Transcript 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
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History
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Clinical
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Special investigations

Detailed family history

Prenatal exposure to exogenous or endogenous
androgens, estrogens or potential endocrine
disruptors
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Maternal virilization during pregnancy
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General examination – dysmorphisms
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Examination of external genitalia
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Phallus
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Orifices
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Labioscrotal folds
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Gonads
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Genetics – 46XX, 46XY, 46 XY/X0
Hormones (see cholesterol pathway)
17 OH progesterone
DHEA
Androstendione
Testosterone level
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Electrolytes
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Ultrasound
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Laparoscopy
Team approach
Family doctor
Paediatric endocrinologist
Surgeon
Geneticist
Social worker
Psychologist
 Involve child and parents
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GENDER ASSIGNMENT
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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
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Medical emergency
do test stat and inform the
parents what the diagnosis is
pros and cons
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Decide gender later and let child decide
Decide gender later and child
involved in decision
Pros and cons
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Surgical treatment of complex genital
anomalies is controversial
Specific surgical procedures at specific stages
dependent on gender assignment
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1. Overvirilization of female fetus (46 XX DSD)
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2. Undervirilization of male fetus (46 XY DSD)
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3. True hermaphrodite (or ovotesticular DSD)
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4. Gonadal dysgenesis
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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
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46 XY
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Defect in testosterone production
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Defect in testosterone metabolism
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Defect in testosterone action
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Ovotesticular Disorder of sexual diffirentiation
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Common in central and southern Africa.
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Both ovarian and testicular tissue present.
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Diagnosis confirmed on biopsy of gonads
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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
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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