CM E
Guidelines for Evaluating and
Managing Children Born with
Disorders of Sexual Development
Ganka Douglas, PhD; Marni E. Axelrad, PhD; Mary L. Brandt, MD; Elizabeth Crabtree, MPH;
Jennifer E. Dietrich, MD, MSc; Shannon French, MD; Sheila Gunn, MD; Lefkothea Karaviti, MD, PhD;
Monica E. Lopez, MD; Charles G. Macias, MD, MPH; Laurence B. McCullough, PhD; Deepa Suresh, MD;
Elise Austin, MS; and V. Reid Sutton, MD
Abstract
C
hildren born with disorders of sexual differentiation
(DSD) pose numerous challenges for the parents, fam-
ily, and treating physicians. The pediatrician is usually
the first medical contact for newborns with DSD or for toddlers
and children who present with DSD at a later time.
Several years ago, we formed a Gender Medicine Team (GMT)
at Baylor College of Medicine and Texas Children’s Hospital
(TCH) to explore and evaluate the most appropriate management
strategies, which had long been a matter of concern and
CM E EDUCATIONAL OBJECTIVES
1. Determine the appropriate workup and management for children
aged 0 to 24 months with ambiguous genitalia or a DSD.
2. Determine sound and appropriate methods approaching sex
assignment in an infant with ambiguous genitalia or a DSD.
3. Educate and refer for the appropriate surgical management of
children aged 0 to 24 months with ambiguous genitalia or a DSD.
All authors are with Baylor College of Medicine Texas Children’s Hospital,
Houston, TX. Ganka Douglas, PhD, is a Postdoctoral Fellow; Marni E. Axelrad,
PhD, is Associate Professor, Division of Psychology; Mary L. Brandt, MD, is Profes-
sor; Elizabeth Crabtree, MPH is Research Specialist, Evidence-Based Outcomes
Center; Jennifer E. Dietrich, MD, MSc, is Assistant Professor and Chief of Pediatric
and Adolescent Gynecology, Division of Pediatric and Adolescent Gynecology,
Department of Obstetrics, and Gynecology; Shannon French, MD, is Assistant
Professor; Sheila Gunn, MD, is Assistant Professor; Lefkothea Karaviti, MD, PhD,
is Professor and Director of the Center of Gender Medicine; Monica E. Lopez,
MD, is Assistant Professor, Division of Pediatric Surgery; Charles G. Macias, MD,
MPH, is Associate Professor and Director of The Center for Clinical Effectiveness;
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PED0412DouglasOLO.indd e1
contention. Subsequently, the GMT, composed of experts in the
fields of endocrinology, ethics, genetics, gynecology, psychology,
pediatric surgery, and urology, formed a Task Force to evaluate the
information available from our own experiences and from reviews
of the literature. Utilizing the Grading of Recommendation,
Assessment, Development and Evaluation (GRADE) system
to assess the evidence and recommendations, the Task Force
developed a consensus statement for clinical management of DSD
and for making appropriate sex assignments.
Laurence B. McCullough, PhD, is Professor, Center for Medical Ethics and Health
Policy; Deepa Suresh, MD, is Assistant Professor, Division of Pediatric Endocri-
nology; Elise Austin, MS, is Genetic Counselor; and V. Reid Sutton, MD, is Associ-
ate Professor and Medical Director of Biochemical Genetics Laboratory, Depart-
ment of Molecular and Human Genetics.
Address correspondence to: Lefkothea Karaviti, MD, PhD, Department
of Pediatrics, Texas Children’s Hospital, Baylor College of Medicine, 6621
Fannin, Houston, TX 77030; email: lpkaravi@texaschildrenshospital.org.
The authors would like to thank Mark Kline, MD, Chairman of the Depart-
ment of Pediatrics at BCM and Physician-in-Chief at TCH, for his visionary sup-
port of the Gender Medicine Clinic; Maria New, MD, for her involvement in
opening the area of sexual differentiation disorders; Lee Ligon, PhD, for her
unique editorial contributions and key input to the manuscript; patients in
the Gender Medicine Clinic, who have been our teachers and made invalu-
able contributions to the development of the guidelines. The authors also ac-
knowledge the editorial assistance of Lynda Jacks, RN.
The authors have disclosed no relevant financial relationships.
doi: 10.3928/00904481-20120307-09
Healio.com/Pediatrics | e1
3/29/2012 8:28:19 AM
 CM E

