new disordersofsexdevelopmentandhypogonadism:...

Hindawi Publishing CorporationInternational Journal of EndocrinologyVolume 2012, Article ID 820373, 2 pagesdoi:10.1155/2012/820373

Editorial

Disorders of Sex Development and Hypogonadism:Genetics, Mechanism, and Therapies

Gil Guerra-Junior,1 Ana Claudia Latronico,2 Olaf Hiort,3 and Rodolfo Rey4

1 Pediatric Endocrinology Unit, Department of Pediatrics, Faculty of Medical Sciences, State University of Campinas (UNICAMP),Campinas, SP, Brazil

2 Lab of Hormones and Molecular Genetics (LIM/42), Endocrinology of Development Unit, School of Medicine,University of São Paulo (USP), São Paulo, SP, Brazil

3 Division of Paediatric Endocrinology and Diabetes, Department of Pediatric and Adolescent Medicine, University of Lübeck, Germany4 Division of Endocrinology, Center of Endocrinology Investigation (CEDIE-CONICET), Children Hospital Dr. Ricardo Gutiérrez,Buenos Aires, Argentina

Correspondence should be addressed to Gil Guerra-Junior, [email protected]

Received 19 March 2012; Accepted 19 March 2012

Copyright © 2012 Gil Guerra-Junior et al. This is an open access article distributed under the Creative Commons AttributionLicense, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properlycited.

Disorders of sex development (DSD) and hypogonadism aregenetically heterogeneous and include a broad spectrum ofphenotypes. Recent advances in biology and medicine haveintroduced impressive improvements in both clinical man-agement and structured research, mainly in new technologiesto study their genetic features and the mechanisms underly-ing their pathologies. Knowledge and understanding of theseconditions have led to the development of successful thera-pies and novel tools to characterize them and provide bettercare to patients. Therefore, both DSD and hypogonadismrepresent an important field in research and clinical setting.

This special issue presents a series of articles mainlyreflecting the difficulties in characterization of DSD in fourpapers, advances in genetics of DSD in two papers, hypogo-nadotropic hypogonadism in one paper, clinical presentationof male primary hypogonadism, like Klinefelter’s syndromein one paper, and long-term followup of female hyperg-onadotropic hypogonadism in one paper, as well as clinicaland molecular data of aromatase excess syndrome in onepaper and an interesting review about the complex associ-ation of androgens and adipose tissue in males in one paper.

Juniarto and colleagues in their paper “Application of thenew classification on patients with a disorder of sex devel-opment in Indonesia” from Indonesia showed how patients’and general society’s opinion on DSD, economic backgroundof the patients, and lack of access to health insurance canaffect the complex management of DSD in a negative way.

Probably, these situations are not restricted to Indonesia, butto all underdeveloped countries, and education of primaryhealth care workers is necessary to prevent morbidity andmortality in some cases. Hersmus and colleagues in theirpaper “Delayed recognition of disorders of sex development(DSD): a missed opportunity for early diagnosis of malig-nant germ cell tumors” reported three independent malepatients with germ cell tumors retrospectively recognized asDSD, showing again, but now in a developed country, theunderdiagnosis of DSD in the newborn and the significantrelevance of early and correct evaluation for identificationof individuals at increased risk for development a gonadaltumor. Wünsch’s paper “Checklist for the structural descrip-tion of the deep phenotypes in disorders of sexual devel-opment” suggest an interesting checklist for the structuraldescription of gonads and internal sex ducts using videoendoscopy and laparoscopy, which can contribute to a com-prehensive definition of the variations of deep phenotype inDSD. Veiga-Junior and colleagues in their paper “Clinicaland laboratorial features that may differentiate 46,XY DSDdue to partial androgen insensitivity and 5α-reductase type 2deficiency”, evaluating 58 patients with sex ambiguity, 46,XYkaryotype, and normal testosterone secretion, reportedclinical and laboratorial features, like consanguinity, familialrecurrence, severity of ambiguous genitalia, penile length,and T/DHT ratio, which may differentiate 46,XY DSD due topartial androgen insensitivity and 5α-reductase deficiency.

2 International Journal of Endocrinology

Barbaro and colleagues in their paper “Multigenerationinheritance through fertile XX carriers of an NR0B1 (DAX1)locus duplication in a kindred of females with isolated XYgonadal dysgenesis” identified another NR0B1 duplicationin two sisters with isolated XY gonadal dysgenesis and anX-linked inheritance pattern. They also studied three fertilefemale carriers of three different small NR0B1 locus dupli-cations and did not find obvious skewing of X-chromosomeinactivation, suggesting that NR0B1 overexpression does notimpair ovarian function. Mooslehner and colleagues in theirpaper “A cell model for conditional profiling of androgen-receptor-interacting proteins” reported preliminary resultsthat allow future studies to focus on replacing wild-typeandrogen receptor (AR) with mutant AR to uncover dif-ferences in protein interactions caused by AR mutationsinvolved in partial androgen insensitivity syndrome.

Beate and colleagues in their paper “Genetics of iso-lated hypogonadotropic hypogonadism: role of GnRH recep-tor and other genes” showed an interesting revision aboutthe genetics of isolated hypogonadotropic hypogonadismand the importance of inactivating mutations in the pitu-itary GnRH receptor inducing GnRH resistance in patientswith normosmic isolated hypogonadotropic hypogonadism.Pacenza and colleagues in their paper “Clinical presentationof Klinefelter’s syndrome: differences according to age”, eval-uating 94 patients with Klinefelter’s syndrome, showed that46.8% were diagnosed between 11 and 20 years, probablybecause nowadays pediatricians are more aware that boysand adolescents with neurodevelopmental disorders andcryptorchidism should be investigated for this chromosomeanomaly. Pantelis and colleagues in their paper “Long-termfollowup of adolescent and young adult females with hyper-gonadotropic hypogonadism” showed that all prepubertalgirl, teenager, or young woman diagnosed with prima-ry ovarian insufficiency should undergo extensive researchby a group of specialists in a referral center, and the finaldecision of therapy should be taken by the patient and herclinician.

Fukami and colleagues in their paper “Molecular basesand phenotypic determinants of aromatase excess syndrome”showed that aromatase excess syndrome represents a novelmodel for gain-of-function mutation leading to humangenetic disorders characterized by gynecomastia. Mammiand colleagues in their paper “Androgens and adipose tissuein males: a complex and reciprocal interplay” reported aninteresting revision about the association between andro-gens and adipose tissue in males. The authors concludedthat adequate levels and balance of circulating sex hormonesare necessary to maintain a correct distribution and size ofadipose tissue, which in turn is fundamental to keep a normalreproductive and sexual function.

Our understanding in DSD and hypogonadism is ad-vancing, and we hope that the readers will find this specialissue enjoyable and helpful in the clinical practice. Inaddition, we would like to take the opportunity to expressour gratitude and thanks to all the authors involved in thisselected issue for the high-level papers they submitted. Wealso thank the reviewers for their time and expertise as well asthe Editor-Chief of International Journal of Endocrinology

for giving us the honor to publish this important specialissue. Enjoy this special issue of DSD and hypogonadism!

Gil Guerra-JuniorAna Claudia Latronico

Olaf HiortRodolfo Rey

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