Disease relevance of 18-oxocortisol

• Glucocorticoid-remediable aldosteronism (GRA), an autosomal dominant disorder, is characterized by hypertension with variable hyperaldosteronism and by high levels of the abnormal adrenal steroids 18-oxocortisol and 18-hydroxycortisol, which are all under control of adrenocorticotropic hormone and suppressible by glucocorticoids [1].
• Tests that distinguished adenomas from adrenal hyperplasia included the postural stimulation test, urinary excretion rates of 18-oxocortisol and 18-hydroxycortisol, and adrenal vein sampling [2].
• Excretion of the 18-oxocortisol metabolite ranged from 2-12 micrograms/day in bilateral hyperplasia and 17-1203 micrograms/day in typical adenomas [3].
• 18-Oxocortisol excretion is increased markedly in the urine of patients with GSA: what role this relatively weak mineralocorticoid plays in the pathogenesis of their hypertension is unknown [4].
• 18-Hydroxycortisol and 18-oxocortisol have been isolated from the urine of patients with aldosterone producing adrenocortical adenomas, but not from those with idiopathic hyperaldosteronism associated with bilateral adrenal hyperplasia [3].

High impact information on 18-oxocortisol

• Cortisol, when incubated with an active source of this oxidase, the bullfrog interrenal gland, was converted to 18-hydroxycortisol and a new C-18-oxygenated steroid identified as 11 beta, 17 alpha,21-trihydroxy-3,20-diketo-4-pregnene-18-al, or 18-oxocortisol [5].
• The disorder is characterized by hyperaldosteronism and high levels of 18-hydroxycortisol and 18-oxocortisol, which are under ACTH control [6].
• Recombinant CYP11B genes encode enzymes that can catalyze conversion of 11-deoxycortisol to cortisol, 18-hydroxycortisol, and 18-oxocortisol [7].
• The technique, based on stable isotope dilution mass fragmentography, measured the tetrahydro urinary metabolites of aldosterone, 18-hydroxycorticosterone, and 18-oxocortisol and unmetabolized 18-hydroxycortisol [8].
• Under these circumstances, both steroids caused thymus involution but only 18-oxocortisol caused kidney enlargement [9].

Chemical compound and disease context of 18-oxocortisol

• These analog steroids, 18-hydroxycortisol and 18-oxocortisol, are produced in small quantities normally, but can be produced in excess by aldosterone-producing adrenal adenomas and in glucocorticoid-suppressible aldosteronism [10].
• 18-Hydroxycortisol (18-OHF) and 18-oxocortisol (18-oxoF) are derivatives of cortisol found in primary aldosteronism but whose origin and regulation in normal subjects are uncertain [11].
• Aldosterone suppression by dexamethasone, and high 18-hydroxycortisol and 18-oxocortisol levels are used to differentiate glucocorticoid-remediable aldosteronism (GRA) from other forms of primary aldosteronism [12].

Biological context of 18-oxocortisol

• After dexamethasone administration, 18-oxocortisol, 18-hydroxycortisol, cortisol, aldosterone and 18-hydroxycorticosterone decreased in the supine position and no increase occurred in 18-oxocortisol, 18-hydroxycortisol and 18-hydroxycorticosterone in the upright position [13].

Anatomical context of 18-oxocortisol

• The ability of 18-oxocortisol to complete with [3H]aldosterone for binding to the cytosol receptor of rat renal slices was 8.1% in comparison to unlabeled aldosterone [14].
• Synthesis of 18-hydroxycortisol and 18-oxocortisol in bovine adrenal zona glomerulosa mitochondria [15].
• The biosynthesis of 18-hydroxycortisol and 18-oxocortisol from cortisol was studied in calf adrenal zona glomerulosa mitochondria [15].

Associations of 18-oxocortisol with other chemical compounds

• The ability of 18-oxocortisol to compete with [3H]dexamethasone for binding to the renal cytosol receptor was 0.2% that of unlabeled dexamethasone and in the HTC whole cell assay was 1.06% and 3.8% that of unlabeled dexamethasone and cortisol, respectively [14].

Gene context of 18-oxocortisol

• 18-Oxocortisol excretion did not differ in patients with normal renin essential hypertension (0.7 +/- 0.7 micrograms/24 h), low renin essential hypertension (0.7 +/- 0.5 micrograms/24 h) and normal individuals (1.2 +/- 0.9 micrograms/24 h) [16].

Analytical, diagnostic and therapeutic context of 18-oxocortisol

• A radioimmunoassay procedure for the measurement of urinary 18-oxocortisol was developed [4].
• The mineralocorticoid activity of 18-oxocortisol in the adrenalectomized rat bioassay was 0.6% that of aldosterone [14].
• We have produced mouse monoclonal antibodies against 18-oxocortisol and polyclonal antibodies against 18-hydroxycortisol and describe a time-resolved fluoroimmunoassay (TR-FIA) technique for the measurement of these steroids in the urine [17].
• An ELISA for 18-oxocortisol and -hydroxycorticosterone was devised which showed improved sensitivity and specificity in comparison to an RIA using a tritiated tracer [18].

References