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Activation of cortisol generation by 11b-hydroxysteroid dehydrogenase (11bHSD) in subtypes of 21-hydroxylase deficiency (21OHD) & establishment of reference values for unusual steroids in subtypes of 21OHD

Grant number: 14/10325-7
Support type:Regular Research Grants
Duration: March 01, 2015 - August 31, 2017
Field of knowledge:Health Sciences - Medicine
Principal Investigator:Claudio Elias Kater
Grantee:Claudio Elias Kater
Home Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil


The metabolism of cortisol involves a balance between their active (cortisol or F) and inactive (cortisone or E) forms, which are interconverted by the action of the enzyme 11ß -hydroxysteroid dehydrogenase (11ß - HSD). 21 hidroxylase deficiency (21OHD) is an autosomal recessive disorder, resulting from mutations in the CYP21A2 gene, which encodes the enzyme 21 - hydroxylase. 21OHD corresponds to more than 90 % of cases of congenital adrenal hyperplasia. The "biochemical marker" traditionally used is 17-hydroxyprogesterone (17OHP). However, studies by our group have confirmed the role of 21-deoxycortisol (21DF) in the diagnosis of various forms of 21OHD, including the detection of heterozygotes. Furthermore, the characterization of distal steroids - so called unusual steroids - such as the 11 - deoxycortisol (S), [17- hydroxylated zona fasciculata (ZF) pathaway] and deoxycorticosterone (DOC),corticosterone (B) [products of non 17 - hydroxylated pathaway], although rarely used, can complement the characterization of different forms of 21OHD . The present study evaluates the activity of 11ß - HSD1 by studying F / E ratio. We hipothesized that 11ß - HSD1 activity may be greater in more severe forms compared to milder forms, heterozygotes and normal individuals. Additionally, unusual steroids: E, S, B and DOC, will be measured. This metabolomic study hopefully will facilitate the diagnosis and management of 21OHD. (AU)