Dis of Sex Diff Flashcards
Define gonadal dysgenesis
→Sexual differentiation is incomplete.
→Usually missing SRY in male, or partial or complete deletion of second X in female
→Also used as a general description of abnormal development of the gonads.
What is sex reversal?
→Phenotype does not match genotype, ie may be male genotypically but externally look like a female
What is intersex?
→Have some components of both tracts or have ambiguous genitalia.
What is androgen insensitivity syndrome?
→Testosterone is made but has no effect
What happens AIS?
→Testes form and make AMH so Mullerian ducts regress.
→No differentiation of Wolffian ducts
→No external male genitalia- no descended testes
→no uterus or fallopian tubes
→External genitalia appear female - abbreviated blind vaginal pouch.
What is a clue for AIS?
→lack of body hair
What does ultrasound and karyotyping reveal in AIS?
→male levels of androgen
What is partial AIS?
→Minor genital deviations go unnoticed or may be surgically repaired.
→At puberty development of male secondary characteristics may not be very pronounced. In some cases pubertal gynecomastia (androgen/estrogen ratio) or ambiguous genitalia surgically corrected. Androgen therapy in some cases.
What happens if XY male is unable to make or respond to AMH in utero?
Persistent Mullerian duct syndrome
→limited to XY offspring
What is PMDS type I?
→from mutations of the gene for AMH on chromosome 19
What is PMDS type II?
→mutations of the gene for the AMH receptor (AMH-RII) on chromosome 12
What happens in PMDS?
→Testes form and either fail to make AMH or AMH receptor absent.
→Mullerian ducts remain.
→Differentiation of Wolffian ducts and masculinised external genitalia
What are the treatments for PMDS?
→Surgery (orchiopexy) to retrieve the testes and position them in the scrotum. If testes cannot be retrieved, testosterone replacement at puberty is an option
→Removal of uterus dissection of Müllerian tissue away from the vas deferens/epididymis.
→Laparoscopic hysterectomy may prevent the occurrences of neoplastic tissue formation
What are the common presentation for PMDS?
→60–70% of cases have intra-abdominal Mullerian structures and testes in a position simulating that of the ovaries
→20–30% have one testis in a hernial sac or scrotum together with Mullerian structures.
→10% have both testes located in the same hernial sac (transverse testicular ectopia) along with the uterine tubes and/or uterine structures.
→All have increased risk of malignant transformation.
What happens if an XY individual produces testosterone but not DHT?
→5-α-Reductase Deficiency
What happens in 5-α-Reductase Deficiency?
→Testes form and make AMH so Mullerian ducts regress
→Wolffian ducts develop
→No external male genitalia
Describe 5a-reductase defieciency
→Testes form, AMH acts, testosterone acts. Internal structures form. External male structures do not fully develop
→May appear mainly female or may have ambiguous genitalia such as labioscrotal folds or clitoridean penis
→Both testosterone and dihydrotestosterone (DHT) are capable of masculinising the brain in non-human primates so some brain
Describe Turner’s Syndrome
→XO have failure of ovarian function. ‘Streak’ ovaries = ovarian dysgenesis
→ Uterus and tubes are present, may be small or other defects in growth and development
What does Turner’s syndrome illustrate about ovarian development?
→we need two Xs for ovarian development
What may those with Turner’s syndrome suffer from?
→hormone deficiency and uterus
What happens if XX female is exposed to high levels of androgens in utero?
→Congenital adrenal hyperplasia
What happens in CAH?
→No SRY so no testes and no AMH.
→Mullerian ducts remain.
→Masculinised external genitalia, but androgen levels not usually high enough to rescue Wolffian ducts.
What does ACTH stimulate?
→rapid uptake of cholesterol into the adrenal cortex
→Upregulates cholesterol side-chain cleavage enzyme (P450scc).
→Increases glucocorticoid secretion
Describe CAH presentation
→May have developed Wolffian structures and ambiguous masculinised external genitalia or hirsutism
