What is the diagnosis for Androgen Insensitivity Syndrome (AIS)?

From the Guidelines

Androgen resistance diagnosis is primarily based on a combination of clinical evaluation, hormonal testing, genetic analysis, and imaging studies, with genetic testing for mutations in the androgen receptor gene being the most definitive diagnostic tool. When diagnosing androgen resistance, it is crucial to consider the patient's physical features, such as ambiguous genitalia in infants or primary amenorrhea in adolescent females, as well as their hormonal profile, which typically shows elevated testosterone levels with normal or high luteinizing hormone (LH) levels 1. The diagnostic process may involve:

• Clinical evaluation to assess physical features and medical history
• Hormonal testing to evaluate testosterone and LH levels
• Genetic analysis to identify mutations in the androgen receptor gene
• Imaging studies, such as pelvic ultrasound or MRI, to evaluate internal reproductive structures Key findings in androgen resistance diagnosis include:
• Elevated testosterone levels with normal or high LH levels
• Mutations in the androgen receptor gene on the X chromosome
• 46,XY chromosomal pattern despite female external appearance in complete AIS
• Absent or underdeveloped Müllerian structures and the presence of testes in various locations on imaging studies A multidisciplinary approach involving endocrinologists, geneticists, urologists, gynecologists, and psychologists is essential for proper diagnosis and management of androgen resistance, as the condition exists on a spectrum from mild to complete resistance, each requiring individualized care approaches 1.

From the Research

Androgen Resistance Diagnosis

• Androgen insensitivity syndrome (AIS) is a disorder characterized by peripheral androgen resistance due to androgen receptor mutations in subjects with 46 XY karyotype 2.
• The diagnosis of AIS can be achieved through genetic testing, including karyotype examination and androgen receptor sequencing 2, 3.
• Laboratory tests showing elevated LH and testosterone levels despite mild or absent virilization may be helpful in diagnosing AIS 2, 3.
• The clinical phenotype of AIS can vary, with complete AIS (CAIS) characterized by female external genitalia, partial AIS (PAIS) characterized by ambiguous genitalia, and mild AIS (MAIS) characterized by mild symptoms of undervirilization 4, 5.

Diagnostic Criteria

• Elevated LH and testosterone levels despite mild or absent virilization 2, 3.
• Genetic testing, including karyotype examination and androgen receptor sequencing 2, 3.
• Clinical presentation, including female external genitalia in CAIS, ambiguous genitalia in PAIS, and mild symptoms of undervirilization in MAIS 4, 5.

Management

• A multidisciplinary team consisting of physicians, surgeons, and psychologists is highly recommended to support the patient and his/her family on gender identity choices and subsequent appropriate therapeutic decisions 2.
• Treatment depends on the phenotype and social sex of the individual 3.
• Open issues in the management of AIS include decisions on sex assignment, timing of gonadectomy, fertility, psychological outcomes, and genetic counseling 3, 4.