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 Opportunities: Regular Research Grants
• Start date: March 01, 2015
• End date: August 31, 2017
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Claudio Elias Kater
• Grantee: Claudio Elias Kater
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

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)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

COSTA-BARBOSA, FLAVIA A.; CARVALHO, VALDEMIR M.; OLIVEIRA, KELLY C.; VIEIRA, JOSE GILBERTO H.; KATER, CLAUDIO E.. Reassessment of predictive values of ACTH-stimulated serum 21-deoxycortisol and 17-hydroxyprogesterone to identify CYP21A2 heterozygote carriers and nonclassic subjects. CLINICAL ENDOCRINOLOGY, v. 95, n. 4, JUL 2021. (14/10325-7)