Cited by 111Sexual Differentiation and DisordersAdrenal Hormones and DisordersGenetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities

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Steroid hormone analysis in diagnosis and treatment of DSD: Position paper of Eu COST Action BM 1303 “DSDnet”

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Kulle, A, Krone, N, Holterhus, P M, Schuler, G, Greaves, R F, Juul, A, de Rijke, Y B, Hartmann, M F, Saba, A, Hiort, O, Wudy, S A, _, _·2017·European Journal of Endocrinology

DOI 10.1530/eje-16-0953PMC PMC5425933

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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.

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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.CC BY · PubMed Central

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Authors: Kulle, A., Krone, N., Holterhus, P. M., Schuler, G., Greaves, R. F., Juul, A., de Rijke, Y. B., Hartmann, M. F., Saba, A., Hiort, O., Wudy, S. A., & _, _.
Affiliations: Christian-Albrechts-Universität zu Kiel (DE)
University of Sheffield (GB)
Justus-Liebig-Universität Gießen (DE)
RMIT University (AU)
University of Copenhagen (DK)
University of Pisa (IT)
University of Lübeck (DE)
Corresponding author: Wudy, S A
ORCID: Kulle, A
Krone, N
Schuler, G
Greaves, R F
Juul, A
Saba, A
Hiort, O
Wudy, S A
Venue: European Journal of Endocrinology
Publisher: Oxford University Press (OUP)
Published: 2017-05
Volume: 176
Issue: 5
Pages: P1-P9
ISSN: 0804-4643 (ISSN-L)
1479-683X
DOI: 10.1530/eje-16-0953
PMC: PMC5425933
OpenAlex: W2587480381
Cited by: 111
References: 53
Citations by year: 2026: 3 · 2025: 8 · 2024: 10 · 2023: 10 · 2022: 9 · 2021: 14 · 2020: 13 · 2019: 16 · 2018: 18 · 2017: 6
FWCI: 5.92
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by
creativecommons.org/licenses/by/3.0/ (unspecified)
Locations: European Journal of Endocrinology (publishedVersion, cc-by)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
White Rose Research Online (University of Leeds, The University of Sheffield, University of York) (acceptedVersion)
Minerva Access (University of Melbourne) (submittedVersion, cc-by)
RePub (Erasmus University Rotterdam) (submittedVersion, other-oa)
RMIT Research Repository (RMIT University Library) (submittedVersion)
CINECA IRIS Institutial research information system (University of Pisa) (submittedVersion, cc-by)
Figshare (submittedVersion, cc-by)
Topics: Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Sexual Differentiation and Disorders
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
Keywords: disorders of sex development, steroid hormone analysis, immunoassay, mass spectrometry, serum and urine samples, saliva, external quality assurance
MeSH terms: Europe, Female, Hormones, Humans, Male, Disorders of Sex Development, Steroids, 46, XX Disorders of Sex Development, 46, XX Testicular Disorders of Sex Development

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Steroid hormone analysis in diagnosis and treatment of DSD: Position paper of Eu COST Action BM 1303 “DSDnet”

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