Disorders of sex development

Question 1

Congenital adrenal hyperplasia

Karyotype:
External genitalia:
Internal genitalia:
Special features:

Answer 1

Karyotype: XX
External genitalia: Ambiguous
Internal genitalia: Uterus and ovaries - normal mullerian
Special features: May have glucocorticoid and mineralocorticoid deficiency needing steroid replacement. Failure to recognise can be life threatening due to salt wasting crisis in neonate.

Due to enzyme deficiency in adrenal gland, usually 21-hydroxylase. Results in excessive production of androgens.

Question 2

Complete androgen insensitivity syndrome

Karyotype:
External genitalia:
Internal genitalia:
Special features:

Answer 2

Karyotype: XY
External genitalia: Ambiguous if partial, female if complete
Internal genitalia: streak gonads/testis, no uterus (Mullerian not developed due to AMH from testis)
Special features: Absent pubic and axillary hair/secondary sexual characteristics, at risk of osteoporosis, gonadal malignancy risk low until >50 years

Phenotypically female (especially if complete), normal breast development, high serum testosterone 
Partial- phenotype more challenging and can vary from ambiguous genitalia to phenotypically male and PAIS identified due to infertility

Question 3

Swyers syndrome

Karyotype: 
External genitalia: 
Internal genitalia: 
Special features:
Puberty:
Fertility: 
Ix:

Answer 3

Karyotype: XY
External genitalia: female
Internal genitalia: streak gonads (absence of second X means ovarian development can’t be sustained) and uterus - mullerian develops due to lack of AMH
Special features: High risk of malignancy, poor breast development, normal pubic and axillary hair
Puberty: absent breast development and primary amenorrhoea. Secondary sexual characteristics develop as androgens present
Fertility: replace oestrogen, can fall pregnant with donor oocytes
Ix: high gonadotrophins, low testosterone and oestrodiol levels

Question 4

5alpha- reductase deficiency

Karyotype:
External genitalia:
Internal genitalia:
Special features:

Answer 4

Karyotype: XY
External genitalia: Female/ambiguous
Internal genitalia: Male
Special features: autosomal recessive disorder. Start off with female phenotype but at puberty develop male secondary sexual characteristics and absent breasts.

Question 5

46XY/XX ovotesticular DSD

Karyotype:
External genitalia:
Internal genitalia:
Special features:

Answer 5

Karyotype: Either XX or XY
External genitalia: ambiguous
Internal genitalia: mix of ovaries and/or testes
Special features:

Question 6

Incidence of DSD

Answer 6

1:2000 approx

Question 7

Investigations for DSDs?

Answer 7

Depends on condition but general principles:

• FSH/LH
• Karyotype
• Testosterone
• 17 hydroxyprogesterone
• USS

Consider:

• DHT
• 5-alpha reductase
• CAH: short synacthen, androstenedione
• oestrodiol
• urinary steroids
• renal USS