Case Report: Role of Imaging in The Diagnosis and Management of Complete Androgen Insensitivity Syndrome in Adults
Case Report: Role of Imaging in The Diagnosis and Management of Complete Androgen Insensitivity Syndrome in Adults
Case Report: Role of Imaging in The Diagnosis and Management of Complete Androgen Insensitivity Syndrome in Adults
Case Report
Role of Imaging in the Diagnosis and
Management of Complete Androgen Insensitivity
Syndrome in Adults
Copyright © 2013 Marco Nezzo et al. This is an open access article distributed under the Creative Commons Attribution License,
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Complete androgen insensitivity syndrome is an X-linked recessive androgen receptor disorder characterized by a female phenotype
with an XY karyotype. Individuals affected by this syndrome have normal female external genitalia but agenesis of the Müllerian
duct derivatives, that is, absence of the Fallopian tubes, uterus, cervix, and the proximal part of the vagina, with presence of
endoabdominal, labial, or inguinal testes. The estimated prevalence is between 1 and 5 in 100,000 genetic males. Complete androgen
insensitivity syndrome can be diagnosed as a result of mismatch between the prenatal sex prediction and the phenotype at birth,
can be detected by chance, or remain undetected until investigations for primary amenorrhea. Imaging can be important both to
diagnose the pathology and to localize gonads prior to surgical treatment. In this paper, we present three cases of complete androgen
insensitivity syndrome in adult women of 34, 22, and 38 years old.
1. Case 1 2. Case 2
A 34-year-old female was referred by the endocrinologist A 22-year-old female underwent two episodes of surgery for
of our hospital. Her older sister had been diagnosed with inguinal hernia before puberty. She was told that she has no
complete androgen insensitivity syndrome (CAIS) at the age uterus at the age of 15, but the diagnosis of CAIS was only
of 17. She had a female phenotype with normal external recently made at another hospital. She had a male karyotype
genitalia, normal breast development, and little axillary and but normal female external genitalia and a vagina of normal
pubic hair. The digital vaginal examination revealed a short, size and depth. The patient had a normal height, weight, and
tight, and blind-ended vagina. An ultrasound (US) exam breast development, with very subtle axillary and pubic hair.
performed in another hospital had suggested the presence of She was now referred to our department by the gynecol-
gonads located in the pelvis. A magnetic resonance imaging ogist for an ultrasound and MRI exam prior to laparoscopic
(MRI) exam (Figure 1) was performed to plan a laparoscopic gonadectomy. US images (Figure 2) revealed a solid nodule
gonadectomy and showed two soft tissue structures sugges- suggestive of testicular tissue located in both inguinal regions.
tive for gonadal tissue located in the right obturator canal The MRI exam (Figure 3) confirmed a testicle in the deep
and along the left external iliac artery. A pericentimetric cyst inguinal ring on both sides and cysts adjacent to them.
was found adjacent to each gonad. Apart from the vagina, no The uterus, cervix, and Fallopian tubes were absent, while
development of Müllerian duct structures was observed. the external genitalia and vagina had a normal appearance.
2 Case Reports in Radiology
(a) (b)
(c)
Figure 1: A 34-year-old female with CAIS syndrome. The axial T2-weighted images ((a) and (b)) show a left testis along the left external
iliac artery and a right testis in the right obturator canal (green arrows) with adjoining cysts (red arrows). Sagittal image (c) shows absence of
Müllerian structures and presence of the lower vagina (yellow arrowheads) (3T magnetic resonance imaging. Axial 4 mm fast T2-weighted
images, TR/TE 5030/119 ms; sagittal 5 mm HASTE-sequence, TR/TE 6500/89).
Figure 2: A 22-year-old girl/female with CAIS. Transabdominal ultrasonography (Hitachi EUB-8500, 14 MHz linear array probe) shows the
presence of the right testis in the inguinal canal.
