INTRODUCTION
Disorders of sexual dysfunction (DSD) may be defined
as the presence of both male and female external and/or internal genital organs
in the same individual, confusing the diagnosis of true sex.1 Simply put, it is described as ambiguity in
genitalia. External genitalia are considered to be ambiguous whenever there is
difficulty assigning gender to a child based on the appearance of the external
genitalia.2
Ambiguous
genitalia is a spectrum of disorders of sexual function with varying patterns
of appearance of the external genitalia, which may range from being a feminized
male to a masculinized female to different extents.1 Better understanding has also significantly
improved management. Ambiguous genitalia may be a part of a syndrome involving
other organ systems.1 Congenital Adrenal Hyperplasia (CAH) is the most
common cause of intersex disorder.3 It is otherwise known as androgenital
syndrome. It is an autosomal recessive disorder due to an inborn error in
adrenal steroid metabolism. There is a lack of cortisol production, resulting
in excess production of Adrenocorticotropic Hormone (ACTH) from the pituitary, which
stimulates excessive adrenal production of androgens with virilization of
female patients. Associated aldosterone deficiency may lead to excess salt
depletion in some cases.3,4
Affected girls
are potentially fertile, and they have normal internal genitalia 4 CAH has been classified into the classic(severe)
and the non-classic (mild) types based on the age of onset and the clinical
presentation.5 Cases of ambiguity of sex detected at birth are due
to adrenogenital syndrome unless proved otherwise. It is important to manage
features of aldosterone deficiency, which may be associated as this may present
as an emergency.4 Surgery remains a valid treatment option for cases
with markedly ambiguous genitalia.6
CASE
PRESENTATION
The patient is a 22-year-old
single undergraduate who resides with her parents. She presented with an inability
to achieve penetrative vagina intercourse due to a lack of appropriately sized vaginal
introitus which was first noticed in childhood but dismissed. This abnormality
became pronounced after puberty with associated clitoromegaly, especially at
sexual arousal. This gradually became a source of embarrassment and distress
for her, and she always avoided being naked in the presence of anyone,
including her female friends. She also reported feeling ashamed when she was
sexually aroused in the presence of her sexual partner due to clitoromegaly.
There was associated poor urinary stream, terminal dribbling, and post-void wetting
of her underwear.
Her
onset of secondary sexual characteristics was at 17 years, and menarche was at 18
years. She had normal, well-developed female
breasts, but she had excessive hair growth involving her face, chest, and
abdomen, requiring regular shaving. There has been associated oligomenorrhea
with cycle length varying between 60 and 120 days. History of minimal expressible
galactorrhea in both breasts. No history was suggestive of salt wasting, hypoglycemic
crises, or stunted growth. She has no
heat or cold intolerance, no neck swelling, no eye pain or recurrent frontal
headaches, no visual impairment, nor absence of perception of smell. There was
no history of insertion of corrosives or other foreign bodies into the vagina
or of abnormal vagina discharge in childhood. There was no history of similar
complaints in any of her two older sisters or other known family members. Mother
did not use non-prescription medication during pregnancy, and there was no
exposure to radiation.
She had
hirsutism, a male pattern of abdominal hair distribution, clitoromegaly with
fused labia marked only by hyperpigmentation, and a narrow introitus of <2cm
between the clitoris and the fused labia. The urethral meatus was only visible
on parting the fused labia, with no palpable gonad in the inguinal or perineal
regions. A capacious vagina was felt behind the fused labia. Digital rectal
examination revealed an anterior rectal wall that is depressible to a length of
about 8-10cm with a firm bulge into its proximal end which is suggestive of a
vaginal canal with proximal ectocervix.
Fig 1, Perineum
showing the clitoromegaly with fused labia
Fig
2. The perineum showing the clitoromegaly with the narrow vaginal introitus in-between parted fused labia
A clinical
diagnosis of a possible disorder of sex development (likely XX variant) was
made. Ultrasound scan showed a small-sized uterus measuring 23 X 33 X 52mm with
an endometrial thickness of 5mm. The
ovaries were normal looking with bilateral functional cysts (Right-20mm; Left-28mm).
The hormonal profile showed slightly elevated luteinizing hormone of 15.8 IU/mL
(1.6 -15.0 IU/mL), normal FSH level – 6.8IU/mL with LH/FSH ratio of 2.3, Serum
testosterone level was normal (1.2 nmol/L). The fasting plasma glucose, serum electrolytes,
urea, and creatinine were normal as well. Karyotyping was not available and
enzyme assays could not be done due to financial constraints as they were not
readily available.
Fig
3. Perineum
post-clitoroplasty and perineoplasty with separation of the fused labia.
Fig 4. Perineum three months
post-clitoroplasty and perineoplasty
She had
regional anesthesia; saddle block technique. Examination under anesthesia is
the same as described above with findings of a urethral meatus obscured but the
fused labia, 2cm (stretchable) opening into a capacious vaginal of about 8cm in
length, and smooth cervix felt. She had perineoplasty with separation of the
fused labia and suturing apart of each leaf to secure hemostasis. She also had clitoroplasty with excision of
the bulk of the erectile tissue. preservation of the neurovascular bundle and prepuce.
Speculum
examination after perineoplasty showed normal normal-looking cervix. An
improvised vagina mold was inserted into the vagina to keep the separated labia
leaves apart for 24 hours. She had a satisfactory post-operation period and was
discharged 5th day after surgery.
Follow-up reviews at 2 weeks as well as 3 months post-operation showed
normal findings. (Figs. 3 and 4 respectively). She has since resumed sexual
intercourse which she describes as satisfactory. She was counseled and referred
to the reproductive endocrinologist and clinical psychology teams.
