
- Spasm muscle
- Muscle weakness
- Numb
- Polyuria
- Polydipsia
- Tingling
- Hypernatremia
- Metabolic alkalosis
Maps Glucocorticoid remediable aldosteronism
Normal Physiology
Aldosterone synthase is a steroid hydroxylase P450 hydroxylase enzyme that is involved in aldosterone formation. It is localized to the inner membrane of the mitochondria. Enzymes have 18-hydroxylase steroid activity to synthesize aldosterone and other steroids. Aldosterone synthase is found in the glomerulose zone on the outer edge of the adrenal cortex. Aldosterone synthase is usually insensitive to ACTH, and is only activated by angiotensin II.
Aldosterone causes the kidney tubules to retain sodium and water. It increases the volume of fluid in the body, and raises the blood pressure.
The steroid hormone is synthesized from cholesterol in the adrenal cortex. Aldosterone and corticosterone share the first part of their biosynthetic pathway. The last part is mediated by aldosterone synthase (for aldosterone) or by 11? -hydroxylase (for corticosterone).
- Aldosterone synthesis is stimulated by several factors:
- by elevated plasma concentrations of angiotensin III.
- by elevated levels of angiotensin II, ACTH, or plasma potassium.
- The ACTH stimulation test is sometimes used to stimulate the production of aldosterone along with cortisol to determine whether primary or secondary adrenal insufficiency is present.
- by plasma acidosis.
- by stretch receptors located in the atrium of the heart.
- by adrenoglomerulotropin, a lipid factor, obtained from pineal extract. Selectively stimulate aldosterone secretion.
- Aldosterone secretion has a diurnal rhythm.
- Control of aldosterone release from the adrenal cortex:
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- The role of the renin-angiotensin system:
- Angiotensin is involved in regulating aldosterone and is the core regulator. Angiotensin II works synergistically with potassium.
- The role of sympathetic nerves:
- The production of aldosterone is also affected at one level or another by a neural control that integrates the opposite of carotid artery pressure, pain, posture, and possibly emotion (anxiety, fear, and hostility) (including stress surgery ).
- The role of baroreceptors:
- Pressure in the carotid artery lowers aldosterone
- The role of juxtaglomerular equipment
- Plasma potassium concentration:
- The amount of secreted aldosterone is a direct function of potassium serum which may be determined by sensors in the carotid artery.
- Plasma sodium concentration:
- Aldosterone is a function of the inversion of sodium intake as it is felt through osmotic pressure.
- Other Settings:
- ACTH, pituitary peptide, also has some stimulating effects on aldosterone possible by stimulating the formation of deoxycorticosterone which is an aldosterone precursor.
- Aldosterone is increased by blood loss, pregnancy, and possibly by other conditions such as physical activity, endotoxin shock, and burns.
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- Aldosteron feedback:
- Feedback by aldosterone concentration itself is a non-morphological character (ie, in addition to changes in cell or structure number) and is relatively poor, so electrolyte feedback dominates in the short run.
Pathophysiology
The genes encoding aldosterone synthase and 11? -hydroxylase 95% identical and adjacent to chromosome 8. In individuals with GRA, there are unequal deviations so that 5 'regulatory region of the 11-hydroxylase gene converges with encoding. region of aldosterone synthase.
The product of this hybrid gene is aldosterone synthase that is sensitive to ACTH in the fasciculata zone of the adrenal glands.
Although in normal subjects, ACTH accelerates the first step of aldosterone synthesis, ACTH usually does not affect the activity of aldosterone synthase. However, in subjects with glucocorticoid-remediable aldosteronism, ACTH increased aldosterone synthase activity, resulting in high levels of aldosterone synthesis and hyperaldosteronism.
Diagnosis
Treatment
In GRA, aldosterone hypersecretion and accompanying hypertension are treated when ACTH secretion is suppressed by glucocorticoid administration.
Dexamethasone, spironolactone and eplerenone have been used in medicine.
See also
- The default error of steroid metabolism
- Hyperaldosteronism
- Pseudohyperaldosteronism
- Clear mineralocorticoid syndrome syndrome
- Aldosterone and aldosterone synthase
References
External links
Source of the article : Wikipedia
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