Following gonadectomy, the patient was planned for hor- (watchful waiting) instead of preventive gonadectomy. The
monal substitution with estrogens. MRI exam (Figure 4) showed two testes with adjacent cystic
components, each located in the obturator canal. There were
3. Case 3 no signs of malignancy. Müllerian derivatives were absent.
A small Bartholin’s cyst was noted on the left side of the
A 38-year-old female was diagnosed with CAIS on the basis perineum.
of primary amenorrhea. She presented with a male karyotype
but female phenotype. She had normal external genitalia with 4. Discussion
a short vagina, normal height, weight, and breast develop-
ment, no axillary hair, and very little pubic hair. She was Androgen insensitivity syndrome (AIS) is an X-linked reces-
referred to our department to exclude testicular malignancy, sive disorder caused by mutations of the androgen receptor
following her informed decision to undergo periodic MRI (AR). The responsible gene has been localized at the proximal
Case Reports in Radiology 3
(a) (b)
(c)
Figure 3: 22-year-old girl/female affected by CAIS. Axial and coronal T2-weighted images ((a) and (b)) revealing the testes (green arrows)
with adjoining cysts on both sides (red arrows). Sagittal image (c) showing absence of the Müllerian structures and the presence of the lower
vagina (yellow arrowheads). (3T Magnetic Resonance Imaging. Axial 4 mm fast T2-weighted image, TR/TE 5030/119; sagittal 5 mm HASTE-
sequence, TR/TE 6500/89).
long arm of the X chromosome at Xq11-12 [1, 2]. According Diagnosis of CAIS is obtained when a male karyotype is
to the AR mutation database (http://www.mcgill.ca/andro- found in individuals with a female phenotype. They typically
gendb), there are more than 1000 different mutations almost all have a female gender identity, normal breast devel-
reported so far. The syndrome was first described in 1953 by opment, little pubic and axillary hair, primary amenorrhea,
Morris as testicular feminization, on the basis of his study of and a blind-ending vagina. Although 77% of patients perceive
clinical features in 82 patients [3]. The syndrome was later their vagina as small and tight, only 35% actually have vaginal
given the name of androgen insensitivity syndrome. hypoplasia on genital examination [7], sometimes requiring
Depending on the type of AR mutation, the failure of vaginal dilatation or surgical reconstruction.
sexual differentiation can be either complete (CAIS), partial CAIS patients are usually taller than women without the
(PAIS), or mild (MAIS). We described 3 cases of CAIS, in syndrome but shorter than the male population [8]. They
which dysfunction of the AR is complete. CAIS patients have have a low bone mineral density before and/or after gonadec-
a male karyotype with female phenotype and despite testic- tomy [9] that can be corrected by estrogen replacement
ular production of testosterone (T) and dihydrotestosterone therapy and/or calcium and vitamin D supplements. Their
(DHT), they do not develop either male genitalia or male serum testosterone levels are within or above the normal
secondary sexual characters; furthermore, since the testicular range for males, and their luteinising hormone (LH) [10] and
Sertoli cells produce Müllerian-inhibiting factor (MIF), they serum oestradiol concentrations are higher than in males but
do not develop Müllerian structures. The testes can be located lower than in females without CAIS [11].
in the inguinal canal, sublabial, or intra-abdominal, and they Karyotyping should be considered in all female infants
are very commonly adjoined by small cystic pouches that are diagnosed with a bilateral inguinal hernia [11, 12] because the
thought to be remnants of the Müllerian or Wolffian ducts latter is rare in normal female infants and associated with
[4]. The prevalence of CAIS is estimated between 1 and 5 CAIS in 1-2% of cases during infancy [12, 13].
in 100,000 genetic males on the basis of a proven molecular An intra-abdominal position of the testes is a well-known
diagnosis [5] (Table 1). cause of malignant degeneration, but since the testes are
4 Case Reports in Radiology
(a) (b)
(c) (d)
Figure 4: 38-year-old girl/female affected by CAIS. MRI T2-weighted coronal ((a) and (b)) and axial (c) images demonstrating the presence
of the testes (green arrows) and adjoining cysts (red arrows). Sagittal T2 weighted image (d) showing agenesis of the Müllerian structures and
presence of the lower third of the vagina (yellow arrowheads). (3T Magnetic Resonance Imaging. Coronal 1 mm SPACE-sequence, TR/TE
1500/133; axial 4 mm fast-T2-weighted image, TR/TE 4500/119; sagittal 5 mm HASTE-sequence, TR/TE 6500/89).
