Download DISORDERED SEXUAL DIFFERENTIATION


Ambiguous genitalia

New term: complex genital anomaly
 Sex
determination
 Sex
differentiation
Murran K, Segal D (2009) Disorderd sexual differentiation (Ambiguous genitalia: an
appraoch to diagnosis and management. South African Paediatric Review Volume 6
no 3: 20-30
Murran K, Segal D (2009) Disorderd sexual differentiation (Ambiguous genitalia: an
appraoch to diagnosis and management. South African Paediatric Review Volume 6
no 3: 20-30
Murran K, Segal D (2009) Disorderd sexual differentiation (Ambiguous genitalia: an
appraoch to diagnosis and management. South African Paediatric Review Volume 6
no 3: 20-30

History

Clinical

Special investigations

Detailed family history

Prenatal exposure to exogenous or endogenous
androgens, estrogens or potential endocrine
disruptors

Maternal virilization during pregnancy

General examination – dysmorphisms

Examination of external genitalia

Phallus

Orifices

Labioscrotal folds

Gonads


Genetics – 46XX, 46XY, 46 XY/X0
Hormones (see cholesterol pathway)
17 OH progesterone
DHEA
Androstendione
Testosterone level

Electrolytes

Ultrasound

Laparoscopy
Team approach
Family doctor
Paediatric endocrinologist
Surgeon
Geneticist
Social worker
Psychologist
 Involve child and parents

GENDER ASSIGNMENT

Based on
-
specific pathophysiology
prognosis for spontaneous pubertal
development
potential for sexual activity
potential for fertility
endocrine function
parental wishes
Psychosexual development
APPROACHES TO GENDER ASSIGNMENT

Medical emergency
do test stat and inform the
parents what the diagnosis is
pros and cons

Decide gender later and let child decide
Decide gender later and child
involved in decision
Pros and cons


Surgical treatment of complex genital
anomalies is controversial
Specific surgical procedures at specific stages
dependent on gender assignment

1. Overvirilization of female fetus (46 XX DSD)

2. Undervirilization of male fetus (46 XY DSD)

3. True hermaphrodite (or ovotesticular DSD)

4. Gonadal dysgenesis




Congenital adrenal hyperplasia – not difficult
to diagnose
Autosomal recessive
Leads to deficiency in enzyme function in the
cortisol and aldosterone pathways
Most common 21 hydroxylase (21OH)
deficiency
•
Girl:
- present with ambiguous genitalia
- low Na , High K
- eventually becomes dehydrated
•
Boy
- presents with dehydration and
hyperkalaemia
- normal genitalia therefore no clue
to diagnosis

46 XY

Defect in testosterone production

Defect in testosterone metabolism

Defect in testosterone action

Ovotesticular Disorder of sexual diffirentiation

Common in central and southern Africa.

Both ovarian and testicular tissue present.

Diagnosis confirmed on biopsy of gonads

Outcome regarding fertility has been disappointing
 Spectrum
of disorders that lead to
the maldevelopment of the
gonads and subsequently varying
degrees of Disorders of Sexual
differentiation




Raine J, Donaldson MDC, Gregory JW, Savage MO,
Hintz RL (2006) Practical Endocrinology and Diabetes
in Children 109-128
Murran K, Segal D (2009) Disorderd sexual
differentiation (Ambiguous genitalia: an appraoch to
diagnosis and management. South African Paediatric
Review Volume 6 no 3: 20-30
Wiersma R True hermaphroditism in southern Africa:
the clinical picture Pediatr Surg Int (2004) 20: 363-368
Sperling (2008) Ambiguous genitalia. Paediatric
Endocrinology 3rd Edition:127-164