Rev Mex Urol 2014;74(2):117-122
ÓRGANO OFICIAL DE DIFUSIÓN DE LA SOCIEDAD MEXICANA DE UROLOGÍA
www.elsevier.es/uromx
Clinical case
Complete androgen insensitivity syndrome: a case report and
surgical management illustration
J. D. Farias-Cortésa,*, F. Minakata-Ochoaa and I. Sedano-Portillob
a
Urology Service, Hospital Regional “Valentín Gómez Farías”, ISSSTE, Zapopan, Jal., Mexico
b
Urology Service, Centro Médico Nacional de Occidente, IMSS, Guadalajara, Jal., Mexico
KEYWORDS
Disorders of sexual
differentiation;
Gonadal agenesis;
Vaginoplasty; Morris
syndrome; Mexico.
Abstract The term “disorders of sexual differentiation” (DSD) encompasses a group of
abnormalities in the development of the genitourinary tract. Atypical development occurs at
one or more chromosomal, gonadal, or anatomic levels. 46 XY genetic males may present with
external genitals that are phenotypically female or ambiguous. Androgen insensitivity syndrome
could be considered a disease caused by resistance to androgenic action due to the Xq11-12
mutation that affects the androgenic receptors. Clinical presentation depends on the degree of
insensitivity: mild (infertile male), partial, or complete, as with our patient. Psychologic and
psychiatric follow-up is required for both the patient and family members so there can be
adequate psychosexual development before and after definitive surgical treatment.
The aim of this article was to conduct a systematic review of published reports in the MEDLINE
database to identify the epidemiology and incidence of complete androgen insensitivity
syndrome and to examine the approach, treatment, and follow-up of these cases.
We present herein a 23-year-old patient, with an unremarkable pathologic history, who began to
be studied by the Gynecology Service at 17 years of age due to amenorrhea and lack of secondary
sexual development. Imaging studies failed to show Müllerian structures. Diagnostic laparoscopy
was performed on 2 occasions in which female sexual organs or vestiges of testes were unable
to be identified. Hormonal study revealed obviously low levels of estrogens and testosterone,
and follicle-stimulating hormone (FSH), luteinizing hormone (LH), and gonadotropin-releasing
hormone were within normal parameters; 46XY karyotype was reported. Psychiatric support was
then offered. It was decided that the patient would continue to be raised and treated as a
female and therefore she was given breast implants. Our service was subsequently consulted for
performing vaginoplasty using an intestinal segment as the vaginal canal.
* Corresponding author at: Av. Soledad Orozco N° 203, Colonia el Capullo, C.P. 45150, Zapopan, Jal., México. Telephone: (33) 1080 6462.
Email: [email protected] (J. D. Farias-Cortés).
118
Palabras clave
Desórdenes en la
diferenciación sexual;
Agenesia gonadal;
Vaginoplastía;
Síndrome de Morris;
México.
J. D. Farias-Cortés et al
Síndrome de insensibilidad completa a los andrógenos: reporte de un caso, ilustración
del manejo quirúrgico
Resumen El término “desorden en la diferenciación sexual” (DDS) representa un grupo de
anormalidades en el desarrollo del tracto genitourinario, en el cual ocurre un desarrollo atípico
en uno o más niveles: cromosómico, gonadal o anatómico. Los genéticamente varones 46XY
pueden presentarse con genitales externos fenotípicamente femeninos o ambiguos. El síndrome
de insensibilidad a los andrógenos se podría considerar una enfermedad causada por la resistencia a la acción androgénica, causada por la mutación Xq11-12, que afecta los receptores androgénicos; la presentación clínica dependerá del grado de insensibilidad, leve (masculino infértil),
moderada o completa como en nuestro caso. Requiere seguimiento por psicólogo y psiquíatra
para familiares y paciente, para un desarrollo psicosexual adecuado, antes y después del tratamiento quirúrgico definitivo.
El objetivo del presente artículo es realizar una revisión sistemática de los artículos publicados
en la base de datos de Medline, para identificar la epidemiología e incidencia del síndrome de
insensibilidad completa a los andrógenos, así como reconocer su abordaje, tratamiento y seguimiento de estos casos.
Se presenta paciente de 23 años de edad, sin antecedentes patológicos de importancia, la cual
inicia su estudio a los 17 años de edad por el Servicio de Ginecología, por presentar amenorrea y
falta de desarrollo en caracteres sexuales secundarios, tiene estudios de imagen sin evidenciar
estructuras Müllerianas; se realiza laparoscopía diagnóstica en 2 ocasiones sin poder identificar
órganos sexuales femeninos o vestigios de testículos; estudio hormonal con niveles de estrógenos
y testosterona evidentemente bajos con hormona folículo estimulante (FSH), hormona luteinizante (LH) y hormona liberadora de gonadotropinas dentro de parámetros normales; el cariotipo reporta 46XY. En ese momento se ofrece apoyo psiquiátrico, se decide continuar con educación
femenina, por lo que se resuelve colocación de prótesis mamaria. Finalmente, se nos interconsulta para la realización de vaginoplastía con uso de segmento intestinal como canal vaginal.