Guidelines for Evaluating and

Managing Children Born with
Disorders of Sexual Development
Ganka Douglas, PhD; Marni E. Axelrad, PhD; Mary L. Brandt, MD; Elizabeth Crabtree, MPH;
Jennifer E. Dietrich, MD, MSc; Shannon French, MD; Sheila Gunn, MD; Lefkothea Karaviti, MD, PhD;
Monica E. Lopez, MD; Charles G. Macias, MD, MPH; Laurence B. McCullough, PhD; Deepa Suresh, MD;
Elise Austin, MS; and V. Reid Sutton, MD

CM E EDUCATIONAL OBJECTIVES
1. Determine the appropriate workup and management for children aged 0 to 24 months
with ambiguous genitalia or a DSD.
2. Determine sound and appropriate methods approaching sex assignment in an infant
with ambiguous genitalia or a DSD.
3. Educate and refer for the appropriate surgical management of children aged 0 to 24
months with ambiguous genitalia or a DSD.

All authors are with Baylor College of Medicine Texas Children’s Hospital, Houston, TX. Ganka Douglas,
PhD, is a Postdoctoral Fellow; Marni E. Axelrad, PhD, is Associate Professor, Division of Psychology; Mary L.
CBrandt,
M E MD, is Professor; Elizabeth
EDUCATIONAL Crabtree, MPH is Research Specialist, Evidence-Based Outcomes Cen-
OBJECTIVES
ter; Jennifer E. Dietrich, MD, MSc, is Assistant Professor and Chief of Pediatric and Adolescent Gynecology,
Division of Pediatric and Adolescent Gynecology, Department of Obstetrics, and Gynecology; Shannon

© iStockphoto.com
French, MD, is Assistant Professor; Sheila Gunn, MD, is Assistant Professor; Lefkothea Karaviti, MD, PhD, is
Professor and Director of the Center of Gender Medicine; Monica E. Lopez, MD, is Assistant Professor, Divi-
sion of Pediatric Surgery; Charles G. Macias, MD, MPH, is Associate Professor and Director of The Center
for Clinical Effectiveness; Laurence B. McCullough, PhD, is Professor, Center for Medical Ethics and Health

T
Policy; Deepa Suresh, MD, is Assistant Professor, Division of Pediatric Endocrinology; Elise Austin, MS, is he treatment of children born with
Genetic Counselor; and V. Reid Sutton, MD, is Associate Professor and Medical Director of Biochemical disorders of sexual differentiation
Genetics Laboratory, Department of Molecular and Human Genetics. (DSD) pose numerous challenges
Address correspondence to: Lefkothea Karaviti, MD, PhD, Department of Pediatrics, Texas Chil- for the parents, family, and treating physi-
dren’s Hospital, Baylor College of Medicine, 6621 Fannin, Houston, TX 77030; email: lpkaravi@tex- cians. The pediatrician is usually the first
aschildrenshospital.org. medical contact for newborns with DSD
The authors would like to thank Mark Kline, MD, Chairman of the Department of Pediatrics at BCM or for toddlers and children who present
and Physician-in-Chief at TCH, for his visionary support of the Gender Medicine Clinic; Maria New, MD,
with DSD at a later time.
for her involvement in opening the area of sexual differentiation disorders; Lee Ligon, PhD, for her
Although the management of DSD is a
unique editorial contributions and key input to the manuscript; patients in the Gender Medicine Clinic,
developing field, the objective always is to
who have been our teachers and made invaluable contributions to the development of the guidelines.
The authors also acknowledge the editorial assistance of Lynda Jacks, RN. determine the best outcome decision at the
The authors have disclosed no relevant financial relationships. time of presentation. In general, unman-
doi: 10.3928/00904481-20120307-09 aged variations in practice lead to wide
variations in outcomes, thus impeding

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TABLE 1.

