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

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.

Development of Laboratory Investigations in Disorders of Sex Development

“…This is the case of the so-called "nonclassic" or "backdoor" steroidogenesis pathway that can be defective in genetic males with insufficient fetal virilization [Fluck et al, 2011] or overexpressed in CAH in whom the increased 17-OH-P could be transformed into dihydrotestosterone (DHT) bypassing T synthesis [Kamrath et al, 2012]. Recommendations for steroid hormone analyses in DSD diagnosis and treatment has been very recently updated in an EU COST Action BM1303 DSDnet position paper [Kulle et al, 2017].…”

Addressing gaps in care of people with conditions affecting sex development and maturation

“…Second, the COST Actions aimed to develop guidelines for the usefulness of specific laboratory analyses and testing conditions. These guidelines were directed toward the implementation of clinical standards for diagnosis and appropriate treatment of DSD and CHH to achieve the best outcomes for patients, no matter where patients are investigated or managed 3,[18][19][20] .…”

“…In a position paper by Alexandra Kulle and colleagues, all forms of DSD were summarized and, for each condition, the required hormonal work-up and suitable analytical techniques were described 18 . The main recommendations were: support the appropriate use of both immunoassay-based and mass spectrometry-based methods for the diagnosis and monitoring of DSD; use of both serum and urine is established and appropriate matrices used for analysis of steroids; and laboratories should aim to participate in activities of peer comparison 18 . The next step for the harmonization of laboratory assessments relates to the important plasma and/or serum analyte 17-hydroxyprogesterone, which is a key marker in the diagnosis of congenital adrenal hyperplasia 21 .…”

“…Specifically, they developed the Action websites DSDNet and CHUV and coordinated and integrated the activities of the other Working Groups. Some of the scientific efforts were translated into public dissemination through a series of articles (full list at DSDNet and CHUV meetings (6 working group meetings and/or workshops for DSDnet, the last one in combination with GNRHnetwork) and position papers 3,5,10,18,22 .…”

Improving Laboratory Assessment in Disorders of Sex Development through a Multidisciplinary Network

“…The working group "Harmonization of Laboratory Assessment" of the COST Action "DSDnet" has already started to work on an EQA 138 program for 17OHP [Kulle et al, 2017]. Recently, a first EQA program for the harmonization of serum dihydrotestosterone measurement has been launched .…”