0185-4542 © 2014. Revista Mexicana de Urología. Publicado por Elsevier México. Todos los derechos
reservados.
Introduction
Case presentation
The recently coined term “disorders of sexual
differentiation” (DSD), previously known as “intersex
condition, hermaphroditism, and pseudohermaphroditism”,
has now been adopted, since experts worldwide prefer this
nomenclature; 1,2 it is a class of abnormalities in the
development of the genitourinary tract and refers to a
group of congenital conditions in which there is atypical
development at one or more levels (chromosomal, gonadal,
or anatomic). Genetic males with DSD (46XY) can present
with phenotypically female, male, or ambiguous external
genitalia, such as in the case of micropenis (length < 2.5
times shorter in relation to chronological age). 3 These
conditions can be caused by chromosomal and endocrine
aberrations that are reflected in the sexual phenotype of
the individual. DSD incidence may vary according to ethnic
group; for example, one out of every 5,000 live births in
Germany vs. one out of every 3,000 in Egypt; this is due to a
higher consanguinity rate.4 Congenital adrenal hyperplasia
and mixed gonadal dysgenesis are the most common causes
of ambiguous genitalia in 50% of the cases, with a worldwide
incidence of 1:15,000 and 1:10,000, respectively. However,
this can vary considerably among different populations.5
A 23-year-old patient, single, with no past history of
remarkable hereditary, familial, or personal pathologies
related to this case, began to be studied at 17 years of age
by the Gynecology Service for presenting with amenorrhea
and lack of development of secondary sexual characteristics.
Imaging studies revealed no evidence of Müllerian structures
or renal alterations and so the patient underwent diagnostic
laparoscopy on 2 occasions in which internal sexual organs
were looked for. No female sexual organs or remnants of
testes were found and an immediate hormone study showed
a total estrogen level of 15 pg/dL. These studies were
repeated various times with no significant differences;
follicle-stimulating hormone (FSH) and luteinizing hormone
(LH) were within normal low parameters and testosterone
was always very low (the last value was 1.07 ng/dL). The
genetics team was called in and they carried out the
karyotype study that reported 46XY (fig. 1).
Genetic counseling as well as psychiatric support was
then offered to the patient and family and they decided to
continue raising her as a female, as had been done all her
life, given that she was phenotypically female since birth.
The case was presented to the Hospital Ethics Committee
and with the consent of the patient and her family she
underwent breast implantation at the Plastic Surgery
Complete androgen insensitivity syndrome: a case report and surgical management illustration 119
Figure 1 Characteristic of the karyotype of the patient, 46XY.
Service. Finally, we were consulted to perform a
vaginoplasty using intestinal segment for the vaginal canal.
Initially, patient preparation was a liquid diet one day
before surgery and enemas. With the patient under general
anesthesia and in the lithotomy position, a midline
infraumbilical incision was made. Dissection up to the
abdominal cavity was done by layers, and detailed
exploration revealed the absence of Müllerian structures
and testicular remnants, a normal capacity bladder, and no
bimanually palpable prostate. The opening of the dome in
the urogenital diaphragm was begun (figs. 2 and 3).
Twelve centimeters of the sigmoid colon were then
selected, due to its extensive vasculature and redundant
mesentery. An end-to-end anastomosis was performed. The
resected segment was taken to the new vaginal canal and
anastomosed and closed in 2 layers (figs. 4-6).
Because the patient progressed adequately, she was
promptly released from the hospital. Follow-up included
20-minute dilations with a Hegar dilator at home, 3 times a
week, with a gradual increase in measurements from 8 to 22
mm at the end of 10 months. At the 6-month follow-up, the
patient presented with a mild discharge of mucus twice a
week, due to the colon segment. She continues to undergo
both psychologic and psychiatric treatment and has a
satisfactory sex life with her current partner, as well as a
normal work life.
Discussion
The androgen insensitivity syndrome can be considered a
disease caused by resistance to androgen action that
influences 2 things: the morphogenesis and differentiation
of body structures and systems that these hormones have an
effect on. It depends on an X mutation in the androgen
receptor gene in which a variety of phenotypes can be
expressed; from infertile males to normal external female
genitals. 6 John Morris 7 was the first to describe this
syndrome, but it was not until 1989 that the exact location
Figure 2 Abdominal surgical exploration revealing the
absence of Müllerian structures and of testicular
remnants.