Laboratory Workups to Identify Phenotypes of Ambiguous Genitalia

Condition Testing
Standard workup (electrolytes, glucose, 17OHP, plasma renin activity, D4 androstenedione,
CAH
testosterone, 11 deoxycortisol, DHEA).

Hypopituitarism/hypogonadotropic Standard workup: testosterone, LH, FSH, glucose, T4 (free thyroxine by equilibrium dialysis);
hypogonadism TSH, testosterone, LH, FSH, random cortisol versus 1 mcg ACTH stimulation test.

Micropenis, undescended testes in the

Testosterone and dihydrotestosterone at baseline followed by stimulation with hCG (500 units
context of primary hypogonadism or in
intramuscularly every day x 3 days for younger than 1 year of age), and draw testosterone,
the context of evaluation of the action or
dihydrotestosterone on day 4.
production of testosterone
Genetic testing as appropriate, depending on karyotype and phenotype, including molecular
Ambiguous genitalia
genetics as needed for 5 alpha-reductase and androgen receptor defects.
Source: Douglas G, et al. Reprinted with permission.

the delivery of high-quality patient care.
Hence, evidence-based guidelines, system-
atically developed recommendations that
can assist the practitioner in providing di-
agnostic accuracy and therapeutic reliabili-
ty,1 are needed. This paper is a continuation
from the Consensus statement developed at
Texas Children’s Hospital for the manage-
ment of DSD.2
Several years ago, we formed a Gender
Medicine Team (GMT) at Baylor College
of Medicine and Texas Children’s Hospi-
tal (TCH) to explore and evaluate the most
appropriate management strategies, which
had long been a matter of concern and con-
tention.3-9
Subsequently, the GMT, composed of
experts in the fields of endocrinology, eth-
ics, genetics, gynecology, psychology, pe-
diatric surgery, and urology, formed a Task
Force to evaluate the information available
from our own experience and from reviews
of the literature.
Four clinically relevant questions were
identified as those that needed to be an-
swered. Utilizing the Grading of Recom-
mendation, Assessment, Development and
Evaluation (GRADE) system to assess the
evidence and recommendations, the Task
Force developed a consensus statement for
clinical management of DSD and for mak-
ing sex assignments.2
We sought to address the most
common scenarios faced by the pedia-
trician, which usually involve answer-
ing the following initial questions:
• What is the appropriate work-
up for children aged 0 to 24
months with ambiguous geni-
talia or a DSD?
• What is the appropriate acute
management for children aged
0 to 24 months with ambiguous
genitalia or a DSD?
• What is the most appropriate
way to approach sex assign-
ment in an infant with ambigu-
ous genitalia or a DSD?
• What is the appropriate surgi-
cal management for children
aged 0 to 24 months with am-
biguous genitalia or a DSD?
We herein summarize our approach
pertaining to the general pediatrician
who is confronted with the challenge
of counseling the patient and family at
the time of diagnosis of a DSD. Our
GMT Task Force recommends:
• A laboratory workup to deter-
mine the items outlined below;
• Immediate management for
acute conditions;
• Sex assignment based on an
ethical framework that includes
educating and involving the
parents; and
• Surgical management.
APPROPRIATE WORKUP
AND EVALUATION OF
AMBIGUOUS GENITALIA
Evaluation will involve elucidating
both sexual determination, processes
that occur between conception and go-
nadal differentiation, and sexual differ-
entiation, processes that occur between
gonadal sex determination and matu-
rity.10 Universal newborn screening
for severe 21-hydroxylase deficiency
has been recommended.11 The work
of other authors and our team confirm
that a multidisciplinary team is need-
ed to counsel the family at the time of
diagnosis.12
The diagnostic workup should in-
clude family history, general examina-
tion for dysmorphic features, and grad-
ing based on the presence or absence
of gonads and their palpability (see
Table): (a) no gonads palpable (46, XX
DSD, congenital adrenal hyperplasia
[21-hydroxylase deficiency] or 46, XY
DSD); (b) one gonad palpable, or ab-
normal gonadal differentiation (46, XY
DSD, mixed gonadal dysgenesis [45
X/46/XY], ovotesticular DSD); and (c)

