Testicular Feminization syndrome

INTRODUCTION:

• Testicular feminization syndrome: Now more appropriately called the complete androgen insensitivity syndrome
• This is a genetic disorder that makes XY fetuses insensitive (unresponsive) to androgens (male hormones).
•  Instead, they are born looking externally like normal girls. 
• Testosterone levels may be Normal/High/Low depending on the degree of androgen resistance and the contribution of estradiol to feedback inhibition of the hypothalamus pituitary axis
• Internally, there is a short blind-pouch vagina and no uterus, fallopian tubes or ovaries. 
• Present with absence of both Mullerian and Wolffian duct structures
• There are testes in the abdomen or the inguinal canal.

• Complete Androgen Insensitivity (CAIS)(Grade 7)
• Absent wolffian duct derivatives
• Absence or presence of epididymides and/or vas deferens
• Abdominal testes
• Short blind-ending vagina
• Limited or absent pubic and/or axillary hair

Partial Androgen Insensitivity (PAIS):

• Predominantly Female (Grade 5 and 6)
• Clitoralmegaly (enlarged clitoris) 
• Fusion of the labia
• Pubic hair growth at puberty
  
• Ambiguous(Grade 4)
• Descended or undescended testes 
• Half way between male and female genetalia
  
• Predominantly Male (Grade 2 and 3)
• Micropenis 
• Cryptorchidism (absence of one or both testes) 
• Perineal hypospadias
• Mild Androgen Insensitivity (MAIS) (Grade 1):
• Impaired spermatogenesis and/or impaired pubertal virilization 
•  Infertility
• Gynecomastia in puberty
• Higher voice 

PATHOPHYSIOLOGY:

• Impairment of normal receptor mediated transcription causes pathogenicity through three distinct mechanisms:
• Virilization: The development of sexual differences.
• Masculinization: The development of both primary and secondary male characteristics.
• Anabolism: The inability to generate larger molecules and compounds necessary for signalling and gene transcription.

FEATURES:

In developing embryo and fetus:

• At 9 weeks: testes secrete androgens.
• Between 11 and 18 weeks: Testosterone peaks stimulates differentiation of the Wolffian duct system into epididymis, vas deferens and seminal Vesicles, followed by prostate development and external genitalia

At puberty: 

• Menstruation doesn’t occur 
• Testosterone levels are high 
• Absent ovaries
• Lack of male secondary hair characteristics 
• No change in voice

TREATMENT:

• General Treatment based on correct diagnosis
• Difficult and complicated decision due to socio-economic implications
• Surgery: gonadectomy( at puberty)
• Hormone replacement
• Counseling
• Specific Cases:

PAIS: 

• Testosterone treatment: promote virilization (male characteristics) of external genitalia before sex assignment. 

CAIS: 

• XY individuals having normal female external genitalia: 
• Individuals raised as females
• Prepubertal gonadectomy 
• Estrogen replacement therapy 
• Vaginal length requires dilatation 
• Psychological support of the family 
• MAIS: promoting spermatogenesis and fertility in a man with MAIS

Exam Question

• 46XY, Primary amenorrhea & Vagina may be present in testicular feminization syndrome
• High testosterone levels is seen in  testicular feminization syndrome
• In Testicular Feminization syndrome Gonadectomy is indicated At puberty
• Androgen insensitivity syndrome the  Phenotype may be completely female
• Androgen Insensitivity Syndrome is present with absence of both Mullerian and Wolffian duct structures
• Short vagina and absent ovaries may be seen in Testicular Feminization syndrome
• Primary Amenorrhea with absent uterus, normal breasts and scanty pubic hair is seen in Androgen Insensitivity Syndrome