A supplemental system of phenotypic grading that uses seven classes instead of the traditional three was proposed by pediatric endocrinologist Charmian A. Quigley et al. in 1995. The first six grades of the scale, grades 1 through 6, are differentiated by the degree of genital masculinization; grade 1 is indicated when the external genitalia is fully masculinized, grade 6 is indicated when the external genitalia is fully feminized, and grades 2 through 5 quantify four degrees of increasingly feminized genitalia that lie in the interim. Grade 7 is indistinguishable from grade 6 until puberty, and is thereafter differentiated by the presence of secondary terminal hair; grade 6 is indicated when secondary terminal hair is present, whereas grade 7 is indicated when it is absent. The Quigley scale can be used in conjunction with the traditional three classes of AIS to provide additional information regarding the degree of genital masculinization, and is particularly useful when the diagnosis is<unk> . Left, 19-year-old man with grade 3<unk>  before initiation of androgen therapy. Right, Habitus after 3.5 years of androgen treatment.<unk>  is diagnosed when the degree of androgen insensitivity in an individual with a 46,XY karyotype is great enough to<unk> ly prevent the masculinization of the genitalia, but is not great enough to completely prevent genital masculinization. This includes any phenotype resulting from androgen insensitivity where the genitalia is<unk> ly, but not completely masculinized. Genital ambiguities are frequently detected during clinical examination at birth, and consequently, a<unk>  diagnosis can be made during infancy as part of a differential diagnostic workup. Pubertal undervirilization is common, including gynecomastia, decreased secondary terminal hair, and / or a high pitched voice. The phallic structure ranges from a penis with varying degrees of diminished size and hypospadias to a slightly enlarged clitoris. Wolffian structures (the epididymides, vasa deferentia, and seminal vesicles) are typically<unk> ly or fully developed. The prostate is typically small or impalpable. Müllerian remnants are rare, but have been reported. The gonads in individuals with<unk>  are testes, regardless of phenotype; during the embryonic stage of development, testes form in an androgen-independent process that occurs due to the influence of the SRY gene on the Y chromosome. Cryptorchidism is common, and carries with it a 50% risk of germ cell malignancy. If the testes are located intrascrotally, there may still be significant risk of germ cell malignancy; studies have not yet been published to assess this risk. Predominantly male phenotypes vary in the degree of genital undermasculinization to include micropenis, chordee, bifid scrotum, and / or pseudovaginal perineoscrotal hypospadias. Impotence may be fairly common, depending on phenotypic features; in one study of 15 males with<unk> , 80% of those interviewed indicated that they had some degree of impotence. Anejaculation appears to occur somewhat independently of impotence; some men are still able to ejaculate despite impotence, and others without erectile difficulties cannot. Predominantly female phenotypes include a variable degree of labial fusion and clitoromegaly. Ambiguous phenotypic states include a phallic structure that is intermediate between a clitoris and a penis, and a single perineal orifice that connects to both the urethra and the vagina (i.e. urogenital sinus). At birth, it may not be possible to immediately differentiate the external genitalia of individuals with<unk>  as being either male or female, although the majority of individuals with<unk>  are raised male. Schematic representation of the Quigley scale. Grades 2 through 5 quantify four degrees of increasingly feminized genitalia that correspond to<unk> . Grades 1 and 6/7 correspond to MAIS and CAIS, respectively. Given the wide diversity of phenotypes associated with<unk> , the diagnosis is often further specified by assessing genital masculinization. Grades 2 through 5 of the Quigley scale quantify four degrees of increasingly feminized genitalia that correspond to<unk> . Grade 2, the mildest form of<unk> , presents with a predominantly male phenotype that presents with minor signs of undermasculinized genitalia, such as isolated hypospadias, which can be severe. Hypospadias may manifest with a<unk> ly formed channel from the urethral opening to the glans. Until recently, it was thought that isolated micropenis was not a manifestation of<unk> . However, in 2010, two cases of<unk>  manifesting with isolated micropenis were documented. bifid scrotum, microphallus-like clitoris, and urethral orifice with terminal sinus urogenitalis Grade 3, the most common phenotypic form of<unk> , features a predominantly male phenotype that is more severely undermasculinized, and typically presents with micropenis and pseudovaginal perineoscrotal hypospadias with bifid scrotum. Grade 4 presents with a gender ambiguous phenotype, including a phallic structure that is intermediate between a clitoris and a penis. The urethra typically opens into a common channel with the vagina (i.e. urogenital sinus). Grade 5, the form of<unk>  with the greatest degree of androgen insensitivity, presents with a mostly female phenotype, including separate urethral and vaginal orifices, but also shows signs of slight masculinization including mild clitoromegaly and / or<unk>  labial fusion. Previously, it was erroneously thought that individuals with<unk>  were always infertile; at least one case report has been published that describes fertile men that fit the criteria for grade 2<unk>  (micropenis, penile hypospadias, and gynecomastia). Comorbidity Histopathology of testicular tissue showing immature germ cells and spermatagonia with decreased tubular diameter. Scattered groups of Leydig cells appearing immature. All forms of androgen insensitivity are associated with infertility, though exceptions have been reported for both the mild and<unk>  forms.<unk>  is associated with a 50% risk of germ cell malignancy when the testes are undescended. If the testes are located intrascrotally, there may still be significant risk of germ cell malignancy; studies have not yet been published to assess this risk. Some men with<unk>  may experience sexual dysfunction including impotence and anejaculation. A few AR mutations that cause<unk>  are also associated with prostate and breast cancers. Vaginal hypoplasia, a relatively frequent finding in CAIS and some forms of<unk> , is associated with sexual difficulties including vaginal penetration difficulties and dyspareunia. There are indications that individuals with an intersex condition may be more prone to psychological difficulties, due at least in part to parental attitudes and behaviors, and concludes that preventative long-term psychological counseling for parents as well as for affected individuals should be initiated at the time of diagnosis. More recent research based on interviews of people with intersex variations indicate a need for more family protection from intervention and more family support. Lifespan is not thought to be affected by AIS.
Partial androgen insensitivity syndrome
Mild androgen insensitivity syndrome
Complete androgen insensitivity syndrome
Androgen insensitivity syndrome
Estrogen insensitivity syndrome
Aromatase excess syndrome
Gonadotropin-releasing hormone insensitivity
Kallmann syndrome