Ambiguous Genitalia

Summary
Introduction
Management
Clinical Evaluation
Investigation
Further Reading

Summary

Be very careful in your choice of words during the diagnostic period and do not sign the birth certificate until a definite decision as to the sex of rearing has been reached.

be aware of associated metabolic problems
palpable gonads imply the presence of testicular tissue
decisions as to sex of rearing may have no relationship to karyotypic, gonadal or genital status in isolation
there is some ongoing controversy as to when is the appropriate time to make decisions as to sex of rearing and who should be party to those decisions

Introduction

Approximately 1 in 4,500 births are complicated by ambiguous genitalia.

This situation is rarely anticipated and can be a source of great distress for parents, delivery room and nursery staff. Often there can be pressure on medical staff to "make it better" and assign a gender to the child arbitrarily in the first few hours after birth. This must be avoided at all costs. Staff must be careful in their choice of words when discussing the baby with parents. It is unnatural not to discuss a baby without using the terms "he" or "she" and it is easy to accidentally refer to the baby in a gender-orientated way. Parents who are often greatly distressed may assume that medical and nursing staff "know" what the gender of the baby "really is". Consequently any terminology used (deliberately or accidentally) will be given great emphasis by parents. This may lead to confusion and distress later if the suggested sex of rearing is at odds with initial "off the cuff" remarks.

Parents may seek advice regarding the naming of their infant. The usual advice is to select non-ambiguous names (ie using gender specific names) since it is thought that by encouraging the use of ambiguous (non-gender specific) names, one is implying an ongoing sense of "ambiguity".

Management

Be very careful in your use of terms when discussing the baby with ambiguous genitalia. Appropriate, non-gender orientated terms are listed in Table 1. Never refer to the baby in question as "it"

Table 1: Suggested phenomenology when dealing with babies with ambiguous genitalia.

FEMALE

AMBIGUOUS

MALE

She

Clitoris

Labia

Ovaries

Vagina, urethra

Your baby

Phallus

Folds

Gonads

Urogenital sinus

He

Penis

Scrotum

Testes

Urethra
The situation should be treated as a medical emergency, with paediatric endocrine advice being sought immediately

Clinical Evaluation

Genital ambiguity can be quantified according to the Prader scale (Figure 1). Other relevant clinical details include

gonads palpable in the labioscrotal or inguinal regions
size of the phallus
pigmentation of the genitalia
syndromic features
metabolic condition of the baby (paying particular attention to glucose, sodium and potassium)

The baby's mother should also be examined for signs of hyperandrogenism.

Care should be taken in the interpretation of examination findings in growth retarded or premature female neonates. These children may exhibit atrophic labia and clitoral oedema giving them an appearance of "pseudo-ambiguity".

It is a moot point where the boundary lies between severe perineal hypospadias and genital ambiguity. Inability to palpate the gonads in this situation may be indicative of a diagnosis other than isolated hypospadias.

Figure 1: Prader staging system for the degree of virilisation of the external genitalia.

Prader 0: Normal female external genitalia.
Prader 1: Female external genitalia with clitoromegaly.
Prader 2: Clitoromegaly with partial labial fusion forming a funnel-shaped urogenital sinus.
Prader 3: Increased phallic enlargement. Complete labioscrotal fusion forming a urogenital sinus with a single opening.
Prader 4: Complete scrotal fusion with urogenital opening at the base or on the shaft of the phallus.
Prader 5: Normal male external genitalia.

(Prader Von, A. (1954). "Der genitalbefund beim Pseudohermaproditismus femininus des kongenitalen adrenogenitalen Syndroms. Morphologie, Hausfigkeit, Entwicklung und Vererbung der verschiedenen Genitalformen." Helv. Pediatr. Acta. 9: 231-248.)

Investigation

Blood should be sent for

electrolytes
gonadotropins (LH, FSH)
testosterone
urgent karyotype
serum 17-hydroxyprogesterone (17OHP) levels (after day 3 of life)

Pelvic ultrasound (carried out by an experienced sonographer) should be undertaken as soon as possible.

Other investigations which may or may not be subsequently relevant include

sinugram
human chorionic gonadotropin stimulation test (to assess testosterone and dihydrotestosterone synthesis capability)

Differential diagnoses

Gonads palpable, 46XY
- gonadal dysgenesis
- partial androgen insensitivity
- biosynthetic defect in either testosterone or dihydrotestosterone production
Gonads impalpable, 46XX
- Congenital adrenal hyperplasia
- gonadal dysgenesis
- exogenous androgen exposure
Mosaic karyotype
- gonadal dysgenesis

Ongoing Management

Decision as to sex of rearing is made after opinions have been sought from the endocrine and surgical teams. It should be undertaken with the baby's parents after all the relevant investigation results have been discussed. The decision that will be influenced by an amalgam of

the baby's karyotype
gonadal status
internal and external genital duct status
potential for fertility and adequate sexual function
cultural influences

Do not complete the baby's birth certificate until the sex of rearing has been decided. There is a 60 day period of grace between the birth of a child and when their birth certificate needs to be completed - hence there is no rush. If the "wrong" sex is entered on the form it is extremely difficult to correct and requires judicial intervention.

Long term care

families require long term medical and psychological support
corrective surgery is usually undertaken within the first year of life
infants with CAH and congenital syndromes have additional requirements for ongoing medical therapy
disclosure to the patient as to their diagnosis is usually undertaken in mid to late adolescence when they have the ability to understand complex issues such as chromosomes, hormones etc, and possess some degree of emotional maturity