Androgen Insensitivity Syndrome

Question 1

Definition

Answer 1

A condition where cells are unable to respond to androgen hormones due to a lack of androgen receptors.
X - linked recessive = mutation on androgen receptor gene on chromosome X.
Extra androgens are converted into oestrogen, resulting in female secondary sexual characteristics.

Question 2

What sex are these patients genetically?

Answer 2

XY chromosome = MALE

Question 3

Why do they exhibit female phenotype externally

Answer 3

The absent response to testosterone produced by gonads which results in regression of Wolffian ducts and the conversion of additional androgen’s to oestrogen result in a female phenotype externally.
Typically male sexual characteristics do not develop, and patents have normal female external genitalia and breast tissue.
Testes continue to produce Anti-Mullerian Hormone so internal female reproductive organs do not develops
Testes remain undescended inside the abdomen anywhere along inguinal canal or even underneath the labia.

Question 4

Which sexual organs do these patients have and why?

Answer 4

The patients have testes in the abdomen or inguinal canal, and the ABSENCE of
- uterus
- upper vagina
- cervix
- Fallopian tubes
- Ovaries
The female internal organs do not develop because the testes produce anti-Mullerian hormone, which prevents males from developing an upper vagina, uterus, cervix, and fallopian tubes.

Question 5

Clinical features

Answer 5

External female phenotype:
- Normal female external genitalia
- Breast tissue
Internal sexual organs:
- Testes present in abdomen or inguinal canal
- Absence of all internal female sexual organs (INFERTILE)
Lack of:
- Pubic hair
- Facial hair
- Male type muscle development

Question 6

What are these patients more at risk of developing?

Answer 6

Testicular cancer unless testes are removed

Question 7

Partial androgen insensitivity syndrome

Answer 7

Where there the cells have a partial response to androgens.
- This presents with more ambiguous signs and symptoms:
= micropenis or clitoromegaly,
= bifid scrotum,
= hypospadias
= diminished male characteristics.
= gynaecomastia

Question 8

How do these patients present in hospital?

Answer 8

• In infancy with inguinal hernias containing testes
• Alternatively it presents at puberty with primary amenorrhoea

Question 9

Hormone test results

Answer 9

• Raised LH
• Normal or raised FSH
• Normal or raised testosterone levels (for a male)
• Raised oestrogen levels (for a male)

Question 10

Treatment

Answer 10

Specialised MDT:
- Paeds, Gynae, Urology, Endocrinology, Clinical psychology
Medical inputs:
- Bilateral orchidectomy (removal of the testes) to avoid testicular tumours
- Oestrogen therapy
- Vaginal dilators or vaginal surgery can be used to create an adequate vaginal length
Generally raised as female but this is sensitive.