Steroid hormone analysis in diagnosis and treatment of DSD: position paper of EU COST Action BM 1303 'DSDnet' - PubMed (original) (raw)

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Steroid hormone analysis in diagnosis and treatment of DSD: position paper of EU COST Action BM 1303 'DSDnet'

A Kulle et al. Eur J Endocrinol. 2017 May.

Abstract

Disorders or differences in sex development (DSD) comprise a heterogeneous group of conditions with an atypical sex development. For optimal diagnosis, highly specialised laboratory analyses are required across European countries. Working group 3 of EU COST (European Cooperation in Science and Technology) Action BM 1303 'DSDnet' 'Harmonisation of Laboratory Assessment' has developed recommendations on laboratory assessment for DSD regarding the use of technologies and analytes to be investigated. This position paper on steroid hormone analysis in diagnosis and treatment of DSD was compiled by a group of specialists in DSD and/or hormonal analysis, either from participating European countries or international partner countries. The topics discussed comprised analytical methods (immunoassay/mass spectrometry-based methods), matrices (urine/serum/saliva) and harmonisation of laboratory tests. The following positions were agreed upon: support of the appropriate use of immunoassay- and mass spectrometry-based methods for diagnosis and monitoring of DSD. Serum/plasma and urine are established matrices for analysis. Laboratories performing analyses for DSD need to operate within a quality framework and actively engage in harmonisation processes so that results and their interpretation are the same irrespective of the laboratory they are performed in. Participation in activities of peer comparison such as sample exchange or when available subscribing to a relevant external quality assurance program should be achieved. The ultimate aim of the guidelines is the implementation of clinical standards for diagnosis and appropriate treatment of DSD to achieve the best outcome for patients, no matter where patients are investigated or managed.

© 2017 The authors.

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Figures

Figure 1

Figure 1

Synthesis and metabolism of hormonal steroids. This figure illustrates the formation of the major hormone classes from cholesterol. Steroid names in conventional script are steroid hormones and precursors; those in italics are urinary metabolites of the aforementioned. The major transformative enzymes are in rectangular boxes, the cofactor (‘facilitator’) enzymes in ovals. Mitochondrial CYP type I enzymes requiring electron transfer via adrenodoxin reductase (ADR) and adrenodoxin (Adx) CYP11A1, CYP11B1 and CYP11B2 are marked with a labelled box ADR/Adx. Microsomal CYP type II enzymes receive electrons from P450 oxidoreductase (POR), CYP17A1, CYP21A2, CYP19A1 and are marked by circled POR. The 17,20-lyase reaction catalysed by CYP17A1 requires in addition to POR also cytochrome b5 indicated by a circled b5. Similarly, hexose-6-phosphate dehydrogenase (H6PDH) is the cofactor-generating enzyme for 11β-HSD1 (HSD11B1). The asterisk (*) indicates the 11-hydroxylation of 17-hydroxyprogesterone to 21-deoxycortisol in 21-hydroxylase deficiency. The conversion of androstenedione to testosterone is catalysed by HSD17B3 in the gonad and AKR1C3 (HSD17B5) in the adrenal. CYP11A1, P450side-chain cleavage enzyme; CYP11B1, 11β-hydroxylase; CYP11B2, aldosteronesynthase; CYP17A1, 17α-hydroxylase/17,20-lyase; CYP21A2, 21-hydroxylase; HSD3B2, 3β-hydroxysteroid dehydrogenase type 2; HSD11B1, 11β-hydroxysteroid dehydrogenase type 1; HSD11B2, 11β-hydroxysteroid dehydrogenase type 2; HSD17B, 17β-hydroxysteroid dehydrogenase; PAPSS2, 3′-phosphoadenosine 5′-phosphosulfate synthase 2; SRD5A2, 5α-reductase type 2; StAR, steroidogenic acute regulatory protein; SULT2A1, sulfotransferase 2A1.

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