DISCUSSION
Ambiguous genitalia represent a rare
but important group of disorders. The
exact prevalence of Disorders of Sexual Development is not known, especially in
developing countries.7 In most developed countries, children with
Disorders of Sexual Development are often diagnosed in infancy, with
interventions planned that may be implemented in adolescence. It is, however,
not unusual for children with ambiguous genitalia in developing countries to
present in adolescence or even much later. This may, however, be associated
with the onset of conflict of sexual identity. Some individuals may never
present but rather develop means to cope with the disorder.1,8 Although
this patient had ambiguous genitalia, which was noticed since childhood, she
did not present until 3 years after her first failed attempt at sexual
intercourse at the age of 22 years.
Ambiguous
genitalia represent a spectrum of disorders of sexual function which may range
from being a feminized male to a masculinized female.2 Ambiguous
genitalia may be a part of a syndrome involving other organ systems.1,2
The decision of the sex of rearing can be critical and must be based on several
factors, including the appearance of the genitalia, the possible outcome of
gender assignment surgeries, and the genetic sex of the patient. It should be
noted that as much as about one-quarter of such children may grow up and be
dissatisfied with their sex of rearing.9 This patient was raised as
female, which was the sole decision of the parents, and at puberty, she developed
female secondary sexual characteristics, and the internal genitals were well-developed
Mullerian duct, as is often the case with Congenital Adrenal Hyperplasia.
Congenital
Adrenal hyperplasia (CAH) is one of the most common causes of ambiguous
genitalia in females. It is an autosomal recessive disorder resulting from a deficiency
of one of the five enzymes required for the synthesis of cortisol. The most
common of which is 21α-hydroxylase deficiency. CAH may be associated with salt-wasting
from mineralocorticoid deficiency and failure of glucocorticoid functions, with
life-threatening effects.5 CAH may rarely be associated with
microcephaly.10 Congenital Adrenal Hyperplasia often has fewer
clinical manifestations in males, except in cases with 5α reductase deficiency,
which may appear as feminization of the male. It is common for such males with
ambiguous genitalia to be initially raised as females until puberty.11
Parents of neonates with
ambiguous genitalia often experience some degree of anxiety with the decision
on gender role assignment. The dilemmas that parents face in the complex and
challenging situation following the birth of a child with ambiguous genitalia
require early support from insightful professionals such as nurses. This
dilemma is worsened by the background of socio-cultural expectations to
determine the gender within a short period of at most a few days after birth. 6
Psychosocial
aspects of the treatment of disorders of sex development (DSDs) concern gender
assignment, information management and communication, timing of medical
interventions, consequences of surgery, and sexuality. Although the outcome is
often satisfactory, a variety of medical and psychosocial factors may jeopardize the psychological
development of children with DSDs. This sometimes results in the desire to
change gender later in life.12 In this case, she was raised as
female and developed female secondary sexual characteristics albeit later than
her peers.
A
thorough evaluation of infants, adolescents, or adults with ambiguous genitalia
should be done to understand the pathophysiology and determine the cause. This
evaluation is often better with a multidisciplinary approach.9
Karyotyping is an important investigation but it is not readily available in
Nigeria, although Barr body examination may be helpful. It is also common that
many of our patients cannot afford biochemical hormonal assays required to make
specific diagnoses of CAH, which are also often not readily available, as it
was the case. 13 Radiological, surgical, and histological
examination of the internal genitals can contribute to diagnosis.13
The Ultrasound scan done here demonstrated essentially normal ovaries and uterus,
suggesting that internal genitalia were female and she had menstrual cycles,
although irregular and characterized by oligomenorrhea. She could not afford
enzyme assays, and karyotyping was not available.
Whereas
surgery may play a significant role in the treatment of the ambiguous genitalia
associated with CAH, it is important to look out for and appropriately treat
the life-threatening complications of salt wasting and glucose metabolism
defects.4 The timing of surgical intervention has been a subject of
debate, whereas some clinicians believe gender assignment must be done early in
childhood, some others argue the need to delay till adolescence or even till
the individual is mature enough to determine their preferred sexuality.6
The type and extent of surgery that can be done will be dependent on the
appearance of the external genitalia.5 The appearance of the
clitoris can be a source of concern and psychosocial distress, and the outcome
of clitoral surgeries may have a significant impact on sexual function. It is
therefore of great importance to counsel the patients and/or their caregivers
on the possible outcomes before taking such a step.14 This patient.
was appropriately counseled on this possibility, and she expressed her desire
for clitoroplasty despite the possibility of reduced sexual function because
the appearance of the clitoris was a source of psychosocial distress for her.
This kind of distress is not uncommon in patients with DSD, and there may even
be associated psychological dysfunctions.14
Clitoral surgeries
remain the most common (over 90%) approach in the management of clitoromegaly,
with good cosmetic outcomes.6 It must, however, be noted that
cosmetic appearance alone is not an adequate measure of success. Surgical interventions
generally have excellent success, at least on a short-term basis. In the short
term, patient. had a satisfactory outcome for cosmesis, body image, and sexual
function. She is to continue follow up with the reproductive endocrinology and
clinical psychology teams for further evaluation and intervention when
necessary.
Conclusion
Disorders of
sexual development, though rare, may have significant psychosocial effects on the
patients. Different variants of these disorders may be seen, and CAH is the
commonest cause. Understanding the pathology with appropriate surgical
intervention may help improve the quality of life of the affected persons. A
multidisciplinary approach to care is necessary to achieve optimal outcomes.
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