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TABLE 2. the appropriate hormonal replacement

therapy immediately.
Prader Staging14 For the evaluation of micropenis
Prader Stage Characteristics and undescended testes in cases of pri-
Slightly virilized female, perhaps only exhibiting isolated clitoral hypertrophy mary hypogonadism most likely in the
I
and without labial fusion. context of dysgenetic testes, we rec-
Clitoromegaly and posterior labial fusion: narrow vestibule at the end of ommend using human chorionic go-
II
which the vagina and the uretha open. nadotropin (hCG) stimulation for the
Greater degree of clitoromegaly, single perineal urogenital orifice, and evaluation of primary hypogonadism
III
almost complete labial fusion. and obtaining measurements of basal
Phenotypic male with hypospadias and micropenis: increasingly phallic clitoris, Müllerian inhibiting substance (MIS).
IV
urethra-like urogenital sinus at base of clitoris, and complete labial fusion. The hCG stimulation test has shown a
Cryptorchid boy: penile clitoris, urethral meatus at tip of phallus, scrotum- positive predictive value of 89% and a
V
like labia and non-palpable gonads. negative predictive value of 100%.16
Source: Douglas G, et al. Reprinted with permission. Peripheral defects leading to mi-
cropenis might be associated with
molecular genetic mutations in the an-
two gonads palpable, or 46, XY DSD, In typical hormone functioning, the drogen receptor (AR). Alternatively,
impaired testosterone biosynthesis (an- GnRH pulse generator has developed micropenis and hypospadias might
drogen receptor defect 5-alpha-reduc- and is functional by the end of the first be a consequence of a defect in the
tase deficiency, ovotesticular DSD). trimester. Levels of follicle-stimulat- conversion of testosterone to dihy-
Approximately 75% of patients who ing hormone (FSH), luteinizing hor- drotestosterone in the context of 5 al-
present in the emergency room with mone (LH), and sex steroid secretion pha-reductase deficiency. Evaluation
ambiguous genitalia with hyponatremia are low in childhood, and male infant then should include studying the AR
and hyperkalemia and a lack of palpable levels of testosterone increase during expression and screening for 5 alpha-
testes will have a diagnosis consistent the second week, reaching a maximum reductase mutations and evaluating
with congenital adrenal hyperplasia at 4 to 10 weeks of life and declining testosterone levels.17,18
(CAH).13 An example of classification to low levels by the time the child is With regard to the production of
based on palpability of the gonads is approximately 6 months old. In cases testosterone involving enzymatic
provided in Table 1 (see page e3). of micropenis with or without cryptor- machinery, administering hCG to pa-
But this approach is relevant to more chidism, it is imperative to exploit the tients to increase androstenedione
than simply diagnosing CAH. Because window of opportunity of the LH and secretion allows for establishing the
of the range of disorders, it is important FSH levels to establish the diagnosis diagnosis in prepubertal individuals;
that pediatricians also use the common of hypogonadotropic hypogonadism. If in cases of suspected complete or par-
distinctions established by Prader14 to the infantile GnRH gonadotropin spurt tial androgen insensitivity, AR gene
identify phenotypes of ambiguous gen- is captured, hypogonadotropic hypogo- molecular testing allows for detec-
italia (see Table 2). nadism would be identified by the blunt tion of hundreds of clinically recog-
In cases of a hypothalamic-pituitary- response or ruled out by the appropriate nized mutations and provides further
gonadal axis issue in the context of peak, thereby precluding the uncertain- confirmation of the clinical diagnosis.
ambiguous genitalia or hypothalamic- ties and delays in distinguishing consti- Performing molecular genetic testing
pituitary hypogonadism, the underly- tutional delay in puberty from hypogo- on the SRD5A2 gene for 5 alpha-re-
ing problem most likely is a hypotha- nadotropic hypogonadism. ducatase deficiency confirms affected
lamic gonadotropin-releasing hormone Accordingly, hormone replace- status suspected biochemically.
(GnRH) pulse generator defect with ment therapy can be initiated at the Genetic testing for ambiguous geni-
subsequent hypogonadotropic hypogo- normal age of pubertal onset. Infants talia includes karyotype analysis on
nadism that might be in isolation or in with micropenis should be adminis- peripheral blood or skin fibroblasts de-
the context of hypopituitarism. To es- tered testosterone.15 We recommend rived from genital skin or other sourc-
tablish the diagnosis of isolated hypo- establishing the presence of hypogo- es; fluorescence in situ hybridization
gonadism in the context of micropenis, nadotropic hypogonadism within the (FISH), which provides rapid analysis
hypopituitarism needs to be ruled out. first 6 months of life and initiating and evaluation for sex chromosome