of the androgen receptor gene was discovered to be on
Xq11-12, where it was demonstrated that the mutation can
present and the disease develop.8 The androgen receptors
are expressed from gestation week 8, and the testes of the
male embryo begin to secrete testosterone at week 9, with 2
peaks at weeks 11 and 18. The epididymis, vas deferens, and
seminal vesicles simultaneously differentiate from the
Wolffian ducts. A more potent androgen, dihydrotestosterone,
originates from testosterone through the action of type 2
5-alpha-reductase and stimulates the differentiation of the
male genital primordium.9
The clinical phenotypes of androgen insensitivity
syndrome may vary depending on the severity of resistance
and they are classified into 3 grades: complete, partial, and
mild.10 Complete resistance, in particular, is characterized
by a short vagina ending in a blind sac, absence of the
Wolffian products such as the epididymis, vas deferens,
seminal vesicles, or prostate. Clinical presentation from
birth is a totally female phenotype, making its early
diagnosis difficult.11 An important pattern helping establish
clinical suspicion is that in puberty there is generally slow or
small mammary growth in relation to chronologic age, with
very little or no axillary and pubic hair. 12 Other clinical
characteristics that can be found are mono or bilateral
inguinal hernia, even though the differences with apparently
female patients are minimal, making an earlier diagnosis
difficult to suspect. This syndrome is the cause of 10% of all
cases of primary amenorrhea.5
With respect to endocrine presentation in these patients,
we can find: normal or increased LH and testosterone
slightly above normal in the first month of life. After that,
LH and testosterone levels are normal until puberty13, due
120
J. D. Farias-Cortés et al
Figure 4 12 cm of the sigmoid colon were taken due to its
extensive vasculature and mesentery.
Figure 3 The surgical exploration revealed a normal capacity
bladder and no bimanually palpable prostate; the dome in the
urogenital diaphragm was opened.
to androgen insensitivity and the lack of negative feedback
of the sex hormones in the hypothalamus and hypophysis.
Testosterone is aromatized and converted into estrogens at
a later time through enzyme action. This is why patients
with complete insensitivity have higher estrogen levels than
normal males and develop mammary growth. In addition,
they can have normal anti-Müllerian hormone levels,
explaining the absence of internal female sexual
characteristics.9
Differential diagnoses in 46XY patients
Among the other diagnoses that should be contemplated
when evaluating an individual with DSD are: Swyer
syndrome, in which the lack of testicular development in
the early stages of the embryonic period leads to the
formation of female sexual characteristics such as the
uterus and Fallopian tubes; paramesonephric duct
participation and the lack of testosterone and anti-Müllerian
hormone sent by the testes results in rudimentary female
sexual development with no ovaries. Among other
differential syndromes are: testicular feminization that
consists of well differentiated female sexual characteristics,
with a short undeveloped vagina, and bilateral cryptorchidism,
but with no uterus,14,15 and ovoteste, also known as “true
hermaphrodite” syndrome, which presents with ovaries with
seminiferous tubes,16 as listed in table 1.
Follow-up
Figure 5 An end-to-end anastomosis of the proximal and distal segment was performed.
It is currently recommended to raise the awareness of the
patient’s relatives in regard to the surgical management,
emphasizing its risks, benefits, and potential outcomes so
that they can participate more actively in the care of their
child. Psychosocial management is the basis of promoting a
positive adaptation. These patients require professional
follow-up to help them manage the sexual dysfunction and
gender dysmorphia as they become present. Group therapy
is also recommended because support is necessary up to
the adult age so these patients can develop a healthy
psychosexual life.5
The risk for acquiring malignant disease in this type of
patient exists, especially for presenting germ cell tumors
such as gonadoblastoma, dysgerminoma, or seminoma,
Complete androgen insensitivity syndrome: a case report and surgical management illustration 121
Table 1 Differential diagnoses in the medical conditions of
disorders of sex differentiation.
Differential diagnoses
Clinical characteristics
Swyer syndrome
Presence of a uterus and
rudimentary tubes
Testicular feminization
Female secondary sexual
characteristics, but
bilateral cryptorchidism
Ovotestis
Presence of seminiferous
tubes in ovaries
Conflict of interest
Figure 6 The resected segment was taken to the new vaginal
canal and was anastomosed and closed in 2 layers.
given that they all belong to the same type of cancer16 and
arise from undifferentiated gonadal tissue.17 Therefore they
should be intentionally looked for and dysmorphic gonads
should be extracted at an early age.18
Today an international database, called I-DSD, is
accessible that includes cases recognized by researchers
from specialized centers, as well as isolated case reports
from private medical practices. This information is available
to patients, their families, and doctors so they can know
where to find the specialized research centers and
information on the disease, treatment, and follow-up.19
Conclusions
Complete androgen insensitivity is included in the term
DSD, and can include patients ranging from infertile men to
those individuals presenting with complete female
phenotype with no internal sexual organs, as was the case
with our patient.
It is a rare entity that has a psychologic impact on family
members, as well as a psychosexual impact on the patient.
Thus, counseling is required from the time of diagnosis, so
that doubts can be cleared up and there can be support
during the sexual adaptation. These patients require
lifetime maintenance from their psychotherapist, as well as
their urologist, who will monitor lower urinary symptoms
and carry out periodic hormone function tests. A database is
currently at the disposition of patients, relatives, and
attending physicians where they can become familiar with
the clinical characteristics of the disease and connect with
support groups.
During surgical treatment it is important to provide
extensive counseling on the expectations of both the patient
and family members in relation to the procedure, clearly
explaining its likely complications. The surgeon should also
intentionally look for hypofunctioning dysmorphic gonads
and remove them, in order to prevent the aforementioned
probability of malignant transformation.
The authors declare that there is no conflict of interest.
Financial disclosure
No financial support was received in relation to this article.
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