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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