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mosaicism and/or chimerism; FISH for
determining the presence or absence
of the sex-determining region on the Y
chromosome (SRY); specialized mo-
lecular genetic testing for Y-chromo-
some deletions; and the array compara-
tive genomic hybridization (aCGH).19
The aCGH is proving useful in
evaluating cases of ambiguous geni-
talia by simultaneously providing the
same information as a standard karyo-
type, evaluating for sex chromosome
mosaicism and/or chimerism, and
detecting the presence or absence of
SRY and other copy number changes
that may cause DSD.20
Hence, the GMT Task Force recom-
mends a multidisciplinary approach
using various diagnostic procedures,
including karyotype, and additional
appropriate testing such as aCGH for
the genetic workup of infants with
ambiguous genitalia or a DSD. The work
of other authors and our team confirm
that a multidisciplinary team is needed
to counsel the family at the time of diag-
nosis.12 Laboratory workups to identify
phenotypes of ambiguous genitalia are
listed in Table 1 (see page e3).
ACUTE MANAGEMENT OF INFANTS
WITH AMBIGUOUS GENITALIA/DSD
For infants with ambiguous genita-
lia or a DSD who present with a life-
threatening complication like the ones
described below, we recommend ini-
tiating treatment with stress-dose ste-
roids immediately while waiting for
laboratory test results.
We concur with other authors11,14
that the emergency conditions should
be addressed as follows: (a) for cases
of suspected CAH (salt-losing vari-
ety), a laboratory workup should be
initiated, and the infant should be
treated with D5 NS (dextrose in nor-
mal saline) and stress steroids (hydro-
cortisone 100 mg/m2/day), with treat-
ment modified after 24 hours, based
on electrolyte correction.
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Mineralocorticoids (fludrocortisone,
0.1 mg by mouth once each day should
be added, with a switch to table salt
(1 to 2 g by mouth once each day,21
given in 24-hour worth of formula or
breastmilk); (b) for cases of micrope-
nis and suspicion of hypopituitarism
(the concern is hypoglycemia), the
pituitary adrenal axis should be assessed
for production of cortisol and treat-
In addition to medical
personnel, our team
approach also includes a
psychologist and an ethicist.
ment (stress steroids: 100 mg/m2/day
hydrocortisone) should be initiated
while laboratory results are pending;
and (c) for cases of suspected CAH
in crisis, hydrocortisone stress dos-
es should be initiated IM or IV. For
long-term management of CAH, we
recommend as per the literature glu-
cocorticoids (hydrocortisone 10 to 20
mg/m2/day, divided by three doses per
day, mineralocorticoids (fludrocorti-
sone, 0.1 to 0.2 mg daily) and sodium
chloride (1 to 2 g or 17 to 34 mmol of
sodium chloride daily).21 Since aldo-
sterone regulates sodium homeostasis,
IV normal saline administered during
adrenal crisis along with emergency
glucocorticoids corrects the hypovole-
mia and hyponatremia.
SEX ASSIGNMENT IN AN INFANT
WITH AMBIGUOUS GENITALIA/DSD
Making sex assignments for in-
fants born with ambiguous genitalia
or DSD involves numerous consid-
erations. Our guidelines not only ad-
dress medical considerations, but also
ethical and legal matters as well.
With regard to whether sex assign-
ment should be physician-dependent
or reside within a GMT, we base our
guidelines on systematic reviews of the
literature,22 as well as our own accumu-
lative experience at TCH,1,12 and rec-
ommend using a consensus approach
that includes an ethical framework for
informed parental decision-making.
Our multidisciplinary GMT ap-
proach used at TCH is designed to
meet the multifaceted needs of in-
dividuals with DSD and is recom-
mended over the traditional physi-
