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Progressive adrenal hyperplasia due to persistent elevation of ACTH results in extreme overproduction of 11-deoxycorticosterone (DOC) by mid-childhood. DOC is a weak mineralocorticoid, but usually reaches high enough levels in this disease to cause effects of mineralocorticoid excess: salt retention, volume expansion, and hypertension. [2]
11-Deoxycorticosterone (DOC), or simply deoxycorticosterone, also known as 21-hydroxyprogesterone, as well as desoxycortone (), deoxycortone, and cortexone, [1] [2] is a steroid hormone produced by the adrenal gland that possesses mineralocorticoid activity and acts as a precursor to aldosterone. [3]
It also catalyzes hydroxylation of progesterone to 11-deoxycorticosterone (DOC) in the mineralocorticoid pathway on its way from pregnenolone to aldosterone. [162] Deficient activity of this enzyme reduces the efficiency of cortisol synthesis, with consequent hyperplasia of the adrenal cortex and elevation of ACTH levels.
Consequently, levels of DOC, corticosterone, and 18-hydroxycorticosterone are elevated. Although these precursors of aldosterone are weaker mineralocorticoids, the extreme elevations usually provide enough volume expansion, blood pressure elevation, and potassium depletion to suppress renin and aldosterone production.
Hyponatremia (due to hypoaldosteronism) - Aldosterone is the end product of the renin-angiotensin-aldosterone system that regulates blood pressure via blood pressure surveillance in the Kidney Juxtaglomerular apparatus. Aldosterone normally functions to increase sodium retention (which brings water as well) in exchange for potassium.
The ratio of renin to aldosterone is an effective screening test to screen for primary hyperaldosteronism related to adrenal adenomas. [ 44 ] [ 45 ] It is the most sensitive serum blood test to differentiate primary from secondary causes of hyperaldosteronism. [ 46 ]
Pseudohyperaldosteronism (also pseudoaldosteronism) is a medical condition which mimics the effects of elevated aldosterone (hyperaldosteronism) by presenting with high blood pressure, low blood potassium levels (hypokalemia), metabolic alkalosis, and low levels of plasma renin activity (PRA).
Corticosterone is converted to aldosterone by aldosterone synthase, found only in the mitochondria of glomerulosa cells. Glomerulosa cells are found in the zona glomerulosa , which is the most superficial region of endocrine cells in the adrenal cortex .
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