18-Oxocortisol
18-Oxocortisol is an endogenous steroid, a metabolite of cortisol.
Clinical significance
18-Oxocortisol has been proposed as a biomarker for certain diseases. In humans, 18-oxocortisol has no biological activity on glucocorticoid or mineralocorticoid receptors. In healthy subjects, the biosynthesis of 18-oxocortisol is low. The highest synthesis of 18-oxocortisol was found in certain cases of hypertension like in type 1 familial hyperaldosteronism and type 3 familial hyperaldosteronism, where the adrenal glands are enlarged up to six times their normal size. Increased synthesis is also found in patients with aldosterone-producing adenomas. ACTH stimulation test increases urinary excretion of 18-oxocortisol, and dexamethasone inhibits the excretion.The measurement of 18-oxocortisol using liquid chromatography tandem mass spectrometry has demonstrated its usefulness in distinguishing between unilateral and bilateral forms of primary aldosteronism. These measurements, along with measurements of 18-hydroxycortisol, provide a non-invasive method for diagnosing and classifying different subtypes of PA, potentially reducing the need for more invasive procedures like adrenal vein sampling. In aldosterone-producing adrenocortical adenoma, which is the main cause of primary aldosteronism, the enzyme aldosterone synthase plays a crucial role in aldosterone production. Somatic mutations in genes like KCNJ5 and CACNA1D can lead to an overexpression of CYP11B2 and increased production of aldosterone. CYP11B2 catalyzes the conversion of cortisol to 18-hydroxycortisol and then further converts it into 18-oxocortisol, making 18-oxocortisol a significant biomarker for diagnosing primary aldosteronism.