cian-determined approach.1 In addi-
tion to medical personnel, our team
approach also includes a psychologist
and an ethicist.1,12 It also includes: an
ethical framework involving a team of
specialists; and education and partici-
pation of the parents in the decision-
making process.
Although specific guidelines have
not been established heretofore, our
experience and the few outcome stud-
ies,18,23,24 have shown that parents and
other family members experience un-
certainty about the future and how to
explain situations to others; they oc-
casionally demonstrate significant
symptoms of anxiety and depression
during diagnosis, medical workup,
acute management, sex assignment,
and treatments.
Patients themselves often experi-
ence various psychosocial challenges
that may require psychological inter-
vention. For these reasons, we recom-
mend including a psychologist on the
multidisciplinary team to provide im-
mediate and ongoing support to both
patients and caregivers.1,12
Our GMT was the first multidisci-
plinary team to include an ethicist. We
base this inclusion on: 1) the identified
need to determine ethical judgments
on an evidence-based assessment of
the affected infant; 2) the centrality of
making decisions in the best interest of
the infant and the child and adult that
infant will become; 3) the obligation of
health care professionals to include the
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parents in the decision-making process
that will also involve providing them
with education; 4) the need to include
the child in the decisions that will be
made appropriate to the developmental
stages; and 5) the obligation to consider
the biopsychosocial variations in sex,
gender, and gender identity, as well as
cultural changes that are likely to result.
Responsible management of DSD
is guided by two ethical consider-
ations: 1) the variations in the dif-
ferent components of biological sex,
including genomic sex, anatomic sex
(internal and external), hormonal sex,
and brain sex, and the variations that
will be observed in subsequent gen-
der, including gender identity and sex-
ual orientation; and 2) the prevention
of irreversible anatomic and physi-
ologic effects of surgical assignment,
particularly when the components of
biological sex do not strongly align.
Descriptions of ethical frameworks
and a statement from an interdisciplinary
research group25,26 confirm our inclusion
of an ethicist. We strongly recommend
consulting an ethicist familiar with ethi-
cal issues in DSD on each case to ensure
that the patient’s individual needs are
addressed in accordance with the ethical
framework established by the GMT.
APPROPRIATE SURGICAL
MANAGEMENT
When to perform surgery and the ap-
propriate surgical management of the
infant with ambiguous genitalia or DSD
have been matters of contention for some
time, especially since the initial studies
by Money27 were challenged. Each case
is different, but certain guidelines have
been established by our GMT.
Surgical Management
for Infants with CAH
For genetically female infants born
with CAH with virilized external geni-
talia, most studies and our experience
indicate that patients benefit from ear-
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ly one-stage reconstructive surgery,11
with the patient’s steroid replacement
increased beforehand. The mainstays
of surgical repair are clitoral reduc-
tion, correction of the urogenital sinus
defect that results from failure of the
vagina to complete the migration to
the perineum, and exteriorization of
the vagina, which may require that the
labioscrotal folds be trimmed, thinned,
and elongated to create labia majora
with a more normal appearance.
Feminizing Surgery
for Patients with DSD
Surgical management of infants
born with DSD is complex and must be
