Disorders of Sexual Differentiation Flashcards
What is the historical view of gender? (3)
General assumption that single feature e.g .presence/absence of penis would predict that all other gender features as concordantly male or female
Bipolar physiological classification (M/F) is paralled by bipolar allocation of psychosocial traits or gender attributes (based on attitudes, expectations + gender roles)
What is the concept of gender identity? (2)
Most individuals have gender identity that are fully congruent with sex
A few individuals may feel their gender identity is at variance with their assigned gender - transgender/transexual
What is gonadal dysgenesis? (2)
Incomplete sexual differentiation i.e. missing SRY in male or complete deletion of second X in female (Turner’s syndrome)
What is meant by intersex? (2)
Some components of both tracts or ambiguous genitalia
Sex of infant difficult to determine
What is meant by sex reversal? (1)
Phenotype doesn’t match genotype (i.e. may be male genotypically but externally look female)
What is androgen insensitivity syndrome (AIS)? (4)
Where an 46XY individual produces testosterone in Leydig cells but it has no effect (no/faulty receptors)
Testes form + Sertoli cells produce AMH so Mullerian ducts regress
But no differentiation of Wolffian ducts (testosterone can’t act on TR) + no external male genitilia (DHT can’t act on TR)
Often feel female
What is the incidence of complete AIS? (1)
1:20,000
What are the signs and symptoms in complete AIS? (10)
Undescended testes (cryptorchidism) - ultrasound scan
No uterus or fallopian tubes
Ext. genitalia appear female
Usually present with primary amenorrhoea
Lack of body hair
Karyotype with male levels of androgens
Hormonal puberty may be feminising without intervention - aromatisation of endogenous androgens to oestrogens
Lack response to androgens
Sex assignment + rearing almost always female
Usually identify as female
What happens in partial AIS? (6)
Unknown incidence as it is a spectrum of phenotypes
From normal female ext. genitalia to ambiguous genitalia (perineoscrotal hypospadias, microphallus, cryptorchidism)
Minor genital deviation may be repaired surgically or go unnoticed
In some cases pubertal gynecomastia or ambiguous genitalia surgically corrected
Androgen therapy in some case
Majority of individuals develop identity correlating with their assigned gender at birth
What is 5-α-reductase deficiency? (4)
5-α-R occurs in a 46XY individual who produces testosterone but not DHT
Testes form, Sertoli cells produce AMH, Leydig cells produce testosterone
Internal male genitalia develops
External male structures do not fully develop
What is the incidence of 5-α-reductase deficiency? (2)
Incidence varies enormously
Degree of enzyme block varies so therefore does the presentation
What are the signs + symptoms of 5-α-reductase deficiency? (4)
May appear mainly female or have ambiguous genitalia e.g. labioscrotal folds or clitoridean penis
Need to assess potential high testosterone level which will occur at adrenarche + puberty may induce virilisation
Both testosterone + DHT are capable of masculinising the brain in primates
So some brain masculinisation in utero is possible with this is condition
What happens in Turner’s syndrome (XO)? (9)
Female gender Failure of ovarian function 'Streak ovaries' = ovarian dygenesis Demonstrates need for 2 Xs for ovarian developmet Uterus + tubes are present but small Other defects in growth + development Wide spectrum of phenotypic disorders + severity May be fertile, may have mosaicism Hormone support of bones + uterus
What causes congenital adrenal hyperplasia (CAH)? (5)
Pathway block in steroidogenesis (21-hydroxylase enzyme deficiency)
Failure to synthesise cortisol -> reduced -ve feedback on ACTH (pituitary)
High levels of ACTH stimulate adrenal hyperplasia + excessive adrenal androgen production
Female is exposed to high levels of androgens in utero
In females this mimics DHT causing masculinisation of external genitalia
How does congenital adrenal hyperplasia present? (5)
No SRY, no testes, no AMH
Mullerian ducts remain
High androgen levels masculinise ext. genitalia
Completeness of enzyme block varies - may have developed Wolffian structures + ambiguous masculinised ext. genitalia of hirsutism
XX patients assignged as girls developed female gender identity but with more masculine childhood behaviour, lower maternal interest