Table 1: Summary table for complete androgen insensitivity syn- of gonadal malignancy increases and is estimated to be 14%
drome (CAIS). (range 0% and 22%) [15].
Although it seems still prudent to perform the laparo-
Etiology X-linked recessive androgen receptor dysfunction
scopic gonadectomy soon after puberty, the timing of gonad-
Incidence 1/20,400 to 1/99,100
ectomy is now becoming controversial in the literature and
Gender ratio Genetic males many women prefer to defer or decline the surgical procedure
Age [15, 16]. In case of suspected malignant transformation before
Congenital syndrome
predilection puberty, the testes can be removed and puberty induced with
Risk factors Unknown estrogen replacement.
Testicular removal after puberty and estrogen CAIS differs from PAIS because of the presence of a
replacement. Vaginal dilatation or surgical hypospadic micropenis and a bifid scrotum that may contain
Treatment reconstruction. Psychological support often the testes. MAIS is not associated with male genital anomalies
needed. Alternative: watchful waiting but presents as infertility [17].
Prognosis Good if testes are timely removed A very common differential diagnosis of CAIS is
Transabdominal US the Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome.
Absence of Mullerian structures Patients affected by the MRKH syndrome have a female kar-
Presence of testes (usually smaller and slightly yotype and normal female external genitalia and ovaries
hypoechoic relative to normal testes) (located high along the pelvic side wall), but with congenital
MRI aplasia of the uterus and the upper part of the vagina (Table 2)
Imaging Axial plane: absence of Mullerian structures, [6].
findings presence of testes and female external genitalia Transabdominal US can be used as a first-line examina-
Evaluation of incidental testicular malignancy tion for CAIS to assess the absence of Müllerian structures
Sagittal plane: absence of uterus. Evaluation of and to locate the testes. Since US is operator dependent and
presence and length of the lower vagina
Coronal plane: presence of testes and female
can remain inconclusive [18], MRI is the study of choice,
external genitalia. Absence of Mullerian structures with a reported accuracy up to 100% for the evaluation
of Müllerian duct anomalies [19]. MRI provides detailed
anatomic information due to its superior tissue character-
normal and not dysgenetic in CAIS, prepubertal tumors are ization and multiplanar capability. US and MRI have an
rare, with an incidence of 0.8% [14], whereas in adults the risk equal sensitivity for depicting pelvic gonads, but MRI has
Case Reports in Radiology 5
Table 2: Differential diagnosis for complete androgen insensitivity syndrome (CAIS). Adapted from Gottlieb et al. [6].
A copy of the written consent is available for review by the [13] T. Hurme, T. Lahdes-Vasama, E. Mäkela, T. Iber, and J. Toppari,
Editor-in-Chief of this journal. “Clinical findings in prepubertal girls with inguinal hernia with
special reference to the diagnosis of androgen insensitivity syn-
Authors’ Contribution drome,” Scandinavian Journal of Urology and Nephrology, vol.
43, no. 1, pp. 42–46, 2009.
M. Nezzo performed the literature search and wrote the final [14] E. Rajpert-De Meyts, “Developmental model for the pathogen-
paper. P. De Visschere chose images and inserted annotations. esis of testicular carcinoma in situ: genetic and environmental
G. T’Sjoen and S. Weyers spoke with the patients and aspects,” Human Reproduction Update, vol. 12, no. 3, pp. 303–
reviewed and interpreted clinical data. G. Villeirs guided and 323, 2006.
supervised the paper. All authors read and approved the final [15] R. Deans, S. M. Creighton, L.-M. Liao et al., “Timing of gonad-
paper. ectomy in adult women with complete androgen insensitivity
syndrome (CAIS): patient preferences and clinical evidence,”
Clinical Endocrinology, vol. 76, no. 6, pp. 894–898, 2012.
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