The term “Disorders of Sex Development” (DSD) was introduced by the Chicago Conference about ten years ago to define congenital conditions, in which the development of sex chromosomes, gonads, and phenotype (genital) are atypical [Hughes et al., 2006]. At that time, the journal Sexual Development was launched, being the first scientific journal dedicated to the multifaced aspects of sex determination and differentiation as well as providing a unique forum for a rapidly expanding research and clinical field. During this last decade, impressive advances in the knowledge of genetic and hormonal mechanisms governing sex development, their evolution as well as the mutations or endocrine and metabolic abnormalities that interfere with normal gonadal development largely expanded, permitting more accurate and quick diagnoses as well as a better approach to the care of people living with these conditions. Some high-quality themed issues updated various aspects related to DSD in humans [see e.g., New Concepts for Human Disorders of Sexual Development (Sex Dev 4 (4-5), 2010), Understanding Differences or Disorders of Sex Development (Endocr Dev 27, 2014), and NIH Workshop: Disorders of Sex Development (Horm Metab Res 47(5), 2015)], but a single topic issue dedicated to the methodological assessment was missing.

Thus, after an extensive review of the development of laboratory investigations, based on the long-standing experience of Laura Audì, this issue focuses on some aspects of the methodological assessment of DSD, and it can be conceptually divided in three subsections. From the point of view of laboratory investigation, first Croft and coworkers report on the role of copy number variants in assessing persons with DSD, Freire and colleagues revise the role of newly discovered testicular protein hormones in the diagnostic work-up, and Bertelloni and colleagues update the actual role of the old hCG test in the evaluation of androgen testicular secretion. Second, Fanelli and colleagues cover a very intriguing “hot” topic in clinical practice which is the reference values for gonadal and adrenal hormones from birth to adulthood. In the second subsection, we can include the relevance of recent imaging evaluation (Guerra et al.), the clinical indications, limitations, findings of endoscopy and laparoscopy (Tafazzoli-Lari et al.), and the pathology of germ cell cancer, including the new environmental and genetic risk factors that have led to a “genvironment” hypothesis (Spoor et al.). Considering the steadily increasing importance of the holistic care of individuals with DSD, the third subsection includes the article of D'Alberton and colleagues who provide guidance relevant to psychological evaluation in the field of DSD, paying careful attention to methodological issues and limitations that may influence the utility of such investigations. Hannema and Rijke give a thorough overview of the opportunities offered by the recent European Reference Network for Rare Endocrine Disorders (Endo-ERN) to ensure equal access to high-quality care for all those affected by a rare endocrine condition, such as DSD, across Europe, and Kourime and Ahmed discuss the qualities that are required by a successful virtual network to collect data on rare endocrine conditions affecting sex and adrenal development. Van Bever and colleagues report on the importance of a detailed genetic and pathological diagnosis as well as the clinical dilemmas in a phenotypical male with 46,XX/ 46,XY tetragametic chimeric, showing the importance of a methodological personalized approach. Last but not least, Olaf Hiort discusses the transposition of advanced research knowledge in daily practice, also on the basis of his outstanding experience as coordinator of the “EuroDSD network” funded by the European Commission in the 7th Framework Programme, the “COST Action DSDnet: a systematic elucidation of differences of sex development (DSD)” and the recent role of Deputy coordinator Endo-ERN - Pediatric chair. Understandably, not all aspects can be covered in this issue; for example, it may be of great interest to analyze the possibility of a better standardization of DSD phenotypes, which has been a major and complex issue and is essential for the interpretation of more detailed genotypes provided by new genetic technologies.

We sincerely hope that the readers will find this themed issue not only enjoyable, but also helpful in their daily care of individuals with DSD. We would like to extend our deepest gratitude and appreciation to all the authors for the hard work and time they invested writing these high-quality articles, making this issue possible. We also thank the reviewers for their time and expertise as well as the Editorial Board of the journal Sexual Development for giving us the opportunity to concretize this special project.

Silvano Bertelloni, Pisa

Michael Schmid, Würzburg

September 2017

Hughes IA, Houk C, Ahmed SF, Lee PA; LWPES Consensus Group; ESPE Consensus Group: Consensus statement on management of intersex disorders. Arch Dis Child 91:554-563 (2006).
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