3 years ago

DIAGNOSIS OF ENDOCRINE DISEASE: 18-Oxocortisol and 18-Hydroxycortisol. Is there clinical utility of these steroids?

Since the early nineteen eighties 18-hydroxycortisol and 18-oxocortisol have attracted attention when it was shown that the urinary excretion of these hybrid steroids was increased in primary aldosteronism. The development and more widespread use of specific assays has improved the understanding of their role in the (patho)physiology of adrenal disorders. The adrenal site of synthesis is not fully understood although it is clear that for the synthesis of 18-hydroxycortisol and 18-oxocortisol the action of both aldosterone synthase (zona glomerulosa) and 17α-hydroxylase (zona fasciculata) is required with cortisol as main substrate. The major physiological regulator is ACTH and the biological activity of both steroids is very low and therefore only very high concentrations might be effective in vivo. In healthy subjects the secretion of both steroids is low with 18-hydroxycortisol being substantially higher than that of 18-oxocortisol. The highest secretion of both steroids has been found in familial hyperaldosteronism type 1 (glucocorticoid-remediable aldosteronism) and in familial hyperaldosteronism type 3. Lower but yet substantially increased secretion is found in patients with aldosterone-producing adenomas in contrast to bilateral hyperplasia in whom the levels are similar to patients with hypertension. Several studies have attempted to show that these steroids, in particular peripheral venous plasma 18-oxocortisol, might be a useful discriminatory biomarker for subtyping PA patients. The current available limited evidence precludes the use of these steroids for subtyping. We review the biosynthesis, regulation and function of 18-hydroxycortisol and 18-oxocortisol and their potential utility for the diagnosis and differential diagnosis of patients with primary aldosteronism.

Publisher URL: http://doi.org/10.1530/EJE-17-0563

DOI: 10.1530/EJE-17-0563

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