Intersex - Classroom Notes

Intersex Normal Development Male - XY Testosterone à wolffian (mesonephric) duce development Mullerian inhibiting factor (MIF) from sertoli cells à atrophy of mullerian (paramesonephric) ducts Testosterone à positive development of external genitalia Female - XX Absence of MIF allows mullerian ducts to form uterus, tubes, and upper vagina Absence of testosterone à external genitalia develop in female form Intersex Most XO result in miscarriage or stillbirth. Can be chromosomal, gonadal or related to 2ndry sex characteristics Chromosomal Turners 1/2500 phenotypic female births, usually 45XO, some have deletion of part of X chromosome, can be mosaic. Maternal X is intact Main features are – Dwarfism Webbed neck Sexual infantilism (poor breast development) with streak gonads (vaginal & uterus in tact) Primary amenorrhoea Infertility Other features can include – shield chest, high arched palate, low set ears, lymphoedema, deafness, coarctation of aorta, pigmented moles Klinefelters 1/500 phenotypic males. XXY Main features – azospermia (à infertility), gynaecomastia, atrophic testes, tall & thin (no pubertal steroid surge delays epiphyseal fusion), scant facial hair, small prostate, high gonadotrophin levels XX/XY chimaerism usually due to dispermic conception. Like mixed gonadal dysgenesis (one gonad, one atrophic streak) Gonadal intersex Ovotesticular states (hermaphroditism) Most 46XX Presence of ovarian and testicular tissue in the same individual (as separate gonads or as ovotestes) Pure gonadal dysgenesis (or agenesis) Can only have a primative streak (undeveloped gonads) but normal chromosomes (XX or XY) Regardless of chromosomes all are phenotypic females (lack 2ndry sexual characteristics) Contrary gonadal development (sex inversion) XY females or XX males – due to deletions or mutations in SRY gene Secondary Sex Characteristic Partial masculinisation of females Congenital adrenal hyperplasia - Steroid synthesis errors due to enzyme deficiency Commonest is 21-hydroxylase deficiency (AR) Female with ambiguous genitalia (enlarged clitorusk, fused labia) Cannot produce cortisol, or aldosterone (so lose salt) Defect in enzyme pathway à extra testosterone produced à masculinisation of females Incomplete masculinisation of males Androgen insensitivity syndrome – X-linked recessive, absence of androgen receptors (androgens converted to oestrogen) à female phenotype with testes (in groin or abdomen). Have short, blind ending vagina but no uterus (no mullerian development so upper 2/3 tract missing), absent/scany pubic hair, Usually present with primary amenorrhoea. Diagnose by karyotype. Gonadectomy recommended because risk of Ca. Failure of peripheral conversion – of testosterone to more active dihydrotestosterone due to enzyme deficiency. AR. The increasing testosterone at puberty causes virilisation of phenotypic females. Presentation At birth – should karyotypes & assess likelihood of normal development Puberty – failure of puberty to occur / contrary feature occur Infertility clinics – due to not being what they appear to be! Management Treatment is not always possible so manage by communication & assessment. Plastic surgery may be appropriate Excision of intra-abdominal gonads may be appropriate as increased Ca risk