designed individually with the follow-
ing goals in mind: preserving normal
genital sensation, creating a normal
introitus, and providing an adequate
vaginal opening at the perineum.
Consensus statements addressing
DSD show a clear trend toward multi-
disciplinary management, with pediat-
ric surgeons, urologists, and gynecolo-
gists advocating individualized ap-
proaches. Most consensus statements
recommend early surgical correction
once the evaluation is completed, al-
though some organizations delay sur-
gery until the patient reaches an appro-
priate age of informed consent.
Our team recommends that cases
be individualized due to the spectrum
of presentation, and that surgery be
delayed until a definitive gender as-
signment can be established.
Masculinizing Surgery
for Patients with DSD
For patients with 46,XY DSD, the
surgical approach also is complex, with
opinions varying on the appropriate tech-
nique and timing of surgical intervention.
The surgical techniques used in mas-
culinizing genitoplasty reconstruction
include staged vs primary hypospadias
repair with chordee release, scrotoplasty,
orchiopexy, open or laparoscopic remov-
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al of Müllerian structures, and insertion
of testicular prostheses.
As with feminizing surgery, the results
have varied considerably. We recom-
mend: postponing surgical management
until concordance is established and med-
ical therapy is given; performing mascu-
linizing genitoplasty and orchidopexy for
under-androgenized male patients with
underlying testosterone deficiency, espe-
cially 17-beta hydroxysteroid dehydroge-
nase deficiency; and providing preopera-
tive testosterone stimulation followed by
hypospadias repair and scrotoplasty, as
well as dihydrotestosterone replacement,
for under-androgenized male patients
with 5-alpha-reductase deficiency.
Gonadectomy Surgery
for Patients with DSD
Several reports describe the associa-
tion of 46,XY gonadal dysgenesis with
gonadoblastoma and risk of malignan-
cy. Predominant risk groups include
syndromes of gonadal dysgenesis and
Ullrich-Turner syndrome. Certain syn-
dromes with splice variants of the WT1
gene are susceptible to Wilms’ tumors.
In cases of gonadal dysgenesis, we
recommend performing early gonadec-
tomy; however, in cases of complete an-
drogen insensitivity syndrome (CAIS),
we recommend delaying surgery until
after the patient reaches puberty.
CONCLUSIONS
Following evidence-based guidelines
is essential in practice to provide patient-
centered, effective, and efficient man-
agement of patients with DSD. Once a
DSD has been identified, the pediatri-
cian needs to rule out a medical emer-
gency in the context of hypopituitarism
or CAH. The appropriate workup needs
to be initiated according to the pheno-
type and clinical assessment.
Based on our experience in this field
and our reviews of approaches taken by
other experts, we recommend after these
steps have been taken that the general
3/29/2012 8:28:23 AM

pediatrician refer the patient to a center
with a multidisciplinary team that in-
cludes an ethicist who can ensure that
the sex-assignment decision is made
within an ethical framework for treat-
ing persons with DSD. We also recom-
mend involving the parents as active
participants after providing them ad-
equate education regarding their child’s
condition, the various options available,
and the likely best outcomes based on
the information available. We target our
management for gender stability by pro-
viding support through a psychologist in
the event of a sex change, should that be
the choice of the individual.
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3. Blizzard RM. Intersex issues: a series
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