📖 About Androgen Insensitivity Syndrome (AIS)
- Genetic Background: AIS occurs in individuals with a 46,XY karyotype. Mutations in the androgen receptor gene on the X chromosome render tissues insensitive to androgens.
- Pathophysiology: Despite normal or high testosterone production, tissues cannot respond. The result is failure of virilisation, leading to a spectrum of phenotypes.
- Types:
- CAIS (Complete): Female phenotype, no uterus, normal breasts, scant pubic/axillary hair.
- PAIS (Partial): Ambiguous genitalia, undervirilisation.
- MAIS (Mild): Normal male genitalia, infertility, gynaecomastia.
🩺 Clinical Features
- Secondary Sexual Characteristics: Normal breast development (due to aromatisation of testosterone → oestradiol), but sparse pubic/axillary hair.
- Reproductive Anatomy: No uterus; short, blind-ending vagina. Intra-abdominal or inguinal testes.
- Fertility/Menstruation: Primary amenorrhoea; infertility.
- Family History: X-linked pattern, may affect multiple maternal male relatives.
- Classic Exam Scenario: “15-year-old girl with primary amenorrhoea, normal breast development, scant pubic hair, absent uterus.”
🔍 Investigations
- Hormonal Profile: Testosterone in male range, low–normal oestradiol, ↑ LH/FSH (loss of feedback).
- Karyotype: 46,XY.
- Imaging: Ultrasound/MRI → absent uterus, intra-abdominal gonads.
- Genetic Testing: AR gene mutation analysis (confirmatory).
💊 Management
- Psychological Support: Early counselling for patient and family on gender identity, fertility, sexuality.
- Malignancy Risk: Undescended testes have ~25% risk of malignancy.
Gonadectomy is usually advised after puberty to allow natural breast development.
- Surgical Options: Vaginoplasty or progressive dilatation if functional vagina desired.
- Hormone Replacement: Oestrogen replacement post-gonadectomy to maintain secondary sexual features + bone health.
- Multidisciplinary Care: Involves endocrinology, gynaecology/urology, clinical genetics, and psychology.
💡 Clinical Pearls
- Triad: Phenotypic female + primary amenorrhoea + absent uterus.
- Red flag: Normal breasts with absent uterus → think AIS or MRKH (Mayer-Rokitansky-Küster-Hauser). Pubic hair pattern distinguishes them (scant in AIS, normal in MRKH).
- Always deliver results sensitively, as gender identity and disclosure require expert counselling.
✅ Conclusion
Androgen Insensitivity Syndrome is an X-linked recessive condition where XY individuals present with female or undervirilised phenotypes due to defective androgen receptors.
It is characterised by normal breast development, scant pubic hair, primary amenorrhoea, absent uterus, and intra-abdominal testes.
Diagnosis requires karyotyping and hormone assays; management is multidisciplinary, focusing on counselling, prophylactic gonadectomy after puberty, and hormone replacement therapy.
